Microbiome testing can be confusing: many companies, different technologies and a lack of standards make it hard to get actionable insights from the data. Find out how technologies and labs differ and what information is actionable from today’s microbiome tests.

In this episode we continue our discussion of the microbiome that we started in Episode 9 and continued with Episode 37. Today we try to help you navigate the confusing field of microbiome testing companies and discuss the pros and cons of different technologies.

Examples and lessons learned from our own testing will give you an idea of how a microbiome test can help you make decisions about your health. Finally, we discuss what we think the future of microbiome testing holds.

[Why microbiome testing is important] is that unlike genomics and genetics and your human DNA, which I find very fascinating, but there’s not a whole lot you can do to change it. Despite the fact that there are a lot of genes that are involved, there’s not a whole lot you can do if you find out that you’ve got the gene for this or that. Whereas with the microbiome you’ve got way more genes and you can change them. And I think those two things are part of the reason that I’m very excited about the microbiome.”
– Richard Sprague

Long-time software executive Richard Sprague discovered his love for science through microbiome self-experimentation, studying questions like “Can I improve sleep by feeding certain gut microbes?” or “What is the impact of a gut cleanse on my gut bacteria?”

Formerly “Citizen Science in Residence” at uBiome, a biotech company, microbiomics is of particular interest to Richard because it is easy to get access to a lot of raw data that let non-specialists like him make interesting discoveries at the cutting edge of medicine and science. Richard shares his experiments and insights on his Medium Publication called Personal Science and the Microbiome and his blog.

The episode highlights, biomarkers, and links to the apps, devices and labs and everything else mentioned are below. Enjoy the show and let me know what you think in the comments!

itunes quantified body

What You’ll Learn

  • Why is the microbiome interesting (5:40).
  • Microbiome testing is now more accessible to the public (7:45).
  • Different technologies for trying to understand your gut and what’s going on there and the pros and cons of these technologies. Technologies discussed include: Cell culture, PCR, 16S sequencing, metagenomic sequencing (9:02).
  • What is the different between a different bacterial strain and a different species and why this distinction is important when analyzing your microbiome (17:40).
  • Cutting edge new technologies to understand your microbiome better: transcriptomics, which looks at what genes are active, proteinomics which looks at the actual proteins and metabolomics, which analyzes metabolites (20:10).
  • The reasons why the results from different labs are different (27:30).
  • The different labs doing microbiome testing and compare notes on the ones they used (33:13).
  • How glucose response and the microbiome are interdependent and knowing more about your microbiome might allow you to predict your body’s glucose response to different foods (51:26).
  • The labs at the bleeding edge of transcriptonomics (57:29).
  • N=2 experiences with the labs used and how they interpret and compare the data they received (59:24).
  • The effects of his ketogenic diet on his microbiome (1:02:44).
  • Discussion of gut microbiome diversity, day-to-day variability and individual difference in the microbiome (1:15:54).
  • A self-experiment he has done to try and change is microbiome taking a probiotic and the effects of traveling and eating different foods on the microbiome (1:20:15).
  • A way to change the nose microbiome using kimchi (1:22:01).
  • Advantages of a varied diet over taking probiotic pills to change the microbiome (1:24:06.)
  • High-level thoughts and recommendations about using different microbiome tests (1:28:34).
  • Why everybody doing lab tests should try to get the raw data from the lab (1:36:30).
  • Discussion of what future technologies and applications will useful to get even more information out of the body’s microbiomes (1:38:23).
  • Improvements that would provide better data and insights from microbiome testing (1:41:44).
  • How travel impacts the microbiome (1:47:03).
  • Where to learn more about the microbiome (1:55:42).
  • Information about what Richard is tracking and his interest in traditional foods and medicine (1:57:37).
Thank Richard on Twitter for this interview.
Click here to let him know you enjoyed the show!

Richard Sprague

Recommended Self-Experiment

Use Kefir to Change Your Microbiome

  1. Tool/ Tactic: Richard found a real noticeable difference in the microbiome after drinking kefir, in particular a couple of microbes that he did not have before he started drinking kefir and that he has now. Interestingly, one is associated with recovery from Crohn’s Disease. See Richard’s academic pre-print paper.
  2. Tracking: to track the effects of adding fermented food like kefir to your diet you need to get your gut microbiome tested before the start of the diet and several weeks or months later.

Kimchi for Sinusitis Treatment

In sinusitis sufferers the sinus microbiome is out-of-whack and the probiotic Lactobacillus Sakei is missing. L. Sakei can work as a sinusitis treatment if put into the nostrils. Kimchi is a natural source of L. Sakei. To experiment with kimchi to treat sinusitis Damien recommends the following:

  • Put a teaspoon in a container with kimchi and scoop up some of the juice.
  • Dip your finger into the liquid and put your fingers up both nostrils spreading the liquid.

More information on how to apply kimchi juice to treat sinusitis can be found here. The scientific paper underlying this approach is also available.

Tools & Tactics

Diet & Nutrition

  • Fasting: Fasting interventions can potentially change the microbiome. In this episode it was discussed as a tool or experiment in particular for any chronic issues/ unidentified health issues that no one knows how to solve.

Sleep

  • Good sleep is essential for the body. Richard experimented with potato starch to boost his bifidobacterium levels. The result of his self-experimentation can be found in his blog. Although this approach did not work for him, other people have seen positive effects and he recommends that people with problems sleeping try potato starch.
  • Damien is experimenting with three different approaches to improve his sleep:
    1. 10,000Lux SAD (seasonal affective disorder) light. Using this light for two hours every morning simulates strong daylight. This approach has worked for him and his theory is, that the strong light in the morning is a way of resetting his sleep cycle. SAD light use to improve sleep and prevent daytime sleepiness is discussed in this study.
    2. Going to bed really early also helps him to maintain a solid 7 to 7.5 hours of sleep per night. He now goes to bed by 9 pm.
    3. Taking a glycine supplement to reduce night wakings.1,2

Tech & Devices

  • 10,000 Lux Lamp: Lamp that replicate strong sunlight. Damien has been using this in the morning to reset the circadian rhythm and as a result improve sleep quality. These lamps are designed to be used with Seasonal Affective Disorder, by providing sunlight in dark months of the year.
  • Sleep Tracking Devices mentioned include:
    • Zeo: A popular fitness tracker that went bankrupt due to issues with its business model.
    • Fitbit: This version of the FitBit integrates sleep tracking.
    • Oura Ring: OURA is a convenient wearable ring that has become popular over the last year. The company is currently participating in studies to understand the accuracy of its sleep tracking. Damien uses it to track sleep duration only – the base metric.(Note: If you’re looking at buying this discount code gives you 75 Euros off “TNBBJDQX49J”).

Tracking

Biomarkers

The biomarkers discussed in this episodes are strains or species of gut bacteria that are part of the microbiome. Tracking these biomarkers require a microbiome test.

A good best practice is to get a baseline test followed by tests over time, especially if you make changes to your diet, travel or experience health issues, to see how the microbiome tracks.

The four major groups of bacteria are Firmicutes, Actinobacteria, Proteobacteria and Bacteriodetes. Changes in the abundances of each of these groups often associate with many health conditions.

  • Firmicutes and Bacteroidetes: are both key players in regulating gut metabolism, and are critical in understanding metabolism dysfunctions. See: “Diet–microbiota interactions as moderators of human metabolism” Nature 2016. The ratio of firmicutes to bacteroidetes from different lab tests was discussed, and has been discussed in the literature, but Richard is wary of relying on a single test, noting that his own ratio is highly variable day-to-day.
  • Bifidobacterium also known as Lactobacillus bifidus are ubiquitous inhabitants of the gut, vagina and mouth of humans. They are found in fermented foods like yoghurt and cheese. Bifidobacteria are used in treatment as so-called probiotics, defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”. This scientific paper published in Frontiers in Microbiology summarized the current understanding of the health benefits of Bifidobacterium.
  • Spirochaete is a phylum of bacteria that contains many pathogenic species, including Borrelia species that cause Lyme disease. Testing for these pathogenic bacteria can reveal important information about one’s health. Damien put together a paper describing how one could use uBiome’s 16S rRNA microbiome sequencing as a pre-screen tool for Borrelia.

Lab Tests

Microbiome Labs Overview

With a number of different labs out there offering microbiome tests it can be difficult to decide which company to use or what the upsides and downsides may be. The table below provides an overview comparison of the different characteristics of each of the labs including.

uBiomeAmericanGutAtlasBiomedDayTwoAperiomicsViome
OFFER Cost $89 per test $99 per test £274 ($379) per test $329 per test $781 per test $399/ year
Breadth of Testing Gut, Mouth, Nose, Skin, Genitals Gut Gut + DNA (+ Metabolomics/ Blood Markers) Gut Gut, Blood, Urine and Oral Swabs Gut + Metabolism (blood glucose regulation) + Body dimensions
Service N/A N/A N/A Nutritionist consultation included N/A N/A
Geographies Served International International UK & Russia US Only International US, UK & Canada
Year Started 2012 2012 2017 2017 2017 2017
TECHNOLOGY PLATFORM Sequencing Type 16S 16S 16S Shotgun Shotgun RNA
Information Depth From Phylum to Genus From Phylum to Genus From Phylum to Genus From Phylum to Species and Strain From Phylum to Species and Strain From Phylum to Species and Strain
Type of Information Metagenomics
(What genes are there)
Metagenomics
(What genes are there)
Metagenomics
(What genes are there)
Metagenomics
(What genes are there)
Metagenomics
(What genes are there)
Transcriptomics
(What genes are expressed/ active)
DATABASE SCOPE Coverage Bacteria Bacteria Bacteria Bacteria Bacteria, Viruses, Parasites and Fungi. Bacteria, Virus, Parasite and Fungi
BENCHMARKING DATA QUALITY Benchmark Data Quality/ Scope Likely largest database currently N/A N/A The Weizmann Institute studies included over 1000 Israeli participants on glucose regulation and the biome. Currently have study underway in U.S. Large whole genome database covering over 37,000 microorganisms, 7500+ of which are known pathogens. Very early stage - likely most limited currently
OUTPUT YOU RECEIVE Actionable vs. Informational? Informational Informational: Detailed reporting. Informational: Limited information (only family/ genus level reported)

Actionable:
Many specific recommendations
Recommends Actions:
Rates each food according to your glycemic response
Highest level of granularity of species reported. Recommends Actions:
Rates each food
Transparency of Recommendations N/A N/A HIGH: Includes reasing and study references for most recommendations MEDIUM: Doesn't Explain Recommendations, but can assume comes from Weisman work HIGH: Discussion with researchers. LOW: No information given on which various inputs explain outputs or why
Raw Data Yes Yes No (planning to add?) No
(but planning to add)
Yes No
(No plans to add)

Note: This is a high level analysis of the current technologies and labs on the market which are primarily focused on metagenomics. There are others that have yet to emerge commercially but will eventually create a broader and more complete landscape and understanding of the biome. These include metatranscriptomics, proteomics, metabolomics, and other meta data.3

Microbiome Lab Tests

  • uBiome Explorer test: Richard used to work for uBiome as a citizen scientist. They use machine learning, artificial intelligence, statistical techniques, and a patented precision sequencing process based on 16S rDNA sequencing to analyze the microbes in a sample.
  • American Gut: this project is run out of Rob Knight’s lab at UCSD and is one of the largest microbiome research labs in the world and the world’s largest crowd-funded citizen science project in existence. Anybody can join the project by making a donation.
  • Atlas BioMed: a UK based company does DNA and microbiome testing based on 16s rDNA sequencing.
  • Doctor’s Data Microbiome Testing: a clinical lab performing specialized testing.
  • BioHealth GI Screens: a company providing functional laboratory testing, including testing of the gut microflora.
  • Aperiomics: identifies every known bacteria, virus, parasite, and fungus in samples. Specializing in identifying pathogens and solving complex clinical infections.
  • Diagnostic Solutions GI Map: microbiome testing based on PCR technology.
  • Gencove: offers DNA testing to explore ancestry and tests the microbiome of the mouth.
  • Arivale: tests the genome, blood, saliva, gut microbiome and is taking lifestyle into consideration.
  • Viome: Analyzes the gut microbiome to help improve health, weight loss and wellbeing. Viome offers an annual plan that includes a microbiome test.
  • DayTwo Microbiome Analysis: provides personalized nutrition based on the to maintain normal blood sugar levels. The company studies individual metrics and gut microbiome and translates their findings into actionable insights. Richard’s review of DayTwo can be found on Medium.
  • Thryve Gut Health Test: assess gut health using 16S sequencing and provides personalized probiotics kits.
  • GI Effects Comprehensive Stool Test and GI Effects Microbial Ecology Profile Test: these are tests available via Genova.

Analysis of the Different Labs

Granularity of Output from the Labs

This graph shows the level of granularity of information different labs provide to the customer in terms of number of species and genus. Some labs like Atlas Biomed only report genus level. The comparison shows that Aperiomics is able to identify more species due to the higher depth of sequencing the lab uses.

Source: Damien’s lab samples

Analysis and Graphs from Richard Sprague

Results from different microbiome testing labs can vary by quite a bit and therefore be confusing. Some of the variety in tests results can be explained when samples are taken at different times. This graph shows gut microbiome diversity over a period of one year.

microbiome labs


Changes in the gut microbiome over a one year period (Richard Sprague)

But variations can even be observed during the course of one day as the following chart shows.

microbime labs

Daily variations in the gut microbiome (Richard Sprague)

But even having the same sample tested by different labs can lead to different results based on the different methods they use. To interpret data from different labs it is important to focus on the bigger picture, do the lab tests find the same type of bacteria in the same order of abundance. A chart that Richard shared emphasizes that point. The results shown in the table are from the same day, swabbed from the same tube submitted to both companies. The results are different but not extremely different. The top phyla are the same and the abundances are in the same order.

Microbiome labs

Comparison of gut bacteria phyla and relative abundance in a sample tested by Day Two and uBiome (twice) (Richard Sprague)

 

Other People, Books & Resources

People

  • Elizabeth Bik (@MicrobiomDigest): Richard recommends following Elizabeth on Twitter. She is one of the smartest microbiome scientists he knows, and is very prolific on Twitter. She reads all the publications, and will let you know the ones that matter.
  • Rob Knight (@KnightLabNews): Rob Knight is a Professor in the Department of Pediatrics at the University of California at San Diego, among many other things he is a member of the Steering Committee of the Earth Microbiome Project and a co-founder of the American Gut Project. This article in the science magazine Nature gives an overview of his work.
  • Eran Segal (@segal_eran): is a computational biologist at the Weizmann Institute of Science. He has shown that there is no “One size fits all” diet, and that the very same foods can be good for some and bad for others. He is also one of the founders of the company behind the DayTwo microbiome labs. Eran was interviewed on Quantified Body with another founder of DayTwo, Lihi Segal, here.
  • Chris Kresser: A functional medicine practitioner and founder of the California Center of Functional Medicine, a group of doctors that treat patients with a wide range of chronic health problems, from digestive disorders, to chronic infections, to autoimmune disease, to hypothyroidism.

Books

  • The Personalized Diet: The Pioneering Program to Lose Weight and Prevent Disease: a diet book by Eran Segal and Eran Elinav that explains why one-size-fits-all diets don’t work and helps readers customize their diet to lose weight and improve health. Robert recommend it specifically because it gives suggestions for how you can test yourself using just a cheap glucose meter.
  • Wired to Eat: Damien recommended this book by Robb Wolf which starts with the 30-Day Reset to help people restore normalized blood sugar levels, repair appetite regulation, and reverse insulin resistance. You can also listen to Episode 49 of this podcast for more information. This book also features standard Paleo – based recipes and meal plans for people who suffer from autoimmune diseases, as well as advice on eating a ketogenic diet.
  • The Longevity Diet: Discover the New Science Behind Stem Cell Activation and Regeneration to Slow Aging, Fight Disease, and Optimize Weight: book by Valter Longo. Valter is the director of the Longevity Institute at USC in Los Angeles, and of the Program on Longevity and Cancer at IFOM (Molecular Oncology FIRC Institute) in Milan. The book describes the 5 Day Fasting Mimicking Diet which promotes longevity, overall health, and reduce excess fat.

Other

Full Interview Transcript

Click Here to Read Transcript

(0:04:43) [Damien Blenkinsopp]: Richard, thanks so much for joining the show. It’s great to have you here.

[Richard Sprague]:My pleasure, I’m a big fan of your podcast. I’m actually a little bit humbled that you’ve asked me to come here and talk today.

[Damien Blenkinsopp]: Well you shouldn’t really be humble because you’re a real data geek when it comes to some of this stuff. So we’ve known each other for a long time because of that.

I can’t remember how we connected? Do you remember how we first connected?

[Richard Sprague]: I’m not sure either. It’s probably some quantified self thing. But I’ve been listening to your podcast since the beginning.

[Damien Blenkinsopp]: It wasn’t in person anyway, it was online. I think you must have posted you know what, I think you posted some uBiome analysis, one of the first blog posts, trying to analyze it or something and I found you on Twitter. It might be something like that.

[Richard Sprague]: It could be.

[Damien Blenkinsopp]: Okay great, so we’re going to talk about the microbiome because Richard, as I just mentioned in the intro, has been looking into this a lot. And really the first thing is just to get you guys up to speed on all of this, because it’s starting to become quite a complex question.

(0:05:40) We hear a lot about this in podcasts and health podcasts all the time. I think it’s quite a lot more complex than we generally hear. So, Richard, what do you think? What’s going on with all of this? Why is it important, and why are the labs important right now to try and quantify it?

[Richard Sprague]: You’ve had several podcast interviews with people who’ve been working in the microbiome science, but to me the way I would summarize it is that unlike genomics and genetics and your human DNA, which I find very fascinating, but there’s not a whole lot you can do to change it. Despite the fact that there are a lot of genes that are involved, there’s not a whole lot you can do if you find out that you’ve got the gene for this or that. Whereas with the microbiome you’ve got way more genes and you can change them. And I think those two things are part of the reason that I’m very excited about the microbiome.

The other thing is that partly because of that scientists are finding out all kinds of new relationships and associations between the microbiome and just about any human condition you can imagine. Everything from allergies and obesity to Alzheimer’s disease, to mental health issues like depression or schizophrenia.

There’s a relationship with the microbiome there; we don’t understand what they are, but in the last couple of years some really awesome new technology has come online that makes it possible not just to be able to go and see what the microbiome is in an individual person, but now it’s coming to the point where it’s at consumer level pricing. So that you and I can go and figure that out as well and not just wait for some scientist to go and figure it out.

[Damien Blenkinsopp]: Right. It’s actually interesting because basically since 2014 there’s been quite a few different labs coming out and these are really some of the firsts.

I mean, genetics was the first with 23andMe and players like that, but it’s one of the first areas where it’s consumer driven testing rather than coming from the medical world, and coming from physicians where they control all that stuff. But really uBiome, which was one of the first commercial players, came out and said this is going to be a consumer driven model at first.

[Richard Sprague]: Yeah.

[Damien Blenkinsopp]: Yeah. So it’s, I mean I think that’s the other reason there’s a lot of chat about it as well, because it’s more accessible to the general population.

(0:07:45) [Richard Sprague]: Yeah, that’s right. And in particular I think the 16S, I call it the Hack, made it possible to do something that people weren’t expecting to happen technologically so quickly.

Because if you think about how long and how much money it took to sequence the first human genome back in 2000. You know, that was billions of dollars and involved the cooperation of hundreds, maybe thousands, of scientists around the world.

Well, now we’re talking about at least 10 times, maybe 100 times more genes in a single human being for microbes, and they’re from thousands, maybe tens of thousands of different species. Well, how in the world would you ever sequence all of those genes? It just seems like an impossible problem.

But somebody discovered this trick several years ago that let’s you just look at 200 base pairs on one partial gene, and you can get a rough idea of what’s going on. And that just revolutionized things, because it made it possible now for people to get a hint of what all those microbes are doing.

And that just revolutionized the field. And what’s cool is like you say, since about 2014 it’s been possible for the rest of us to go and access that same kind of technology for basically under 100 dollars.

And that’s just opened up all kinds of new, interesting discoveries.

[Damien Blenkinsopp]: Yeah, yeah. So, we’ll get into why the 16S works, and how it works, in a bit.

(0:09:02) Let’s take a step back because obviously there’s quite a few different technologies out there. When you go to see physicians, when you’re using these technologies, when you’re trying to understand your gut and what’s going on, there’s a fair amount of options. And there’s different options that are being used.

So, Richard could you just give us a quick overview of what kind of technologies are being used currently?

[Richard Sprague]: The first one is culturing. And that’s been around for hundreds, arguably thousands of years, because you essentially, if you know that there’s a microbe involved and if you know which one you want, it’s well understood what kind of things they eat.

So you just take a little bit of a sample, and you put it into a Petri dish and you wait to see what happens. And, scientists know how to culture a lot of the microbes that are important, in particular the pathogens. And that’s kind of the classic way to do it; even today it’s still the gold standard. If you have some kind of medical issue where a doctor wants to confirm for certain that you have such-and-such pathogen, everybody will trust the culturing results.

So that’s kind of the first thing. The problem with culturing is that it only works on certain organisms. And they have to be alive, and it takes a while. It might take several days, or weeks in the case of some microbes.

So the next step was the development of PCR, which is if you know which microbe you’re looking for, you can put into a special machine, polymerase chain reaction, which is well understood technology that’s been around since the early 1990’s.

And they will confirm or deny whether a particular sequence of DNA base pairs are in there or not, which is another way of saying a particular microbe. And that works very quickly; that’s a few hours in some cases. And you can find out for certain whether a particular microbe is there. So the big advantage there is speed.

[Damien Blenkinsopp]: And also the accuracy, because you can really pinpoint something and if it does show up in the test, you can be sure it’s there.

Whereas even with the cultures, I think one of the issues is contamination. Because you’ve got these Petri dishes growing stuff, who knows sometimes. I’ve done some cultures in the past for different things, and I’ve been very suspect about the actual results that came out in the end. I was like, I think…

[Richard Sprague]: Yeah, you have that contamination problem with everything. The bigger issue with culturing and contamination, I think, is that sort of by definition you’re just sitting there waiting for something to happen. And sometimes it happens, sometimes it doesn’t. And, for example, if the pathogen of interest, if it somehow died on the way to the Petri dish, for no good reason, you’re not going to find it

And vice versa if the lab technician somehow exposed something or other to this or that on the way to the Petri dish then you’re going to see something you weren’t expecting.

So the next step up is, we were talking about 16S sequencing. It’s called 16S because there’s a line on the centrifuge when you take a sample and you spin it around enough, there’s a like that’s called the 16S line, which is if you skim off the goop that you find there, you will get one particular gene called the ribosomal rRNA gene. That is part of the genome that’s responsible for building the ribosome, which is an essential part of the way that all cells work.

Well, in bacteria it turns out that all bacteria use a very similar gene. We call it the 16S, the ribosomal gene. And because bacteria are all going to have that same one, in evolutionary terms it’s called conserved, throughout evolution, that it becomes possible to be able to tell the differences in bacteria based on slight variations in that gene.

The gene itself a couple thousand base pairs. But it’s one particular part of that gene called the B4 subunit that’s only, I think it’s 200 base pairs. And so if you just sequence those 200 base pairs, you got a pretty good idea of which microbe it is. Because all the different bacteria that have ever been found on Earth will have that 16S gene, and they will differ just slightly.

And if you’ve got a reference database to be able to see which one is which, and especially if you know that this came from a human gut, right there you’ve suddenly been able to eliminate having to do a gazillions of sequences. Because, sequencing something for only 200 base pairs is pretty cheap, you’re able to get the whole cost down to less than 100 dollars.

[Damien Blenkinsopp]: Yeah. So they called this hyper-variable because, I mean the interesting thing about this is that that region just varies greatly. So that’s why you’re able to identify these different genus of these sometimes species, if it happens to be a species that has more variation on that. But that’s really the key to it; it just varies so much that you’re able to identify the different things in it.

[Richard Sprague]: Yeah, and it’s pretty cool. It’s a really amazing shortcut, when you think about it.

[Damien Blenkinsopp]: Right

[Richard Sprague]: That you’re able to go from literally millions of genes, down to exactly which biome species it is. That’s pretty cool.

(0:13:44) [Damien Blenkinsopp]: And so those were the first tests that came out with the uBiome, the American Gut and some others. There’s Atlas BioMed now in Russia and the UK as well, but I’d say most of the labs are using it, the 16S. Is that the one you’ve seen because you’ve seen some others in their states, and new ones that I hadn’t come across.

[Richard Sprague]: That’s right. I mean there are lots. It’s not that hard for a lab to do 16S sequencing. In fact probably most universities do this routinely. So anybody who’s got an Illumina gene sequencer can do 16S sequencing. It’s not, the basic ideas are pretty well understood.

Also the pipeline, the software pipeline where you go from the output of the gene sequencer to actually telling you which part of the taxonomy it is. All of that stuff is available on Open Source software. Just about anyone, any feasible lab can go do it.

[Damien Blenkinsopp]: For me, when I was first getting my uBiome stuff I was trying to understand it better and I just accessed the Open Source stuff. And actually, you think it’s going to be super complicated. I didn’t do a degree in bioinformatics or anything, but actually it wasn’t that complicated.

I managed to look into, and you’ve been doing a lot of that and posting your results up online as well. That’s how you got into it. So it’s actually very accessible, which is great as well.

[Richard Sprague]: That’s right. And it’s pretty easy if you have questions to find bioinformatics experts around who will answer your questions. Because like I said, this whole technology and the basics behind it pretty well understood.

(0:15:04) So, that’s 16S. The next step up requires a lot more detail and a lot more sequencing. People call it metagenomic sequencing. And essentially what you’re doing is you’re taking the entire sample, you blow it up people say you shoot a shotgun at it and you get all these little parts flying out.

And then a computer takes, it’s almost like a big jigsaw puzzle and reassembles it. And the advantage of metagenomic sequencing is that now you’re not just looking at that one 16S rRNA gene, you’re looking at all the genes. And so it’s a lot more comprehensive.

[Damien Blenkinsopp]: And then you can get species, strain level identification.

[Richard Sprague]: That’s right.

[Damien Blenkinsopp]: Because the one thing I struggled with when I was doing a few little projects on this was sometimes if you’re unlucky and you’re trying to identify some certain species or definitely strains or even genus in some cases the 16S can’t work. It’s very difficult to get that type of level of granularity of information out of it sometimes.

[Richard Sprague]: Yeah, that’s right. And unfortunately that matters. So one of the reasons why something turns into a pathogen, it turns into a pathogen and your body isn’t able to fight it off because it may be only off one or two base pairs.

So there are versions of E-coli that are only a couple of base pairs different than the ones that are highly pathogenic. And that’s because the bacteria are able to mutate much faster than a human can. Obviously it takes us a whole lifetime before you pass on a genetic mutation.

Whereas the bacteria do this all the time. So, unfortunately most of the pathogens that you’ll see out there are just a couple of base pairs different, and you can’t tell them apart with 16S.

[Damien Blenkinsopp]: So when you say a couple of base pairs, that’s the strain level? Is that the level of strain difference?

[Richard Sprague]: That could be the strain level or the species level, it depends where on the gene the mutation happened.

(0:16:50) [Damien Blenkinsopp]: So strain for the guys at home is the absolutely tiniest, basically if you think of a human mutation, that’s kind of a strain. Do you say that’s correct Richard?

[Richard Sprague]: Yeah, the way I would describe it is that you take a dog or a wolf, both are part of the genus canine. Okay? It would matter a lot to to whether it’s a dog or a wolf at your door, it matters a lot.

So just knowing the genus didn’t help you a whole lot. The species will tell you now that it’s a dog versus a wolf. The strain would tell you that it’s a poodle or a bulldog.

[Damien Blenkinsopp]: Yeah, that’s a good example.

[Richard Sprague]: Now, there are lots of cases where it might make a big difference whether it’s a Rottweiler or…

[Damien Blenkinsopp]: A poodle, yeah.

[Richard Sprague]: Yeah. So you’ll need this kind of metagenomic sequencing to be able to tell that level of difference. And unfortunately a lot of times it matters.

(0:17:40) [Damien Blenkinsopp]: Yeah. So I had on a PCR test, just in November, fibrocholera. In other words, cholera turned up in my test. And I was looking at it like, this can’t be.

You start looking into it and you’re like, wow. I had diarrhea, stool problems, for about a week, which was very unusual, liquid diarrhea. And so I looked into this and thought, I can’t have had cholera.

And when you look into it, there’s only two specific strains of that with small modifications which cause the epidemics. The other ones, they’re dangerous, they’re not nice, they give you diarrhea for a week and it’s not nice. But it’s actually some very rare strains that come out, those are the only ones that cause the really lethal epidemics that we’ve seen in the past.

[Richard Sprague]: Could be. And in fact, and this is where it gets really complicated, it could be that the particular strain that you have will out-compete the bad guy. So having it will actually help prevent you from getting cholera.

That’s the sort of thing that happens. That’s why it’s really hard to look at the presence or absence of a particular microbe and say in isolation whether this is good or bad.

Usually it will turn out that something that’s pathogenic will have one other characteristic, which is that it is super hyper-competitive, and it will just eat up everything else and take over. And you’ll know within days, maybe hours, whether it’s bad or not.

[Damien Blenkinsopp]: Yeah.

[Richard Sprague]: So a lot of times if you just see a little bit of this or that in there, that’s just life.

[Damien Blenkinsopp]: Yeah. But I think this is really, really important because I think a lot of the people who are finding species and I think we’ve both been guilty of it too, Richard. We find a species in one of our microbiome tests, so we dig into it and we research it. Especially with the 16S lab, where it’s maybe at a higher level that it’s been identified, I think it can lead to a lot of work with no outcome there, because you’re not as sure what you’re actually dealing with.

And the best thing there is probably to escalate it, basically. If you found something in a 16S you could escalate it to a shotgun, or better PCR for the specific one that may be a concern.

[Richard Sprague]: Yeah, that’s right. And the other kind of thing to always keep in mind with all those sort of testing is that we do have a lot of data. And that’s dangerous because now suddenly you’re being flooded with a whole bunch of data, and it’s easy to overreact. Because you’ll find all kinds of things, and it takes a long time to be able to sit back and look at it a little bit more objectively and say you know what, this is just the nature of the technology. We’re at the cutting edge; we’re going to find some stuff, don’t get too excited.

(0:20:10) So, going back to the list of different ways you can measure the microbiome. One of the other areas that’s been very exciting, this is kind of where the real cutting edge is now. It’s called transcriptomics, and that’s based on the observation that just because a gene or a microbe is there, it doesn’t mean anything in and of itself.

What you really care about is whether that gene is producing the proteins that are the building blocks of life. And the way that you tell that is by the RNA that it’s producing while it’s doing all of it’s copying and transcribing these genes. So people call it transcriptomics because you’re transcribing this gene into RNA.

And there are some new tests that are coming on that let you be able to look at that. Now, that has been extremely expensive. Like I said, it’s the cutting edge and you’re talking about RNA, which is a very difficult to handle molecule; it takes special kinds of labs to be able to do that.

And what’s very exiting is that now that is becoming possible to do at consumer level pricing as well. But that’s definitly, I think most of us would agree that that’s where the future is going to be.

[Damien Blenkinsopp]: Yeah, and then after that you have proteinomics, actually looking at the proteins. Because basically what we’re talking about is the chain of events in order to create the different molecules in your body.

[Richard Sprague]: Yeah.

[Damien Blenkinsopp]: And it goes all the way down the line from genetics, transcriptomics, proteinomics, to metabolomics.

[Richard Sprague]: Metabolomics, yeah.

[Damien Blenkinsopp]: And it’s all great stuff.

[Richard Sprague]: Yeah

[Damien Blenkinsopp]: The beauty of it is one day we’ll probably have all them and actually understand what’s going on in the body.

[Richard Sprague]: Yeah, that’s right, yeah. I should also mention there are lots and lots of different tricks along the way to try to mimic what you get out of metabolomics or transcriptomics without having to do a full blood panel and that sort of stuff. One of them is called functional genomics.

For example, uBiome you can get this thing called a KEGG analysis. And that’s fairly common. That’s kind of a way to guess what sort of metabolites might be produced by this particular gene.

I don’t think it’s of super huge value. A lot of people will point to that as being evidence that such-and-such type of metabolite is present in my body. And you’ll hear that every now and then, it’s called KEGG analysis, another way to talk about it. But what I’m excited about is that now I think we’re able to move beyond that to looking more directly at what the specific thing going on in your body is.

[Damien Blenkinsopp]:With the transcriptome?

[Richard Sprague]: That’s right, yeah.

[Damien Blenkinsopp]:Yeah, I mean you can see that on uBiome, right. If anyone has a uBiome test at home they have the functional part that is displayed. Do they still have those charts, I haven’t checked for a while.

[Richard Sprague]: That’s right, yeah.

[Damien Blenkinsopp]: So that would be your KEGG analysis you’re talking about, correct?

[Richard Sprague]: That’s right, yeah.

[Damien Blenkinsopp]: And it’s things like, they’ll say you have caffeine metabolism and other things going on.

[Richard Sprague]: Or yeah, Vitamin D or this or that, yeah.

[Damien Blenkinsopp]: Yeah, yeah. I thought it was interesting because you told the story of where that came from and why we should be maybe a little conservative in thinking that that’s accurate.

[Richard Sprague]: Well it’s based on some experimental studies that were done a long time ago in Kyoto actually that’s why it’s called KEGG. It’s Kyoto something or other, EGG.

They essentially took a lot of genetic samples and they looked to see what kind of metabolites were produced. Well based on those experiments and they were carefully done experiments people are estimating when you’ve got a particular set of genes in your sample what kind of metabolites they might produce as well.

And that’s arguably better than knowing nothing at all, but I wouldn’t rely on it to be able to tell exactly how much caffeine I’m metabolizing or Vitamin D, etc.

You find a lot of this kind of stuff with genomics where somebody’s got some kind of tool, and it’s experimental. They’re just trying it out, and we’ll see how it works. And this is one of those cases. So I wouldn’t put a whole lot of stock in it.

(0:17:40) [Damien Blenkinsopp]: Yeah. Right. Great. I think another important question is why use genomics lab to understand the microbiome versus the other ones? The cultures, for example. They’re all genomics, right? The PCR, the…

[Richard Sprague]: Yeah. The biggest advantages of the genomic approaches are that it works on all of the microbes that are in the sample.

Remember with culturing, unfortunately, unless you reproduce the exact environment of your gut, which means anaerobic, no oxygen there, it’s got all the different microbes in combination and some of them are producing things that the other ones eat and need. There’s this whole community, so unless you’ve got that whole thing you can’t necessarily culture what you’re looking for.

Whereas the genomics which just says, you know what, we’re just going to look at every single gene in the whole thing. As a result, people have found that it’s well over 90 percent of all the microbes in your body can’t be cultured. We find brand new ones all the time.

[Damien Blenkinsopp]: Right. So that’s what’s going on, and that’s only been enabled by the genomics approach.

Because as you’re explaining, it’s super complicated; all the interactions between the bacteria and they rely on each other to survive.

As soon as you remove them and you’re trying to culture them or something, you remove that whole environment that they’ve been able to survive and breed in. And they need the metabolites, the things coming from the other bacteria and they’re just not there, potentially, because you kill them off.

The way that culturing works is basically you’re trying to separate out the things you’re trying to grow so that they show up in color and stuff. But by separating out and killing off the other stuff and not letting it grow, you’re basically killing off the ones that you want to grow anyway, in some cases, because they need the other bacteria.

[Richard Sprague]: Yup, that’s right. And it turns out that in a lot of interesting cases like some of the pathogens, maybe that’s good enough. But if you’re really trying to understand the whole richness of the microbiome, you’ll have to go to the genomics approaches.

[Damien Blenkinsopp]: Excellent.

[Richard Sprague]: So, now I will say, and I think we should put a big caveat in here. The genomics approach is nice to be able to get a look at all the genes that are there.

When I first started studying this, I thought, wow this is awesome, I’ll finally know what’s going on in my body. But I discovered that it’s actually much, much more complicated than it looks. As you can imagine, if you’ve got millions of organisms in a sample and you want to turn that into some useful data summary, there are a lot of steps that the lab has to go through.

And the steps are everything from the way that you happen to insert the sample into the vial, and it goes through the mail, and then how the lab tech handles it. All the way up to the bioinformatics pipeline where they’re going to process all of these numbers that come out of the sequencer and turn that into whatever taxonomy.

There are dozens of steps involved, and in any of those steps if the lab does it slightly differently than the other lab, you’re going to get different results.

[Damien Blenkinsopp]: Correct me if I’m wrong, because Richard has been at uBiome for quite a while so he’s had a closer experience with all of this. It seems like the bioinformatics pipeline, which is basically a series of calculations you’re going to make based on a database you have of references.

[Richard Sprague]: Yeah

[Damien Blenkinsopp]: And that comes from research of things saying that this piece of code means that this species, genus, exists, and so on. So you’re using a database of references in order, and you’re pushing it through this pipeline of algorithms, basically, that looks at the database checks and categorizes things. So that’s what that bioinformatics pipeline is actually doing.

And it turns out that everyone’s creating their own bioinformatics pipeline, and they’re using different databases, different reference databases

[Richard Sprague]: That’s right.

(0:27:30) [Damien Blenkinsopp]: And then we get quite different results, which is the next question I wanted to bring up. Why are we getting different results from different labs?

[Richard Sprague]: Yeah. And this is a little scary for me when I started digging into this, because I had spent a lot of time getting to know the different papers and the different labs and the different conclusions that people had come up with.

And you can put it in the show notes, but there’s a chart that I like to see that was from a publication in Science a couple of years ago where somebody actually went through and compared all the different big microbiome categorization projects and looked at just some of the common genus level microbes that they found in there. (publication referenced by Richard)

And it’s a little scary, because you look at it and you see that oh, the Human Microbiome Project says that such-and-such genus is dominant, and this one big study of like 4,000 individuals in the Netherlands found that no, that’s not the one that’s dominant, it’s a different one. And we’re talking about hundreds of thousands of individuals, so you’d think that they would all kind of average out, but that’s not the case.

And even American Gut and uBiome, if you look at their overall pictures, when they look at firmicutes versus bacteroidetes, or some of the other common ones, the results are just different. And you could say that, well maybe that’s because the type of people who send samples to uBiome are different than the ones who don’t.

But you’re talking about enough people that that’s a little bit harder to swallow. So what’s really going on is that a lab makes just one little change in, for example, how many times they PCR something before they submitted the sequencer, just one little change like that will express different levels of DNA, and then poof, you’ve got a different result.

And each of the labs if they use different reference databases, like you were saying, those references could be slightly different. If they find that a particular gene, they look it up in one reference database and it says that, oh this is bifidobacterium such-and-such. Well another lab might have called it something else.

So you just have to be a little careful. The good news is, and this is the way I look at this, if you’re going through the same lab most labs, I give them the benefit of doubt that they’re usually pretty careful. And the scientists behind this are usually pretty cautious about how they do protocols.

So you could usually trust when you submit a sample to one lab that it’s comparable to the sample the next time you submit it to the same lab. It’s just you have to be a little bit careful if you see a paper that says that they found that such-and-such microbe is associated with such-and-such condition, don’t just automatically assume that, oh my uBiome results says I have that microbe then that must mean I have such-and-such association.

[Damien Blenkinsopp]: Yeah, you could look at which lab did they use. Basically. And it’s a shame that there isn’t a standardized reference database, but it’s also the nature of the technology and the way it’s developing really.

[Richard Sprague]: That’s right, yeah.

[Damien Blenkinsopp]: Because it’s been opened up, and we have this commercial model. Which is actually enabling really the explosion of data gathering.

I don’t know how many samples, but basically there weren’t enough samples out there being collected and so on to advance science, right? So you have these commercial companies, like uBiome and so on, and they’ve made it feasible to get a large number of samples. I don’t know if you know how many samples uBiome has now, or if that’s disclosable.

[Richard Sprague]: I think the last announcement they’ve made is it’s well over a quarter million. I don’t know the exact number what they’ve announced, but it’s a lot of samples.

[Damien Blenkinsopp]: Right. And then you learn a lot from that massive data, you start the see the correlations. All the labs have, I think, questionnaires filled in as well so that they can start to see if there are some things that are related to Paleo diets, Keto diets, to antibiotics abuse. Not that many people like to abuse antibiotics in particular, but it has been done.

So I think it’s really interesting that all this data is being collected. And the nice thing, also, is that they keep the sequences, correct? This is definitely an area you’ll know more about than me, but if we wanted to run this through a different bioinformatics pipeline later, could we do that?

[Richard Sprague]: It would be tricky. Are you saying like if I submitted the same sample to uBiome and later on to someone else?

[Damien Blenkinsopp]: No I’m saying uBiome has a million samples, for example. And they have a particular bioinformatics pipeline today which says that, for example, I have a species we’ll talk about the cholera species that came up in my PCR test recently. But maybe in the five years time they’ll improve their reference database.

[Richard Sprague]:Yeah, that’s right. So, in fact, they could just go back to the shelf and look up and see your old sample and then run it through something else, and they might find something new. That’s right, yeah.

[Damien Blenkinsopp]: Right, so if they ever do decide that it’s important to change their bioinformatics pipeline, they could…just run it again.

[Richard Sprague]: Yup, you could run it again. And in fact, if you have the fast Q file, the raw output from the sequencer, it’s possible to run it through a different pipeline there as well. And if in the future somebody comes up with a better reference database, for example, it’s possible to take that same exact fast Q file and come up with a different answer.

(0:32:28) [Damien Blenkinsopp]: Well exactly. So they have all these fast Q files on a server somewhere, I’m guessing. Right? So these are the things you could run through a bioinformatics pipeline and get different answers. So that data is going to be invaluable, incredibly valuable.

[Richard Sprague]: Yeah, you’ll be able to find new insights from the old data in the future.

[Damien Blenkinsopp]: Right. Richard and I were just talking before we started this episode, some of this stuff may be challenging to get without visuals.

Whenever we’re mentioning something and it sounds complicated, we’ll probably throw a chart in there because we’ll realize that, and we’ll be like yeah, that one deserves a visual chart. So we might go over the concept relatively quickly, because we realize we’re not going to get there on audio but try and provide some visual aides in the show notes.

(0:33:13) Let’s talk about the actual labs now. What are all these labs? We’ve just kind of bounced around a few of them already, but what’s the landscape look like? It looks like it’s kind of exploding in the last few years, right? So I think uBiome and American Gut were around in 2014, and since then there’s quite a few different labs that have come out.

[Richard Sprague]: Yeah, that’s right. I’m actually curious also about you, because you’ve done more of the culturing than I have. And what kind of labs you’ve had experience with on the culturing side.

[Damien Blenkinsopp]: Yeah, so there’s basically a lot of functional medicine practitioners and hospitals in general will use the culture approach.

So I’ve done many, many different cultures over time and eventually this led me to running two different cultures; this was quite a few years after having started the Doctors Data and the BioHealth lab side-by-side, because they have different strengths and weaknesses. They’re both culture based test, and pretty consistently some things would turn up, but not necessarily on both of them.

I was working with Chris Kresser’s California Center of Functional Medicine there. And I like those guys because they’re very conservative about tests; you may have come across them as well Richard, I know they were talking to uBiome.

And they’re very conservative about their tests. They look for the studies, they look and they have a very large population of clients as well. And they’ve been running for many years. So I like the fact that they’ve been doing that for a while, and they have changed their tests over time.

And they, I think they may have moved on a little bit from these tests, but a couple of years ago when I was doing a lot of this with them they were running both of those side-by-side. That’s a little bit expensive, but it did tend to give us pretty clear…

[Richard Sprague]: So, did you submit the same exact sample to two different labs?

[Damien Blenkinsopp]: Yeah. Each time. Yeah, that was their protocol. Basically they…

[Richard Sprague]: And can I ask you, those culturing labs were they, did you have to poop in a box or did you just send a swab?

[Damien Blenkinsopp]: We used these kind of tiny vials for the uBiome, right? Where you put this really little vial, I mean basically the size of the end of your thumb. The culture labs, they’re larger; kind of three times a test tube size. They’re like a big test tube.

[Richard Sprague]: So a couple of tablespoons?

[Damien Blenkinsopp]: Yeah. And normally, actually, you have four of those for each kit. So there’s a lot of spooning and scooping that goes on for a little while into these different containers because they’ve got different assays they’re running there and they’re trying to preserve and do different things in each of those vials so they can look for different things, parasites and so on.

So it was quite a time consuming process when you’re doing that.

[Richard Sprague]: Yeah. And did you have to go to the hospital or the doctors office to do it?

[Damien Blenkinsopp]: Yeah, you do these from home. They send you the kits, and you sit on the floor scooping. I would lock myself in there for half an hour and scoop away.

[Richard Sprague]: And did the tests agree with each other? You said you submitted from the same sample.

[Damien Blenkinsopp]: Sometimes, sometimes they didn’t.

The reason they were using those in particular was because they felt they had different strengths as well. The last I heard some people feel BioHealth was a little more useful and picked up more stuff.

And again it comes back to our discussion of sensitivity, whether it’s picking up stuff. And that is the concern with a lot of physicians that it’s not picking up stuff, and it doesn’t do it reliably.

So I actually experienced this because I did many of these, over time. We were doing them every couple of months or so to see if the treatments we were doing against parasites like blastocystis hominis I had that for a while, and it’s quite a common thing but it can be a bit of an annoyance in the gut.

And we would do a protocol to get rid of it; we would retest it, it’d be gone. And we’d wait. You have to wait after your treatment, obviously, in order to let things settle down and then see if they grow back. And it would be gone for maybe two tests, and then it would come back again; it would just pop up on one of the tests.

So there’s a bit of inconsistency, and it’s a little bit worrying. For that reason you end up doing a lot of these, and they can be expensive.

[Richard Sprague]: Yeah, interesting.

I don’t know too much about Doctors Data or Biohealth.

I talked to functional medicine practitioner who used GI Effects. And that seems to be, at least in the Seattle area where I am and a lot of naturopaths, that seems to be kind of the one that most people use. The functional medicine people that I talk to are pretty positive about it, and they say that it actually produces very actionable results for treatment.

[Damien Blenkinsopp]: Yeah.

[Richard Sprague]: It seems the one to beat.

[Damien Blenkinsopp]: That was actually the first one I ever did, I think back in 2011 or something. It was MetaMetics previously and Genoma acquired that company. And MetaMetrics was very well respected as a company, so it was a good acquisition.

It came up with some stuff. And that is a combination of the culturing approach and PCR which we were talking about later, which is a genome sequencing but quite accurate. If you see something with PCR, it’s there. That’s a high probability.

[Richard Sprague]: Yeah, and I would say I’m not a doctor and please don’t trust my advice but if I did have some kind of gut issue I would want the functional doctor to use what he or she is familiar with and comfortable with, and they seem to be comfortable with this. And I would trust those results because they’ve been used for years and years and doctors have learned what work or don’t work about them.

I look at the other genomic results like the 16S and metagenomic results as being kind of cool for someone like me, and definitely worth watching for future potential. But if I were really sick, I would want to stick with what the doctors trust.

[Damien Blenkinsopp]: Yeah, exactly. And so I know some functional medicine practices have evaluated 16S based testing, and have done trials with it. But so far they’re like, this isn’t going to be good enough in terms of diagnostics, and also just the cost. Maybe it would pull out some things sometimes and be a little bit indicative of something, or just help you to explore doing a PCR with something. But they felt like the cost benefit and just the kind of time involved in getting a patient to do it wasn’t worth it at this point.

(0:39:10) [Richard Sprague]: Yeah, maybe. Now, on the other hand, there are a lot of conditions where the traditional culturing, or even the PCR approaches, can’t find out what’s wrong, and they don’t know what’s going on.

And that, I think, that’s where the place is for a little bit more experimental and you want to look at a bigger picture. And that’s where you get the 16S and metagenomic approaches because you will see a lot more.

[Damien Blenkinsopp]: Absolutely.

[Richard Sprague]: And after you’ve looked at zillions of samples the way that I have, you do start to see patterns. And you start to see when something looks anomalous, and you say, hmm. And those are the kind of things that if you’re just relying on culturing approaches you probably wouldn’t be able to see

[Damien Blenkinsopp]: Absolutely.

I’ve been really interested in the shotgun approach in particular for this, to pick up things that, as we said before, with PCR basically you have to say I want to find a poodle. You know? Or I want to find a dog in the mass of everything in the world. So you have to really know what you’re looking for, otherwise you’ll just get a negative and it costs money.

Whereas the shotgun, if you don’t know what you’re looking for but you think there’s something there it’s a good idea to do a shotgun to give you an indication. So I did a recent one, Richard and I were talking about the shotgun approach which is looking for pathogens and things like this, which is the Aperiomics, the lab test.

And I did a shotgun sample of my poop and, you know, there were a few different pathogens and some others that came up which were unknowns. A lot of them were unknowns, actually, because it’s a relatively new service; and this is where you see the bioinformatics pipeline, their reference database and so on.

They told me the benchmarks they have so far. They don’t have enough data, so there’s some interesting stuff, but there’s a lot of unknowns; we don’t know if its pathogenic or not because a lot of people have this and they’re going fine.

But I think that for me was an interesting test because it was using shotgun just to potentially pick up something interesting, and then go after it with PCR.

[Richard Sprague]: Yeah, that’s interesting. And I would love to see results that people do side-by-side if you submit the same sample to two different labs. It would be really interesting to compare that.

(0:41:12) [Damien Blenkinsopp]: Yeah, so I did that with the GI Map from Diagnostic Laboratories. Also uBiome, but unfortunately somehow that was lost, either in the post or I don’t know what happened with it. And I did Free Labs.

GI Map, we haven’t discussed, is a PCR based test. And that’s from Diagnostic Laboratories. And there’s a lot of functional medicine practitioners who are now looking at that one. Because it is PCR based, so again if you pick something up and it’s looking for quite a number of problematic bacteria, parasites, and so on, then it can be pretty useful. It’s a little bit more expensive, but that’s a good one.

So I ran that next to the Aperiomics, and I had that back. And I was trying to cross them, but nothing crossed actually.

[Richard Sprague]: Oh you didn’t find any, there was no consistency between the two?

[Damien Blenkinsopp]: No, I didn’t find the same. So I found the cholera in the GI Map. So I trust that because it’s PCR based. It didn’t turn up in the shotgun, which could be the reference database that they haven’t put that species in, or that specific strain in even. Or it could be the bioinformatics pipeline that they haven’t built out yet.

There’s so many different reasons that that might not be. But it goes back to what Richard was saying earlier, is that if you’re using different labs it’s not necessarily going to pick up the same stuff at this stage.

[Richard Sprague]: That’s interesting if they couldn’t find cholera in two different samples.

Part of it also could be if we’re talking about minute amounts, even the metagenomic approaches you’re only looking at a certain number of, you’re not looking at every single gene in there. You’re still looking at a subset of all the different genes, because you can’t sequence all gazillion of them.

The PCR approach though, you’re looking for a particular one. So you stick in some primers that will cut every single copy of DNA that has that one in there. You’d have to ask somebody who’s more knowledgeable about lab science than I am to state this more unequivocally, but when you do that you will know that the following DNA snippets came from that microbe.

Whereas with the shotgun approach, you’re going to know at a broad level, because you’ve looked at as many as you could, but you haven’t looked at every single one of them

[Damien Blenkinsopp]: Yeah.

[Richard Sprague]: And when you’re talking about minute amounts, that might make the difference.

[Damien Blenkinsopp]: Yeah, I think the nice thing about, going back to genomics, is that it will get better over time, as these databases, these bioinformatics pipelines, as each company basically gathers data and experience. And eventually, hopefully, there will be some type of collaboration. I don’t know what would be up in the future, but it would be nice if there was a way to match these together and get…

[Richard Sprague]: That would be neat, yeah. That would be neat to have a bunch of people all comparing our results from the different labs.

[Damien Blenkinsopp]: Yeah, and trying to build conversion tables or something. Something like a pool where you can convert your uBiome into your American Gut, or whatever you wanted. And it would be more comparable.

(0:44:07) [Richard Sprague]: And see how you compare, yeah. In fact, actually it’s funny because American Gut is one of the few labs that you submit the sample dry. In other words, you just put it on a Q-tip and you send it in dry. You don’t put it in a special upright vial.

[Damien Blenkinsopp]: Nothing? Okay, interesting.

[Richard Sprague]: And I asked the lab about that, because that’s kind of odd. And they know that there are certain species that when they are dry they continue to multiply. Because it’s not dead when it comes out of your body. And some of them when they’re exposed to oxygen immediately die, but some of them don’t. In fact, some of the thrive, and you get a bloom actually in some species.

And what American Gut does and they’ve written a paper about this, they’re very upfront about it they run, in their bioinformatics pipeline, they’ve already tested which species are thriving in an oxygen environment, and they filter those out. And they say oh well you collected a sample on such-and-such date, that means that this much time has passed which means that likely this much of this species has bloomed. And we’re just going to go and adjust the final result that way.

[Damien Blenkinsopp]: Whereas basically uBiome’s test and others, they’re killing all the bacteria straight away to preserve them in the state they were in the stool.

[Richard Sprague]: Yeah. And again, that’s going to be a difference in the pipeline. You’re going to get different results.

[Damien Blenkinsopp]: I mean, I can imagine. I mean that introduces basically another variable. I wonder why they didn’t decide to eliminate that.

[Richard Sprague]: Well the reason they didn’t do that is because the people at American Gut are super careful scientists, and what they care mostly about is consistency across all their different samples. They want to make sure that every single sample is conducted under the same conditions.

And they also at least in the beginning were working a lot in environments like outside the United States where maybe the collection procedure was maybe a little bit more erratic. And they just wanted it so that they could take all the different samples and treat them exactly the same way.

They’ve got a paper on this where they show, you know, that it doesn’t matter as much as you might think, but still. Yeah, it’s another area where the pipeline is going to be different.

(0:45:55) For you guys at home, just a quick reference there. I spoke to Rob Knight from the American Gut a while back, so if you wanted to know more about what he was doing there. He talks about where they got the first data and so on for that project.

(0:46:10) Okay, great. How about the 16S labs? Because you know all the 16S labs really well.

[Richard Sprague]: Yeah, well let’s talk about the 16S.

Now, first of all, I want to repeat in full transparency, I am a friend of uBiome. I’m a former employee. I’ve been a happy user of them for a long time. But I have spent time with their scientists; I trust their scientists. I think they’re pretty careful about how they put stuff in the lab.

Now that said, there are lots of other labs that I’ve worked with as well, and I’ll just go through the differences.

We talked about American Gut. I think that American Gut is scientifically they’re the most sound lab. You’ve had Rob Knight on this show, you know he’s a very smart guy, well published, extremely careful scientist, and knows everybody.

They have published a lot of results based on their American Gut cohorts, and they’ll continue publishing. They take their science very seriously. The other thing about them is they’re ultra transparent.

Every single one of their software tools that they use are all Open Source. They anonymize, and then anybody who wants to can go look at their data and reproduce their results. In fact, they even have Python notebooks where if you don’t trust something that they publish in a paper you can go run it yourself down your own Python and see.

So it’s very transparent from that point of view.

The other company that I would call out is a newer company called Thryve in Santa Clara. They’re focusing on personalized probiotics, but the CEO Richard Lin is an example of the kind of person I like to see running one of these companies because he cares a lot.

He’s been trying to solve some of his own issues, and so he founded a company, essentially, to go and help resolve that. So he cares a lot and he’s especially focused on actionable results. So I like them.

There are lots of other labs; I won’t go into all the names, I haven’t tried a lot of them.

One that I will bring up though is a company called Gencove that focuses mostly on genomics. So they’ll take a mouth sample. But what’s cool about them is that they’ll run their mouth sample, the swab that you give from your mouth, you get the DNA results just like with 23andMe; it’s very comparable to 23andMe. But they also give you the microbiome breakdown.

So there’s that company. And there are lots of other companies that are doing 16S in one form or another.

(0:48:20) [Damien Blenkinsopp]: So that’s very similar to the Atlas Biomed guys, who actually came from Russia. So they were doing studies in Russia, and now they’re in the UK as well, so they got the two populations. So they’ve combined in their interface the DNA and the microbiome.

So it’s quite interesting. I would say they’ve got a lot of recommendations. We’ll get into this in a little bit but they got a lot of recommendations in there, and study references and stuff like that. It’s quite interesting; they’re quite strong on the recommendations from the data.

[Richard Sprague]: Interesting. Do they, what kind of sample do you give them? Is it a mouth swab, or both, or blood? What do you give them?

[Damien Blenkinsopp]: Sorry, this is for the gut, right?

[Richard Sprague]: So it’s just gut, okay.

[Damien Blenkinsopp]: Oh, for the DNA it’s saliva, you’re correct.

[Richard Sprague]: Yes.

[Damien Blenkinsopp]: And then for the gut it’s the usual poop thing.

[Richard Sprague]: Yes, okay.

[Damien Blenkinsopp]: So you do the test and the same time. Or you can send the DNA whenever you wanted.

[Richard Sprague]: So they’re two separate samples?

[Damien Blenkinsopp]: Yeah, that’s right.

They’re trying to combine to get more information, to see correlations, things like that.

[Richard Sprague]: That’s real interesting.

 

[Damien Blenkinsopp]: And their plan is, I think this will get more interesting. I went to see them last week and so I was talking to them a lot.

And basically their plan is now to get into blood tests as well. And to bring this kind of information to clinicians, where you combine DNA microbiome and blood tests results, metabolomics. And some of the standard stuff as well, like information whatever it is that doctors have been using for a long time. And you can give a bit more context.

So they haven’t figured how they’re going to do that, but the idea is to provide more context around these blood tests to try and make the links and stuff like that to provide a better tool, basically, for looking at patients.

And I think if it’s done that way, led by blood tests which have been used for a very long time in diagnostics anyway, and you add information and context with the DNA and the microbiome, then that actually sound quite useful.

(0:50:11) [Richard Sprague]:That’s right. There’s another company in the US called Arivale, based here in Seattle, and they are now available in the West Coast, California and here. They might be nationwide at this point. But it’s a very similar kind of thing.

I think it’s 1000 dollars, for a one year program. They do a 30x genomic sequence. They test your microbiome, they do your blood test, and there are a couple of other things. They give you a FitBit and measure activity.

And then they assign you a personal nutritionist and you have once a month meetings with them, and you can ask them email questions, and that sort of stuff. And they work with you on whatever issue you want.

And I think that is the direction that I think if you’re seriously trying to solve a problem, that’s what you should be doing. Because it’s this holistic look at the blood results, the microbiome, the genetics and all that stuff together.

[Damien Blenkinsopp]: And consultation. And experts who actually help you work through it.

Because right now, frankly, a lot of these services had to start a consumer facing in order to get the volume of data and build up their databases, right? Because that was the only way that you were going to get enough data to be able to start seeing patterns and start getting past this first hurdle.

And I think it was always sold like that anyway; this is informational, it’s not diagnostic, it’s not supposed to be used like that. That’s really the idea.

[Richard Sprague]: Yup.

(0:51:26) [Damien Blenkinsopp]: Okay. So that’s 16S, and like I said Atlas Biomed that was a 16S as well. And then we have the metagenomic shotgun ones, which I was quite excited about.

I spoke to Eran Segal and Lihi Segal in a previous episode about their work, and that resulted in Day Two. So I was kind of looking forward to that, because it was the first shotgun service to come out that was a reasonable cost. I think at that time it was like 200 or 300 dollars.

[Richard Sprague]: Yeah, that’s right.

[Damien Blenkinsopp]: Yeah. So there’s that one. And you’ve done that as well, and you published a review about it. So what did you think of Day Two?

[Richard Sprague]: I thought Day Two is very cool. You submit the sample, it took a while to get back, but they’re just getting started.

What’s neat about it is Eran Segal, as you mentioned, did a lot of really cool research where they were able to identify, I guess, glucose response levels and it’s dependence on what’s going on in the microbiome. And so by looking just at the microbiome they’re able to tell, oh your insulin levels are likely to respond to what’s in your diet.

And they ran this big machine learning algorithm against all the different kinds of food types. And they had, I think 1000 volunteers and they did a whole bunch of studies.

And now Day Two gives you an app that goes through the food groups and tells you how likely you are to respond, well or poorly, to a particular type of food. It’s very well done.

[Damien Blenkinsopp]: In terms of glucose response, right? It’s just glucose response. So we know that.

It’s been pretty cool. And they had large studies; they had a pretty large population, over 1000 people.

[Richard Sprague]: Yeah. It was, and they’re careful scientists and they published their results.

And kind of the interesting take-away from Eran Segal’s work was that there are some people who, your standard diet advice says you should always eat the whole grain version instead of the white bread version. But there are some people who it’s the exact opposite advice. And this algorithm seems to be pretty good at telling which one you are.

So in my case, for example, with Day Two it’s showing that I should be eating things with more fat in them.

So yeah, there you go Mr. Ketogenic guy. And it was pretty accurate for me. It showed, for example, I’m not lactose intolerant; I can handle dairy and it recommends that I have dairy. And I found most of the suggestions to be reasonable.

The other nice thing about them is they’re not based just on a particular food, but they recognize that food is in context. So having a slice of toast is not the same as having a slice of toast with some butter on it; the way that your body is going to respond is totally different. And they have a lot of recommendations for that.

[Damien Blenkinsopp]: Absolutely.

[Richard Sprague]: So I’m pretty impressed. I’m waiting to see how they do. A lot of the initial research was all done in Israel. So they’re running a study now I guess in the United States. And I think actually when you had them on your podcast I think one thing they mentioned, they’re doing something with Mayo Clinic, I think.

[Damien Blenkinsopp]: Yeah, exactly. Yeah.

[Richard Sprague]: So I’m looking forward to seeing how that turns out in the next couple of years.

[Damien Blenkinsopp]: Yeah, that would be pretty cool when they get more data. Because I think, personally, glucose response is one of the highest impact things you can do relatively simply by changing your diet. Sometimes sleep and other factors as well, but it’s really important.

So going back to this personalized…

[Richard Sprague]: Just one quick thing, did you see the new book that Eran Segal and his co-author put out?

[Damien Blenkinsopp]: No, I didn’t.

[Richard Sprague]: It’s called The Personalized Diet. That’s worth reading. Yeah, that’s worth reading. It’s called The Personalized Diet.

[Damien Blenkinsopp]: Okay, great.

[Richard Sprague]: Go check it. It just came out, and I just read it it’s a wonderful book.

[Damien Blenkinsopp]: Oh, awesome.

[Richard Sprague]: It goes into a lot of… And what’s cool is in the end, he gives suggestions for how you can test yourself using just a cheap glucose meter, and gives suggestions as part of it. It’s kind of cool.

[Damien Blenkinsopp]: Excellent. That sounds a little bit like the Rob Wolf test that was in Wired to Eat.

I put some charts up on that. It’s a standard actually glucose tolerance test to different foods. But you learn a hell of a lot. I don’t know if it’s the same, but it can be done; just a blood meter can tell you a lot of information.

[0:55:22] So I’ve been doing this a lot. One of my other pastimes, currently I’ve been developing a food which uses different fibers because I don’t want it to by glycemic, because I’m not a fan of high glycemic responses. So, similar to the Eran Segal guys.

So I’ve looked at a lot of different fibers and I can tell you that there is definitely a lot of variation between. Because when I go to a company and I ask them for a fiber, there’s many of these. There are a lot of different fibers that are created by companies now in different ways.

Basically fibers are carbohydrate which is resistant to getting broken down in the body. So that’s the way you’ve got to look at it. So there’s a potential high glycemic response from a fiber because your biome may be able to digest it and turn it into glucose, whereas someone else’s maybe not. And it’s going to pass through them and they get no glycemic response.

So I’ve had quite a fun time testing a lot of different fibers and collecting a lot of data on that and seeing the different responses. And I plan to now do that on a population, because I understand that just because I get these particular responses doesn’t mean that everyone’s going to get that response.

But it’s actually tricky with these fibers and everything. There’s a lot of products that state low-carb or whatever, but they often have different fibers in them. And it’s just not that simple, unfortunately.

[Richard Sprague]: That’s very interesting. It would be especially interesting if you could trace it to which microbe is involved.

[Damien Blenkinsopp]: Oh yeah. I know, right.

[Richard Sprague]: There might be a simple little change to the formula, where you add a particular microbe or you add something that that microbe likes to eat and suddenly now that fiber that caused the bad glucose response is suddenly just fine.

[Damien Blenkinsopp]: Yeah, exactly. It’s people like Day Two are going to have the best information because they’ve collected it. I always think about all this whole area and everything, I’ve been thinking about this for quite a whole in terms of us trying to get ahead.

It’s like, who has the data? If you want an answer to something, go find the people with the most quality data it has to be quality data and you’re going to be the closest to the answer at that point. You know, if you can get talking to those guys and what they’re doing with that.

(0:57:29) [Richard Sprague]: Yeah, that’s true. That’s right. So we should also talk about Viome, which is the other metagenomics company. They’re the transcriptomics one that we talked about.

They just came out, and I just got my results back a month or so ago. And again, they give you this big, it’s an app where they’ll give you a big breakdown of the different microbes that you have. Actually, it’s the different, they try to stress that it’s not the microbes themselves it’s the activity of the microbes.

And then they break it down and tell you what kind of foods that you should eat or not. And it’s a pretty impressive list of people backing the company; if you look at their board of advisers it includes people like Ray Kurzweil and Aubrey de Grey, the Life Extension guy, and the bulletproof empire, Dave Asprey is a big fan them. And you’ll see a lot of, Ben Greenfield Fitness, etc.

[Damien Blenkinsopp]: They’ve got their name out in the media more than most companies quicker.

[Richard Sprague]: Yeah, that’s right.

And they’re founder, Naveen Jain, one of the things I respect about him is he really genuinely believes in it himself. So he’s out there himself personally pitching the product, and he’ll talk about his own results. He’s got a private Facebook group where they talk about it, and he’s one of the active participants answering questions about it. So they’re very serious, and they’re hiring a lot of people.

They claim that they’re based on some lab science that was developed out of the Los Almos lab in New Mexico over many years. I’ve had a hard time figuring out from a scientific point of view exactly how they’re doing the work.

One of the things they, if you go to their website they say specifically that they’re not going to release the raw data. So it’s a little hard to tell exactly what’s going on, and how they’re coming up with the recommendations.

And it’s something that I hope that they’ll be a little bit more transparent about.

[Damien Blenkinsopp]: Yeah, and this is something, you know we wanted to talk about, is basically if you’re thinking about doing some labs what kind of things do you want to take into account.

(0:59:24) Let’s talk a little bit about what we’ve actually run. Like what labs have we both used? Because I don’t know you Richard like, what labs have you run over the last, is it four years?

[Richard Sprague]: Well, okay. So, I’m a little crazy. I’ve done well over 500 samples from uBiome, another several dozen from other different labs. Probably all told I’m up at close to say 600 samples.

[Damien Blenkinsopp]: And at uBiome you were doing daily ones, right?

[Richard Sprague]: That’s right. Yes. So I had daily samples for more than a year.

[Damien Blenkinsopp]: Which means you were pooping every day. At least once.

[Richard Sprague]: Yeah, that’s right.

Well actually I should say, I should be more precise. No, not every single day. That’s right. There are a couple of gaps in it, but generally speaking I had near daily samples for more than a year. And then I have other fairly regular samples going back through to 2014.

What’s also cool about it is I tracked all of the food that I ate the whole time, and my exercise and my sleep and that sort of stuff. So I’m able to run all these cool correlations to figure out what I learned. So that’s really cool.

I’ve done also Viome testing, Day Two, Thrive, I mentioned Gencove. Let’s see, who else. I’ve not done any of the culturing tests. But what’s also cool is I’ve done a lot of these side-by-side just to see, to cross-compare them among themselves, which has been interesting.

[Damien Blenkinsopp]: A lot of these labs have interfaces where you have to access the data. So I can’t do it for all of them, but I’ll put up samples of any that I’ve done that are basically PDFs or something that you can actually see.

[Richard Sprague]: Yeah, I’m happy to show mine as well.

[Damien Blenkinsopp]: Yeah, so we’ll combine our things to try and give you a picture of what most of these look like. Can’t be all of them just because some don’t actually deliver the information in that approach, but it should give you a good idea of what all these things look like, and the kind of microbes they’re looking at and stuff like that.

From my side, I started with uBiome when they launched and that’s when Richard also go into it, I believe. And they were one of these Kickstarter campaigns, or that was Indiegogo, because…

[Richard Sprague]: Indiegogo, yeah.

[Damien Blenkinsopp]: Kickstarter and all that kind of stuff…

[Richard Sprague]: Back in 2013.

[Damien Blenkinsopp]: Yeah. This is kind of amazing that it was already that long ago.

So I’ve just done seven uBiome tests. Quite a bunch of those were the five I don’t know if you’re doing the five…

[Richard Sprague]: That’s the five sites, yeah. I’ve done it, it’s gut, mouth, skin, nose, genitals. I’ve done them all.

[Damien Blenkinsopp]: Yeah, I’ve done semen as well, because I was curious. [Laughter] I was like playing around with different stuff. Which they don’t normally do, and they haven’t got a lot of benchmark data on that.

So the standard ones that you said are the mouth, the genitals, and the skin. And they did teeth as well, actually. They did the dental one.

[Richard Sprague]: That’s right, yup.

[Damien Blenkinsopp]: Yeah, so they have quite a bit of data on those.

[Richard Sprague]: Yeah, and we could talk forever about some of the things that I’ve learned from all of my studies. And I’ll give you a link to my, I’ve been writing some of my results up. But don’t forget, the microbiome is more than just the gut and you can learn a lot of things from skin and from mouth and nose as well.

[Damien Blenkinsopp]: Right, exactly. And there’s actually a little hack, we’ll talk about some hacks we’ve done on things that have actually potentially done something in a little bit.

[Richard Sprague]: Yeah.

[Damien Blenkinsopp]: So the other ones I’ve done is the Viome one as well, Day Two, so both of us have done that. I’ve done the Atlas Biomed one, because I’m based in the UK. And I’ve done quite a few of those culture and PCR based tests, so it’s a little bit different there.

(1:02:44) Alright, let’s just dive in to see what kind of things we found from this. First of all, what can we say about comparison of data? We were talking about how they’re not necessarily comparable.

[Richard Sprague]:Yeah. That’s an interesting thing. So I have done comparing my 16S results with both Viome and Day Two, and I find that at the high level, they’re actually fairly different.

I shouldn’t say, you know it’s sort of like you can see the chart here. For example, in Day Two it says that my furmicidies level is about 50 percent. When I tested it on uBiome, one of my uBiome tests shows it’s like 59 percent. My bactorides in Day Two is like 45 percent, uBiome tested it out as more like 30 percent.

There are, that sounds like a fairly significant difference, but if you’ve seen a lot of samples you realize that it’s probably not as significant as it might sound, because there’s a lot of variability in day-to-day anyway.

The one thing that I did notice was that, however, the ordering, in other words which was the most dominant, the second dominant, etc, was pretty consistent. Which is nice to know. That means at least at the biome level you can kind of trust that if it says that you’ve got higher furmicidues than bactroidides then maybe you really do.

The other part is that if it says that you’ve got verrucomicrobia, which is the phylum that includes akkermansia, which is an important one for eating the musilin level and is considered important for health. If Day Two shows that you have it, it’s likely that uBiome will show that you have it as well. Which it’s nice to see a little bit of consistency there.

[Damien Blenkinsopp]: Alright we were talking about this a little bit earlier, because I was comparing all the species that I’ve picked up in different ones. And, you know, obviously they don’t correlate all the time.

So Richard was saying that probably the way to look at it is that if it turns up in two tests, and it’s not in one test, then it could be just that it’s likely it’s there. And it might be worth doing a PCR or whatever, but it’s likely it’s there. And it’s the bioinformatics library of the other one maybe doesn’t include that species, right? They haven’t got the references in their database or something.

But that’s kind of like a starting assumption you can start with in your exploration to try and nail it down, whether it’s there or not.

[Richard Sprague]: Yeah, that’s right. It could be and the other thing, again I would emphasize look at presence versus absence, and be a little bit less concerned about the abundance, and that’s going to vary a lot.

[Damien Blenkinsopp]: Well that’s, on your Viome you’ve got this spirochaete of…

[Richard Sprague]: Yeah, the Viome one is interesting. And I don’t know how to interpret that, because it shows that I have 79 percent spirochaete…

Damien Blenkinsopp]: It’s off the charts compared to the others, yeah.

[Richard Sprague]: It’s off the charts, yeah. And now what they’ll say is that that’s the one that we’re after, those are the microbes that are active.

[Damien Blenkinsopp]: What level is that? Is that the family or the genus?

[Richard Sprague]: It says, my test result says 80 percent spirochaetes at the phylum level, and then it shows at the genus level, the genus spirochaete is 46 percent.

[Damien Blenkinsopp]: So it’s missing one.

[Richard Sprague]: Yeah, there’s just something that doesn’t add up about it, and I don’t really understand how to interpret the results. And I’ve asked them and

[Damien Blenkinsopp]: Right. It sounds like their library isn’t quite there yet, and maybe there is…

For people who don’t know at home, spirochaetes get a bad rep because Lyme Borrelia, which is of course quite a bit of a problem for some people, is a spirochaete. That’s the family it’s in.

So when people see spirochaetes, typically, and when they’re talking about them they’re talking about pathogens. So when you see it in your samples and I’ve seen it in my Ubiome as well. It’s something, I actually did a little project on it, which I’ll, in the show notes we’ll put up anything we talk about, all that usual stuff.

But yeah, I bet you were interested when such a high amount of spirochaetes turned up, and you were like woah okay, but what kind of species is there.

[Richard Sprague]: Yeah, and the results show it broken down by phylum, genus and species. And what was odd is that at the phyulum level it said 80 percent spirochaetes, at the genus level it said only 46 percent, and there were no spirochaetes at the species level.

And the genus level, all of the different genera added up to, I think it was something like 90 percent. In other words, so they think they identified all the genera that were in there, but it didn’t add up. So I’m not sure exactly how that works.

[Damien Blenkinsopp]: Yeah. So I had a little problem as well. When I got my results, I had 30 bacteria in the total, which was showing up, which I felt was relatively low. And so I talked to them a bit about that, and at the time they felt that was correct.

That was when Viome first came out sometime last year. I got my results relatively early. So things may have moved on since then. I would expect as they’re working on the databases and all that kind of stuff that I’ll have more. And I think I haven’t counted them recently, but I need to count them up again but I think I now have more that have turned up.

[Richard Sprague]: Yeah, and they’re pretty clear about, they’re selling a subscription. So right now it’s like 400 dollars a year, or something like that, and so they claim it’s a subscription because they keep updating your results as they learn more information.

So, anyway, so I don’t know how to interpret that.

The other part about it, Viome, like Day Two, has a list of foods that you should eat or not eat. And what I found was there was some consistency between the Day Two algorithm and the Viome algorithm.

For example, both agreed that I can handle dairy products, lactose. Both agreed that I should stay away from grains, although Viome thought that whole grains were okay in a lot of cases. And then there were just some odd ones, like for example Viome says that I shouldn’t eat pork.

[Damien Blenkinsopp]: I think I may have had that too. I had some quite odd things in there.

The issue I had with it was that there’s no reasoning. For the Viome we don’t really know what they’re looking at and why they’re making these decisions. We discussed Day Two, basically we know what it’s based on. It’s based on the glycemic response.

[Richard Sprague]: And there’s an academic paper where they showed the reasoning behind it, and you can, all the caveats that you would see, normally, in any kind of academic study, but at least you kind of know what direction they’re coming from

[Damien Blenkinsopp]: And they’re very focused just on the glycemic response. So you know where that recommendations coming from and they give the A, B, C, D grades.

I would have loved if they showed the average glucose response for someone with mine. That’s what, I actually sent in a support email or something like that in to them for that, because I would be like wow that would be much cooler, rather than these A, B, C, D categories.

[Richard Sprague]: You know they changed it recently, right? They’ve changed it; now it’s not A, B, C, D it’s, they give you a number from 1-10 I think now.

[Damien Blenkinsopp]: Okay. So that’s a bit better, that sounds better. Yeah, that’s good.

Alright, cool. But the problem with Viome is you have no rationale, no methodoloy, and it says you shouldn’t eat something that you love. I think it told me I shouldn’t eat chocolate. So, it’s like, you know I kind of like chocolate and I don’t have any reason.

[Richard Sprague]: Give me a reason, yeah. Give me some kind of…

[Damien Blenkinsopp]: Give me a reason, give me a study. I need something to give up chocolate, you’ve got to give me… Because I don’t even know, maybe you think I’m allergic to it. I don’t know, I don’t know what you’re trying to get at.

So Atlas Biomed has a lot of recommendations as well in their interface, but what I did like is wherever there’s a recommendation there’s always papers, study papers, left there. And there’s always the reasoning.

And you can argue that with 16S and some of the other limitations they have, maybe they’re pushing the edge in terms of their recommendations, but at least they’re trying to give, you know, a reasoning and structure. And there’s a transparency.

So, with Viome, the thing for me is it’s not transparent, so you can’t, you don’t know what you’re getting, what the output is. So it’s like, how can you do anything with it really. At the moment.

[Richard Sprague]: Yeah, you kind of have to trust their scientists, or whatever the results is of this thing. Yeah.

And the other part of it is, remember also it might say, eat apples. Well, there’s lots of different ways you can eat apples. There’s a Fuji apple that’s different than a this kind of apple, there’s an apple that was just picked versus one that has been sitting in a truck for a while.

There’s lots of different kinds of things. And to just say a blanket statement, eat more apples, is, you know, I don’t find that as scientifically satisfying as it could be.

That’s why I like the Day Two approach more to talk about, well we’re not going to say apple versus not apple; we’re going to say apple with cheese versus a meal made out of apple pie, or something like that.

[Damien Blenkinsopp]: Yeah. I was talking with a guy who runs another bioinformatings company just the other day about this, and basically a lot of people have a religion about food. It’s not like everyone’s really objective about this.

Vegans are vegans, and ketogenic people are ketos I’m guilty of that one. And it tends to be an emotional thing. I try to be more objective and numbers driven, but, you know…

The problem is also, when we’re doing these tests, if you tell me not to eat my favorite vegan food and I’m a vegan, you’ve really got to and the argument is, say, glycemic response, and a lot of vegans don’t care about glycemic response, right? I think.

So if you actually gave us the reasoning, then different types of people with different approaches and thinking towards their eating style will be able to choose. They can be like, but I don’t care about that. I don’t care about glycemic response, or I don’t care about the other factor, or I don’t care about allergies. Or whatever the reasoning is. And at least that would give you a better framework in order to make a decision.

[Richard Sprague]: That’s a good idea, yeah. Have you used Inside Tracker? The blood testing company, Inside Tracker?

[Damien Blenkinsopp]: I haven’t. I know they were on a show a while back.

[Richard Sprague]: That’s another company I have a lot of respect for. It’s not the microbiome, but they have, it’s all about blood testing. And they’ll do exactly that. You can type in, you could say, I’m a vegan. Now give me your suggestions. Or, I’m a carnivore, now give me your suggestions.

And it’ll be tailor-made for you, because they recognize, like you say, that you may have another framework that you’re thinking about. And if your diet suggestions can’t fit in my framework, I may have to either give up my framework, or maybe I’ll give up you.

[Damien Blenkinsopp]: And this is something I’m seeing more in my results. When their recommendations come up and when I’m looking at them, I’m like oh, you know, that doesn’t fit with the ketogenic diet. That’s where I am currently.

[Richard Sprague]: Yeah.

[Damien Blenkinsopp]: So you want me to eat more of that, but I’m just not interested.

[Richard Sprague]: Yeah.

[Damien Blenkinsopp]: So there you go, even if I’m being objective. But if I had more information I might reconsider it a bit more.

[Richard Sprague]: Yeah, exactly.

(1:12:55) [Damien Blenkinsopp]: Okay, so what other kind of interesting stuff have we discovered here?

The other contrast, like I was referring to, I was trying to do earlier, was the Aperiomics, which is a shotgun sequence as well. And I was trying to compare it with the PCR to identify similar things. But that didn’t quite go as well, either.

So I think the shotgun technology, although it’s more detailed than the 16S, it’s going to take time for those databases and bioinformatics pipelines to evolve so that it’s picking up everything.

[Richard Sprague]: Yeah, I think you’re right. And like I said, I think you probably can trust a single lab over time. So if you’re doing A/B testing on a particular kind of intervention, and you follow the same lab both times, you may be able to trust that. But looking at the results from different labs, I just don’t know how useful that is a lot of times.

Especially when you get down to the species level, or down to something very, very particular. There’s just too many ways that they can be different.

(1:13:51) [Damien Blenkinsopp]: So because I’ve mentioned the ketogenic diet, one interesting thing is that if you look at some of the studies they suggest that if you’re on a ketogenic diet so I’ve been on a ketogenic diet for something like, since 2011, and then really seriously since January 2016. I was actually blood testing and stuff to make sure.

What they say is you should see increased microbes of the genus bacteroides and decreased firmicutes. And if you look at all my early uBiome tests, 2014, 2015, 2016, a lot of the time it’s the opposite.

[Richard Sprague]: Hmm.

[Damien Blenkinsopp]: Yeah, and I’m firmicutes dominant. I remember looking at this when I was first, I was like that doesn’t really sound like me.

And I think this goes back to the papers sometimes, as well. The studies when they’re looking at these things. I’ve got a team working looking at them, ketogenic studies and stuff like that.

When you look at a lot of the ketogenic studies, they have very different diets in them, unfortunately. You know, 40 grams carbs, 5 grams carbs, 50 grams carbs and doing different things. So a lot of things, when you look at these studies, even, you have to kind of look at the details of the studies. What they were actually doing, and then the diet.

So, you know I complained, I think. And I would bet that the reason I’m getting a different result there is because I have a, what I would call, a well-formulated ketogenic diet. Which means that I eat a lot of vegetables and, you know, fibers and things like that.

Because I think the main hypothesis there is that someone on a ketogenic diet is eating less fiber, basically, to feed his gut biome, and therefore you’re seeing that inversion.

[Richard Sprague]: Oh, I see.

[Damien Blenkinsopp]: But I’m not seeing it, so I think its because the type of ketogenic diet I’m running is different to that. So even when you’re looking at some of these studies, you have to be careful to look at the details of them as well, and does it exactly resemble you.

[Richard Sprague]: That’s true, yeah that’s true because not all ketogenic diets are going to affect the microbiome the same way. Yeah, that’s right. And then you get into the whole definition issues, of some people say that this or that is ketogenic and other people would dispute it. Yeah, that’s all tricky.

(1:15:54) Let’s talk about some of the things that we’ve done. In your show notes, I hope we can put some of these images that I’ve put up here, but there’s one in particular I guess if you’re asking me my take-aways. I think people need to recongize that a broad measure, something like diversity, which is something a lot of people care about, it’s real hard to tell what that means. And it’s very hard to just put a single number on the concept of musilin.

We all sort of intuitively understand that having a diverse microbiome is a good thing because you’ll be able to respond better to different challenges that might come up in your environment. But if you have a diversity of pathogens that’s not necessarily a good thing. It sort of depends on what’s in there.

And the other part is, and this is true of generally I find through daily microbiome testing is that there’s a lot of variabilty day-to-day.

So one of the charts that you can look at in here is just showing the diversity that if you tested me on a Monday you would say I have low diversity. In this case I have like 1.8. But if you tested me on Tuesday I was all the way up 2.3. And then if you wanted until the weekend, by Saturday I was at, maybe, it was still hovering around 2.1, but then suddenly on Sunday I plunged to under 1.8 again.

[Damien Blenkinsopp]: So we understand, with these diversity algorithms, right, that they’re running, is that looking at species diversity?

[Richard Sprague]: No it’s looking at the family level, which makes sense because the family level is kind of a good level to look at because you still have a lot of coverage. You’ll get close to 100 percent of all the different things that are there, unlike say genus or species where there are lot of ones that just won’t show up in the 16S.

[Damien Blenkinsopp]: In the 16S, yeah they won’t show up so you wouldn’t be — yeah that’s what I was getting at.

[Richard Sprague]: So they test it at the family level. And there are a couple of different ways to measure, but one way to measure it is, you can think of it as the probability that if I grabbed two things at random, two microbes at random from my gut, the probability they would be the same,

And in the case of if you, for example, if you’re firmicutes dominant and a lot of people would have 70 percent firmicutes, it’s pretty likely that if you grabbed two random microbes that both of them will end up being firmicutes. But it’s very unlikely that two of them would be something else, and that’s the way you measure diversity.

There are a couple other different measurements for diversity, but they all rely on the this idea that in aggregate we’re looking at, like how much information is in this signal. And that’s a little difficult to be able to really pin down.

Now that said, the other thing that I pointed out is that although it’s variable day-to-day, if you look at my picture and we can put this in the show notes too if you look at my diversity across the year, yeah there’s a lot of day-to-day variabilty but there’s a trend. There’s kind of an average there.

And I’ve looked at this with other people as well, and it’s unique to me. So there’s something different, something special about my gut that is different than your gut. And even though there’s a lot of day-to-day variability in how that works, I think there really is something there. There’s some kind of signal, we just have to understand better what that signal is.

[Damien Blenkinsopp]: Right. So you’re saying diversity is interesting but we don’t understand why it oscillates.

[Richard Sprague]: Yeah, and it’s partly because we don’t understand diversity, or know what that really means.

[Damien Blenkinsopp]: Well I think it would be really interesting. You’re saying it works at the family level, and that’s because…

[Richard Sprague]: That’s how we measure it, at the family level usually.

[Damien Blenkinsopp]: Right. So that’s what we’re measuring currently. And it’s not the ideal, right. I mean, ideally, maybe with the shotgun. And I don’t know if there’s studies actually on this. Because I’m assuming that the studies were all done on a 16S for diversity.

[Richard Sprague]: Oh no, people do diversity metrics for any sort of sequencing.

[Damien Blenkinsopp]: Okay. So they’ve done it on shotgun as well, but they still do it at the family level?

[Richard Sprague]: No, just generally speaking, if you want to be able to compare two different samples that were done on 16S, you’ll probably want to compare at the family level.

[Damien Blenkinsopp]: Yeah.

[Richard Sprague]: But there are other ways to measure diversity too that might be useful. Like just counting up the total different number of species that were found in your sample versus my sample. And you might find that you had 150, I had 130. And that’s kind of interesting to know that you have some microbes that I don’t have, and maybe vice versa.

[Damien Blenkinsopp]: Yeah.

[Richard Sprague]: But that’s hard to capture in a single number, and a lot of people, like the Viome test wants to be able to say in one chart, what is your diversity. People sort of care about that.

I’m just, in my experience that’s hard to pin down.

[Damien Blenkinsopp]: Right, and it’s hard to say it’s actionable or you can even say, okay I’m diverse, I’m well. It seems too abstract in terms of a biomarker.

[Richard Sprague]: People who complain about having low diversity, I’d say why don’t you test yourself tomorrow and see. You might like the test results you get better tomorrow, I don’t know.

(1:20:15)The other, just to quickly show you one more of my charts that I think is fun.

So I tested myself doing a probiotic, taking a pill, to see what would happen. And in this chart you’ll see there’s a little red splotch on there that shows there’s about a nine or ten day period that I was taking this pill daily to try to improve my levels of bifidobacterium.

And on this chart you’ll see that it’s hard to see there’s much difference in the level of bifidobacterium, but there’s another huge spike in my bifidobacterium that happened several months before I took that.

[Damien Blenkinsopp]: And we are talking huge, guys. You’ve got to look at the chart.

[Richard Sprague]: It’s totally, totally different. And the fact is that that month of September I happened to be traveling in New Orleans and eating a lot of red beans and rice, which apparently affects my bifidobacterium levels. And that’s kind of the take-away lesson for me is that often the best interventions you’re going to have are going to be some kind of food that you eat.

[Damien Blenkinsopp]: Probiotic.

[Richard Sprague]: Like a prebiotic, yeah. Because I think what’s going on is these microbes all interact with one another. And so just increasing one is sort of like poking on one little thing hoping that that’s going to improve it, but really that’s going to create a cascade effect of a whole bunch of other things.

[Damien Blenkinsopp]: Absolutely.

[Richard Sprague]: And the only way to really improve things is probably holistically.

[Damien Blenkinsopp]: Yeah, yeah, absolutely. It comes back to the whole foods approach and everything, right? That we can’t approximate, we can’t invent a food with our food science because we don’t fully understand what’s in a whole food. Right?

That was one of the concepts out there. And so we should just eat whole foods and then we’re going to get everything that we need. And one day when science has really understood all of the tiny details we can maybe mimic it. But for now it’s probably just not a good bet to be able to do that. So, really interesting.

[Richard Sprague]:Yeah, that’s right.

(1:22:01) [Damien Blenkinsopp]: One of the things I came across in terms of a test was putting kimchi up your nose.

[Richard Sprague]: Yes, I’ve heard about that, yes.

[Damien Blenkinsopp]: Right. Because I think we discussed it before on a past call. So this was something recommended to me by a physician, because I had experienced some sinus headaches.

And people have been experimenting on this we’ll put up the links on the internet and blogs about this approach to reducing the incident, or eliminating, sinus headaches. And basically there’s certain types of kimchi that contain cayenne, which is in all of them today because there’s a lot of different kimchis on the market.

And they have to be unpasteurized. And basically you take, you don’t put kimchi up your nose literally. Thankfully, you take some of the liquid in that, so you put a teaspoon in, pull it out, then you dip your finger in it and you put your fingers up your nose, both nostrils, to get some of that in there.

So you’re snorting the juice, basically. And the idea is you get lactobacillus sakei up there, and that helps to populate the nose if you’re doing that every day. And that helps to counter some of the microbes that are potentially causing the sinus headaches by their overgrowth. So it’s countering their growth, basically.

It did seem to have a positive effect for me, but unfortunately I wasn’t doing any biome test or anything like that at the time, so there’s no data on that. It’s just an idea that someone might want to test. And I’d love to see some biome or something else results on it if you do do it.

[Richard Sprague]: It would be interesting, yeah. So my daughter suffers from sinus headaches now and then, and I told her about what you had suggested. We have this big jar of kimchi still in the refrigerator, but she just wasn’t interested.

[Damien Blenkinsopp]: It’s kind of a weird sensation at first, I have to say.

[Richard Sprague]: It’s like the other advice that I got on the internet was you should simulate, what is it called, the brain burn that you get if you have some very cold ice cream or something. And she doesn’t mind doing that, eating a lot of ice cream when you have a headache. But kimchi up the nose thing was a little bit hard for her to try.

(1:24:06) [Damien Blenkinsopp]: So obviously there’s a lot of probiotics on the market right now. A lot of them, and I think going back to what you were talking about, when you introduced one of those into this environment and we have been talking about that there’s a homeostasis of that environment.

They work together, they feed each other, and you just throw one in there, he’s basically getting thrown into an alien population. Because if you’re adding them, it’s probably because you don’t have them, so it doesn’t really fit in with that environment right now. And that’s my assumption why they’re not growing, not sticking in a lot of results like yours that you’ve seen.

Because it’s probably, he depends on some other guys, some other bacteria. That would be interesting studies. Like, bifidobacterium, everyone knows that these are beneficial, what other species do we need in there to support them, and then concoct basically a probiotic which maybe allows that. And maybe adds prebiotics as well. I mean, that sounds good to me.

[Richard Sprague]: Yeah, and people tried doing that. And I’ve looked at a lot of people who’ve done A/B testing, where they test their microbiome before and after, and I have yet to see convincing evidence that any of them makes any difference. Yeah.

[Damien Blenkinsopp]: Right. And they’re quite expensive, some of them, right now.

[Richard Sprague]:Yeah, that’s right.

Now, that doesn’t mean that it doesn’t work. And there have been studies like BSL-4, I think, is the one that people talk about. They’ve done randomized controlled trials and they show that such-and-such marker is actually improved, or such-and-such disease state is improved after taking the probiotic. I just haven’t seen that demonstrated…

[Damien Blenkinsopp]: In the data. But that’s also like, okay, so maybe it’s something that’s not being picked up in that particular sequence, the bioinformatics pipeline, or whatever. And it will turn up in two years when we’re finally tracking it. That’s the problem with where we are right now; something could be happening and could be beneficial, and we’re just not finding it in the data is all.

[Richard Sprague]: Yeah, who knows. Or it could be that they way they do the testing, these randomized trials, maybe they all drink a glass of orange juice after they take… Who knows.

Yeah but I do think in general, a lot of people ask me after all my testing, What do you think about taking probiotics pills?

And my general, I just have not seen any good evidence that any kind of pill really helps. If you want to make a difference to your microbiome, do something involving food.

[Damien Blenkinsopp]: And a variety. I think a wide variety makes sense. If you’re trying to get diversity, a variety of vegetables which is supposedly a good rule of thumb for micronutrients and other reasons as well it can’t be a bad thing to do.

[Richard Sprague]: Yeah. You can have, you can put up a link to the, I’ve got a medium place where, medium.com, where I posted a bunch of my microbiome experiments. But a few of the things I’ve tried are like, kombucha, soy lint, makes a difference in the microbiome.

[Damien Blenkinsopp]: Oh right, that’s an interesting one. Yeah, so the whole, whole…what do they call it. Nutritionally complete food.

[Richard Sprague]: Yes, right.

[Damien Blenkinsopp]: Yeah. There’s like 60 companies that have started those now. I didn’t realize until I looked into it the other day. Didn’t you do a colonic at one point? Was that you?

[Richard Sprague]: I did, I did that as well. Again, my take-away was that I was hoping that there would be some ability to make a major change afterwards, by feeding myself the right kind of things. But it just bounced right back to the way it was. Two weeks later I was right exactly where I was before.

[Damien Blenkinsopp]: But that’s actually, that was good feedback for me because I spoke to one physician who’s been working in environmental medicine for a very long time about something that I had.

And he suggested six colonics within two weeks. And he didn’t know why, but he’d been doing it for 30 years. And he said, I don’t understand completely the mechanism, but it really helps with this specific thing.

So, I did it. But I was concerned about my biome, obviously, doing that and colonics and stuff. So when I heard your story I was like, okay.

[Richard Sprague]: Yeah, and who knows. I’m just one guy, so.

[Damien Blenkinsopp]: Right. N=1.

[Richard Sprague]: The other thing that people should realize based on my experiments that I don’t have an appendix. It was removed when I was five years old. And the appendix is known to include, that’s where the bacteria gets stored when you…

[Damien Blenkinsopp]: It gets stored. Yeah.

[Richard Sprague]: Yeah. So who knows what’s going on in my gut.

[Damien Blenkinsopp]: But that’s a good test though, because then you don’t have that storage device, basically.

[Richard Sprague]: You’d think, yeah, but who knows.

[Damien Blenkinsopp]: Yeah but that is a pretty important N=1 difference there.

[Richard Sprague]: But nevertheless, for me at least, everything just seemed to bounce back. And I’ve found that my microbiome is pretty resilient to just about any kind of change.

[Damien Blenkinsopp]: Yeah, hard to change.

[Richard Sprague]: Yeah, that’s kind of the bottom line.

(1:28:22) [Damien Blenkinsopp]: Alright, so we’ve dived through some of our own personal experiences there, trying to change it. And as you’ve kind of heard it’s not easy to change your microbiome, it seems. But it doesn’t mean it’s not worth experimenting with.

(1:28:34) So the thing I’d thought we’d do now is kind of take a step back and look at the big picture of all of these labs and everything. To see where they are and what kind of, you know, thoughts we have about using them, I guess, right now. What’s valuable to you, you the guys at home, to be doing with these right now and potentially in the future.

Richard, what are your overall thoughts?

[Richard Sprague]: Well, so, it’s hard to beat the price of 16S. And it is something that’s also pretty easy to do; you don’t have to poop in a box, you don’t have to put tablespoons, laying on the floor kind of thing like this. It’s relatively easy to do. And for that reason alone, I think it’s worth doing a 16S test. Do a couple over time, or if you’re trying to check out the effect that it has on one particular thing, it’s cheap and easy.

[Damien Blenkinsopp]: If I can just jump in there, I think that’s interesting also because of what we’ve said about the bioinformatics pipelines and the databases will be evolving and getting better over time. And that sample is part of your history, which could be useful if and this is actually Jessica, she came on the show way, way, way back and she suggested it was good.

Say you get sick in the future, it could be gut related, and you have that sample. As the bioinformatics and the database evolves, you could then look back at that and be able to see what the difference is. And you would be able to formulate some kind of plan to try and get back there, at least.

So just for that reason, for this historic storing your sample if you ever need it in the future, it’s a reasonable idea.

[Richard Sprague]: Yup. I think that’s something everybody should do. And we talked about the other tests.

I told you about Day Two, I like the science behind them. It’s like 300 something dollars, I guess. Little bit expensive, I think, but a lot of people would find it would probably be useful for you if you were looking at a particular condition, particularly any of the metabolic diseases like diabetes, I would think that you would want to do this.

Because it’s going to tell you based on these peer-reviewed studies, it’s going to tell you something about your glucose response to different kinds of foods.

[Damien Blenkinsopp]: Yeah. If you’re overweight, if you’re really overweight, it’s probably interesting.

[Richard Sprague]: Yeah.

[Damien Blenkinsopp]: Because it might just pick out one of those foods that is your main go-to every day.

What I like to think about these kinds of tests, because we’re saying it’s not 100 percent, but it’s a good broad picture. And if some of these foods that you’re eating every day come up as red in their algorithm, you can then go and test them properly. And you’ve saved a lot of time and effort because it gave you that broad look at all of the foods.

And it gave you some way of basically strategically focusing on like five different foods that you’re eating a lot and turned up red there. And then you could do a proper glucose test with a meter on each of those. Whereas obviously you couldn’t do that on the thousands of different foods you’re eating, or hundreds, that you’re eating each week.

[Richard Sprague]: Yeah, that’s right. And like the example I give is I have always eaten a lot of bananas. Now, I’m aware of the carbs, and the sweetness, and everything else. Bananas I always thought were nutritious; it’s a fruit, it’s healthy and it’s easy to eat.

But both my tests Day Two and Viome results came back saying that I should avoid bananas. Which I thought that’s kind of interesting evidence. And so that’s the kind of thing I probably wouldn’t have thought about.

[Damien Blenkinsopp]: Have you, my first question, have you tested your glucose response to that? I’d really like to see.

[Richard Sprague]: I mean I test my glucose response, but I haven’t noticed any major differences. I have not tested my glucose response after eating a banana, I should do that. It would be interesting.

[Damien Blenkinsopp]: Right, that’s what I would love to see, to marry that up. Yeah.

[Richard Sprague]: Yeah that’s a good idea, I’ll try that.

[Damien Blenkinsopp]: Please do, and we’ll chat about it later.

 

[Richard Sprague]: Yeah. And I guess those are the big commercially available ones in the US. You mentioned Atlas Biomed and Aperiomics is that what you said?

(1:32:11) [Damien Blenkinsopp]: So Aperiomics is designed, their whole thing is focusing on pathogens. They mostly work with physicians , and they mostly get people who have strange illnesses and haven’t been able to figure anything out. I mean, she’s got some interesting stories.

I’ll tell you, because I’ve been talking to the girl that runs the lab. And I figure I’m going to use it a little bit more, because it appears like a lot of us and I’ve been talking with other scientists about this a lot of us carry a bunch of pathogens around with us all the time.

Depending on where your immune system is and everything else, you could be fine. But that doesn’t actually mean you want to harbor these things for the rest of your life. Because they do see some correlation later in life to certain neurological diseases and stuff to some of these pathogens.

And so I think it’s a preemptive. Because I’m a bit anal, I’m quite interested in that to screen for certain things that I might decide to try and remove for the long-term benefits of removing those things.

So I’m actually going to run a blood sample through her as well. But she’s got some interesting stories. Like she had some patient come in with some sample and they couldn’t figure out what the problem was. And it was a species of leprosy.

[Richard Sprague]: Ooo, okay.

[Damien Blenkinsopp]: Yeah. And apparently this specific one isn’t supposed to be around anymore. So they’re picking up stuff that is kind of presumed dead or gone in the past.

So I think her lab will be interesting. I’m not sure how fast she’s accumulating data. But if anyone’s got something, some really strange medical condition out there it might be an option to just try and get some ideas on the table.

[Richard Sprague]: Yeah, I think that’s a good point that especially for people who have some kind of misdiagnosed chronic condition, where your doctor and maybe doctors, and you’ve consulted lots of people and they don’t know what’s going on. And they’re just, can’t figure it out.

I do think that any of these tests is going to be valuable as an additional data point. Now whether it’s going to produce something actionable for you or not, I don’t know. But I’m really glad that we have the technology available for us to better ourselves.

[Damien Blenkinsopp]: Yeah, it’s exciting. It’s starting to give us ways to try and decipher these mysteries. Or at least get us closer to the results more quickly. And often it’s kind of leads.

Obviously it’s not, that’s why they’re not being used by physicians that much is because they can’t give you a diagnosis. But they can give you leads and patterns, and eventually someone can figure something out from that.

[Richard Sprague]: Yeah, yeah. And like my example of bananas, I think that a lot of times just doing a different test like this will maybe point out something that you had not been focusing on; you had sort of taken it for granted that this was just the way things are.

This is the way that I live. And sometimes they’ll kind of shake you up a little bit and say, well wait a minute. Have you tried rethinking this previous assumption? And I think that’s valuable too.

(1:34:52) [Damien Blenkinsopp]: So what did you think on the 16S versus shotgun? I mean, they’re not that far apart now in terms of price.

[Richard Sprague]: Yeah, I mean again. Well, I mean.

[Damien Blenkinsopp]: It depends on your budget, right?

[Richard Sprague]: Depends on your budget, yeah. And I know a lot of people who would say 400 dollars, or 300 dollars, is a lot of money to spend on something that’s not quite that well understood. And I understand that argument. I think that if you can, I think it’s definitely worth it. I think you’re getting some new insights that you wouldn’t have had otherwise.

We talked about the question that we have about the transparency of the results of Viome and where they got their…

[Damien Blenkinsopp]: I think transparency is key because, it’s also, I think it’s a little bit about the ethos of the company. Like the ones that are already transparent, you can see, as we were saying, these samples they have them, they’re going to evolve over time. So it’s going to become more valuable provided that it’s transparent.

[Richard Sprague]: That’s right, yeah. Yeah. I do want to know why it is that you gave that recommendation, and then I want to know and trust that if someday you discover new science that makes you retract your recommendation then I’m going to hear about it. And you’re going to be honest and up-front about it.

[Damien Blenkinsopp]: Right.

[Richard Sprague]: Because here’s the thing about science. Real scientists, they want to be proven wrong. They’re constantly working, it’s why their…

[Damien Blenkinsopp]: Exactly. The search for truth. Yeah, exactly.

[Richard Sprague]: Exactly. And I always get a little suspicious when I’m talking to one of these companies where they act like, What do you mean, are you questioning my science? Are you questioning my results?

You know what, yeah. They should be glad for that.

[Damien Blenkinsopp]: Well they don’t give you full access to the data. If you don’t give me my raw data, I get nervous.

[Richard Sprague]: That’s a red flag right there, yeah.

[Damien Blenkinsopp]: Yeah. So, Richard just brought that up. We’ve got a little table here we’re going to throw up. He was like, oh yeah raw data, and I was like damn I forgot that one.

(1:36:30) When you can, raw data is going to be really helpful. And it just proves that they’re transparent as well. I think that’s a really important thing when you’re going for one of these services, to ask about.

[Richard Sprague]: Yeah.

[Damien Blenkinsopp]: And I think most of them are going to provide that. We spoke a bit about, some of them haven’t done it quite yet but they say they’re going to do it soon.

[Richard Sprague]: Yeah. I look at it as a reputable lab will be happy to give you the data because their real value that they had is in the interpretation side. And they have access to additional, maybe proprietary data or insights that you don’t have.

Which is fine, that’s where they’re going to be differentiating themselves. But the raw data itself, it’s just data. It just comes right out of, it’s your data; it’s about your health. You should be able to look at it. That’s my attitude.

Plus, in the case of something like uBiome, one of the reasons I’m very, very excited about uBiome’s raw data is that we’re able to go and take that data and do things with it that uBiome just doesn’t have the time or the, maybe just the bandwidth to go and pursue. And so a lot of these charts that uBiome sent me, I did that because I had access to the raw data. I wouldn’t have been able to do that otherwise.

[Damien Blenkinsopp]: Yeah. I actually had, anyway. That’s a long story. I had a little project to identify a species which I thought would be useful to the 16S. Basically like a strategic screen for pathogens using some tools. So I actually got that sent to uBiome, and they were like, ìThis is really interesting, but we have a lot of other projects that are taking up all our time right now.î

So there’s a lot of stuff these technologies could be used for in the future. And I think that’s one of them. A very cheap method for some doctor to get a strategic screen, and then for pathogens, for a list of pathogens. And if something comes up, you then do the PCR, which is more expensive. But you’ve done it really cheaply. So I think that’s going to be, hopefully, a really interesting application in the future.

[Richard Sprague]: Yeah, that’s right.

(1:38:23) [Damien Blenkinsopp]: What other things do you think might be cool in the future? Or what applications do you think these are going to turn out to be pretty useful for? Or, what do you think you would use it for today, if you’re going to use it for something?

[Richard Sprague]: Like I said, I think that most people talk about gut microbiome, but there’s a lot of interesting things you can learn in the other microbiomes as well. And I think we’re going to see a lot, in the future I think we’re going to see more emphasis on, say the mouth and the skin. And there’s just these very intriguing associations.

For example, one of the things about Alzheimer’s disease, one of the early symptoms of Alzheimer’s disease is a lack of smell. And there is some evidence that the nasal microbiomes of people with Alzheimer’s are different than those who are not. And could it be that there’s a microbe that just sits in the nose for years and years, decades and decades, and finally migrates into the brain and that’s what triggers the disease?

And we’re going to find all kinds of associations like that.

[Damien Blenkinsopp]: Yeah. And I think it’s often going to be multi-factorial as well. And that’s why data from all of these places is going to be so invaluable, because we’re going to be like, oh look, when you get these 20 factors together.

I mean this is why we haven’t been able to figure this stuff out yet because we focus on one factor, and we just can’t see the big picture. Which is way more complicated.

(1:39:39) [Richard Sprague]: And talking about AI is becoming kind of a buzzword, but I do think that the ability to be able to go and look at all these different tests all holistically and be able to look at all this different data and then see patterns, that is one thing that AI is good for.

[Damien Blenkinsopp]: Yeah.

[Richard Sprague]: And we may be surprising ourselves in the kinds of insights that are possible.

Damien Blenkinsopp]: I know, right. It’s going to be really interesting what comes out. And some people are going to get really annoyed by some of the stuff AI brings out. It’s going to trash some stuff we’ve been doing for a long time.

[Richard Sprague]: It probably will.

(1:40:05) [Damien Blenkinsopp]: One cool thing that’s actually going on is, and Richard eluded to this with another company before, but Day Two, what’s interesting about these companies is they’re evolving pretty quickly as well.

So Day Two when I did it, was just a test. But now when you buy it, you actually get a nutritionist consultation. So they’re embedding that with it.

[Richard Sprague]: Yeah, that’s right.

[Damien Blenkinsopp]: Did you get that when you signed up for it?

[Richard Sprague]: I just, I never talked to the person. I probably should at some point.

[Damien Blenkinsopp]: You, follow up. I’d love to know what they talk about.

[Richard Sprague]: Yeah, well the frustration I was having is because I want to know a lot more technical details about stuff, and they usually don’t know the answer.

[Damien Blenkinsopp]: Well, you find out. You never know, you might hit the jackpot.

[Richard Sprague]: Yeah. In the case of both Day Two and Viome I was very impressed that they reached out to me. I got a call out of the blue from someone from Day Two, and they just said, We wanted to talk to you about your test and what you thought about it.

[Damien Blenkinsopp]: Wow.

[Richard Sprague]: It was like, how did you get my phone number? And they said, ìWell you put it down when you registered for the product, and that’s what we’re calling it for, because we wanted to know what you really think.î And I chatted at length with somebody and told her exactly what I thought about the product.

So I’m encouraged that they are going out of their way to do this. Similar with Viome, I know; they are calling people up and saying…

[Damien Blenkinsopp]: Are you saying uBiome, or is there another company?

[Richard Sprague]: No, Viome.

[Damien Blenkinsopp]: Oh, Viome. Okay, got ya.

[Richard Sprague]: They’ve been very proactive about making sure that people send their samples in, and find out why it is that you’re not sending the samples. So I’m encouraged that the whole industry is undergoing this kind of push to be more customer centric. And maybe really trying to solve people’s problems as opposed to just a fast way to make money.

[Damien Blenkinsopp]: Yeah, exactly. Solving results, giving people results is where it’s at.

[Richard Sprague]: Yeah.

(1:41:44) [Damien Blenkinsopp]: Okay, so what do we think are the things that have to be improved? I mean, we kind of touched on this already, but to get to something that’s going to be far more valuable, like all of these services, so that we’d be saying everyone should be getting these done and really using them.

What has to happen with the technology? What has to happen, and do we have any kind of reasonable timelines?

[Richard Sprague]: So there’s kind of a movement. A lot of these companies are trying to add better access to the literature.

So for example Thrive now, they’re proud of the fact that they did some kind of machine learning thing, where they went through all the literature and looked at all the references to different microbes, and they’re going to tell you this and that about it. So there’s some activity around that. I think that’s helpful.

I think it’s nice to be able to have some way other than just googling the name of a microbe to find out what it is. If we can get more into, more vetting of the literature that would be good. Even if you spend any time with this area you’ll notice that there are thousands of new articles coming out, new journal articles, new peer-reviewed journal articles coming out every day.

You can’t keep up with them all. And a lot of them are self-contradictory. It’s just very hard to tell.

So if maybe there was a little bit more emphasis on curating the results a little bit better, that might be useful.

[Damien Blenkinsopp]: Standardization. Somehow.

[Richard Sprague]: Right. The way the labs really report the results, the way that they publish the results. That kind of standardization I think would be great.

[Damien Blenkinsopp]: So I was talking with a bioinformatist who’s working in the nutrition area. He’s got one of these apps similar to, that tracks food. Food intake and all of that. And he was telling me that the databases that all of the companies with these apps, all of them, are using are really low quality.

So then it’s a very similar instance, and I’m sure it’s similar in most of these areas where the quality of data is actually very poor. And we’re just talking very basics here, like the macro content of a food, which is being put in their database. Then you take the photo, or you enter, you pick it from their library, and you think you’re getting that macro content but you’re not because the data is quite bad.

So they’ve personally just been building a very low volume database. So it has less in it, but it’s high quality. And they’re thinking about just throwing it out there as Open Source to try and bring the industry up a bit. To try and get people using that and building on it. And improving on it.

But I think what’s happened is a lot of people have been conscious that their databases aren’t broad enough, or don’t have enough volume in it. So it can be very frustrating for customers and all of this stuff. So they’ve chosen other approaches like just get customers to add the information in, or whatever. And these are low-quality approaches, and then you end up with a lot of garbage, unfortunately.

So, this is a very important topic for quantification in general, and getting actionable information out of it at the end of the day.

[Richard Sprague]: Yeah, and everybody kind of wishes there was Wikipedia of knowledge about the microbes and about the food benefits and all that kind of stuff where anybody can go and add their results. I guess that’s Wikipedia.

[Damien Blenkinsopp]: There is value in crowd sourcing, but it’s those processes and things that you have to put in so that you get a volume, but then it’s filtered, and filtered, and filtered. So that you maximize the benefits of building volume through crowd, but at the same time there’s that mechanism to ensure that quality eventually ends up there.

[Richard Sprague]: Yeah, and it works for things like, MyFitnessPal has any kind of food you can possibly imagine in any culture, any language, anything and they’ve got it in there. Because they’ve got this crowd sourced thing figured out to a science.

And in fact they were telling me that when Nabisco put out some new packaged good, they had the calorie information in their database before Nabisco.

[Damien Blenkinsopp]: That’s ridiculous.

[Richard Sprague]: It’s like somebody just immediately.

Yeah, but you know it’s of unclear quality. And in a lot of cases, particularly with foods, and with the microbiome, like we were talking about apples; there’s a lot of difference between what was tested in a lab somewhere and what you’re actually putting on your plate.

[Damien Blenkinsopp]: Yeah, and I can tell you, because I’ve been digging into food science and stuff for one of my companies, and when you see an ingredient on a label, there are 20, 30, 40, 50, 60 different versions of that that would fit into that name. And they have quite different properties in some instances.

We’re picking three different ones, and we’d go through ten of them until we get to one that does what we want to. So there can be a lot of variation on this. So when you’ve got these ingredients and they’re using these ingredients as well to pull the macros and everything. It’s just not the same.

[Richard Sprague]: Yeah, and I think with labelling, in some ways it may be a dis-service that governments around the world force companies to put the labels on because it gives this false sense of security on your part. That you think, of it’s got sugar in it. Well, what kind of sugar.

[Damien Blenkinsopp]: Exactly.

[Richard Sprague]: And the reality is just way more complicated than they can summarize in a label. And I almost wish that there was instead like a competition among lots of private companies that will compete on the best label that they supply for a particular food.

[Damien Blenkinsopp]: Yeah, because right now everyone hides behind it, basically.

[Richard Sprague]: Exactly, yeah. And in the US it’s particularly bad because we don’t give, it’s not per 100 grams, it’s per serving, whatever that means.

[Damien Blenkinsopp]: I was actually looking at that the other day, and I was like this makes it really hard to do the calculations in my head. Because you always have to have it working on the 100 otherwise you can’t compare.

[Richard Sprague]: And, you know, smarter companies know how to manipulate that. For example, what is it, the little sugar packets that you get for coffee? I guess they’ve arranged it so that they make the size exactly at the cut-off, where now they can say it’s zero calories because it’s like 4.9 calories, but it’s under 5 so they can report it as zero calories.

[Damien Blenkinsopp]: Yeah. There are so many tricks in the food industry. They have mastered the game; they’ve had a while to do it. And I think regulators are never going to be able to solve that, it really has to be transparency coming through because companies want to do it to please their customers. Because regulators, it’s just not their job. You can’t fit a structure that forces people to do it.

[Richard Sprague]: Yeah, and that’s where for the microbiome stuff, as we get more and more companies involved in it and more and more labs that are doing this sort of thing, I do hope that there emerges some sort of independent verification lab, or something.

And I think, was it LabDoor I think that you had on your podcast a while ago is an example of that company that, I love that. They go out and they specifically go and evaluate these things. And it’s independent, and they’re just looking to see kind of, on behalf of consumers, whether you can trust what you’ve got or not.

It’d be neat if there was a similar kind of thing with the microbiome world, wouldn’t it?

[Damien Blenkinsopp]: This is happening, you know the software world has made itself, has been very good at this.

When I think of telecoms, and software, and these IT industries compared to the health industry where it is, there’s a lot of silos in health. And everyone’s got their own lab, and you don’t know if they interrelate, and they don’t, I mean even in the big labs that hospitals have been using for a long time and so long.

And what we really need is a similar structure to what they’ve done in telecoms and software, where you have these big open standards of organization, and everyone gets together and says, we know it’s going to be more valuable for the industry; we know we’re going to make faster progress, and the economics are going to be better, so we’re going to make this.

And maybe it just needs a few people to stand up. So if you’re listening out there, and you’ve got a role in this, go for it please. Because you could add so much value to this industry. People need to start putting things together.

And then I think the other analogy is a lot of integrator kind of companies in software area and the internet now, where things like Zapier and IFFT and all these other apps are relying on all of the rest of them in the ecosystem. And maybe like a conversion app or other ones would add so much value to all of the other things out there.

So I think there’s ways to better integrate these things over time, and it’s going to happen. And there’s plenty of business ideas out there, potentially as well.

[Richard Sprague]: That’s right, yeah. You know, it’d be interesting to look maybe at the history of how, even say like blood testing for standardized.

Because I’m sure they had the same kind of problems in the beginning. Like, how do you decide how to measure Vitamin D, or how do you decide to measure all of this stuff? And it looks like they’ve kind of figured that out. I wonder if some of those same lessons could be applied…

[Damien Blenkinsopp]: Largely, however, I’ve had problems with blood tests in terms of variants. In particular between different countries.

So I was in Spain at one time trying to get labs, and I actually left the country because I gave up completely. Because the data wasn’t correlating with stuff I’d seen in the US and the UK and stuff. So I think there’s still, there is interlab…

[Richard Sprague]: Maybe it’s more complicated than I think.

[Damien Blenkinsopp]: I think there’s still…

[Richard Sprague]: Yeah, a lot of these things, the more you dig into the details the more you realize how messy it all is.

[Damien Blenkinsopp]: Yeah. It’s a crazy world we live in. And this is something you’re constantly working on. You still work on this stuff, do you? Or have you kind of moved on a bit?

[Richard Sprague]: I do. I mean, [most of my situation] right now is I’ve got so much data that I’m spending a little bit more time trying to do the analysis of the data. It is kind of cool though, because every time, lots of people send me their samples and ask me what I think, and every time that somebody sends me a new sample, I get more information.

[Damien Blenkinsopp]: Yeah. Are you offering…

[Richard Sprague]: Yeah. I mean, anybody who wants to, you can send me your uBiome data. I’m happy to look at it and tell you what I think.

I’ll find out little things like, the other day there was a New York Times article about heart disease or something I read this every single day and they’ll mention the particular microbe that was involved. And so I’ll just go look it up and I’ll see, oh, huh. And I log into my computer and I see, okay how does that microbe look in me and what was I doing at the time.

And I’ll find all kinds of interesting correlations. I’ve found things like during travel there are particular microbes that bloom in me. And just we need to understand why, and what is that thing doing, and is it a good thing, a bad thing? I don’t know.

[Damien Blenkinsopp]: I was just also thinking that you’ve travelled a lot, right? You lived in China.

[Richard Sprague]: Yeah, I spent two years in Asia.

[Damien Blenkinsopp]: Right, so we both did that. We both traveled a lot. And I think that influenced our biome a little bit. You found some stuff in there.

[Richard Sprague]: Yeah. One of the things, I mean one of the things I think is really cool is there’s a particular microbe that was identified a few years ago as letting Japanese people, so their digestive systems can handle seaweed, and metabolize seaweed better.

[Damien Blenkinsopp]: And you have it.

[Richard Sprague]: And the study that did this was comparing a lab in Japan versus a lab, I think it was in Saint Louis. And they concluded that North Americans don’t have this, and Japanese people do. And I thought that was pretty cool, but when I looked at my own results I found out I have it too. And that was kind of cool.

In fact, that’s the reason that got me excited about the microbiome, is that it does appear that there are ways that you can change your microbiome.

[Damien Blenkinsopp]: Like living in another country for a while.

[Richard Sprague]: That’s a big one, yeah.

In fact, actually speaking of probiotics. So a lot of people have sent me A/B testing of their probiotics, and one guy sent me, he had three samples. One when he’d been living in the UK, another when he had moved to California and started taking probiotic, and then a month or so later he did another sample. And guess what, you can’t really tell the difference between the two samples taken on the probiotic, but you can tell the difference the sample when he was living in the UK.

(1:52:18) [Damien Blenkinsopp]: Yeah, so if you really want to change your biome, move. So I wonder, I have lived in countless countries. I think my microbiome might be confused, potentially

[Richard Sprague]: Yeah, maybe. But you know what, the microbiome is pretty resilient too. I like looking at, so I compare my father who lives in the Midwest in the United States. And he has kind of stayed in the same place, and that’s where I grew up.

But it’s interesting to look at our microbiomes. I’m essentially a superset of his. So, whatever microbiome I inherited as a result of living in his household for the first however many years of my life, and eating kind of, we have similar tastes in food, and similar diets to this day. But yet I have a superset of his microbiome, because I’ve lived all over the place and he hasn’t.

[Damien Blenkinsopp]: Yeah, exactly.

[Richard Sprague]: And again, that’s kind of a neat thing to know that we do have some influence over how this whole thing turns out.

I run into a lot of people who ask me questions about, like what can I do to change something. And that’s a big one, geography. But there are a lot of things that people don’t necessarily think about, either.

And a big one that I always tell people is about fasting. That’s a fast and easy way to change your microbiome that a lot of people just don’t do. It’s surprising how often you’ll run into somebody who, if you ask them when’s the last time you went a full 24 hours without eating food?

[Damien Blenkinsopp]: Have you seen samples before and after from fasting? I mean, I’m into a lot of fasting so I’d be interested to [know].

[Richard Sprague]: No, I haven’t. And I would like to be able to see that. I would like to see somebody doing a serious job at fasting.

[Damien Blenkinsopp]: I can tell you you need to nurture it back to life after a 10 day fast with fibers. Actually with fibers and stuff, I tried to eat other things, but I was like, it just doesn’t work. So you have to kind of feed it, like I juiced fibers, basically, like vegetables, and actually added some fibers in order to kind of get myself back to normal.

[Richard Sprague]: Yeah. The reason why it’s been hard for me to test this, I mean I do fast occasionally, but it’s hard to test it because when you don’t eat anything, usually you don’t produce anything either. And so.

[Damien Blenkinsopp]: Well, I can tell you a way after a fast to generate poop, just liquid poop, very fast. If you just take fats, that’s not a good idea after fast of five days or so. So that would generate a result quite quickly, but I don’t know what you’d get. It might be completed biased. Yeah, it would be completely biased.

[Richard Sprague]: It would be biased. Yeah.

[Damien Blenkinsopp]: But the other things is, so the solution I found is actually juicing. So if you juice fibers in plants and stuff, and have that as your first couple of drinks, you should after the fast be able to poop quite quickly.

[Richard Sprague]: Yeah, it’s just, you’ll poop something differently than, we don’t know what’s going on in your microbiome before that happens.

I mean, I have tested my skin microbiome extensively like before and after going camping, let’s say. Where I’ll go for several days without a shower to see what happens. And there’s a difference; it’s noticeable. I assume the same thing is happening in the gut microbiome.

[Damien Blenkinsopp]: Yeah. Okay.

[Richard Sprague]: But when I run into people who have some kind of gut issue, that’s one of the first things I suggest is just give it a shot. Because I have talked to people who will say that, you yourself can comment on how fasting does make a difference.

[Damien Blenkinsopp]: Yeah, and that goes back, I always like to quote Valter Longo’s work, where he’s actually got a book out now. But I had my episode on the fast-mimicking diet. Anyone who’s got some weird, chronic issue and that no one knows how to solve it, the cycling of fasting just could be an interesting tool.

[Richard Sprague]: That’s right, and it’s worth tying.

(1:55:42) [Damien Blenkinsopp]: Yeah. Okay, so let’s learn a bit more. Where could someone learn more if they wanted to go an investigate this stuff? Where would you tell people to go and learn more about the microbiome? If they found this whole discussion really fascinating and they want to learn more about the labs and everything.

[Richard Sprague]: Yeah. Where I would start with is, and you can put up a link to it, is I’ve written a post on Medium where I’ve listed my favorite ten books about the microbiome. And that’s what I would look at.

But the number one book I think is Rob Knight’s book about, it’s written a couple of years ago but it’s a great summary; it’s relatively easy and quick to read. It will tell you a lot of the different things that you need to look at. But I do try to read just about every mainstream book that comes out about the microbiome.

And I’ve selected the 10 that I think

[Damien Blenkinsopp]: There’s quite a few coming out now.

[Richard Sprague]: There are a lot of them, yeah. And a lot of them are really excellent. So take a look at my top 10 list. And I’ve tried to keep that up-to-date of the ones that I think are particularly good.

(1:56:32) [Damien Blenkinsopp]: Excellent, excellent. What are the best ways for people to connect with you and learn more about what you’re up to and your work?

[Richard Sprague]: Well the best way is to look at my Twitter handle, just @Sprague. I try to post something pretty regularly. And people are welcome to contact me there. You can also look at my website, richardsprague.com, just my personal website where I kind of post things as they come along.

[Damien Blenkinsopp]: Right. You’ve got your blog over there, right.

[Richard Sprague]: Yeah.

(1:56:57) [Damien Blenkinsopp]: Right, now who besides yourself would you recommend to learn more about the microbiome? Who would be your go to, like your favorite people…

[Richard Sprague]: The favorite person I have is Elizabeth Bik, who on Twitter is @microbiomedigest. And she’s one of the smartest microbiome scientists I know, and she’s very prolific on twitter. She reads all these publications, and she will let you know the ones that matter. So that’s the one I would recommend for that.

[Damien Blenkinsopp]: Wow. Excellent. Is there anyone else?

[Richard Sprague]: A lot of them are the ones that you’ve already featured on your program. Obviously Rob Knight, Eran Segal from Day Two. Those are all good people, that I trust their science and always eager to hear what next thing they’re going to come out with.

(1:57:37) [Damien Blenkinsopp]: Excellent, awesome. Thank you for that. Okay, let’s talk a bit about you. What is your personal approach to improving your body and user tracking? And this is not just microbiome but really anything? Including microbiome.

[Richard Sprague]: Yeah, I’ve been a quantified self-tracker for a long time.

I track my daily amounts of sleep. I track a lot of the main foods that I eat. I don’t do it as rigorously as I’ve done in the past; so like a lot of us there have been times in the past where I rigorously checked. I used to have a Zeo device that I slept with, and I could tell you for years exactly how much REM sleep I had.

And I tracked my activity. Not so much now, I don’t carry a Fitbit or anything, but from time to time I’ll look at just… Because I’ve got such food baselines in the past. If I’m going to make a major change I’ll track myself again.

But the number one thing, I mean I hate to keep on harping on this, but I track my microbiome. I think that’s really fascinating. And it’s something I recommend people, even if you’re not going to track it every day track it once. Get a baseline, and see how it is, and I think you’ll learn a lot.

[Damien Blenkinsopp]: And so what are the things you’ve stuck with now? What are you going to do the next month, or the next three months?

[Richard Sprague]: Well I am interested now in, I’ve been interested in fermented food. One of the things that I discovered from tracking my amount [unclear], power of kefir, because it’s one of the few things that I’ve noticed makes a real, noticeable difference in the microbiome.

And I’m doing a couple of experiments on myself just to see… I’ve noticed a couple of microbes that I did not have when I was before I started drinking kefir and that I have now. One of which is associated with recovery from Crohn’s Disease. So it seems like it’s probably an important microbe.

And I’d like to find out more ones like that. So I’m constantly on the lookout for new kinds of…

[Damien Blenkinsopp]: That’s interesting, and I may be able to help you with that one because I went for a kefir about a year of kefir daily, and I was doing the uBiome test during that period. So there might be in there.

[Richard Sprague]: Oh, interesting. So the data that’s, your uBiome data would include the kefir drink?

[Damien Blenkinsopp]: It would be around it. I think it would be either side of it.

[Richard Sprague]: No, I’ll take a look, because it would be interesting to look to see if you’ve got the microbes that I found in mine.

[Damien Blenkinsopp]: Yeah, that’s what would be interesting, because the first test probably wouldn’t have anything, and then maybe the last test would.

[Richard Sprague]: Yeah. I’m especially interested in traditional, both traditional foods and traditional medicines, because I think that’s an under explored area for finding new interesting microbial solutions to things.

Chinese medicine and Indian Ayurvedic medicine, they have a lot of things that to Western eyes look kind of weird. But if you look at it from the point of the microbiome, suddenly you have a vocabulary now to talk about something in more scientific terms. And I’m really interested in that.

Somebody told me about this, there’s some droplets that apparently Indian mothers give their babies when the babies have colic. And I bet that’s a microbial thing; it probably affects the microbiome.

You know, there’s just little things like that that happen all the time.

[Damien Blenkinsopp]: Right. And before we used to say, there’s no way they can do anything. But as we add these new layers of science on, we start saying actually there’s a potential mechanism there.

[Richard Sprague]: Yeah. And when people have tested some of this stuff, ìscientificallyî, when you look at the details of how they test it, a lot of the times it’ll be something where they, there was some kind of Chinese medicine and somebody will say well let’s bring some people into the lab here in California and let’s give some of them this and some of them that.

Well it’s different conditions than it is when it was administered by a barefoot doctor in rural China, where there are microbes all over the place that are affecting the results. You’re not necessarily comparing apples to apples.

So I think there’s probably a lot of things like that in traditional medicine or food that have a bigger, positive effect than we know. And it’s the kind of thing I wish I knew more about.

[Damien Blenkinsopp]: Cool, very interesting. What I realized now actually is, what kind of insights have you got about your biology from your quantification? And have they led to any changes in behaviors or any actions that you’ve taken? So actually, you know, changes in your life you’ve made.

[Richard Sprague]: Yeah. I would say that I’m pretty healthy. So I’ve not had any real issues that I’ve been concerned about. And so that makes me a little bit, I’m kind of odd. A lot of people who are involved in the microbiome, they have some kind of story about their journey trying to recover from something.

So I don’t really have that. But that also makes me, I think, an interesting case because I’m able to look and see over time how my health as shifted as I get older, and how different things. One of the things that I’m intrigued right now about in particular is sleep.

I’ve always been a reasonably good sleeper, but I get less sleep than a lot of people; I average at around 6.5 hours, and I have for decades. I’m interested in getting better and deeper sleep.

I have found a relationship with potato starch, is one thing that we’ve talked about before, that some people use that as a way to increase the amount of bifidobacterium in their body. It’s something that I would try, if you know somebody who’s having trouble sleeping, that’s one thing to look at.

[Damien Blenkinsopp]: Yeah. Okay, so this is a bit random, but I’ve been working on my sleep for quite a while. I’ve really got to do a full episode on this kind of stuff. And I’ve, like you, had actually worse. At times I get 4 hours sleep, 4.5 hours sleep, and it was very difficult to stay asleep; I can get to sleep, but I can’t basically stay asleep.

So there’s two things that I’ve done that, among all the others, which I think… actually three things. The first is get one of these. So I’m showing Richard a SAD light, 10,000 LUX. SAD Light.

And you put it on and I got this from a Parkinson’s study, because they have problems with sleep as well. And when they showed this, they basically put this on for two hours in the morning.

So it’s basically simulating strong sunlight, right? And you put it next to your desk or something, and you get that. And I’ve found that helps. I think, potentially what’s going on in the mechanism is it’s resetting your sleep cycle. Because we’re not getting enough light; we’re indoors all day, we’re not getting enough light and stuff.

So that seemed to make quite a bit of difference. And the other thing is, which

[Richard Sprague]: So you just turn this light on in the morning?

[Damien Blenkinsopp]: As soon as I get up, I walk into the… I find it’s actually to wake me up as well, better than coffee. Sometimes I’ve forgotten to have my coffee because it’s already done the job, basically.

[Richard Sprague]: Yeah, interesting.

[Damien Blenkinsopp]: So I really

[Richard Sprague]: You just turn it on in the morning, and the rest of the day you turn it off and just live your day?

[Damien Blenkinsopp]:Yeah. And I love this thing.

And I’ve tracked the data and stuff, but I still, I’m still tracking. I got the Oura, which isn’t the best. But I think duration’s not so bad. So I’ve been tracking that over [a longtime]. I’m still kind of waiting to see the results on it.

The other thing is, and this is most people aren’t going to like this, is going to bed really early. And so I started to go to bed, I now, like first of all I said I’m going to get to bed by 11pm. Right?

Because I noticed it seemed that in my Oura data and everything I was like sleeping a longer duration if I got to bed earlier. So that worked a bit. I pulled it back to 10. Worked a bit better. Pulled it back to 9, I’m having 7 hours, 7.5 hours consistently every night, which I’ve never done in my whole life.

And I don’t know why it is. But I can give you like reference of celebrities and people who do this. There’s a lot of people out there that go to bed at 9 and get up at 4. I get a lot more work done as well, now. And I feel much better, but it is a bit of a lifestyle. Most people don’t want to fit in with it.

[Richard Sprague]: Yeah. And that’s interesting that you say that. So are you taking supplements or doing anything special to improve sleep, or just

[Damien Blenkinsopp]: I’ve taken lots of supplements. The only one I still take is glycerin. There’s some studies showing that that helps to reduce night wakings, which is…. So that I do stick with.

In another one of my companies we actually recommend it to anyone, and have them doing it when they have sleep issues and sleep interruptions and that. And it seems to be working consistently across those people.

[Richard Sprague]: Interesting. Yeah, interesting. Yeah, I really miss my Zeo, because before they went out of business that was far and beyond the best way to track your sleep.

[Damien Blenkinsopp]:Everyone misses them.

Well I’m hoping the Next Door is going to be more accurate as well. So that’s coming out, due for delivery in April I think.

[Richard Sprague]: Yeah, it’s hard to see how anything’s going to beat looking at the brain waves, which is what Zeo did.

(2:05:41) [Damien Blenkinsopp]: Okay, right. This is quite an important thing. If you were to recommend one experiment someone should try to improve their body, health, performance, longevity, anything like that, with the biggest payoff, what would that be and how should they track it so they can understand that payoff, and that it’s actually happening for them?

[Richard Sprague]: Yeah. Again, I would look at the microbiome. And probably the number one thing that I see that people could improve with their microbiome is their bifidobacterium levels.

And that’s the thing that, I know you know, it’s associated with sleep, and with serotonin levels. And so just an overall mental stability, all those sorts of things. And what I found in my, looking at lots and lots of samples is that people who don’t have any bifidobacterium, they almost always have some kind of problem.

So the number one thing that I would say for people who are interested in this is to test yourself, see what your bifidobacterium levels are, and then look at different ways to be able to increase it and improve it.

[Damien Blenkinsopp]: Have you got any ideas on what might work?

[Richard Sprague]: Unfortunately, I don’t have really good ideas that work for everyone, but I would start with things like, you can try potato starch which is, if you eat it raw it is known that it’s a particular type of resistant starch that feeds bifidobacterium and it’ll make it through your digestive system. You can try that.

For some people beans work, as I’ve said with my example of going to New Orleans. And then I would test myself in a couple weeks and see if I got any bifidobacterium in me. And I think that’s like the number one thing that I would recommend for people to look at is the bifidobacterium levels, and see what works for changing that in you.

[Damien Blenkinsopp]: Yeah, so that’s a good one. I had non-existent bifidobacterium when I started doing uBiome, but now it pops up in all my tests. So, unfortunately, I can’t say what I did, because I did many different things over that period. But it’s definitely possible.

[Richard Sprague]: Yeah, that’s good news.

[Damien Blenkinsopp]: So that’s good news.

Well, Richard this has been a great discussion. We’ve gone all over the topic, and it’s really great to catch up with you and talk about all this stuff. So thank you for your time.

[Richard Sprague]: No, thank you. It’s always a pleasure talking to you. Damien, you have so many things that you know about, and we’re kind of kindred spirits on this whole quantified journey. So, thanks a lot, it was great talking to you.

Study References

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Looking at an example of Machine Learning applied to functional medicine with the goal of helping athletes optimize performance. The question – with the help of artificial intelligence, can a 7-minute questionnaire identify physiological weaknesses and bypass the need to spend money on expensive lab tests?

This episode focuses on Machine Learning and Artificial Intelligence. These topics are massively discussed in investor and entrepreneurial circles, as well as the media in general. There is a trickle of that starting to move into areas of health tech and health data. There is a lot of potential and discussion around what that could mean.

It was about time that we tackled this subject to see what potential it has to help make better use of all the data that we are collecting on health. I have been spending more time on the conference circuit around this topic looking for technology that is adding value in this area. This means helping us make better decisions with less error and less effort.

This is a health data podcast, and as you will have understood through listening to previous episodes, there are a lot of challenges to getting actionable information and value out of today’s health data. So machine learning looks promising to potentially help us bridge that gap.

This will be the first of many episodes where we look into the subject, and today is a bit of an intro into the subject.

Where modern medicine really falls down is with (chronic) diseases of modernity, like diabetes or obesity. Medicine is just not designed to solve those types of problem…. We’ve got a machine learning algorithm that will identify the problem sooner and more easily. But the solution remains the same: you need to move your body, you need to eat appropriately, you need to handle stress appropriately.”
– Christopher Kelly

This episode’s guests are the Nourish Balance Thrive team, Christopher Kelly and Tommy Wood. Chris and Tommy are friends of mine whom I bump into often on the functional medicine conference circuit. Chris and Tommy run the Nourish Balance Thrive podcast and are constantly digging into functional medicine and related areas to see what they can extract to help athletes perform better.

They’ve used the data they’ve collected over the last three years that they’ve been working with athletes – as an input to a machine learning tool, to cheaply predict what an athlete should prioritize working on to improve his or her performance. This is, to my knowledge, the first time that machine learning has been applied to the area of functional medicine.

We have an output from the algorithm; for each individual prediction, we have a sensitivity and specificity. Our H. pylori prediction has 100% sensitivity and a 98% specificity. That’s basically a gold standard test. That’s as good as doing the real test.”

– Tommy Wood

You can run the test yourself to understand what we’re talking about better by going to TheQuantifiedBody.net/machinetest. That will take you through a series of questions before predicting the issues that blood, urine, and stool tests would uncover for you, without actually investing in those tests.

The episode highlights, biomarkers, and links to the apps, devices and labs and everything else mentioned are below. Enjoy the show and let me know what you think in the comments!

itunes quantified body

What You’ll Learn

  • Mutual respect between guests and host for their work (4:23).
  • Using machine learning to determine patterns in very large data sets (4:33).
  • Artificial intelligence is on the rise in the health market – will be the topic in future podcasts (7:29).
  • Machine learning is useful in functional medicine because of the ability to produce simplifying algorithms for detecting complex physiological processes (8:06).
  • The process of developing the Nourish Balance Thrive (NBT) questionnaire for assessing five major performance issues (10:47).
  • The basic and advanced biomarkers tested on individuals during the development of the NBT algorithm (13:36).
  • In some cases, machine learning algorithms determine health issues with more precisions compared to the judgment of individual medical practitioners (15:47).
  • Power output in athletic performance depends on oxygen deliverability  – in large part, determined by levels of oxygen-binding protein (hemoglobin) in red blood cells (19:04).
  • The importance of choosing the right study – population of people based on whose results machine learning algorithms are developed (20:28).
  • How algorithms are re-validated and the reasons Chris is confident in the predictive power of the developed model (22:47).
  • The NBT questionnaire retains high sensitivity and specificity in predicting results which individual athletes would obtain when actually testing the algorithm’s predictions (25:31).
  • The logic behind how algorithms make predictions in answering input questions (28:05).
  • Combining small decision trees into an overall big algorithm with real-life predictive power (29:36).
  • The background leading Chris to journey into artificial intelligence and machine learning fields of study (30:12).
  • A practical walk-through into how the NBT machine test works and how they interpret results (33:17).
  • The NBT machine test provides test clients with rankings of where each person stands in terms of 5 main performance issues and determines which issue to focus on the most (34:59).
  • Based on algorithm results predictions, clients are usually asked to come to the US for getting specific follow-up tests done (37:49).
  • Tommy hopes to accumulate success stories of tackling athletes’ performance issues, thus prove the actionability of the developed algorithm (39:49).
  • After detecting weak points in athlete performance, the used interventions have a base in low-risk diet and lifestyle modifications (41:12).
  • The potential of machine learning to revolutionize important aspects of life, including human health (42:29).
  • Compared to traditional medicine, functional medicine considers the multi-complexity of factors influencing health (45:48).
  • Developing useful applications in health doesn’t always require really big data – ex. NBT uses data from a relatively small study population of 1000 athletes (48:15).
  • The amount of data necessary for machine learning application in health depends on the artificial intelligence tool used for computing patterns (49:09).
  • Machine learning applied to detecting specific root causes of chronic illness (50:52).
  • Modern medicine solves acute health conditions but there is a strong need to utilize proactive approaches in chronic illness prevention (52:49).
  • Resources for learning more about the complexities and applicability of machine learning (56:50).
  • Picking up machine learning is accessible and available, even for beginners with no programming skills (58:00).
  • How best to connect with Chris and Tommy and learn more about their work (58:50).
  • Influential people in the field of functional medicine (59:52).
  • The biomarkers Chris regularly tracks to uncover and solve underlying causes of health issues (1:01:45).
  • The importance of optimizing both mind and body towards better health – including diet, exercise and meaningful relationships with others (1:03:56).
  • Monitoring blood glucose is an effective self-experiment which has a big payoff for health, performance, and longevity (1:05:35).
  • Using the Wim Hof method towards improved management of blood glucose metabolism (1:09:11).
  • Ketogenic dieting and why aiming for overall stability in blood glucose regulation is among the most important health strategies (1:11:01).

Thank Chris and Tommy on Twitter for this interview.
Click here to let them know you enjoyed the show!

Christopher Kelly & Tommy Wood, Nourish Balance Thrive

Machine Learning Applied in Functional Medicine

  • Nourish Balance Thrive Test: This recently developed 7 minutes questionnaire-based test is able to detect performance issues in athletes. It serves as a filter for which aspect of optimizing performance an individual should focus on improving the most. Give it a try!
  • Short Explanation Video: How the Machine Learning test uncovers underlying root causes of physiological weak-points which are holding athletes back from their peak performance.

Recommended Self-Experiments

Monitoring Blood Glucose

This experiment involves tracking measurements of glucose (blood sugar molecules) concentration in your system. It reflects the body’s ability to properly metabolize food and feed cells with essential energy in the form of glucose molecules. Fasting glucose means testing first thing in the morning before eating anything. As such people are enabled to follow overall functioning of the body’s energy metabolism – whether glucose levels are used up in a stable way.

By making use of continuous glucose monitoring (see below), more specific information about glucose metabolism can be derived. For example, Chris has detected that elevated levels of blood glucose after a meal (post-meal glucose spikes) are sufficiently reduced when he takes a walk after eating. He has also discovered that intense exercise drives his glucose levels up to 180 milligrams/deciliter meaning that eating food is not the only reason for elevated glucose concentrations.

Tracking

Biomarkers

  • Glucose Tolerance Tests
    • Fasting Glucose: One of the most researched biomarkers in human health. Optimal fasting glucose levels are between 83 to 88 milligrams/deciliter.
    • Fasting Insulin: The cells in the pancreas release insulin into the bloodstream in response to increases in blood glucose concentrations. Insulin functions to enable the intake of glucose from the bloodstream into the cells of your body. Optimal fasting insulin is above 5 microunits per milliliter.
    • Hemoglobin A1C: One of the most useful markers in testing for glucose intolerance. Its interpretative power comes from the connection between glucose and hemoglobin – the protein in red blood cells (RBCs) which carries oxygen. Because RBCs live approximately 3 months, Hemoglobin A1C reflects the average blood glucose levels over this period. Higher levels of hemoglobin A1C indicate poorer control of blood glucose levels with optimum HbA1c levels being below 5%.
  • Lipid Profile Panel
    • High – Density Lipoprotein (HDL): The traditional measure of ‘good cholesterol’ used by doctors and healthcare. For example, levels above 60 mg/dL are protective of cardiovascular disease.
    • Low-Density Lipoprotein (LDL): The traditional measure of ‘bad cholesterol’. Less than 100 mg/dL is an optimal level, while levels between 160-189 mg/dL increase the risk for cardiovascular disease.
    • Lipoprotein(a): Lipoprotein molecules carry cholesterol and similar substances through the blood. Tests can measure a specific type of lipoprotein called lipoprotein-a. Higher levels of this marker imply risk of artery damage. Dr. Kahn states that in most labs normal reference ranges for lipoprotein(a) should be under 30 mg/dL.
  • Thyroid Functional Test Panel: This panel of tests typically includes testing for circulating levels of thyroid hormones such as Thyroid Stimulating Hormone as well as the thyroid hormones triiodothyronine (T3) and thyroxine (T4). Proper functioning of the thyroid gland is key to athletic performance. The thyroid serves as a regulator for speeding up or slowing down human metabolic processes (conserving vs. using up energy, based on energy availability).
  • Liver Function Tests: When liver functioning is physiologically stressed, the blood levels of liver enzymes Alanine Transaminase (ALT)Aspartate Transaminase (AST), and Alkaline Phosphatase (ALP) get to a higher level.
  • Hemoglobin: The protein in red blood cells that carries oxygen throughout your body and is usually known for its role in diagnosing anemia – a sometimes serious health condition characterized by low oxygen delivery throughout the body. Because the Nourish Balance Thrive team strives to enable athletes to perform optimally, the team sets hemoglobin ranges higher than the standard upper ranges for eliminating anemia. As such, ranges are above 13 grams/deciliter in females and above 14.5 in males aiming for peak athletic level oxygen deliverability throughout the body.
  • The 25-hydroxy Vitamin D Blood Test: The most accurate way to measure how much vitamin D is bioavailable to your body is the 25-hydroxy vitamin D blood test. Optimum vitamin D levels range between 50-70 ng/ml.

Lab Tests, Devices and Apps

  • Differential Blood Cell Counts: includes measuring concentrations and important ratios between different types of cells found in blood including white and red blood cells, platelets, or immune system specific cells such as neutrophils or basophils. This is a very common test and differential diagnosis uses it – seeing whether particular aspects of a person’s physiology are functioning more strongly than others or if there is a need for follow-up medical tests.
  • Blood Chemistry Panel: This test includes measuring of blood chemistry parameters including sodium, potassium,  glucose, urea nitrogen, creatinine, total protein, albumin, globulin, cholesterol, triglycerides, total iron and other markers. This is also a very common test which serves to examine the overall physiological functioning of organ systems which are most important in human health.
  • Dried Urine Test for Comprehensive Hormones (DUTCH): A lab test which uses mass spectrometry analytical methods. These methods are significantly more precise in measuring hormone levels compared to blood or saliva tests – most of which use antibody-based immunoassay analytical methods. Mass-spectrometry also allows for comprehensive analysis of metabolites of hormones and thus provides a more – comprehensive physiological picture. For athletes, the Nourish Balance Thrive team suggests that optimal scores are above 4 points, considering the test’s internal reference ranges for providing scores on hormonal balance in a person’s body.
  • Organic Acid Test: This test provides an accurate evaluation of gut yeast and bacteria functioning, thus offering a snapshot of an individual’s nutritional and metabolic profile.
  • GI-Map Test: Stool testing which uses DNA sequence analytical detection techniques of gut microorganisms including opportunistic organisms, normal gut bacteria flora, parasites, and fungi. The strong confidence in results stems from the ability to quantify the amounts of specific individual microorganisms instead of merely detecting their presence in the gut.
  • Comprehensive Stool Analysis: A test which measures key markers of digestion, nutrient absorption (intake into the bloodstream after digestion), and inflammation in the gut.

Tools & Tactics

Diet & Nutrition

  • Ketogenic Diet:1 A high fat, moderate protein and low carbohydrate diet. This diet is particular in that it changes the metabolism so that it burns ketones instead of glucose for fuel. 2 A ketogenic diet usually leads to elevated fasting glucose levels but it would be a mistake to apply standard fasting glucose reference ranges for long-term ketogenic dieters. This is because fasting glucose epidemiological studies do not consider special ranges for subpopulations of people who make use of a ketogenic diet.

Supplements

  • Matula Tea: A type of herbal tea which is potentially effective in removing H. Pylory – related gut dysbalances causing health and performance issues. This is a relatively low-risk intervention compared to taking antibiotics as first treatment.
  • Sulforaphane: A chemical found in abundance in broccoli sprouts that people can either grow at home or grind up the seeds. Sulforaphane can potentially eradicate H. pylori infections.

Interventions

Tech & Devices

  • Measuring Blood Glucose6
    • Pin-Prick Glucose Tracking Devices: The most popular and easily accessible devices for checking blood glucose. The most popular devices, and ones we’ve discussed before, are the Precision Xtra Blood Glucose and Ketone Monitoring System in the U.S. and the Freestyle Optium Neo Glucose/ Ketone meter in the UK.
    • Continous Glucose Monitoring (CGM): A device containing a small sensor just underneath the skin that measures glucose continuously (ex. every 5 min). A transmitter then sends wireless data to a receiver which displays glucose trends. One of the most popular CGMs on the market is the Dexcom G4.
  • FitBitThis company offers wearable devices which include cardiovascular fitness tracking. The Fitbit Surge is a fitness watch that offers GPS tracking, heart rate monitor, all-day tracking, and sleep tracking. The Fitbit Charge HR monitors physical activity and sleep quality.

Other People, Books & Resources

Organizations

  • Quest Diagnostics: A company in the United States offering easy access to most of the basic lab tests, ex. blood cell counts or lipid profile panels.
  • Great Plains: A company which offers an Organic Acids Test (OAT) featuring testing of more than 70 markers from a urine sample.
  • Genova Organix: While the NBT team mainly utilize data from the company Great Plains, they sometimes also use data from Genova Organix because this company also offers organic acid testing and some clients have already done it.
  • Diagnostics Solutions: This company offers the (Gastro Intestinal) GI-Map Test and are among leaders in the field of precision genetic profiling of gut microbiome.
  • Doctor’s Data: A company which offers stool sample test featuring testing of microorganisms functioning in the gut flora.
  • 23andMe genetic testing: The largest personalized genetics company offering direct to customers testing. Analogous to the Nourish Balance Thrive test serving as a strategic filter, 23andMe genetic testing also does not lead to diagnostic results but focuses on guiding individuals to focus on specific aspects of their health and performance.
  • Regenerus Labs: This company is in the United Kingdom and focuses their services in the area of functional medicine. The company is discussed in the context of there currently being difficulties in obtaining functional medicine – relevant tests in countries other than the US.
  • Doctor’s Data: A laboratory testing company which offers heavy metal burden, nutritional deficiencies, gastrointestinal function, cardiovascular risk, liver and metabolic abnormalities testing profiles.

People

  • Dale Bredesen: An expert in the mechanisms of neurodegenerative diseases including Alzheimer’s disease. He offers courses in his approach to treating this health condition.
  • Ben Greenfield:7 A professional competitor and endurance-training athlete. Previously Chris has discussed the story of his health decline and recovery on Ben Greenfield’s podcast and this story has strongly resonated with listeners who are athletes.
  • Robb Wolf:8 A former research biochemist who is quite influential in bringing Paleo to the mainstream.
  • Jeremy Howard: Offers courses for people who have basic coding skills but are beginners in the machine learning field. Compared to Chris, Jeremy uses a different sub-branch of machine learning known as Deep Learning which is currently very popular. Tommy discusses how Deep Learning can help to detect lung cancer from Computer Assisted Tomography (CAT) scans of people’s lungs.
  • Bryan Walsh: A naturopathic doctor who produces a youtube video series on interpreting blood chemistry results, as part of the Wellness FX company. Brian has previously participated in Robb Wolf’s podcast discussing adrenal fatigue and the effects of low cortisol.
  • Chris Kresser: Works in ancestral health, Paleo nutrition, and functional and integrative medicine.
  • Mark Hyman: A doctor in the field of functional medicine who works to tackle the root causes of chronic disease.

Books

  • The Master Algorithm: A book written by Pedro Domingos in which he discusses the applicability and future potential of machine learning. Previously he has been on the Nourish Balance Thrive podcast to discuss how machines can learn. 

Other

  • NIH PROMISThe National Institute of Health has sponsored the development of the Patient-Reported Outcomes Measurement Information System. This is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. Based on personal experience with athletic performance and informed intuition about health, Chris selected the questions which are part of the Nourish Balance Thrive machine test from this free NIH PROMIS database of questions.
  • XGBoost: The algorithm used by Nourish Balnce Thrive to develop their test in the field of functional medicine. This algorithm is most popular among the Kaggle community. Kaggle is a place where the world’s leading practitioners complete (usually, but always, for a prize) to solve machine learning problems. The particular model of this algorithm used by Chris does not require much computing resources in order to train the models.
  • fast.ai: Jeremy Howard’s website where he teaching online courses in Deep Learning. While Deep Learning turned out not to be the algorithm applied in the Nourish Balance Thrive project, fast.ai DeepLearning courses are useful for machine learning practitioners of any type. Most Deep Learning applications are computationally expensive and require more than only your laptop to perform. For example, you might have to sign up to Amazon S3 data storage services and purchase computer hardware (likely from the company Nvidia) in order to be able to train models using Deep Learning algorithms.
  • IBM Watson Health: Overview of healthcare applicability of the IBM Watson’ artificial intelligence platform. Functional medicine differs from traditional medicine in that it focused more on personalized, integrative and preventative health. It might be argued that IBM Watson’s program is, in fact, using traditional medicine approaches while adding machine learning as another layer of understanding patterns in health.
  • Artificial Intelligence in Medicine Conference: Chris attended this AI conference, focused on using Deep Learning to uncover the root causes of chronic disease. One main argument discussed was that root causes may be less important compared to being able to diagnose health issues and apply treatment solutions. However, while machine learning is powerful in diagnosing health issues, it remains a tool which requires an understanding of the process.
  • Google Deep Mind: By analyzing million hand-labeled images of diabetic retinopathies (damage in the eye caused by high blood glucose levels), the team created a learning algorithm that predicts diabetic retinopathies better than a human could9 The same potential science can also be applied in preventative medicine measures – by integrating diet, exercise and lifestyle factors to study, for example, prevention of diabetic retinopathies.
  • Python: The programming language Chris uses which is a language that is readable and non-obscured in any way – thus offering user-friendly access to programming.
  • AmazonYahoo: Chris has worked in these companies which use machine learning to optimize their business in analytical ways.

Full Interview Transcript

Click Here to Read Transcript

(0:04:23) [Damien Blenkinsopp]: Hey Chris and Tommy, welcome to the show.

[Christopher Kelly]: Thank you for having us. I am delighted to be here. It’s a privilege and an honor. I’m a long time listener, so it’s very exciting to be here.

[Tommy Wood]: Yeah, likewise.

(0:04:33) [Damien Blenkinsopp]: It’s awesome. Yeah, having seen you guys at various conferences over time and obviously having many discussions, it’s about time.

So today we’re going to dive a little bit into machine learning, because you guys have been playing around with that. Chris and Tommy, what is machine learning? Is it the same as artificial intelligence?

I think, first of all, we’d better just give a bit of background. I think what people are looking at in the news and everything you could think it’s anything, and maybe nothing, and maybe it’s the end of the world, Terminator style, pretty soon. So what is it really, and what is it today?

[Christopher Kelly]: That’s a really good question.

I get the sense that people are starting to use the term ‘Machine Learning’ like people used the term ‘Internet’ in 1999. There were internet companies popping up all over the place. And there are machine learning companies popping up all over the place now and I think that maybe is a bit of a warning sign that maybe there’s some hype going on here.

Like anything else, machine learning is just a tool and really what you care about is the application. So I think that’s maybe an important point to note.

I should make it clear that I’m a practitioner of machine learning, and not necessarily an expert of the academic sort. And this may be important for people listening because I want to encourage people to take part in this activity, especially if you’re already a code or computer programmer of some sort.

I would say that you need to know how the controls work.

Imagine you’re driving a car. It’s important that you understand what happens when you turn the wheel, and it’s important to know what happens when you press the pedals but you don’t necessarily need to know how internal combustion works in order to drive the car. And I think the same is true of machine learning; it really doesn’t need to be very, very complex unless you’re going to be researching and developing new algorithms.

So to answer your question specifically, machine learning, in my mind, is a sub-branch of artificial intelligence.

And I spent most of my life writing computer programs, very carefully, by hand coding algorithms. IF-THEN-ELSE, that type of construct that some people will be familiar with. In machine learning, I’m doing something different.

Over the last three years, we’ve collected lots and lots of data–about 100,000 total features–from about 1,000 athletes. And then I’ve used that data to train an algorithm. So I’ve shown an algorithm many, many examples of the pattern that I would like to identify in the future, and then the machine–it’s kind of a funny thing to say–learned how to predict the patterns that I was interested in.

At no point did I ever hand code an algorithm, and I think that’s what makes machine learning different from regular programming.

(0:07:29) [Damien Blenkinsopp]: Thanks for that overview, Chris.

So what is artificial intelligence?

I’ve seen a lot of the hype. I can tell you, I go to conferences now and a lot of start-ups are talking about adding machine learning and AI to their apps just to be a bit cooler and to attract investment and so on. So there’s definitely a bit of hype around it, which I think is why it’s worth talking about.

In contrast to machine learning, which is what you’ve been doing, what is artificial intelligence?

[Christopher Kelly]: Yeah, that’s a good question I would rather not answer.

[Damien Blenkinsopp]: Okay, yeah it’s fine. We can explore it in a later podcast.

This is a topic I’ve been fascinated with and digging into. And I know it’s pretty complex. So, let’s just skip that one, shall we?

[Christopher Kelly]: Yeah.

(0:08:06) [Damien Blenkinsopp]: Right. So one of the unique things about what you’ve done is you’ve applied it in the area of functional medicine, which I don’t think I’ve seen done before. We’ve started to see a few applications for health.

But what do you think, if you’re looking at the area of health, where do you think it could be applied usefully just from how you’ve got to it? So you’ve done it for prediction of results. Is that the main area you see it as useful? Or are there other areas which you see that it could be applicable?

[Christopher Kelly]: Oh no, so yeah. Our application is just one tiny thing.

So to give people a bit more background, we’ve worked with about 1,000 athletes over the past three years, and the way that we’ve helped those people is we’ve uncovered the underlying root causes of the things which are holding them back from their peak performance.

We’ve used blood chemistry, and urinary organic acids, and urinary hormone testing, and then also stool microbiology, and then also PCR DNA analysis. And obviously it’s quite difficult to get some of these tests done. Blood chemistry is ubiquitous, obviously, but the other tests I talked about are quite difficult to get done. And they’re also quite expensive.

So the thing that I would like to achieve is first to make it much easier to do our program. See, you know, can I predict the results of these tests without you doing them. And then of course potentially it could bring the costs down in the long-run.

So when someone does one of our tests, somebody in a lab somewhere is putting a sample into a machine. And they’re doing some mass spectrometry, obviously that’s an expensive machine that is taking somebody’s time, and that costs money.

So one of the things I think that machine learning will be able to do in medicine is reduce the cost in the long term. And then it will provide greater access to people who perhaps might not otherwise be able to get a hold of these fancy tests.

[Damien Blenkinsopp]: Right, so it’s like a filter, so that people don’t necessarily have to do all of the tests.

Because when we look at the functional medicine process today, basically a functional medicine practitioner takes your history, right. He talks to you, and then he decides on an array of tests. As you said, this can be pretty expensive depending on how many you’re going to run.

And I think that’s one of the biggest issues for functional medicine right now, for it’s greater acceptance. Some people basically can’t afford the tests that they’re being told to do.

So what you’re saying is you’ve used a questionnaire that you give people, and you’re using the data from that to predict what the results would be in the tests.

(0:10:47) [Christopher Kelly]: Yes, exactly.

So we have 53 questions which form part of our standardized health assessment questionnaire. Those questions I chose personally from a large data bank of questions that are available online for free. It’s the NIH Promis data bank of questions.

And it’s a whole other story that I won’t get into now, but I was not feeling good in 2014. I chose these questions based on the way that I felt. Some of them were very relevant to me, and then others that I saw in the data bank I thought, well now that’s not really right.

They’ll ask you things like, ‘I was so tired I couldn’t get out of the bath.’ Or, ‘I couldn’t even leave the house, I didn’t have enough [energy].’ So this sort of chronic fatigue type questions. And I was definitely feeling bad, but not that bad. So I selectively cherry-picked these questions from this data bank.

Then we had 1,000 athletes go through our program. It almost became a standing joke that we would see the same person and the same problems over, and over, and over again.

So that’s what got us thinking. Is there some way that we could predict the results of these fancy tests using just these 53 close-ended questions that you could answer in seven minutes by clicking on radio buttons.

[Damien Blenkinsopp]: Right, so you’ve been giving that selection, your cherry-picked selection of questions, to everyone that you’ve worked with over the last three years.

[Christopher Kelly]: Exactly right.

So, everybody that’s been through the program, they’ve done [it]. We’ve worked a bit differently maybe from some other functional medicine providers that you’ve met in the past in that we always do the same set of tests.

Obviously, each person is unique. They have their unique history, situation, and goals. But the tools that we use to identify the underlying root causes don’t vary much from person to person. We use the same set of tests on everyone. And then at the same time they do the tests, we have them do the health assessment questionnaire.

I always have that data for every single person that goes through our program. So that’s how I was able to train the machine. I had the 53 close-ended questions and then alongside that, I have all the blood chemistry, the urinary organic acids, the DUTCH test, the stool culture, the stool PCR test.

So if you can imagine a great big spreadsheet with all of these things in columns. Then the final thing I’m trying to predict is do you have circadian dysregulation, or do you have gut dysbiosis, or do you have a glucose tolerance problem, or do you have an oxygen deliverability problem?

So that’s a higher order function that I’ve calculated using some of the other biomakers which form the columns of the spreadsheet.

(0:13:36) [Damien Blenkinsopp]: Okay, excellent.

Could you just go through the lists of tests you used? Because we talk about tests all the time on this show, so people will have run into them in past ones, and so on. So what’s the blood chemistry you’re running specifically?

[Christopher Kelly]: Sure. Do you want to talk about the blood chemistry, Tommy, because it was largely you that designed that panel.

[Tommy Wood]: Yeah. So we’re obviously based in the United States, and most of the blood panels are run through Ulta. So you do the tests at Quest Laboratory. And it’s stuff that people will be very familiar with.

I’m a big fan of doing the basics, because we know the basics work, and that include doing the history. So everybody comes in and does the history; that’s really important and sort of gave us the basis for how we could predict some of the results, like Chris was talking about.

And then the blood tests are a basic blood count, an extensive thyroid panel, a liver function test, a kidney function test, there’s calcium and [unclear 0:14:32], vitamin D, insulin, HbA 1 c, fasting glucose, and basic lipids test.

All the things that people will be familiar with that they can get from their doctor. And it’s also something that even if somebody is not in the United States it’s usually something they can get locally as well.

So those are the real… We cover those basics just because we know what they mean and how they apply to the physiology. Then it gives us some grounding to then expand into the newer tests.

[Damien Blenkinsopp]: Excellent. And so the newer tests you’re talking about, is that The Great Plains?

[Tommy Wood]: Generally. We do have some data from the Genova Organix, because some people have done that too, but it’s mainly The Great Plains organic acids test.

Then, like Chris mentioned, we do the urinary hormones, the DUTCH. The stool tests that we’re currently using are the Doctor’s Data–a comprehensive stool analysis with parasitology–and the Diagnostics Solutions GI-Map with the PCR. That’s the whole panel.

[Damien Blenkinsopp]: Right, great. So you’ve taken this data for everyone, and what you’re saying is you’ve seen correlations which will lead to five different outcomes that you’re looking for. Five problems to target.

(0:15:47) [Tommy Wood]: Yeah, so what the machine learning particularly–and Chris knows more about this than I do, definitely–what it’s really good at doing is predicting patterns. There’s the well-known example of the algorithm that was trained to identify lung cancer on X-rays, and it was able to do that better than the best radiologist in the world.

So if you give it enough X-rays which say this X-ray shows lung cancer then it learns what that looks like. And then you give it future X-rays and then it says okay this is lung cancer, this isn’t lung cancer. And it can do that more or better, more accurately, than a human radiologist can.

So, this makes me think of a time Chris and I went to Dale Bredesen’s training course last year to learn about how he treats Alzheimer’s disease. And Chris stands up and tells Dale Bredesen’s personal radiologist that at some point machine learning is going to make radiologists completely irrelevant because the machines are going to be able to do all the radiology for us.

That’s what machine learning is really good at. So if we give it specific patterns we want to look for, and the ones that Chris mentioned were low oxygen deliverability – that’s basically just another word to describe lower than optimal hemoglobin, which people probably will have heard of.

Then we talked about glucose intolerance. That is three different predictions in one group; so it’s high fasting blood glucose, high HbA 1 c, and high fasting insulin.

We obviously have tighter levels than most people would probably think of. We’re talking above 88 milligrams/deciliter blood glucose or a fasting insulin above 5. So that’s kind of our level of where we’d like to see things.

Then, if we talk about the dysbiosis we’re predicting things like H pylori, or clostridium, or a general bacteria overgrowth, yeast overgrowth on the OAT, something like that. That’s based on the lab values that you get from, say, The Great Plains Organic Acid Test.

And then hormonal balances, so that’s low estrogen in females, low testosterone in males, again based on the DUTCH references ranges. And then circadian dysregulation, which is basically having a cortisol marker outside of the normal range at a given time point during the day. Again on the DUTCH you need at least a 4 point. Now it can be a 5 point if you take a sample in the middle of the night.

So based on all of those things, we can kind of drill down, and the machine will tell you what the ranking of those different problems is for you. So maybe glucose intolerance is the most likely issue that you have, and then it will rank the other ones too.

Then sort of the back-end we can look at the percentages, and we know how accurate the machine is at predicting each individual thing. Have like a sensitivity and specificity for each individual one, so we know how accurate it is, and what the likely issue is. And that means we can get people started very quickly.

Because we know if someone’s going to come to us with blood glucose dysregulation. We take a little bit more of a history and we know exactly what we need to do. We don’t need to do any blood tests first because we know what issues there are going to be. We can start people very quickly without them having to do all the tests first.

(0:19:04) [Damien Blenkinsopp]: Yeah, excellent.

The only one I don’t think we’ve come across before is low oxygen deliverability. Could you give us a little bit more background on that? Where does it come from, and what type of people have it?

[Tommy Wood]: Yeah, basically it’s based on hemoglobin.

People will have heard of hemoglobin when it comes to anemia. So if you have low hemoglobin–that’s the protein in your red blood cells that carries oxygen–then you’re considered to be anemic. It’s one of the markers of anemia. So people may have heard of that.

We have ours slightly higher. We know what levels athletes need to be at in order to perform optimally; so it’s above 14.5 grams/deciliter in males, above 13 in females. So those are higher cutoffs. Those don’t define anemia, but it defines what we’d like to get an athlete to if we can so they can perform optimally.

So we don’t call it anemia because we’re not detecting anemia. We’re detecting low oxygen deliverable, which is basically your blood doesn’t have as much hemoglobin as it could hopefully have. This means that you’re not delivering as much oxygen. You don’t have the capacity to deliver as much oxygen as you’d quite like to.

So the phrasing is important because we’re not detecting frank anemia. We’re detecting something else that we know is important for athletic performance because power output tracks very nicely with hemoglobin. So if you can increase that, you’ll definitely increase somebody’s athletic performance.

(0:20:28) [Damien Blenkinsopp]: Right, excellent.

And that brings us to a very important point of where your data comes from, and what the focus of it is.

I understand that data set of people that you have is quite important. You have to be quite careful of the selection and use of it. Why is it that important?

[Christopher Kelly]: So I’ll take that. I think it’s really, really important.

I went on to the Ben Greenfield podcast in 2014 with another one of my doctors – Jamie, my founding medical doctor, she’s a pro mountain biker. And I told this story of my health decline and then recovery and the use of some of the testing that we’ve talked about so far in that recovery.

And that story resonated with a particular type of athlete that listens to then Ben Greenfield podcast. And they were the people that came forward to work with us. I also talked on the Robb Wolf podcast and from my perspective, it was difficult to identify the two different types of people.

They seem to be very similar in their personality and their problems and their goals. All completely wonderful people and I’ve had a fantastic time over the past three years. But I already mentioned that I cherry-picked those questions out of this huge data bank of questions that were supposed to be for all people and all things.

So I think that the algorithms would not be particular good at predicting the results of these tests of people who didn’t fall into that same category. I don’t know, I haven’t tested this. But that is my suspicion because remember we said that machine learning was teaching a machine how to learn based on labeled examples.

So when Tommy talked about the X-rays there, a real radiologist had labeled this X-ray as this one is a malignant tumor, this one is not. And in my data set, we’ve said this one has low hemoglobin, this one does not. And we’ve taught the machine how to learn to identify this pattern using examples.

If I then went into a completely different population of people, let’s say people who only had chronic fatigue syndrome, well they might answer something completely different to my health assessment questionnaire. And so I don’t know whether I would be able to predict with the same accuracy.

I think this is something that we should experiment with.

(0:22:47) [Damien Blenkinsopp]:And when you’re going into this, how can you re-validate it for the other populations? Is that something you’re going to be doing on a long range basis, or how does that work? I imagine for some people you’re going to be collecting test data as well, rather than simply relying on the questionnaire for everyone.

So how do you see this going forward? How do you think it might work on insuring that it’s continuing to be valid? Is it going to be continuing to machine learn, or have you basically done a cut-off based on the training it’s already had?

[Christopher Kelly]: Sure. The analysis is already live on my website, and so I’m collecting some data already through people who are just visiting my website and seeing the analysis there, and taking it.

And then I’ve also spoken on a few different podcasts about the analysis. For each podcast that I’ve spoken on – and I should do the same for this one – I will provide a custom link that you can find in the show notes and that custom link allows me to identify the source of the traffic.

By definition, you are a particular sort of person if you listen to The Quantified Body podcast, and I think that might be important in the predictions. So the custom link, I think, is going to be really important. And it’s only once I’ve collected a certain amount of data will I be able to say this is a very strong prediction and maybe this is not so good.

And of course some of the people that do the analysis will go on to do the real tests. You can get started more quickly when you do the analysis, but for now we’re still doing all of the tests. So once I get back the real data – the real blood chemistry, the real urinary organic acids, all of that – I’ll be able to compare what the machine predicted versus what we actually tested.

Now, I’m not really expecting any surprises for some groups of people because when I was training these models, I deliberately held out 20% of our data. So I said we had data from 1,000 athletes. I held out 20% of that, set it to one side and then I only used that data once I had finished training the models. So I used that to test the models, and so that’s how we know how accurate they are.

I wouldn’t be here talking about it if I didn’t think the models were any good. And the reason I know they’re so good is because of this held out data set.

[Damien Blenkinsopp]: Great. And so, does it give back a correlation or something like that? Did you get a number like this is 90% accurate with the last 20% you used, or something like that, to give you that confidence?

[Christopher Kelly]: Yeah. So, Tommy, do you want to talk about the sensitivity and the specificity of the tests?

(0:25:31) [Tommy Wood]: So people maybe have heard of sensitivity and specificity, which is basically something we often use or calculate in medicine if we’re comparing a new test to a gold standard test. This is exactly what we want to do.

And basically the sensitivity tells you the likelihood that a positive result is truly positive. And the specificity tells you the likelihood that a negative result is truly negative. So you want both sides of that coin.

You could say that if you have 100% sensitivity, you’ll pick up everybody who is going to be truly positive about one thing. But if you don’t have any specificity then you’ll have loads of false negatives. There are lots of ways to balance that out. So you want both to be, essentially, as high as possible.

We have an output from the algorithm; for each individual prediction we have a sensitivity and specificity. So I’m looking at one right now. Our H pylori prediction has 100% sensitivity and a 98% specificity. That’s basically gold standard test. That’s as good as doing the real test.

Some of the other things are not going to be as accurate. Bacterial overgrowth has a 94% specificity. So they’re up there; I think the lowest one is maybe in the 80% in terms of specificity. If somebody has a negative prediction there’s a small chance they might still have a yeast overgrowth on the actual test results.

So it’s really close. It’s at the level where you could say that we’re close to being able to predict something as well as the test would be able to.

[Damien Blenkinsopp]: Wow. That’s pretty impressive. Just through 53 questions.

[Tommy Wood]: I just have to say that I actually couldn’t believe how good this was. And Chris has run it multiple times.

So originally we were going to do tests or predict urine results and stool results from blood test results. Then eventually we sort of worked our way back, and we got to the point where we were just using the questions. And it’s almost too good to be true, but I promise you it is actually true.

[Christopher Kelly]: That was my original idea. I thought blood chemistry is ubiquitous; anyone in the world – or that’s not true, but most people have access to blood chemistry. If you give me your CBC, for example, can I then predict the arabinose, which is a marker of candida overgrowth on the urinary organic acid test? Because that would still be quite cool.

And it turns out that does work, but what works even better is just me asking you these 53 close-ended questions.

(0:28:05) [Christopher Kelly]:But one thing I’d like to point out is there are five different answers, 53 different questions. So I believe that is 5 to the power 53… It’s 1 times 10 to the power 37 different permutations. So that’s a lot of different ways to answer this health assessment questionnaire It’s really a lot.

[Damien Blenkinsopp]: Right. It’s like this huge tree of permutations that’s going on there.

[Christopher Kelly]: Exactly.

[Damien Blenkinsopp]: So you’re getting people to take a lot of different paths, and eventually they’re coming to one outcome. So that’s where that specificity is coming from, from all of those permutations you’re driving them through.

[Christopher Kelly]: Right, exactly.

And that’s exactly how this particular algorithm works. We’ve used this algorithm called XGBoost, which is very popular from the machine learning website I would encourage people to visit called Kaggle.

Kaggle is a place where you could launch a competition and have the world’s leading practitioners compete – usually for prize money but not always – to solve your machine learning problem. And XGBoost, the algorithm that we used, has been a constant winner in the Kaggle space. And that is exactly how it works; it’s a boosted decision tree.

So, think about what happens when you call up the electricity board; you get presented with all these different options. You have to press one for customer service, two for sales, and all of that. So you can see that pans out into a decision tree, and that’s exactly how our XGBoost algorithm works. It’s a large number of these small decision trees.

(0:29:36) [Christopher Kelly]: And another really interesting thing that’s so simple it’s almost worth not talking about, and you can’t believe how well it works.

Each one of these small decision trees, they’re slightly better than chance. So if I’m trying to predict the results of a coin flip, then it gets it slightly better than chance. And it turns out that when you have thousands, or even millions, of these small decision trees that are slightly better than chance. And you combine them all together amd get a really strong learner that’s very good at predicting things.

So that’s how this algorithm XGBoost works.

(0:30:12) [Damien Blenkinsopp]: Great.

Chris, I know you’ve been going through artificial intelligence and machine learning for a few years now. I was just wondering if you could talk a little bit about your experience in this. You ended up choosing this particular approach to it.

Was it easy when you jumped into it and you wanted to learn it? I myself have been looking at it, also, because it’s this whole new world with all this potential. How have you found it? How has your journey been through it?

[Christopher Kelly]: I’m glad you asked that question, that’s a great question.

I have an undergraduate degree in computer science, and I’ve worked my whole life for big tech companies. I’m 41 years old now, and I’ve worked for Yahoo – they were the company that brought me from London to Sunnyvale to their headquarters. I’ve worked for Amazon. And I’ve worked for a search company within Amazon, and I’ve worked for two hedge funds.

All of those companies make heavy use of machine learning, but somehow the technology evaded me for the longest time. And the reason was, every time I tried to get into it I just found the subject matter so incredibly dry.

So if you go and read some academic papers on some machine learning algorithm, typically what you encounter is an abstract, or a small amount of text at the beginning of the paper that makes a lot of sense. Then you turn to page two and there’s this wall of equations, and you’re like, okay. And then you just put page one back on top of page two, move it to one side, and carry on hand coding your algorithm.

And that’s just been the way with the academic computer science community. It seems to be dominated by people who are very strong in mathematics and mathematics is the language that they use to communicate. But it’s not necessarily the best language for all computer scientists.

And so I’ve found some other resources very, very helpful. In particular, Jeremy Howard has been running some classes in San Francisco designed exactly for people like me. Luckily, those classes are now available online. And those were wonderfully helpful.

And it turns out that Jeremy Howard is using a different sub-branch of machine learning. He’s using something called Deep Learning, which is very, very popular at the moment. I had tons and tons of fun.

So Tommy mentioned the trend to identify the malignant tumor on an X-Ray; it’s a Deep Learning algorithm that’s doing that. So it’s different from what we’re using. We’re using XGBoost.

So Jeremy is arguably more state of the art, but he’s solving different types of problems. Deep Learning is better at solving these computer vision problems, and other things too.

So those courses, I think, were absolutely fantastic. That was what allowed me to get past this wall of mathematics and become a machine learning practitioner.

[Damien Blenkinsopp]: Excellent, thank you for going into that, because I think it would be amazing if more people started to apply this to health and functional medicine. And there’s a lot of listeners on this show – entrepreneurs, venture capitalists, and all sorts of types – who might find it a little bit easier and approachable knowing that there are ways around that.

(0:33:17) [Damien Blenkinsopp]: Another thing I wanted to do on this podcast is take the people listening through a practical walk-though of how it’s being used. So people are going to click on this link and go to the page where it is, and then what happens?

[Christopher Kelly]: Sure.

I’m a very visual person; I like to learn with audio and visual stuff. So I’ve paid someone to make some whiteboard explainer videos, because obviously this stuff is complex. So there’s a video, if you come to the show notes you can see the video. It’s the whiteboard explainer video that hopefully summarizes things that we’ve been talking about and explains how these things work.

And then as you go through the analysis, it’s really quite simple to do. All you do is you click on radio buttons and answer the questions. I’m going to ask you things like: ‘In the past seven days I’ve felt tired.’ And then the answers will be something like always, sometimes, never. I can’t remember the five different permutations, but you just answer the questions honestly.

They’re grouped into sub-categories that you’ll recognize, and anyone who has spent any amount of time not feeling good will recognize these questions intimately, I’m sure. And that’s it really.

Just walk through for seven minutes, and then at the end you’re presented with the results, which, as Tommy alluded to slightly earlier, we don’t give you the output of the model because it’s kind of confusing. You need to know quite a lot about how the model is made in order to interpret the output. It’s actually talking in probabilities, which are quite difficult to understand.

So the model is going to say whether it thinks you probably do match the criteria or you probably don’t. It’s mostly a binary classification.

(0:34:59) [Damien Blenkinsopp]: So to just highlight that point.

Basically as Tommy was saying earlier, it’s going to highlight whether you’re in a specific range in one of the tests. Is that the output for you guys? It’s going to say there’s this risk of H pylori, for example?

[Christopher Kelly]: Yeah, that’s exactly right.

The gut dysbiosis model, for example, is a composite of the H pylori prediction, the bacterial overgrowth, and yeast overgrowth. So we just lump all of those things together and call it gut dysbiosis. And so if the model thinks that any one of those things is true, then it’s going to predict a binary classification for the most part.

So we kind of argued about it–not argued but debated it–for a while about what we should show the user. In the end what we went for was just a rank. What you see on the results page are the things that the model thinks are most important for you. Because it’s kind of hard to interpret the output of the model, this probability as a percentage.

[Damien Blenkinsopp]: Right. So, I went through it myself, and you have the display of the five areas. And then it looks like a percentage, basically, right?

[Christopher Kelly]: Yes, that’s the number that in the end we decided to hide from the user, because it was confusing.

And so we can still see on the back-end, but for the user now what they’re seeing is just the rank of things. So these are like the order of importance of the five different categories.

[Tommy Wood]: Damien you used a slightly earlier version where you could still see the percentages.

It eventually turned out that that was becoming kind of confusing. So we thought that people could just focus on what the most important thing is, and that’s how people would then follow up through the system. But we have obviously all of the data to help.

[Damien Blenkinsopp]: I see. So it’s just going to highlight one of the items that is the most important to look into, for example if low oxygen deliverability is the thing you should focus on. Is that the point?

[Tommy Wood]: Yeah, well, you’ll get your ranking for all five. The order of importance for all five. So you’ll get some follow up, that Chris can tell you about, and that will be based on whatever was ranked number one.

[Damien Blenkinsopp]: Okay, got it.

And that’s the use of the tool, really, helping people to focus on the area. I mean, I used to talk about DNA tests like 23andMe as something useful to help you focus on things.

It’s not entirely accurate, it doesn’t give you a diagnosis or anything, but using it as a strategic filter to say: ‘There’s a lot of things popping up in lung cancer risk in my genetics, I should probably have a deeper look into that.’

So it sounds like you’re kind of proposing this to be used in the same way. Basically it’s a strategic device to look at where should I focus my efforts and have a look more into it.

[Tommy Wood]: Yeah.

(0:37:49) [Damien Blenkinsopp]: Great.

Have you got any case studies of people who have used it already? Anything that’s come out of it since you’ve been playing around with it?

[Christopher Kelly]: No. It’s totally brand new. In fact, just this morning I just signed up our first client who is a British guy living in Spain. So he could do it; it’s still possible to get the tests done, but it’s not easy. So…

[Damien Blenkinsopp]: It’s impossible in Spain. It’s really, really hard.

When I lived in Spain, I ended up moving to the United States because I got so frustrated. I was getting an MRI done and they gave me just the completely wrong results, and I thought, I’m done, I’m out of here. And I left, it was the end.

[Christopher Kelly]: Yeah, so that’s what we normally do. We do have clients from all over the world, and that’s what we normally say, ‘Can you come to the United States?’

And for most of the athletes that we work with, they can. So if you’re an IronMan Triathlete, for example, there’s a good chance you’re going to want to come to the United States for a race. And when you do the race, you can just stay in a hotel or an AirBnB, whatever it is. And then you can do all of the tests either at home or you can take a trip to Quest and get the blood drawn there.

So for this guy in Spain, I didn’t show him the exact output of the models, as we discussed previously. But when I looked on the back-ends, the models were really, really confident about several things which I know how to fix right away.

[Damien Blenkinsopp]: So it’ll be interesting to see how that goes.

[Christopher Kelly]: Exactly.

[Damien Blenkinsopp]: It’s incredibly good use case because so many people struggle with tests outside of the United States.

[Christopher Kelly]: Right.

[Damien Blenkinsopp]: It’s getting a little bit better in the United Kingdom now. There are some guys called Regenerus Labs who are doing a fair number of the functional medicine and other tests now by post and they handle that. But overall, it’s still really, really complicated, and I’m constantly getting questions about it.

This sounds like a really useful use case for it, for people who are also in Europe or even in places like this where they can’t get their hands on the tests in the first place.

(0:39:49) [Tommy Wood]: This is a really important part of the process. We think we can predict things with a very high degree of accuracy, but how well can we treat those things when we don’t have the full set of data. And we’re very confident that we can, but the only way you can find out is to actually do it.

Particularly with people who fit very nicely into the group that we used to train the data. So just more of the same kind of client that we’re used to working with and we get very good results with, that’s the ideal test bed. And then we can show that we can really do what we think we can.

[Damien Blenkinsopp]: Yeah. It would be really interesting to have you guys a few months or whatever down the line, once you’ve run it for a while and got some test results and some experience and so on.

And maybe it sounds like basically trial and error. You’ll just put someone through a program, say they’re living in Spain, and if it fixes him you’ll be like, okay, that worked. That’s a good data point for the model.

[Tommy Wood]: And maybe we’re just doing what Voltaire said, which is that we’re just entertaining the patient enough while nature cures the disease.

[Damien Blenkinsopp]: It would be great.

[Tommy Wood]: But in reality, I think we know how we would approach each of those different things. So if we’ve got a model that predicts something with a very high degree of certainty, then the likelihood that this person will see benefits based on what we suggest based on the algorithm is really, really good.

(0:41:12) [Christopher Kelly]: And we should talk about some of the interventions as well, because I think that’s important. It’s not like we’re predicting things and then asking people to take drugs that may have unwanted effects. We’re talking about lifestyle medicine here.

So let’s say the model predicted that you had a glucose intolerance problem. Well I can coach you, my wife can coach you, and any one of my coaches can coach you with how you can improve your glucose tolerance.

So you could do things like time-restricted eating where you only eat during daylight hours. That could improve glucose tolerance. Or you could move your body more. Maybe you could do some whole body resistance training that’s going to create an intracellular glucose deficit and make the glucose that’s in your blood go into cells more easily. And maybe that would improve your glucose tolerance.

Do you see what I’m saying? It’s mostly diet and lifestyle interventions.

[Tommy Wood]: Really low risk.

[Christopher Kelly]: Very low risk.

[Damien Blenkinsopp]: I’m guessing the ones where we get closest to actually some kind of medicine are gut dysbiosis, where you guys are using herbals and probiotics and things like that, primarily, aren’t you?

[Christopher Kelly]: Exactly. For example, this tea, there’s a Matula Tea. There’s a company on the internet that guarantees you that it gets rid of H pylori. And it’s very expensive, but they give you your money back if you send them a test and you’ve still got the bug.

And there’s other things like broccoli sprouts, sulforaphane, that people can either grow at home or just grind up the seeds. That may help with eradicating an H pylori infection. So fairly low risk compared to taking antibiotics, I would say.

(0:42:49) [Damien Blenkinsopp]: I thought we would take a little bit of the big picture look at this machine learning.

Having gone through this experience for yourselves, how transformative do you think machine learning could be? Or will not be, for that matter, for health over the next 10 years, given the examples you’ve seen? I know Chris, you’ve been to conferences and stuff and seen some examples as well.

What do you think the power of this is? Or isn’t?

[Christopher Kelly]: Oh yeah, I mean it’s going to completely revolutionize everything, I think. Almost everything. And it’s interesting that some of the jobs that I think are going to go are the white collar jobs.

So I know this from talking to Pedro Domingos, he’s been on my podcast. And I would highly recommend his book, The Master Algorithm, where he talks obviously in detail about this.

But it’s the white collar jobs, so anything where you’re doing something over and over again that doesn’t really require any manual movement. So some people I think mistakenly believe it’s the workers that are going to go, that they’re all going to be replaced by robots. But that’s not true.

When you look at, say, the skills of somebody building a house, those motor skills they’re using and their dexterity took millions of years to evolve. Computers haven’t got there yet. Whereas, identifying a malignant tumor on an X-ray, that’s just a pattern recognition thing that computers have already learned how to do.

So, if you’re laying bricks and mortar for a living, I think your job is safe. If you’re a lawyer or a radiologist, or somebody who issues patents, then I’m not so sure your job is safe. It’s very interesting.

[Damien Blenkinsopp]: I was reading a case study on J.P. Morgan and they were talking about deals, like mergers and acquisitions, and it was taking hundreds of thousands of hours of lawyer work before. Now it’s being done by a computer in a day.

[Tommy Wood]: There’s one thing we discuss a lot, sort of on the back-end. We’re basically it’s like we’re discussing things pretty much continuously. And one thing that comes up a lot, particularly as it relates to health, is the machine is only going to be as good as the person who is training it and the way that they train it.

So if you think about, I was reading something recently about how IBM’s Watson in health hasn’t produced as much or as fast as they thought it would. We wonder if part of the problem is the fact that you’re taking traditional medicine approaches and then just trying to add machine learning on top.

And as we know, the current approaches we have to chronic diseases or cancer aren’t necessarily the right ones. And these aren’t getting us anywhere as fast as we originally hoped. Because we’re still working around an acute care system for chronic diseases.

So there’s definitely the possibility that until we keep trying and failing this in various different arenas we’re just going to get the same wrong answers, but we’re just going to get them faster.

(0:45:48) [Damien Blenkinsopp]: Right. And I think Chris you brought this up in an email that sometimes the system we have is focusing on one marker, or is focusing on one diagnosis driven by one single input to that. There’s one reason why you get sick.

Whereas in the world of functional medicine we’re looking at a multifactorial, multicomplex, everyone is kind of different with different inputs, sort of problem situations. And from what I’ve seen with machine learning is it could be the answer to this because it will just look at all of the data and it will say if you look at these five things and how they vary, you get these different situations.

Whereas I guess the limitation of our human brain is we tend to focus on one thing and we’re just trying to say this leads to that, and it’s a linear fashion.

[Christopher Kelly]: Yeah, absolutely. So that’s a really good example, actually.

If you think about my analysis, most people could hold it in their working memory that maybe gas, bloating, and diarrhea might be related to gut dysbiosis. And a practitioner can hold that in their working memory.

But what about these 50 other questions? Maybe you can’t go for very long without eating, and that is a sign of gut dysbiosis. How many of these things can you hold in working memory at once? It’s really, really complex.

When I went to a conference last autumn, the Artificial Intelligence in Medicine Conference down at Dana Point, which overall was very good, I enjoyed my experience there. They where taking questions at one point and I asked the question, ‘Could we use Deep Learning to uncover the root causes of chronic disease?’

And the commentator, he turned to the panel and he said: ‘What do you think? Do you think we really need to understand the root causes, or is it just enough to be able to diagnosis the problem? Because once we have the diagnosis, then there’s the treatment, right? So do we really need to understand the root causes?’ And I just like put my head in my hands.

So it’s frightening because machine learning, obviously it’s so very powerful, but like Tommy said, it’s just a tool. You still have to understand how to use the tool in the most effective way in order to get the result that you’re looking for.

[Damien Blenkinsopp]: Absolutely.

A lot is going on in the world of health, right? Conventional medicine is starting to use big data and train algorithms and so on. But there’s not a lot going on in functional medicine, which is the area and the conferences which we explore more because it’s related to the origins of problems and so on.

(0:48:15) [Damien Blenkinsopp]: Have you seen any other examples of people trying to apply some kind of machine learning? It would be something I’d really love to see more of. I’ve been thinking about it for a little while, that’s why when you guys told me about this I was like, yes!

[Christopher Kelly]: Yeah, so, maybe part of the problem is that everybody thinks that they need big data.

When I was listening to some of these talks that were presented at this conference last year, there were hospitals there who were doing 16,000,000 blood tests per month. That’s probably more than Nourish Balance Thirve will ever do in our lifetime, I think. That truly is big data.

But I think we’ve been able to do something really good without actually having big data. We’ve only had data from 1,000 athletes. So maybe this idea of big data needs to go away. Perhaps we don’t need big data; each individual practitioner already has enough data in order to do something useful.

(0:49:09) [Damien Blenkinsopp]: Well yeah, and especially the ones that have been practicing for 10 years. There’s many of those, and they’ve got a ton of data. I think that’s one of their biggest attributes there, this asset of data they’re sitting on from past patients.

How much data is necessary then? Did you just try this and it worked out?

Or do you think it’s because you were focusing on a niche and there was a tight correlation between the people and that’s why it worked out? Whereas if we do these population studies, I think the view is it can be a bit all over the place, so it can be harder to see those patterns potentially.

[Christopher Kelly]: Yeah. We only had 100,000 total features, which is really quite a small data set. But, there’s no reason why we can’t keep these data sets separate for specific populations.

So let’s say Mark Hyman wants to train models based on his data set. And then Chris Kresser is over here and he sees a lot of thyroid patients so maybe he wants to train on his specific data set. You could still use the same code base, and you could still use the same algorithms.

With the particular model that I’ve used, XGBoost, it doesn’t take that much compute resources in order to train the models. So this is in stark contrast to Deep Learning, for example, where really it’s not possible to do much on your laptop.

You really have to spin up an S3 instance, a Cloud computer with lots of fancy hardware probably made by Nvidia that will allow you to do the training of these algorithms. So computationally it’s very expensive.

That’s not true of the algorithms I’ve used. There’s no reason why people couldn’t just run separate instances of the algorithms on their own personal data sets.

(0:50:52) [Damien Blenkinsopp]: Great. That’s great to hear. I hope this episode inspires a few more people to look into this.

Are there any specific areas you think it should be applied to beyond, or at, or where you think it’s going to be more exciting?

[Christopher Kelly]: That’s a good question. It’s a question I don’t know if I’ve got any good answers [for].

Yeah, so we talked about how there’s so much complexity in the root causes that are causing chronic illness. Tommy has a really good talk that he did on the underlying root causes of insulin resistance.

It’s tempting to believe that the only thing that causes that are refined carbohydrates. And that’s technically true, they maybe do cause insulin resistance. But then there’s endotoxins in the gut, and there’s circadian dysregulation, and there’s loneliness, and there’s other types of stress. There are all these different things, and I feel like it’s going to be almost infinitely complex.

What we really need is some kind of algorithm that could really uncover all of these root causes. Keep everything in working memory at once, and figure this out in a way that no human ever could. I think that Tommy has done a better job on insulin resistance than any other human I’ve met so far. And that includes all the people I’ve interviewed on my podcast. But I have a feeling that a computer might do even better, should someone choose to sit down and apply one in that area.

[Damien Blenkinsopp]: Yeah, that’s great, thanks for that feedback.

I think functional medicine is actually an area where they’re dealing with some of the most complex problems. If you look at things like Lyme disease, where there’s of course a ton of controversy because it’s so complex; people say it doesn’t exist or it exists.

I’d love to see this kind of thing applied to those areas to finally bring some clarity to it and say this is what the machine is coming up with, based on just data. To get past all the opinion and everything which seems to kind of cloud these types of areas.

And chronic fatigue syndrome, you brought that up earlier, that’s another one of these dubious areas where…

[Christopher Kelly]: Yes, that’s death by a thousand cuts, I’m sure.

(0:52:52) [Damien Blenkinsopp]: Yes, excellent.

So is there anything we’ve missed that’s important about your thinking on this subject, or your application and what it’s doing currently?

[Christopher Kelly]: The only thing I wanted to say, another example I saw which I thought was a bad use of this technology, was there’s a paper that came out of the Deep Mind group, which is now part of Google. They did something astonishingly clever, it’s absolutely amazing.

They took a million – a million – hand labeled images of diabetic retinopathies, this is damage done to the eye through high blood glucose. And they created a learning algorithm that would predict diabetic retinopathies better than a human could. And so it’s kind of all amazing, that’s absolutely brilliant.

But then you realize that had the person who’s retina was being scanned done an oral glucose tolerance test with insulin 20 years previous. They maybe could have altered their eating patterns, the food they’re eating and when they’re eating it, and their movement patterns, exercise. Then potentially we could have saved their eyesight, which I think is a much greater win than being able to diagnose them with diabetic retinopathy 20 years later.

So I really wanted people to know about some of the uses and abuses of this type of technology.

[Damien Blenkinsopp]: Yeah so it’s a question of thinking about where they greatest impact is going to be had. And also there’s this question of trying to diagnose the end conditions rather than trying to proactively trying to tackle a problem for the future.

It’s just that mindset, which I don’t know if it’s a lobbying philosophy or how eventually that mindset switch is going to take hold. It seems to just be engrained in the education system, I guess. The systems and everything and the process people are taught on how to approach problems.

[Christopher Kelly]: Yeah, medicine is a really funny beast.

Initially when I started Nourish Balance Thrive, I thought medicine was broken. And then more recently I’ve come to understand that medicine is not broken at all. It’s doing exactly what we designed it to do, which is treat acute and episodic illness.

So if you get hit by a bus or you get an infection, then medicine is really, really good at treating that, for the most part. Where it really falls down is with these diseases of modernity, like diabetes or obesity. Medicine is just not designed to solve those types of problem.

And so we need something completely different, and that is what the Nourish Balance Thrive program is. Now we’ve got a machine learning algorithm that will identify the problem sooner and more easily, but the solution remains the same; you need to move your body, you need to eat appropriately, you need to handle stress appropriately. All of those things.

So, I’m hoping that by doing the cheap and easy diagnosis sooner, it’s going to bring people’s attention to the real problems more easily and sooner so they can rectify them before it really becomes a chronic disease.

[Damien Blenkinsopp]: Yeah, it’s interesting. As you were talking about the system there, I was thinking basically the same problem we have with machine learning we have on a society level, right?

If medicine’s focus, or any organization’s focus, is on something else, it doesn’t matter what you put into it it’s not going to get the ideal outcome. Just like with the machine learning programs; if you set it on the wrong task or the wrong focus, it’ll get the wrong result. And the more money you put into it, the worse it will get.

So it’s interesting like that. Maybe it’s just mimicking humans.

[Christopher Kelly]: Well that’s exactly right. That’s a really good point that you bring up.

Especially with the Deep Learning algorithms, it’s a deep convolutional neural network. It is a model of what happens inside the human skull, literally. That’s how it works. So if you set it on the wrong task, it’s going to get the same wrong answer that humans did.

(0:56:49) [Damien Blenkinsopp]: Yeah, exactly.

OK, so where should someone look first to learn more about this? Are there any good books or presentations on the subject? You’ve mentioned a couple of resources already. Are there any others?

[Christopher Kelly]: No, I don’t think so.

Definitely my two favorite things are, The Master Algorithm by Pedro Domingos–and it was Pedro, when he came on my podcast he said: ‘Oh you should use XGBoost for that.’ And I said, ‘Okay.’

Until then I had been trying to use Deep Learning to solve my problem, not really getting very far. And then Pedro said that one word and he was right. Absolutely amazing book; I absolutely love that book, The Master Algorithm.

And then check out fast.ai, which is Jeremy Howard’s website where he’s teaching these online courses in Deep Learning. And even though I just said that Deep Learning turned out to not be the algorithm that was best for me, Jeremy is an amazing practitioner that will teach you all of the skills that you need in order to become a machine learning practitioner of any type.

So even if you end up using XGBoost or some other algorithm, you’re still going to need all of these other tools that sit around the periphery that will be very valuable no matter what algorithm you use. So that’s fast.ai.

(0:58:00) [Damien Blenkinsopp]: Excellent.

Just to clarify there, if you have no programming background is this still something you can look into and learn more about it and it would be useful, do you think?

[Christopher Kelly]: I would like to say yes, that learning how to program shouldn’t be much more difficult than learning how to speak. It’s really getting that easy.

Python is the programming language that I use and I really don’t think it’s that hard. You can read it just like you can read English. It’s not obfuscated in any way.

Having said that, Jeremy Howard’s course is designed to teach machine learning to people who can already code. I know that some of the people on his classes were coming from a background that was completely different, like mathematics, for example. So maybe they didn’t have any ability to code.

But if you’re smart, you’re going to be able to solve this. Learning is the only skill that really matters.

(0:58:50) [Damien Blenkinsopp]: Cool.

What are the best ways for people to connect with you and learn more about you and your work, you and Tommy’s work at Nourish Balance Thrive? Are you on Twitter, have you got a podcast, or Facebook? Where are you most active?

[Christopher Kelly]: Sure. So what I would really like people to do is come to Damien’s show notes and use the custom link and do the seven minute analysis. Then once you’ve done the analysis, I’m going to follow up on email and send you links to my best podcast episodes on some of the problems that we found.

Tommy has done some fantastic interviews all over the internet–even I have trouble keeping track of them all. So we sat down and thought okay, which are the best things on glucose intolerance? So you’re going to get an email with links to our very best stuff.

I do have my own podcast, a Nourish Balance Thrive podcast, but yeah I would encourage people–you do fantastic show notes, Damien. You do the best show notes I’ve ever seen on the Internet. They’re amazing. So if people are listening and they’ve never seen Damien’s show notes, they should definitely come and check those out.

(0:59:52) [Damien Blenkinsopp]: Thanks, I appreciate it. Of course everything you’ve mentioned in the whole show will be in the show notes, as usual. So, thanks.

Who besides yourself would you recommend to learn about machine learning, or just functional medicine? On your journey, because I know we’ve been to the same space, who do you recommend to check out their work?

[Christopher Kelly]: That’s a really good question. I think my favorite person, the guy that’s been most influential to me, is Bryan Walsh.

Bryan Walsh is a naturopathic doctor from Maryland. If you search online, this is like a hidden gem on the internet. Nobody knows about this. His videos on Youtube, some of them still only have a 1000 views, and I swear most of them are me.

So if you search for Bryan Walsh WellnessFX, which is the blood testing company you’ve probably heard of, you’ll find these videos on Youtube and they are amazing. No one teaches blood chemistry interpretation like Bryan Walsh.

Bryan also has a biochemistry training course for health and fitness professionals called Metabolic Fitness Pro. By the way, I have no financial affiliation with any of this stuff. This is just someone that’s been really, really helpful to me in learning over the years.

Bryan is now on the road teaching weekend seminars on how to do blood chemistry interpretation. I’ve done a whole bunch of training courses. I’ve done FDN, I’ve done Kalish, I’ve done other things, and really Bryan’s stuff is by far the best for me.

[Damien Blenkinsopp]: Excellent. I’ve seen some great stuff of him looking at cortisol dysregulation and adrenal fatigue, if it exists or not.

[Christopher Kelly]: Yeah, exactly, The Artist Formerly Known as Adrenal Fatigue. Bryan has been talking about how that’s nonsense for at least five years, probably longer.

He did a really good interview with Rob Wolfe about this. Really, really good. I love Bryan. He’s been really helpful to me.

(1:01:45) [Damien Blenkinsopp]: Great. Thanks for that.

So I’d love to get to know you a bit more, as well, just in terms of what you actually do to improve your body, and how you use tracking today.

Do you track any metrics or biomakers for your own body on a routine basis? And if you do, why?

[Christopher Kelly]: Well, I still do all of the testing that we talked about. I was at the lab yesterday getting the blood panel that Tommy designed done. I still do urinary organic acid, I still do stool testing.

Already, I said that I ran into some health problems a few year ago. When I did the stool testing, I found a pinworm infection, I found a raging yeast overgrowth. I had almost certainly what most people would call SIBO, although I never did the breath test. I had a belly like a basketball, where I’m still quite lean but for some reason I look like I’m six months pregnant.

So those tests, they were really helpful in uncovering the root causes of my health problems. I took a whole bunch of botanical herbs to solve those issues and that worked really well. So I still do all of that type of testing.

In terms of tracking things on a daily basis, in the end I found it more helpful to track the behavior that leads to the desired outcome. And I can explain that with an example.

So I know that I don’t walk enough–that was one of my problems. I’m a mountain biker, so I pedal lots and lots, and I sit lots and lots when I’m working, but I don’t really walk around too much. The reason I didn’t use to walk around too much was because I found it really, really boring.

So I first thought I would get a FitBit and track the number of steps I’m taking each day. And that was horrifying. I was doing 400 steps a day or something on some days, working from home. Really, really low. And in the end, the solution was not FitBit, it was to get a dog.

A few months ago we got a dog – and I apologize, he barked earlier and I had to kick it out of the room. So not so great for podcasting but great for walking. Now I walk at least an hour a day, and I really enjoy it. It’s really fun.

So maybe sometimes the answer is not to track the number of steps or track whatever it is you’re interested in, but instead insert some interrupt into your life that’s going to lead to the behavior change that gets the desired outcome.

(1:03:56) [Damien Blenkinsopp]: Yeah, that’s really clever, changing your environment like that. Definitely one of the most effective things I’ve found is changing your environment.

So, you’ve had a lot of insight, and it sounds like you’ve made a lot of changes over time. Are there any other more recent changes or things you’re thinking about based on any of these things that you’ve tracked or that have come up? Or are you basically optimized now and you’re quite happy?

[Christopher Kelly]: I am very happy, actually, but I am worried.

One of the reasons I’ve been so good at doing–I say so good. People have told me I’m quite good at doing the podcast, and then also the client calls. It’s because I was so able to relate to the other person’s specific situation, because I had also been through that same situation. I’m worried that I’m losing that now.

But, I do continue to think about it, and maybe there’s something I’m missing, but one of the things I advocate is that it really isn’t that hard. There aren’t that many things to think about.

Diet, which we talked a lot about on the podcast. There’s appropriate management of stress; you’re never going to get away from stress, but you need some way to appropriately manage it. Whatever you do, don’t be lonely. That’s like smoking 15 cigarettes a day. Just because you live in London doesn’t mean you’re not lonely; it’s perfectly easy to be lonely even though…

[Damien Blenkinsopp]: Well especially with all of our devices these days. I think a lot of people choose that route rather than…

[Christopher Kelly]: Exactly. Yeah. So these real relationships are being replaced by Facebook and Twitter and all the rest of this stuff.

And then what else is there, there’s movement, appropriate movement. You need to walk, I think, and you need to occasionally lift heavy things and maybe sprint. And that’s really all there is to it. It’s not that complicated. Or at least it didn’t take me long to say it.

(1:05:35) [Damien Blenkinsopp]: Yeah, excellent.

If you were to recommend just one experiment that someone should try to improve their body – and it could be to improve health, performance, longevity, whatever they’re after or whatever you think is most important – with the biggest payoff, what would that be?

[Christopher Kelly]: Definitely monitoring blood glucose, without a question.

[Damien Blenkinsopp]: Okay. Is that with the CGM or a blood meter? How should they do that, and how…

[Christopher Kelly]: I think most people are not going to have access to the CGM.

I have worn one, personally. Somebody sent me one from New Zealand. So I’m in Santa Cruz in California and I believe that you still need a prescription from a doctor to get one, which is unfortunate, and I’m sure that will change in the future. Somebody sent me one from New Zealand and I did learn a couple of things.

The first was that when I walk, my blood glucose goes down quite surprisingly rapidly, even walking with a three year old girl. So most people would think that’s nothing, that’s not enough exercise to have any impact on anything. But it turns out that it is.

So I can prevent postprandial glucose spikes just by going for a walk with my three year old daughter. And I never would have known that without the continuous monitor. You just wouldn’t know to stick your finger to see that it’s happening.

And then the other thing I found out from the CGM was that intense exercise really, really raises my blood glucose. I don’t know whether its cortisol or what, I haven’t done continuous cortisol monitoring. But when I do intense exercise I can get my blood glucose up to 180 milligrams/deciliter, no trouble at all. So, that kind of makes you aware of the fact that it’s not just the food you put into your mouth that can raise blood glucose.

The place to start is with the finger stick test that everybody has access to. You can go to your local drug store, anywhere in the world, and pick up one of these finger stick tests that I know you’ve talked about on the podcast before. Then just check your blood glucose first thing in the morning.

Optimal evidence based reference range for fasting blood glucose is 83 to 88 milligrams/deciliter. So that’s what one of our models is trying to predict, being out of range. So that’s where I think you should be, and that’s where I am now. It took me a while to get there, but I am in that optimal range.

[Damien Blenkinsopp]: Is that throughout the day? So they can check it at any time away from food or…

[Christopher Kelly]: I’m not sure.

I wouldn’t want to see excursions too far out of that reference range. Once you go above 120 it becomes questionable whether you’re doing yourself any good. Obviously there’s going to be some excursions. If you’re eating any carbohydrate at all then it’s going to go above 100, I would expect.

But I think the fasting value is really interesting because we have some epidemiological data that shows hazard ratios go up significantly once you get above – or below actually – that 83 to 88 milligrams/deciliter in fasting blood glucose.

[Damien Blenkinsopp]: Right. So is that first thing in the morning then?

[Christopher Kelly]: Exactly. As soon as you get up, you stick your finger before you’ve had a chance to move around too much or eat anything.

[Damien Blenkinsopp]: Yeah. I do think sometimes that’s a tricky one for some people, like me, because with my CGM I’ve seen over time really quickly after I wake up I start to get a rise from cortisol.

[Christopher Kelly]: Okay.

[Damien Blenkinsopp]: And so it’s always made me wonder.

I’ve been going to get my blood’s fasting glucose for years, and it didn’t necessarily come back ideal. But then if I look at the whole day, I’m basically in the optimum range all the time. And it’s just this one little spike when I wake up in the morning.

I think I do have some cortisol dysregulation, but I think it’s relatively common as well.

(1:09:11) [Damien Blenkinsopp]: Just on your exercise thing you were talking about. I maybe have a little bit of information for you there. I’ve been testing the Wim Hof method recently.

[Christopher Kelly]: Oh yeah. I am familiar, I’ve tried it.

[Damien Blenkinsopp]: Have you? Oh cool. Well how are you finding it?

[Christopher Kelly]: It’s hyperventilating, and it made my face tingle, and I felt kind of funny. I could see that it was doing something. But yeah I’m not sure what else to say about it.

[Damien Blenkinsopp]: I’ve been through the whole program and taking it pretty seriously. It’s actually helping me with some things which I’ll cover in a later episode.

But I’ve tracked it extensively as well with CGM and things like that, and the breathing, the hyperventilation, whacks up your blood sugar every single time.

Yeah, with a cortisol response. So it makes you wonder if when we get an exercise response, is that due to the breathing? Because when we’re exercising hard, we’re actually breathing really hard as well. Or is it the actual exercise as the actual trigger?

[Christopher Kelly]: It’s a hormetic stressor, is what it is. It has to be.

So some part of your brain thinks that you’re being chased by a tiger, so it’s trying to liberate energy. It’s trying to liquidate your assets. Let’s just get some glucose moving. I bet if you were to measure blood levels of fatty acids, you’d see the same thing; that energy is going up too.

So you’re just liberating your assets so that you can escape from whatever this danger is. But your brain doesn’t know that it’s not really a tiger that’s chasing you, your just doing the Wim Hof thing.

But eventually it leads to you getting stronger. So the same thing happens when I do kettle bell swings, or if I go in the sauna, or if I ride my mountain bike for long enough. And so it’s a hormetic stressor; eventually, hopefully, you get stronger.

[Damien Blenkinsopp]: You do feel it as well, when you first start. You feel this slight anxiety when you’re doing the hyperventilation, and over time that goes away, which fits with your explanation there as well.

(1:11:01) [Damien Blenkinsopp]: But anyway just to come back to your fasting glucose thing, there is that slight variation you have to be aware of, but overall the morning is probably the best time. Is that what you’d advise?

[Christopher Kelly]: Yeah, I think so. It’s overall stability that you’re probably shooting for.

Just because you see, maybe you’re eating a ketogenic diet. And we nearly always see elevated fasting blood glucose with someone who’s been eating a ketogenic diet for a while. But does it mean anything anymore based on my evidence based reference range, because that’s epidemiological data and you can bet your bottom dollar that those people that were in that data set were not eating a ketogenic diet.

So at that point, all bets are off. But for the ketogenic dieter, they’re still achieving overall stability, which may be the most important thing.

[Damien Blenkinsopp]: Right.

Chris, it’s been a really interesting episode. Thanks for all your thoughts and for building your little tool here, which is a great first in functional medicine, I think. So congrats on that, and of course I’ll give the link and everything in the show notes for everyone to follow up with. It’ll be interesting to see what everyone gets from it.

[Christopher Kelly]: Yeah. I’m very excited to know what people think. If you think I’m an idiot and I should stop doing this, please tell me, because otherwise I won’t know.

[Damien Blenkinsopp]: Great Chris. Talk to you again soon.

[Christopher Kelly]: Thanks Damien.

References:

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What is carbohydrate intolerance? Do each of us have a personal tolerance or intolerance of carbohydrates? Does this also vary by source of carbohydrate? Learn how evolutionary tools may explain appetite regulation and carbohydrate metabolism and offer ways to regain carb tolerance through diet and lifestyle modifications.

In this episode, we explore how carbohydrate intolerance works. We look at the evolutionary template (basically the Paleo template), neuroregulation of appetite, carbohydrate tolerance, insulin resistance and sensitivity, and the factors that drive all of these.

Once the person is insulin resistant, particularly when they are heading down this road towards prediabetes and potentially diabetes, there is without a doubt one intervention that seems to work remarkably well. That’s reducing carbohydrate level to a point where it’s no longer toxic to the individual.”
– Robb Wolf

Robb Wolf (@RobbWolf) is basically the man responsible for bringing Paleo to the mainstream, in part via his New York Times Bestseller, The Paleo Solution. He also has a new book out, Wired to Eat, which covers many of the topics discussed in this episode.

Robb is a former researcher biochemist and review editor for the Journal of Nutrition and Metabolism, and the Journal of Evolutionary Health. He is a consultant for the Naval Special Warfare Resilience Program and has provided seminars in Nutrition and Strength to organizations such as NASA, the Canadian Light Infantry, and the United States Marine Corps.

One of the takeaways from Robb’s new book, Wired to Eat, is using a 7-Day Carb Test. That’s testing a different type of carb seven days in one week to see what these do to you, and what your personal tolerance is to different carbs, because not every one of them affects you the same way, or like it would any other person.

I ran that test myself and the results are further down this page. This gives you a concrete example of what Robb is talking about when he talks about the 7 Day Test, how to measure blood glucose and how to understand how these carbs are affecting you differently.

The episode highlights, biomarkers, and links to the apps, devices and labs and everything else mentioned are below. Enjoy the show and let me know what you think in the comments!

itunes quantified body

What You’ll Learn

  • Damien extends his gratitude to Robb for getting him back to eating meat in the year 2010, which greatly improved Damien’s health (03:45).
  • Robb’s book Wired to Eat approaches health from an evolutionary neuroregulation of appetite as starting point and progresses with dieting self-experiments (04:01).
  • The insulin resistance theory and how the 7 Day Carb Test is useful in coming up with personalized diet plans aimed at improving health (10:46).
  • The potential for low-carb / paleo diet and intermittent fasting to improve carbohydrate tolerance (18:50).
  • Robb’s plans for experimenting with donating blood to reduce potential iron overload inflammation (19:58).
  • The value of lipoprotein insulin resistance (LPIR) panel in determining ‘hidden’ insulin resistance, otherwise not detected by fasting glucose levels alone (21:05).
  • Anthropometric measures, such as the waist to hip ratio, are only somewhat reliable markers of insulin resistance (24:28).
  • Making use of the 7 Day Carb Test to track the process of recovering carb tolerance over time (24:53).
  • Why sleep is the most important health parameter and how HRV is useful for tracking sleep quality and overall health (29:39).
  • Integrating physical exercise into a busy life and optimizing exercise intensity (36:41).
  • The ketogenic diet offers numerous therapeutic and health maintaining benefits (41:35).
  • The role of the circadian rhythm in tuning meal consumption with the body’ demands throughout the day (45:35).
  • People to follow & material for learning more about this episode’s topics (51:39).
  • The best ways to connect with Robb Wolf and learn more about his work (53:14).
  • The biomarkers Robb Wolf tracks on a routine basis to monitor and improve his health, longevity, and performance (53:45).
  • The labs using NMR spectra technology to detect LPIR components with high precision (57:58).
  • Robb’s one biggest recommendation on using body data to improve your health, longevity, and performance (58:28).

Thank Robb Wolf on Twitter for this interview.
Click Here to let him know you enjoyed the show!

Robb Wolf

  • Main Website: Short life & career summaries of Robb Wolf and his team.
  • Paleo Diet: An introduction on the Paleo Diet written by Robb.
  • Robb’s Instagram: Where he spends most of his social media time and answers almost all posed questions.
  • The Paleo Solution Podcast: Robb’s long running podcast exploring every area of evolutionary and paleo based lifestyles as well as many of today’s chronic health challenges.

Recommended Self-Experiments

7-Day Carb Test

  1. Tool/ Tactic: This test is described in detail in Robb’s Wired to Eat book and on his blog here. It consists of consuming 50g of carbohydrate from different carbohydrate sources (e.g. rice, lentils etc.) each day for one week.The goal is to identify which carbohydrate sources have the biggest impact on blood glucose levels, and thereby identifying which ones you are least carbohydrate tolerant for.In creating this test, Robb was inspired by the Weizmann Institute of Science’s Personalized Nutrition Project. We discussed personalized nutrition and interviewed the lead researcher, Eran Segal, from this project in Episode 48.The test entails preparing 50g of effective carbs, or another carb source, and eating only one type of this meal first thing in the morning (with the exception of coffee and water).
  2. Tracking: Track the food types, your blood glucose level before you consume the food and the time at which you eat. Exactly two hours later, test and record your blood glucose reading again.Is your blood glucose at the 2 hour mark over 115mg/dl? This can indicate carbohydrate intolerance with respect to that specific food.By understanding the carbohydrates you are personally intolerant of you can reduce your blood glucose variability significantly by just removing these from your diet (while still enjoying other carbs that your body is tolerant of).

    Robb recommends that the 7-Day Carb Test is repeated approximately every 3 months, such that the time intervals are close enough to track improvements in particular carb foods insulin sensitivity, as well as tracking the body’s overall insulin sensitivity.

Damien’s 7-Day Carb Test Results

Before recording the interview with Robb I followed his carbohydrate testing protocol for some of the carbohydrates that appeal to me more.

I made a couple of modifications of the protocol to fit my profile better.

  • First, as I’m on a ketogenic diet, I also tracked blood ketones to understand the impact of each carbohydrate source on my levels of ketosis.Did a particular carb drop me below the performance ketosis threshold (1.5 mmol/L)1? Or did it drop be below the nutritional ketosis threshold (0.5 mmmol/L)?
  • Second, from my using a Continuous Glucose Monitor for the last 3 months I know that my blood glucose readings in the mornings are not stable. They rise and fall after waking very predictably, but to greater or lesser amounts depending on sleep, stress and possibly other factors.On the other hand, since I only eat once a day typically, at my evening meal, I know that my blood glucose in the afternoons is always flatline. So I ran my experiments in the afternoon knowing that the variables were better controlled. This is not the situation for most people as Robb describes in his book, so you are most likely better off running the test in the morning as he advises.

In my case the takeaways from this self-experiment were:

  • Lentils had the least impact on my blood glucose levels and ketone levels. My blood glucose had dropped back to near baseline, below 90 mg/dl, within 90 minutes.
  • White rice had the largest relative impact on my glucose levels, but didn’t necessarily have the largest impact on my blood ketone levels. It was the only carb for which I found myself ‘carbohydrate intolerant’, as it failed to return below the 115 mg/dl cut off mark. It also had potentially not even peaked at the 2-hour mark. It was still rising as of last reading, and was just over 130 mg/dl.
Blood Glucose Response to 50g of Effective Carbohydrate

carbohydrate-tolerance-glucose2

Blood Ketone Response to 50g of Effective Carbohydrate

carbohydrate-tolerance-ketones-2

Notes for Context & Additional Observations
  • Average readings of two or three blood glucose readings were taken for each blood glucose data point. From discussions with blood meter manufacturers I’ve learned that blood glucose meters have a high variance in their readings, so when you want accurate results you need to take several readings depending on the variance of the readings (two readings if the first two readings are < 0.5 mmol apart, or three readings if they are over 0.5 mmol apart). Researchers I’ve spoken to also follow this protocol to normalize readings.
  • Unfortunately I ran out of ketone strips for the last experiment which was the black beans. This was particularly annoying since the ketone response looked pretty unique for these – so I will likely rerun this particular test in future (especially as I dabble in black beans at Chipotle every once in a while).
  • I experienced some gut intolerance/ some negative symptoms from the lentils. This was the only carb that I experienced this with and seems to go against some assumptions that autoimmune/ auto-inflammatory responses are behind the largest glycemic responses to foods. The glycemic response in my case, was the lowest for lentils while it was the only one I experienced gut intolerance with.

Sleep

  1. Tool/ Tactic: Sleep is the most important physiological parameter, and poor sleep or inadequate sleep is excessively damaging to the body. Robb argues that if one feels good when going to sleep and waking up, then this is a reasonable indication that the body is performing in healthy shape. Tactics for improving sleep quality from Robb’s blog include: reducing light saturation, reducing noise in the environment, doing intense exercise earlier in the day (due to potential shift in circadian rhythm with late evening exercise), stopping all work a few hours before sleep and making a list of your thoughts before going to sleep – then agreeing with yourself that you are best able to take care of this list after a good night sleep.
  2. Tracking: In Robb’s opinion, it is key to subjectively track physiological concepts in our bodies and to make use of understanding these perceptions. For example, this entails paying attention to feeling tired before or rested after sleeping, or feeling background symptoms of inflammation (eg. in the joints). Robb discusses the use of Heart Rate Variability (HRV) for tracking sleep quality in his blog.

Tracking

Biomarkers

  • Waist to Hip RatioAnthropomorphic body markers, such as waist to hip ratio, body weight, or Body Mass Index (BMI) are useful for understanding carbohydrate tolerance, ex. as a complement to evaluating 7 Day Carb Test after a diet intervention. However, anthropomorphic markers are not very specific measures of insulin resistance. For example, people who are lean still face carb toxicity. Alternatively, people also sometimes face inflammation caused by the immune responses to other specific food types, ex. eggs or soy.
  • Fasting Blood Glucose: Elevated fasting glucose levels indicate a progression toward diabetes. Fasting glucose is usually taken first thing in the morning after an 8 hour fasting period and optimum levels range between 70 and 90 mg/dL.
  • Hemoglobin A1C: Used to identify the average plasma glucose concentration over prolonged periods. Higher levels of hemoglobin (A1C) indicate poorer control of blood glucose levels. Normal levels are less than 5.7%, pre-diabetes levels range between 5.7 to 6.4%, while higher than 6.4% is indicative of diabetes. Both fasting glucose levels and hemoglobin A1C are useful in identifying a level of blood sugar dysregulation, but cannot be used to quantify insulin resistance at an individual level.
  • HDL & LDL CholesterolHigh – Density Lipoprotein (HDL) is the traditional measure of ‘good cholesterol’ used by doctors and healthcare. Levels above 60 mg/dL are considered protective of cardiovascular disease. Low – Density Lipoprotein (LDL)) is the traditional measure of ‘bad cholesterol’ – the type which causes cardiovascular disease. Less than 100 mg/dL is considered an optimal level, while levels between 160-189 mg/dL increase the risk for cardiovascular disease. While both measures are important biomarkers, these are not indicative of insulin resistance status.
  • LPIR (Lipoprotein Insulin Resistance) Score: The LPIR Score is constructed as a weighted combination of 6 lipoprotein subclass measures and reflects the concentrations of each into one score. The final result ranges from 0 (most insulin sensitive) to 100 (most insulin resistant). Recent studies have been using the LPIR as a more accurate approach to assessing insulin resistance improvements via interventions.2
  • GlycA: A novel biomarker useful for predicting predisposition to insulin resistance and Type 2 diabetes3, cardiovascular diseses4 and inflammation-driven diseases including cancer5. Normal GlycA levels are below 400 μmol/L. Concentrations tested above this cut-off value are considered high and indicate the need to take steps towards preventing health issues.
  • FerritinSerum ferritin acts as a buffer against iron deficiency and iron overload. Levels are measured in medical laboratories as part of the workup for detecting iron-deficiency anemia. The ferritin levels measured usually have a direct correlation with the total amount of iron stored in the body. Female normal reference range is 12-150 ng/mL and for males it is 12-300 ng/mL.
  • HematocritThe hematocrit (Ht) is the volume percentage (vol%) of red blood cells in the blood. It is normally 45% for men and 40% for women. Robb checks ferriting and hematocrit as markers for tracking iron saturation which he plans to tackle by experimenting with donating blood and because these are useful in determining iron saturation which he suspects is the potential cause of some inflammation.

Lab Tests, Devices and Apps

  • NMR Lipoprofile: The LPIR score is part of the NMR Lipoprofile run by Labcorp (example report output here). It is an additional biomarker that was added to the panel more recently. The NMR Lipoprofile was originally run by the company LipoScience, which was acquired by Labcorp. As a result, Labcorp is now the company that runs the most advanced labs using NMR Lipoprotein analysis.
  • GlycA Test: The GlycA test is also offered by the company LabCorp.
  • BioForce HRV Set: BioForce HRV is a for tracking HRV which allows users to include their choice of sensors. There is a standard Bluetooth heart rate strap or a newly developed and finger sensor. Both sensors are compatible with all iOS and most Android devices and are constructed to deliver the precision necessary for accurate HRV measurements.

Tools & Tactics

Diet & Nutrition

  • 30 Day Diet Reset: A diet scheme based largely on a Paleo diet type template, aimed at healing the gut and re-normalizing the neuroregulation of appetite. Following Robb’s guidance in Wired to Eat, the 30 Day Diet Reset should be done before the 7 Day Carb Test such that the results of the test can be objective.
  • Fasting: Damien has seen improvements in his carb tolerance with the use of fasting as a tool in various formats. Having tracked his glucose and ketone levels, he concludes that the switching point of burning ketones, instead of glucose, occurs at approximately the 72-hour mark. Over several fasts, it becomes easier on the body to switch to ketogenic (therapeutic) ranges with the switch occurring quicker (e.g. 48-hour mark). The glucose/ketone ratio charts look flatter indicating a more controlled physiological response to fasting.6
  • Ketogenic Diet: A diet which restricts carbohydrate intake, over time causing the body to switch from using glucose to burning ketones as the main fuel. There are many potential benefits from ketogenic dieting. For most people who are overweight and insulin resistant, a lower carb intervention wins out as an approach to solving these health issues. A therapeutic state of ketosis is determined by reading fasting blood glucose levels (which should be below 80 mg/dL in the morning after 8h of no food intake), while β-hydroxybutyrate (blood ketones) should be higher than 0.8 mmol/L. See Episode 7 with Jimmy Moore on optimizing ketogenic diets.

Interventions

  • Donating Blood: Robb plans to experiment with donating blood, with the aim to reduce some potential low-grade inflammation caused by iron overload. He plans to track iron saturation before and after 3 months of donating blood on a consistent basis and reach conclusions based on the data. Robb compares his case to Chris Masterjohn who personally controls an iron toxicity predisposition by optimizing his blood donation schedule. Chris discusses this topic in Episode 46 of this show, an episode focused on micronutrient status optimization.

Tech & Devices

  • Blue Light Blocking Glasses: FDA registered blue light blocking glasses used for digital light eye strain prevention. These glasses are a useful way to reduce light saturation for a few hours a night before going to sleep.

Other People, Books & Resources

People

  • Christopher Kelly: An athlete and founder of Nourish Balance Thrive which is a service offering a science-based, personalized support program to help people regain optimal performance.
  • Marty KendallAn engineer with an interest in nutrition who seeks things numerically who founded Optimizing Nutrition. Marty aims to consolidate a range of paleo and ketogenic ideas into an algorithm that will enable an individual to tailor their diet and bring about health goals.
  • Tim Ferriss: An all-round successful man, who runs a podcast focused on deconstructing world-class performers – other successful people in various niches or businesses. His podcast is often ranked #1 across all of iTunes and is also selected for “Best of iTunes” for three years and running. Robb interviewed Tim in an episode of his podcast.
  • Joel JamiesonJoel Jamieson is considered among authority figures on strength and conditioning for combat sports and has trained many athletes since 2004. Joel stands behind the BioForceHRV project, aimed at tracking HRV and implementing it in optimizing exercise to the condition of your body. Joel introduced Robb to the BioForce tracking platform which he has used ever since.
  • Alessandro Ferretti: An optimum nutrition researcher who formed Equilibria Health Ltd, which is now recognized as one of the leading providers of nutrition education in the UK. Alessandro actively does Judo and Karate and has discovered that he performs efficiently with a ketogenic diet – meaning feeling energetic, being able to undertake fasts, and remain lean.
  • Bill Lagakos: A biochemistry professor focused on circadian rhythms and nutrition. Following on Bill’s work, Robb has adjusted his diet to time-restricted eating, meaning that shortened feeding windows are assumed to be beneficial for a variety of physiological reasons. Moreover, based on his research in biological (circadian) rhythms, Bill Lagos advocates the idea that more carbohydrates should be eaten earlier in the day, such that carbohydrate backloading can be avoided. Because of these reasons, Robb has adjusted his fasts to approximately 14-16h, whereas before he would 18h fasts. Following a fast Robb eats a robust full meal, but he usually times this with jiu-jitsu exercise 2-3 hours later. This is an example of optimizing both how diet volume and the intensity of exercise.
  • Chris Masterjohn: Robb appreciates Chris’s ability to dive into the biochemistry and pathophysiology of when things are right and wrong in the body, as well as to develop whole food and supplement solutions based on his research. Chris was a guest on our show in Episode 46.
  • William Cromwell: A physical chemist who studied NMR spectra technology lipoproteins, serving as Director of Cardiovascular Disease at LabCorp.

Books

  • The Paleo Solution: A book by Robb Wolf following his perspective as both scientist and coach on the benefits of Paleo dieting, and this along with exercise and lifestyle changes can change one’s appearance and health for the better.
  • Wired to Eat: A book written by Robb which starts with the 30-Day Reset to help people restore normalized blood sugar levels, repair appetite regulation, and reverse insulin resistance. This book also features standard Paleo – based recipes and meal plans for people who suffer from autoimmune diseases, as well as advice on eating a ketogenic diet.
  • Myth of Stress: A book explaining how much of what we perceive as stressful in day-to-day life is actually generated by our brain’s anxiety response, but is not actually a legitimate stressor in terms of evolutionary times scenarios, when our brains evolved the stress response. Robb interviewed author Andrew Bernstein in an episode of his podcast.

Other

  • I, Caveman Show: Robb took part in this Discovery Channel reality show where they had to live mimicking the stone – age hunters and gatherers. It took place at 8,500 feet in the Colorado Mountains.

Full Interview Transcript

Click Here to Read Transcript
(0:03:45) [Damien Blenkinsopp]: Robb, thank you so much for joining the show.

[Robb Wolf]: Hey, huge honor to be here, thanks.

[Damien Blenkinsopp]: Yeah, it’s a huge honor on my side, because you got me back into eating meat back in 2010, just as we discussed a few minutes ago. That was great and that vastly improved my health, so thank you for that.

[Robb Wolf]: Awesome, awesome.

(0:04:01) [Damien Blenkinsopp]: Yeah.  So you just released this book, Wired to Eat, which I went through, and it’s building on what you’ve done in the past, and also looking at some of the things you’ve learned over time with all the practical experience you’ve had implementing this.

What would you say is basically the crux behind this book? Is it the neuroregulation of appetite, or how would you think about it?

[Robb Wolf]: Yeah, it’s kind of two pieces. So the front of the book is really starting this conversation from the perspective of the neuroregulation of appetite.

So I’m kind of known as being one of the Paleo guys, and I definitely use that evolutionary biology, evolutionary medicine framework to inform the question and answer process that I bring to strength and conditioning and nutrition, and what have you, but it’s a starting place. It’s not the endpoint.

And I think that’s where, in some ways, the efficacy of that whole methodology has been lost. People assume that that’s where you start and stop. Whereas for me it’s always been this is the starting place.

We’re not yet able to take a Star Trek type scanner and run it from toenails to earlobes and then say okay you need to eat this and train this way. Stuff like that may happen eventually, but we’re still very much in this empirical process.

So then if we’re in this empirical experimentation process, where the heck do you start? And I throw out this really insane, over-the-top, greasy used-car salesman notion that maybe evolutionary biology can inform some of where we start this health and performance story from.

There’s this model in evolutionary biology called the Discordance Theory. That’s basically you have an organism that is pretty well matched for it’s environment. The environment can be the weather, the food, it can be a ton of different factors, it could be bacterial or parasitical. But if things change, it could be beneficial, negative, or it could be neutral.

But if we start seeing disease processes prop up that we don’t see in the natural free-living environment, or in the pre-environmental change story, then maybe there’s something to be learned from that. That’s my crazy suggestion is that possibly our genetics are wired up for a life way and a time that no longer exists, and that as great as so many of the elements of modern civilization are, there might be downsides to it.

For example, antibiotics are amazing for preventing septic illness and death, but there might be some downsides related to mitochondrial function in our own bodies, and then changes in our gut microbiome, which we’re now understanding may have huge implications for our overall health.

Again, I use this as an orientation tool. And at the beginning of Wired to Eat I’m laying that foundation with the neuoregulation of appetite. Really trying to understand if we looked at high carb diets or low carb diets, what are the things that allow people to eat in a way that they support their activity level, support a healthy body composition but tend not to overeat.

And there are some commonalities there. The efficacy of some of these nutritional approaches becomes really obvious why they work when we better understand the neuroregulation of appetite.

And the goal on the front end of this – and it’s kind of funny because it’s fairly touchy feeling stuff – but my real goal is to help people understand that it’s not your fault if you find it difficult living in the modern world and navigating the snack aisle of the supermarket. It’s totally reasonable and understandable.

Now I’m not one of the fat accepting guys either. I do recognize that overweight and metabolic issues are damaging to our health. They are a huge cost to society.

So I’m not recommending that we just roll over and die and let life have it’s way with us, but I’m suggesting that if we can unpack all that emotional baggage and understand that this process might be hard but it’s doable, then we’re starting off at a good footing.

And then the implementation part of the book is where we get really granular in a more progressive fashion. We start things off with a triage process where we do some subjective elements, such as asking how do you feel between meals, what’s your cognitive function like, how long can you go between meals and still maintain good physical and cognitive performance.

And then we get more specific. We look at things like the waist to hip ratio, we look at fasting blood glucose. We really lean heavily on this thing called the LPIR score, the lipoprotein insulin resistance score, because for me it’s kind of the most powerful direct means for understanding where we are on this insulin sensitivity insulin resistance spectrum.

And if we are more insulin resistance then we tend to do better on a lower carb intake. And there’s a lot of variability with that. But we also have people that are overweight or experiencing some other health related issues but they are actually insulin sensitive, and these are the people that tend to do better on that moderate to high protein, high carb, low fat diet. So there are examples of both ends of this spectrum working pretty well.

But we use this triage process to get a handle on where we are in that insulin sensitivity insulin resistance spectrum. We use a 30 day reset, based largely around a Paleo diet type template, to heal the gut, re-normalize the neuroregulation of appetite. And then from there we use the 7 Day Carb Test.

There we pick a battery of different carb foods and we eat an allotted amount, which is 50 grams of effective carbohydrate. We check our blood glucose at a two hour mark. If your blood glucose is at or below a certain level, that’s usually an indicator that’s a good amount and type of carb for you.

If it’s above that, then we start asking some questions about should we reduce the portion size or is this really a good food for you. Because sometimes our elevated blood glucose level is not just from the carbohydrate content of the food but it’s from the immunogentic properties of the food.

If someone is reactive to wheat or eggs or soy, they may actually get a significantly elevated blood glucose response. And it’s not from carbohydrate, it’s from the stress response that occurs when we eat a food that we have an immunogenic response.

[Damien Blenkinsopp]: Thanks Robb. A real big download there.

[Robb Wolf]: Yeah, that was… (laughter)

(0:10:46) [Damien Blenkinsopp]: Let’s talk about a couple of the things you mentioned that stood out.

First of all you were talking about insulin resistance.

Do you see this as one of the cruxes of the issues? Is this one of the main factors? I know you’ve had a lot of practical experience in clinics and studies, and so on. So what have you seen in the populations out there in terms of how important the insulin resistant piece is?

[Robb Wolf]: Yeah. And this is a really contentious topis because people are still in pissing and squabbling matches about what brings about insulin resistance. Is it just in response to elevated insulin levels?

I think it was an interesting theory but over the course of time that has not borne out to be the best theory. It still seems to relate to an overabundance of energy causing systemic inflammatory responses within the cells that then tends to up-regulate this insulin resistant response.

But once the person is insulin resistant, particularly when they are heading down this road towards prediabetes and potentially diabetes, there is without a doubt one intervention that seems to work remarkably well. That’s reducing carbohydrate level to a point where it’s no longer toxic to the individual.

My analogy to this is basically photo exposure in getting a sunburn. Depending on what type of skin pigmentation you have you will be able to handle greater or lesser amounts of UV radiation before you get a sunburn. And if you do have a sunburn, there’s really only one intervention that makes sense, and that’s to reduce your exposure to the toxic levels of UV radiation.

And so that insulin resistance and the resulting metabolic derangement, which includes but definitely isn’t limited to elevated blood glucose levels, you can tackle that in a variety of ways. You can starve people down on a high carb low fat diet, and it can work. But in that insulin resistant state we tend to have a really serious dysregulation of the appetite and the tendency to want to eat a lot of carbohydrate.

And so this is where for most people who are overweight and insulin resistant that lower carb approach seems to work pretty magically. Even in these free-living populations where people can make a variety of choices, the lower carb intervention tends to win out.

[Damien Blenkinsopp]: I guess that refers to the saying carb-cravings, that we often hear.

I don’t know if you’ve seen this, but some people have a lot of difficulty with fasting. They’ll have dreams about food if they fast for 24 hours. I know friends who have fasted with me [for whom] it was a bit difficult. Or they get ‘hangry’ – I know that’s a term you coined in your book as well.

Have you found that that correlates with some of the lab tests? Is that kind of a symptom of potential insulin resistance?

[Robb Wolf]: Yeah. So here’s a good example of this.

My wife and I did this 7 Day Carb Test, and we’ve known empirically that I just don’t do as well with carbs.

I remain 100 percent gluten free because if I get a gluten dose, the first bathroom I hit will require a priest, an exorcism, and probably needs to be bricked over and never used again. So there’s no upside to consuming gluten such that I willingly do it. I get some cross-contamination stuff occasionally.

But I’ll have a little rice, or some corn, here and there. We’ll go to Mexican food or Thai food and I’ll kick my heels up once in a while. And I usually feel pretty rough. And I may feel rough for a day or two afterward.

Whereas my wife, I’ll ask her, “Hey are you feeling kind of carb headed from that?” And she says, “Yeah, it lasted for 20 minutes.” I wonder what’s going on with that.

And so we dug into that deeper, using this 7 Day Carb Test. And we ate the same amount of carbs – 50 grams of effective carbohydrate — and we picked the same foods. It was, white rice, white potatoes, sweet potatoes, applesauce, gluten-free bread, and a couple other items. And it was really interesting.

So with the white rice, at two hours post-meal my blood glucose was still in the 180s, damn near diabetic levels. Terrible. And I felt terrible. And Nicki at two hours was a 121, 122 or something like that. Just across the board, she had remarkably better blood glucose levels than I did.

So that was interesting, and it was kind of validative of what we had seen previously. So then kind of out of nowhere she said, “Hey, I’m going to do a dinner to dinner fast.” I was like, okay, that sounds good. We’ll check that out. And it was interesting.

So she did her dinner, and didn’t eat again the following morning. She worked out. We have a 10 month old Rhodesian ridgeback puppy that requires a ton of training, and she’s really diligent in training the dog, but it’s active. So she did her workout and then she’s running the dog around.

And we have two daughters under the age of five. So it’s a really active life that we both live, and particularly my wife being at home in that scene most of the time. By 23 hours she was getting hungry, but she was still totally cognitively on point. She felt good.

Right at that 24 hour mark we checked her blood glucose level, which was 71. That’s low, but a good low, particularly for a fasting scenario. And her ketones were at a 0.8. So she was already in a therapeutic ketosis range. And she was effectively just right at that 24 hour mark.

This is something that we just don’t see all that often in Westernized populations. This exact type of study hasn’t really been done specifically in hunter-gatherers and pre-Westernized societies, but what we see in those situations is these folks may go a day or two without eating.

They are hungry, they are definitely wanting to eat, but they don’t have a decrease in physical performance or cognitive function. You aren’t a very effective hunter-gatherer or horticulturalist if you are leaning against a tree drooling on yourself because you are in metabolic shutdown because you have to eat every two hours to keep yourself going.

So your question was — and I know that this is the longest answer to the shortest question in history. I seem to be good for that. But the question, was do we see specific lab values that tie into this?

What I’ve noticed is a tendency towards, if you are more insulin sensitive – and that will be determined by your total choleric load, your stress load, your sleep, your gut microbiome. There are lots of factors that go into that.

But if you tend to be more insulin sensitive, we tend to see more metabolic flexibility. If you have a higher carb meal, it doesn’t really knock you out and you don’t get super high blood glucose levels. You don’t have hypoglycemic crashes. And on the flip-side of that, if you need to go 6, 10, 12, 24 hours without eating, you may be hungry but you are still functional.

Whereas that insulin resistant individual, they do a piss poor job of dealing with large carbohydrate boluses. They get a super high blood glucose level, they get a rebound hypoglycemic response. And then when they have carbohydrates restricted significantly, the first couple of days – usually 72 hours – they’re in hell, because they have neither adequate glucose to fuel what’s going on and they’ve not yet kicked over to converting fats into ketone bodies in an effective way.

There are hormonally driven elements to this, and then there are also possibly mitochondrial considerations, where the mitochondria themselves may be damaged to a degree. It’s like taking a lawnmower that’s been out in the garage for two years, and it’s got some water in the carburetor and you just have to really rip the cord on that thing to get it to turn over and start using the fuel that you want it to use.

So let me know if I answered that. I know it was a long, rambly story.

(0:18:50) [Damien Blenkinsopp]: Yeah, I think you really did. Out of interest, because you noted that your blood sugar spiked to 180, how long have you been low carb for?

In a sense it seems like it’s not therapeutic, even if you’ve been low carb and Paleo for a long time, it doesn’t necessarily mean it’s going to mend these type of things, this dysregulation when you eat some rice.

[Robb Wolf]: Yeah, it’s interesting. Over the course of time, I’ve been able to push that carb tolerance up.

So now on my heavier Brazilian jiu-jitsu days I’ll be somewhere between 120-150 grams of carbs, and I do fine with that. But I also keep an eye on the types, and then I tend to put more of the carbs in the post-workout period, and similar to that. Whereas before 120 grams of carbs would have just crushed me.

So I’ve definitely recovered a lot, relative to where I was previously. And I’m still tinkering. I’m not sure if there’s still some gut health considerations. I’m actually just getting ready to start donating blood on a consistent fashion, because of some thoughts around some potential low-grade inflammation from iron overload.

So I’m going to play with that, and what I’ll do with that is I’ll probably go through three months of consistently donating blood, check the before and after numbers with regards to ferritin and iron saturation, hematocrit. And if we get to whatever delta we get from the start and the finish with that, then I’m going to revisit this 7 Day Carb Test and see if we get some improvements on that.

So that might be one final stone that I need to turn over and explore. I know Chris Masterjohn had talked about really reversing some significant insulin resistance. He had no idea what was going on, and he felt it was largely driven by that iron overload status.

(0:21:05) [Damien Blenkinsopp]: Wow, that’s interesting.

I have iron overload as well, and many other things like infections. So for me it’s a bit difficult to pinpoint what it is. But my carb tolerance has got a lot better with fasts.

So I’ve tracked with fasts, and I’ve seen that switching point you were just talking about, the 72 hours. It gets a lot easier and would happen a lot quicker as well. My ketones would go up faster, and glucose would go down quicker. And it’s been flatter over time. So it’s really, really interesting.

So you mentioned another panel just a bit earlier, a lipoprotein insulin resistance panel. What’s that?

[Robb Wolf]: So people are usually familiar with HDL cholesterol and LDL cholesterol. The cholesterol is a fat soluble, not water soluble, substance. So it would be like trying to mix oil and water together; it just doesn’t work that well.

But we need to move these substances around the body, so there are these things called lipoproteins, which actually are the vehicle that carries the cholesterol passenger around the body. And triglycerides are also, to some degree, carried around [by these], although they have their own carrier molecule as well. But these lipoproteins usually correlate pretty directly with the amount of cholesterol that we have, both HDL and LDL cholesterol, but not always.

There are certain folks that exhibit this phenomena called discordance, where you may have lots and lots of small dense lipoprotein particles and then a relatively low cholesterol level. And these are the folks that often, like a 35 year old triathlete and they work out all the time but they’re also a shift working firefighter or something and they suffer a heart attack at age 35 or 40.

And it’s like, wow, we never saw that coming. Their triglyceride to HDL ratio looks pretty good, which is a decent correlate or indicator of insulin sensitivity. And then their total cholesterol levels didn’t look that high, but under the hood looking deeper the lipoprotein numbers were super high.

And so there’s also a way that we can look at the lipoprotein numbers and their relative ratios. And there have been some really phenomenal correlation studies to tie this link together so that we can tie that lipoprotein insulin resistant score to the real world.

And there are some other methods for tracking that. There’s looking at fasting blood glucose, but there are limitations to that. There are ways that that can be misinterpreted both on the up and the downside. Fasting insulin is similar, it’s helpful but there are ways that can be circumvented. A1C [is another].

So we do like looking at several of these numbers, in the beginning in particular, and then checking back on them periodically, because it provides a lens. In particular a lens to help us better understand that 7 Day Carb Test. Because those carbohydrate numbers just in isolation can also be a little bit confusing.

But with that lipoprotein insulin resistant score, what we found in the police and fire populations that we work with – I’m on the Board of Directors of the Medical Clinic here in Reno, Nevada – we found that with the other methods for tracking insulin resistance we were missing people, particularly folks that were sleep-deprived and/or hyper-vigilante.

So they had consistent adrenal cortical response, some HPT axis dysregulation. Those people were insulin resistant, and often times significantly so, but we didn’t see it in fasting insulin levels. Specifically blood glucose levels may not have been that bad at that point, but we were seeing some really consistent long term insulin resistance when we looked at that LPIR score.

(0:24:28) [Damien Blenkinsopp]: So it sounds like it could be uncovering people that we normally miss.

How about the waist to hip ratio? That’s a nice easy thing that anyone can do at home. Did you also find the same thing, that it doesn’t necessarily capture people? Like you can be pretty thin and slim and have these same issues.

(0:24:53) [Robb Wolf]: Absolutely, and that’s where again we use it to build a case, but you can’t hang your hat 100 percent on anthropometric measures like that.

[Damien Blenkinsopp]: Great. Have you looked at how people can basically recover carb tolerance? Or have you seen that kind of period, the timeline?

Any indication of, say they did a 7 Day Carb Test now, when would it be useful to retest? Maybe 6 months after following a clear Paleo diet and all of your proscriptions. You talk about all of them.

[Robb Wolf]: That’s a really good question. Part of the inspiration for even doing the 7 Day Carb Test came out of research from the Weizmann Institute in Israel, and it was looking at personalized nutrition by tracking the individual glycemic response.

And what they did in these folks is they had them wear a CGM, a continuous blood glucose monitor – just a little disk that gets slapped on the back of your arm – and it measures your blood glucose levels once a minute, every minute for the duration of the test. I forget, but it was two or three weeks and they had 800 people signed up on the study.

So it was a massive amount of data; they had over a million blood glucose samples. They then did a gut microbiome sequencing on these folks, they did a full genetic analysis, and the standard kind of lipidology based blood work. And then they started feeding these people different meals. And the blood glucose responses were all over the map.

It was similar to myself and my wife, where one person would eat white rice and [their] blood glucose would go to the moon, [whereas] another person would eat white rice and they had a barely perceptible increase in their blood glucose response.

And then there were wacky things like hummus. Even though I’m the Paleo guy and legumes are theoretically problematic, hummus is protein and fat and fiber. There’s hardly any carbohydrate to it, but hummus was about a coin toss as to whether or not you had a good or a bad blood glucose response.

And the one thing that they did figure out with this was that if you determine the amounts and types of food that kept your blood glucose within lower bound levels, then your gut microbiome tended to improve and your inflammation and insulin sensitivity tended to improve over time.

So I don’t know that I have an exact timeline on this that I could relate, but what appears to happen is if you eat in a way where you’re not consistently deranging your blood glucose, which seems to have knock-on effects with the gut microbiome. There are some interesting theories around how acellular or processed carbohydrate can shift the way that our gut microbiome is existing. It’s a pretty interesting and elegant model.

But if you keep things within good bounds, then things tend to improve in kind of a virtuous cycle, and then conversely if you are consistently driving blood glucose out of what we would consider to be healthy bound, the gut microbiome tends to shift towards a more pro-inflammatory state. We see elevated inflammatory cytokines on circulation, we tend to see elevations in insulin resistance.

And in the book I make a recommendation that maybe quarterly. We don’t necessarily need to do a full reset as far as a 7 Day Carb Test, but I really recommend sitting down and just paying attention.

“Hey, how long can I go between meals and still feel good? If I do a little bit of fasting training, how do I feel with that? How’s my sleep? What’s my creakiness in my joints, what’s my subjective measures of inflammation?”

I am fairly geeked-out on the quantified self stuff, and I find a lot of it valuable, but I still like to get people back in their own skin so they can get a sense of where things are going right or potentially going wrong.

And a quarterly recheck, at least on the subjective level, seems to be frequent enough that if things are sliding sideways we haven’t slid so far that it’s terribly hard to get things back on a good track. But it’s also not so frequent that you just throw your hands up in disgust and you’re just done with the whole process and don’t pay attention to anything anymore.

(0:29:39) [Damien Blenkinsopp]: Yeah, absolutely. On my own journey I’ve quantified so much stuff, but at the end of the day it’s how you feel that matters. And you can even improve a whole bunch of biomarkers, but if you don’t feel better or feel less inflammation it’s not that helpful. It can be insightful and give you clues, but we’re still at quite a rudimentary level yet.

I actually interviewed Eran Segal in just the last episode of this podcast, actually. He inspired me to get into CGM, amongst some other people. So ever since I’ve been playing around that and have found it very instructive.

And not just for the food intake, but also sleep, which you talk about a lot in your book, and stress.

How important do you think those are in your experience, compared to the food? Because we always talk about the carbs and the food.

[Robb Wolf]: Even though I’m the food guy and we used to run a gym, so you would think that I would say that exercise is most important, or exercise and nutrition, but sleep is it. I mean, sleep is it. And here’s my argument for that.

You could eat the most wretched diet imaginable, and it’s going to be hard for you to kill yourself in anything short of a couple of decades. Some people can do it, but it takes a pretty Herculean effort to do yourself in with even the worst dietary practices you can imagine.

But sleep-deprivation is so injurious to our physiology that the Guinness Book of World Records, they will let you jump a rocket motorcycle across the Grand Canyon, they’ll let you juggle chainsaws that are lit on fire, but they will no longer entertain people trying to do unbroken longer periods of sleep-deprivation. The last two people that have tried it, they got right around that 9 to 11 day mark and they just died. And they don’t know why, but they are dead rather quickly.

So the sleep piece is just so incredibly important. The stress piece is important too, but there was a great book that I read and I interviewed the author, it’s called the Myth of Stress. It was really a fascinating reframing of this whole stress story. And so much of what we experience in day-to-day life that we perceive to be stress is completely generated between our own ears.

It’s anxiety about finances, it’s anxiety about how this meeting is going to go with our boss. It’s all these different things that really at the end of the day, we have an opportunity to either let this stuff eat us alive, or we can reframe it and just say that’s not actually a real threat, and so I don’t have anything to be worried about. So there’s actually comparatively little in the modern world that is in fact a legit stressor.

Now the caveat with that, we do a lot of work with police, military and fire, and those folks legitimately live in hyper-vigilant states a lot, because they have life-or-death scenarios that they’re dealing with every day all the time. So there are caveats to that.

But a shlep like me, where I live out on a small farm, we have some animals, I have two kids, I do the business stuff that I do, I can let myself get spun up and feel stressed out. Like, oh my god, one of the goats got bit by the neighbor’s dog.

This did happen this time last year, and the poor goat it’s eat got peeled off. But it was fine, we had a vet come out and gave it some antibiotics. We had to catch the little bugger and wrap it’s ear up for about a week, and then he was totally fine.

But when it first went down, I was like, why did we ever move out here, what are we doing, this is a waste of my time. And all this just internal dialogue and stress. Then I stopped and I was like, well I love living here. The kids love the animals.

There’s sometimes pain in the ass elements to this, but I’ve turned this from an acute event into what is now for me a long-term stressor, but I did it to myself. So I would throw out there that a lot of what we perceive to be stress is mainly self-generated.

And again, circling back to the sleep part, I just can’t think of a greater return on investment than trying to go to bed a little earlier, sleep a little longer, within the boundaries of what’s normal for you. Just blackout your room, have a really solid sleep hygiene process where you go to the bed at the same time each night.

It may not do wonders for your social life, but then again maybe it will because you may not be a cranky cantankerous prick because you’re actually well rested. So it’s hard to tell. And it’s liable to pull 5 years of aging off of you in just a matter of a week.

[Damien Blenkinsopp]: Yeah. Sleep is the hardest part.

Just curious, do you use anything to track your sleep? To try and keep a bit more responsible, or have you seen anything that works for people?

[Robb Wolf]: Really HRV is kind of the best thing that I’ve seen. Some of these actigraphy things are interesting. It is interesting, again, even though I’m a biochemist, I don’t know if I’ve weighed and measured so many things that I’m just like, oh my god I don’t want to do it anymore.

But I’ve just gotten into a point now, and it’s interesting. Folks like Tim Ferriss and some other folks I’ve interviewed with, they were like, “What’s your morning ritual?” And because I have kids, the morning ritual is super variable. I don’t know if somebody pooped their pants, and they’ve got poop from their earlobes to their toenails. That’s a way different morning than if that doesn’t happen.

But what I have found is I tend to have really good control over my go-to-bed ritual. So when the sun goes down – and this varies with the seasons, our days get longer so we stay up later – but when the sun goes down then, we installed dimmer switches in our house when we did our remodel last year and we drop the lights down to a super low level. We put on some blue blocker Swannie sunglasses.

Usually not too long after that I do a little bit of reading and I just fall asleep. And it’s like a ninja blow dart hits me. And when I’m consistent with that, and if I also happen to be tracking my HRV pretty consistently, I just see that HRV score improve. And then if I do have an off-night of sleep, we see some pretty immediate impact on that.

But the actigraphy, I haven’t found to be super helpful. If we had someone that was waking up in the middle of the night or something like that and we had some HRV score feedback. The thing about HRV is it tells you something is up, but it doesn’t tell you what that thing is.

It could be that we’re having a low blood sugar response in the middle of the night, so we get some cortisol release, and that suppresses melatonin production, so it pops us up out of sleep. So maybe we need more calories overall, maybe we need more carbs near dinner. Maybe we need fewer carbs near dinner, because some people are experiencing that rebound hypoglycemic event.

There’s not a one size fits all answer with it, but in general I just kind of gauge [when] I wake up in the morning, I stand up [and see] do I feel clear headed, do my joints ache because of jiu-jitsu and being 45, or do I feel good? And if all of that stuff feels good, then I’m pretty good to go. And particularly if that HRV score just stays nice and consistent.

(0:36:41) [Damien Blenkinsopp]: Yeah. I’ve been a fan of HRV also for a long time. I’ve been tracking it.

I also find it difficult, the same way you do. It captures everything, and if you’re someone who’s got some kind of chronic health or some issue like that on top of potentially not sleeping correctly, over-training. You’re doing Brazilian jiu-jitsu, so I’m sure that’s happened a few times.

And there are these different factors and you have to kind of piece the story together. But it can give you that overall number.

I’m just curious, what do you use, do you use a sort of an app or is there something specific you like because of convenience or something?

[Robb Wolf]: Yeah, I’m just kind of old school. Joel Jamieson hooked me up with the BioForce platform and I’ve pretty much just like hung out on that.

I know there are a lot of cool stuff out there and I do have a few others but I’m again, a little busy and kind of lazy with that stuff. I’ll check in on it occasionally, but it’s generally a deal where once I get a baseline established, and it’s a thing again that I know if I’m getting into bed, falling asleep, and waking up feeling good, everything else is fine.

And then on my training side I do a little strength and conditioning, a little bit of weight work, gymnastics, and also some low level cardio to support the Brazilian jiu-jitsu. I just keep my volume and intensity really modest on that. 80 percent of my rolling is more in a drilling and aerobic fashion, and about 20 percent is that white buffalo in the sky.

Like the 20 year old three stripe white belt is trying to take my head off my shoulders, and so it’s a battle for survival. But I don’t do too many of those. Maybe one day a week that there’s some pretty hard training that goes on.

And so long as I do that, everything is good. Everything is really, really good. I just try to make very small, incremental progress, in mainly the jiu-jitsu side, and so all of my strength work, all my conditioning work, all of that is of a remarkably low volume and intensity for the most part. Just to support jiu-jitsu.

If I feel the least bit knackered after a cardio session or something, I went too hard. Because I need to save that energy for rolling, and not for getting better at the Airdyne or something like that.

[Damien Blenkinsopp]: Yeah.

So when you’re talking about volume, how many hours are you doing of exercise, jiu-jitsu, and all kind of mixed together?

[Robb Wolf]: So jiu-jitsu is between three to five days a week, and usually an hour to two. Shorter classes if I’m time pressured, then I get the one hour class which is a mix of drilling and then a little bit of live rolling.

A couple days a week I usually will stay for a half hour to an hour of just continuous live rolling. I try to grab partners where we don’t set a timer and we just try to roll. We just try to keep moving, and it forces a pace that you could maintain for about an hour straight. And I really, really like that. You get lots of repetitions in in that regard.

And then as far as the weights and gymnastics stuff, I just drop in a little bit of gymnastics bodies, mobility and strength work during the course of my work day. Usually once a week I either squat or deadlift. Once a week I might do some heavier weighted press and pull weight room style stuff for the upper body.

But those weight room workouts, I warm up and I’m done in less than 20 minutes. Occasionally a little longer than that if I’m doing a lot of mobility work in between, but even then it’s not like I’m doing a CrossFit work out.

I have two minutes of rest between sets. I’ll do a set of weighted chins, a set of weighted dips, and then some weighted shoulder dislocates to work on my thoracic mobility in between those sets. So it’s not a frenetic pace.

And then the recovery cardio, I will go longer on that if I can. It may be 40 or 60 minutes occasionally, but a lot of those – my oldest daughter now is five years old and has gotten pretty good on her little dirt bike. So I will drive her and and myself over to a park right next to our house that has some dirt trails and she’ll ride her bike and I’ll run at a nice easy pace. So I’m outside and I’m spending time with my kids.

So there’s like somewhere between three and maybe eight hours a week of jiu-jitsu, there’s maybe two more hours total a week of weights and cardio. But I do try to do a ton of stuff. I’ll stick the younger kid in a backpack and go for a hike for as long as she will put up with it. We have a three acre farm where we have animals to deal with, and we just run around playing hide and seek, and stuff like that.

So I do a lot of physical activity running around with the kids, but in the gym stuff between jiu-jitsu and strength and conditioning and all that is less than 10 hours a week, for sure.

[Damien Blenkinsopp]: Yeah, so you keep the intensity monitored.

I just looked up the Myth of Stress. Was that Andrew Bernstein?

[Robb Wolf]: Yeah, Andrew Bernstein.

[Damien Blenkinsopp]: Okay. Bernstein. Cool. That sounds really, really interesting.

Does that tie in with the gratitude stuff? We hear a lot about gratitude and I’ve been practicing it for a little while. I think a lot of people have. Did he mention that at all?

[Robb Wolf]: Yeah. He would be a great interview. He’s a solid guy, a really, really good guy.

(00:41:35) [Damien Blenkinsopp]: Yeah. Excellent.

Okay. So I thought we’d also jump into a little bit of ketones, ketosis, and fasting, because I know you’ve played around with this yourself and your levels of carb. And it’s such a big topic at the moment.

You’ve spoken a bit about you can’t really do the really low carb and the Brazilian jiu-jitsu and that you can’t get away with it. What’s you overall feeling on the whole ketones and ketodiet?

[Robb Wolf]: Yeah, the last chapter of the book is called Hammers, Drills, and Ketosis: the one tool your doctor will never use. Fortunately, that story is changing. Therapeutic fasting and ketogenic diets are incredibly powerful as potential adjuvants or adjuncts to things like epileptic treatments, potentially working in synergy with conventional cancer therapeutics.

Just huge potential there, but it’s crazy because you don’t see people get into huge pissing matches about whether or not you should use a hammer, a screwdriver, or a handsaw to get something done. If you’ve got a 2×4 and you want to cut it cleanly into two pieces, a hammer and a screwdriver are terrible options, the handsaw is a great option. There’s just not a lot of drama around that.

But then whether or not you should be higher carb or lower carb becomes this religious doctrine thing. And there is a little more nuance to it, there is a little more depth. But just empirically we’ve seen people do pretty well at the power athlete end of the spectrum, the real short time indexing end of the spectrum, and quite low carb.

And we’ve also seen some people doing this ultra-endurance work at a pretty good level going very low carb. And interestingly that looks like catering to the ATP creatine phosphate pathway and also mainly the aerobic pathway.

Where we have a kind of deadzone, a no-man’s land, appears to be these really glycalitically demanding sports like soccer and MMA and CrossFit and jiu-jitsu. And there’s just, man you don’t see a lot of just empirical success there. You see people like me that try, and try, and try.

There are a few examples, there are a few people out there that are figuring out how to do it. Probably the highest level, most sophisticated person I’ve seen looking at this problem is Alessandro Ferretti. He’s in the UK. Man, that guy is smart.

And he is just doing some shockingly interesting work looking at [it]. And he does Judo and Karate, so not exactly the same as Brazilian jiu-jitsu but he’s found he runs great on a ketogenic diet, he has great energy, he can fast, and he’s lean. All the stuff is great, but then he will get kind of adrenalized and burned out in the process of doing too much high-intensity activity.

And what he’s done is just try to map out the volume and the intensity of the training he will be doing, and then match that with a maltodextrin solution or maybe a maltodextrin plus fructose, because there are some arguments for repleting some of the hepatic glycogen preferentially. And he does some really amazing work.

Now, for me, because I’m kind of lazy, it also looks a little bit like a calculus problem. Alessandro is like six times smarter than I am, and he runs a really well done clinical intervention, where they’re just collecting tons of data on people.

I’m kind of a knuckle-dragger. So where I’ve arrived out with all the stuff is I just tend to eat between 75 to 120 grams of carbs a day. Higher end on training days, lower end on non-training days.

But the overall story I think is ketosis and fasting hold enormous therapeutic potential. Potentially some great performance enhancement under certain circumstances, but it’s also a powerful tool. And like any other powerful tool it can be misused, or inappropriately used.

[Damien Blenkinsopp]: Yeah, Absolutely. I know Alessandro, I talk to him quite often too. He’s a great guy. I have to get him on this show soon.

[Robb Wolf]: Yeah.

(0:45:35) [Damien Blenkinsopp]: So thanks for all of this. Last thing on this carb thing is it doesn’t sound like you time your carbs at all before or after training, or anything like that. It sounds like you’re very much focused on the practical, which is probably 80 percent of society who aren’t super self-disciplined and robotic about this.

[Robb Wolf]: Yeah, I do time it a fair amount, in following a guy Bill Lagakos. He’s a professor of Biochemistry, I believe, in the East Coast, and really super sharp on circadian rhythms. And he kind of alerted me to this idea that time restricted feeding, the shortened feeding windows, seem to be quite beneficial for a variety of reasons.

But he made a really strong case for this idea that we would do better to eat more of the calories and more of the carbs earlier in the day. And I know there’s carb backloading. This becomes, again, if you want to get a contentious pissing match on the internet, just throw one of these concepts out there.

But Bill made a really interesting case that there’s an argument based off of circadian biology that we should eat more carbs, more calories earlier. And that is one thing that I’ve focused on.

So I will do, whereas before I might do an 18 hour fast, I’ll just do 14 and 16 hours now. And I will do a really robust meal, and then maybe 2 to 3 hours after that I have a Jiu-jitsu session. And then that meal ends up being much higher in carbohydrate. And I again kind of base it off the volume and intensity.

But then usually my dinner… I do two to three meals a day. Probably 80 percent of the days it’s three meals, 20 percent of the days it’s two meals, and that tends to be more the weekends when I’m just hanging out with family and I just want to be lazy and I don’t want to cook yet another meal for myself and all that.

I do partition closer to the pre-workout period but I’m not like taking a maltodextrine drink right before and one right after, and all that type of stuff. There might be some upside to that, but I have noticed for my digestion that the digestive process, for me, does much better with less frequent feedings, and less refined foods and all that type of stuff.

So I’ve had a pretty darn good degree of success with that so far. And I mean it is dead simple. I would be hard-pressed to think of a more simplistic way of eating and fueling. It is really, really simple.

But at 45 years old, I just got my purple belt last Saturday and I’m doing great on that. And body composition is good. My wife is still willing to sleep with me with the lights on most nights. So life’s pretty good in that regard.

[Damien Blenkinsopp]: Congrats, I saw that purple belt. It’s quite an achievement.

[Robb Wolf]: Thank you.

[Damien Blenkinsopp]: So is there anything we’ve missed that’s important about your most recent thinking on this subject?

[Robb Wolf]: No, I don’t think so. You did a great and thorough job asking this stuff.

Again, I would just encourage people to think about, if they feel off-put by this idea of Paleo diet type stuff, just give some thought to this. Is there any merit looking at biology and thinking about the evolutionary underpinnings, particularly when we see things go south?

If we don’t see health or other parameters that we would ideally like to have, if something significant is changed in that organism’s environment, do we have any insight from looking at what the environment preceding that event? So that’s kind of the totality of my greasy used-car salesman pitch on this stuff. Is there anything we can learn from that?

And it’s not just around food. It’s around sleep, and photoperiod, community, gut microbiome. All of these things really, when we see problems popping up, it’s this discordance model again. And modern medicine is shockingly well-suited for dealing with acute injuries and infections, and it has been an appalling failure with regards to chronic, degenerative disease.

And people may get their back up about that and say we work very hard. I don’t doubt that people do, but if you simply look at disease rates and incidence – Type II diabetes, Parkinson’s, Alzheimer’s – they’re increasing at exponential rates, yet we know more about the disease process than we’ve ever known in history.

Our iPhones, iPads and computers get cheaper and better every single year, and it’s because we properly apply the technology and knowledge that we have around that topic to improving the product and the outcome. We do not do that in health and medicine, and it’s because we do not start the story from this evolutionary biology perspective, and start having the conversation from there. Because if you do that, chasing symptoms no longer works, and filing people into these arbitrary buckets of disease or not-disease doesn’t really work anymore.

In the 1900s, the previous century, was the century of eradicating infectious disease, for the most part. This century is going to be about dealing with chronic, degenerative disease due to affluence. And it is not going to be solved by a pill or a potion. It’s not going to be solved by telling people to eat less and move more, everything in moderation. Because all of that completely ignores every element of our fundamental evolutionary biology.

[Damien Blenkinsopp]: Thanks, so much for that roundup.

To learn more about this, they can go and get your book. That’s available at Amazon. There were some bonuses or stuff. Is there anything like that still available?

[Robb Wolf]: The bonuses might pop back up again, but most of that was for saying thank you for people who were early adopters on it. But we’ll see. Maybe a couple of months down the road we might pop the bonuses back up.

(0:51:39) [Damien Blenkinsopp]: Okay, cool. Are there any other good books or presentations on this subject that you’d recommend?

[Robb Wolf]: Oh, man, if people are not following Chris Masterjohn, they’re really missing out. That guy is brilliant.

And he’s been doing a deep dive on kind of a series of different nutrients that you need to pay attention to. And he kicked the whole thing off, actually, with iron. Both the iron deficiency, anemia, stories and also the iron overload stories.

So he gets into the biochemistry and the pathophysiology of when things are right and wrong. And then he also starts off at whole food solutions and also makes supplement solutions, and man he is just doing brilliant work.

Who else is doing great work? The folks at Nourish Balance Thrive are doing phenomenal work. Marty Kendall over at Optimizing Nutrition. They’re just some brilliant people.

It’s funny a lot of them had an engineering background and either they got sick or spouse got sick, and then they got in and started looking at this stuff. And it’s interesting. They come in with no medical training biases, and after they start retro-engineering, literally, the disease process, they arrive at something that looks like kind of an appropriate carb, Paleoesque looking nutritional intervention with a focus on sleep and gut microbiome and all that.

I don’t know if that’s just confirmation bias, or really smart people applying their training to figuring out a process. But it certainly caters to my confirmation bias, so I tend to like that stuff.

(0:53:14) [Damien Blenkinsopp]: Cool.

What are the best ways for people to connect with you, and learn more about you and what you’re up to? Twitter or Facebook?

[Robb Wolf]: The blog and podcast live over at Robbwolf.com. The bulk of my social media time I spend on Instagram these days. My handle there is @dasrobbwolf, and I answer just about every single question that is shot across the bow there. So I do the best job I can to stay on top of that.

(0:53:45) [Damien Blenkinsopp]: Excellent.

Just a few more details maybe on our personal approach through using any tracking. I know we’ve already spoke about them, so just really to see if there’s anything else.

I was wondering if there’s anything you track yearly, or every six months, or anything like that that we haven’t already spoken about.

[Robb Wolf]: So, I do check-in on my lipoproteins, that LPIR score, or LDLP, LPPLA2. There’s kind of a suite of somewhat obscure lipoproteins which I keep an eye on about once a year.

And part of that is because at the end of my last book, I was pretty beat up from that. Then I went on a Discovery Channel reality show, called I, Caveman. And we had to live like Stone Age hunter-gatherers. We had stone tools, we lived at 8,500 feet in the Colorado Mountains while there was still snow on the ground.

We basically starved for 10 days until I killed an elk with a hand-thrown spear, and that was the first food we ate. But the long and short of that is I lost 18 pounds in 10 days, and was super beat up. And I ended up with some HPTA axis dysregulation. My thyroid was super low, I had adrenal issues, testosterone was kind of tanked out.

And so an interesting sideline with that was that my lipoprotein numbers were sky-high. My LDLP was 2,800 or something like that. Really, really high. And the clinic that I’m on the Board of Directors of here, we do tons of lipidology work. And the doctors were freaking out, you need a statin. And I said no I don’t, I’ve got other stuff going on.

So we did some poking around, and I actually went on some Nature Throid, which is kind of like armor but a T3/T4 thyroid deal. And I did kind of a classic adrenal restoration story, high dose Vitamin C, some licorice, some adaptin. And I quit traveling, and I started really paying attention to my sleep.

And within three months I was off the thyroid medication, testosterone had more than doubled, both free and total. And I felt remarkably better after that, shockingly. And my lipoprotein number, my LDLP, had gone from 2,800 to, I want to say, 1,100. And eventually it settled out at 800 or 900.

I do check back in on that every once in a while though, because that combination of super low testosterone and disordered thyroid. The low circulating T3 that really down-regulates your LDL receptors in the liver. So you just don’t clear LDL particles, so they accumulate in circulation. And once they start accumulating, then the potential for them to oxidize is much greater.

And then I also potentially have a little bit of iron overload going on. So I had a really kind of nasty situation brewing there. So I do check in on that, just to make sure everything is bumping along good. So I do a really thorough thyroid assessment, which is TSH, T3, T4, reverse T3, thyroid uptake, and then some of the just kind of background iodine status. And that gives me a pretty good benchmark about where that is.

And then I’ll check testosterone, estrogen, estrodiol, DHT, to kind of see where that part of the hormonal axis is. Because again, based off inflammation, fatty acid ratios and what not, you can start pushing more testosterone towards the DHT pathway, which can be problematic for the prostate under certain circumstances.

So I pay attention to those things, but it’s usually about once a year. But again, I’m a lazy cuss when it comes to that stuff. I know some people test it like once a month. I’m more of a once a year, maybe once every six months on some things. But more of a once a year deal.

(0:57:58) [Damien Blenkinsopp]: Thanks for that, very, very interesting. And the fact that you recovered, and you obviously see that as an actionable metric that you can keep up with.

I’m just wondering, which labs were there? If there’s any specific place, or are these just standard Quests, or something like that?

[Robb Wolf]: We tend to go through LabCore because LabCore ended up purchasing LipoScience, which is the [unclear 58:09] that developed the NMR technology around looking at lipoproteins. There’s other ways of looking at it, and they have pluses and minuses to them, but in my opinion that NMR spectra that looks at the LPIR score and lipoprotein count is head and shoulders above everything else out there.

The guy that largely developed it, William Cromwell, he was a physical chemist, a believe a PhD, which is basically a physicist who studies chemistry. And then he went to medical school, and he got into this NMR spectra jockeying type stuff, and developed this whole technology around looking at these lipoproteins. They have some really interesting correlation studies that they’re doing.

There’s a biomolecule called glycA, and by looking at glycA in relationship to some other lipoprotein fractions, they’re claiming that they can see things like Parkinson’s, Alzheimer’s, and insulin resistance decades ahead. And they’re still awaiting FDA approval on that. But it’s really interesting. So I tend to really put some pretty heavy weight on that lipidology side with regards to that LPIR score and that whole NMA spectra technology.

(0:58:28) [Damien Blenkinsopp]: Thanks very much, that’s very, very interesting stuff.

I think I know what you’re going to say here. If you were to recommend one experiment someone should try to improve their body health, performance, longevity, chronic health issues, whatever, with the biggest payoff, what would it be?

[Robb Wolf]: Sleep.

[Damien Blenkinsopp]: Okay.

[Robb Wolf]: Sleep. I mean, maybe a blood sugar deal I can make an argument for, but if we improve your sleep, there is nothing else that you could do that’s going to improve everything else more.

And the one caveat with that, if we have say a shift work population – police, military, firefighter, new parents, medical caregivers – who can’t control their sleep, then they really need to get a handle on the glycemic load of their diet and get it to a level that’s non-toxic for them.

But even then, the shift-workers, they need to pay even double attention to the sleep. When they do sleep, they need to sleep well. When there is sunlight, they need to get out into the sunlight at appropriate times. It becomes doubley important for them.

But the greatest return on investment anybody’s going to get on any of this health and wellness stuff is putting more emphasis on their sleep.

[Damien Blenkinsopp]: And should they just track hours slept, something simple like that?

[Robb Wolf]: Hours slept is good, but it’s more the ritualized process. When the sun goes down, then you dim the lights. And if you’re still on the computer, you flip on the f.lux, and you put on some Blue Blockers, and you set up a ritual.

To the degree that we set our lives up that we have to live and die by self-control, we’re mainly going to die. We’re going to fail. And so we have to set up a kind of a habituated process so it really takes the thinking out of it; it’s just what we do. So I would tend to focus more on that.

And then certainly if you want to keep an eye on approximate duration in bed, but that’s a whole other interesting feature too, is when you start paying an over the amount of attention to those things, then you start getting anxious about it. And I just see this damnable downward spiral in the quantified self space, where I just want to put a black bag over these people’s heads, drag them out into the woods and stick them in a tent.

And it’s like, there’s a creek full of fish. We’ve got them trapped behind a fish weir, you need to get them out by hand and gut them and cook them. Here’s the kit to make a fire. We don’t make it ridiculously hard, but you’re going to have to work to get your dinner, work to stay warm. And when the sun goes down you’re going to make a decision, do I want to sit up in the dark, feeding this fire on the limited firewood I have, or am I going to go crawl into my sleeping bag and go to bed.

They’re not quantifying a goddamn thing under those circumstances. And all of a sudden, all of the digestive issues disappear, and the sleep disturbances disappear, and they’re three body fat percentage point is lower after a week and it’s not because they’re hypocaloric, it’s just because they’re not inflamed and insulin resistant.

And so again, I try to get people to just live. I’ve really been harping on this thing of track what matters. And the longer that time goes along, I’m just finding fewer and fewer things that matter, relative to the experiential process. Be in your body, experience what is going on. Be in contact with what your emotions are, and develop a little bit of a zen and stoic process, where you can see these things occurring, and then you can choose to how you respond to it.

Whereas if we’re so tied to external devices for every little bit of feedback, then we’re essentially dependent on that. And I hate dependency of any variety.

[Damien Blenkinsopp]: Thanks so much for that, this is really, really interesting. It’s been a fantastic episode. And thanks for being so open, just giving all these details of your own experiences and your life. It’s a great, great show. Thank you.

[Robb Wolf]: My pleasure. It’s a huge honor being on. Thank you.

References:

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Is your glucose metabolism driven by your personal microbiome? Recent research reveals how the microbiome influences blood glucose, weight gain and weight loss. And how the new company, “Day Two”, is using microbiome sequencing data to provide personalized nutrition recommendations.

In this episode we discuss how personal your blood glucose response and regulation is. We look at how glucose metabolism can differ from one person to another, and how it differs based on typical measures, such as the hypoglycemic index. Most research studies try to understand what a diet or food does to an average person. But the question is whether you or any of us is an average person? Will your body respond to inputs in the same way as it will for an average person?

I found out that collecting personal data for myself is more useful than following the recommendations that come out of the studies that are looking at a statistical human person, rather than a real individual person. Data which is unique and personalized is usually most helpful to act on, especially when the derived conclusions differ from the mainstream nutrition studies proposals.

In the past, we have covered several aspects related to this episode. You may find it helpful to do some background listening on previous episodes before digging into this one. These include the blood glucose metabolism episodes, Episode 43 on Continuous Glucose Measurement and Episode 26 on Biomarkers of Aging – in which we discussed blood glucose as a biomarker of aging.

On microbiome testing and its use, we have had episodes that are relevant to this one. There is Episode 9 on Quantifying the Microbiome with uBiome and Episode 37 on Health Impacts of the Microbiome with Robert Knight, a well-known researcher.

“We study many different aspects of the microbiome as it relates to our health. This is another study where we studied another very basic phenomena, the yo-yo diet. What we showed there is actually that even after you complete a diet and lose weight, your microbiome doesn’t go back to what it was.
– Eran Segal

This is a two part episode with two guests. We have Eran Segal who heads up the Segal lab, which undertakes research in computational and systems biology focusing on nutrition, genetics, microbiome and gene regulation, and their effects on health and disease. This lab has released a series of studies over the last years on microbiomes and how they may be impacting blood-glucose regulation.

These studies have been heavily featured in the mainstream press because they put into question lots of our assumptions of how diets and food work, and how they impact blood glucose. Eran Segal earned his Ph.D. from Stanford in 2004, and in 2011 he was made a professor at the Weizmann Institute of Science, which is very well-known in Israel.

“What we do is give you a mobile application. So you get a personalized mobile app that you download, and it’s tailored just for you. It gives you a microbiome report, because we did it and we have it… We’re giving you your top food and meal recommendations. You have your top breakfast, your top lunch, your top dinner, your top fast food, because even when you eat fast food once in a while, you can still choose healthier fast food than others.”
– Lihi Segal

Our second guest is Lihi Segal – same last name but, no relation. She is the CEO and Co-Founder of DayTwo, which is the new microbiome lab-testing and personalized diet and recommendation service that has licensed, and is applying the research from the Segal lab, on the microbiome. Lihi has held a series of CFO and COO positions in start-ups over the years. Previously, she was COO and CFO of Sisense Limited, a provider of business intelligence and analytic software. She holds an MBA from Northwestern University.

itunes quantified body

What You’ll Learn

  • Studying the glucose response as a quantifiable effect food has on our bodies (05:43).
  • Post-meal glucose levels represent direct tracking of response to different foods (13:00).
  • Tracking glucose spikes and quantifying the body’s post-meal blood glucose regulation (14:17).
  • The accuracy and usefulness of continuous glucose monitoring – new devices and helping research (14:55).
  • Constructing multifactorial algorithms for personalized prediction of blood glucose response (18:53).
  • Using high-resolution microbiome sequencing to detect specific strains of microbiome bacteria (20:31).
  • Compared to BMI or blood tests, the microbiome is a more significant factor in predicting glucose metabolism in a personalized way (22:55).
  • Different microbiome features contribute to the overall prediction of response (22:56).
  • The propensity to gain weight and the effects of artificial sweeteners (26:11).
  • The microbiome’s acquired ‘memory’ regulates weight gain mechanisms (26:53).
  • Relapsing weight-gain is regulated by the microbiome, including by regulating genes involved in energy expenditure (26:53).
  • The microbiome remains stable over time, such that consistent long-term diet changes are required for profound health effects (30:20).
  • Unlike micronutrients, small fibers are digested solely by gut bacteria – but consumption of either has sustained effects on glucose metabolism (33:38).
  • Artificial sweeteners currently being examined by Segal Lab (34:52).
  • What DayTwo does as a company and personalized services to expect in near future (35:20).
  • Providing actionable information for glucose management (42:00).
  • The basic data inputs for using the DayTwo service and integrating lifestyle into personalized diet feedback (43:26).
  • Instead of being a diagnostic company, DayTwo offers recommendations under a predictive model (45:52).
  • Where DayTwo microbiome testing and output to users stands out – comparison with competition companies (46:38).
  • DayTwo collaborates with the Mayo Clinic to replicate the Israeli microbiome study on US population – calibrating the algorithm for American foods (50:59).
  • DayTwo’s success story in Israel, public recognition, service available for pre-order in the US (53:15).
  • Plans for bringing DayTwo to the UK and European markets after first tackling the US market (55:24).
  • DayTwo US release is not dependent on the Mayo Clinic trial, but more data means continuous predictive algorithm improvement (57:34).
  • Reasons why numerous lab testing companies operate in Arizona (58:53).
  • Pricing of DayTwo services and a lower US pre-order price (59:42).
  • DayTwo takes a direct to consumer approach – offering customizable nutrition advice delivery for different individuals (1:01:51).

Thank Eran Segal and Lihi Segal on Twitter for this interview.
Click Here to let them know you enjoyed the show!

Prof. Eran Segal, Segal Lab

Lihi Segal, DayTwo

  • DayTwo: A microbiome lab-testing company and personalized diet recommendation service. Lehi co-founded DayTwo where she currently serves a CEO function.
  • MyNetDiary: LabTwo’s database for the American market is on this network’s nutrition database featuring 400,000 different US-based foods.

Tools & Tactics

Diet & Nutrition

We discussed the studies that reveal several tactics with respect to weight loss and weight gain, as well as optimizing blood glucose metabolism towards health impacts. Important aspects from Prof. Eran’s team’s research include:

  • Predicting Diet Response: We discussed the health effects and potential benefits of various diet types. A key takeaway is that nutrition can be personalized based on predicting post-meal blood glucose responses.
  • The Microbiome & Artificial Sweeteners: Segal Lab has tested for the effects of non-caloric artificial sweeteners (NAS) – namely saccharin, sucralose and aspartame compounds. They determined that artificial sweeteners induce glucose intolerance by altering the gut microbiome. Xylitol and stevia are chemical formulations currently being examined by Segal Lab.
  • Post-Diet Weight Regain: Eran’s team have shown that persistent microbiome alterations modulate the rate of post-dieting weight re-gain. As a general rule, a low carbohydrate diet is most beneficial for weight loss because this diet prevents post-meal blood glucose spikes. Compared to a meal which spikes blood glucose levels, low response meals are associated with more fat burning and with losing weight over time.

Tracking

Lab Tests

  • DayTwo: This test offers analysis of your blood glucose metabolism as a response to particular food types or complex meals.
    • The most novel feature is microbiome sequencing with the greatest resolution offered on the market – known as ‘shotgun sequencing’. This method covers the entire genetic content found in a stool sample.
    • Current price in the US is $299 pre-order, but will later cost $399 as a standard price for the US market. This is cheaper compared to Israel, where the price is $500. In Israel, DayTwo incorporates continuous glucose monitoring for all users, thus requiring more for the glucose monitor everyone receives.
  • uBiome: A company which offers microbiome testing services, using 16S sequencing technology for microbiome analysis. We covered the applicability of uBiome’s service in Episode 9.
    • While it is cheaper than DayTwo sequencing, 16S sequencing does not allow looking below the genus level of bacteria. 16s sequencing looks only at one small region of RNA rather than the whole sample and for this reason does not provide the same resolution or ability to differentiate between different species for lack of information. 16S sequencing is the most popular today for cost reasons.
    • Differentiating between specific species of pathogenic vs. benign E. Coli is not possible with 16S sequencing, but is a standard with shotgun sequencing (DayTwo testing).

Devices & Apps

  • DayTwo Food & Activity Logger: A mobile application providing personalized day-to-day nutrition and diet recommendations.
    • The app offers analysis of your microbiome in report format, based on the required LabTwo testing.
    • Additionally, it features your top breakfast or lunch food components, allows searching through a food database, and makes recommendations on alterations – e.g. substituting rice for pasta whenever fit for your body’s blood glucose response.
    • Over time, the impact of using this app should be improved health by consuming food with the aim to optimize your blood glucose metabolism.
  • Freestyle LibreThis device is used for continuous glucose monitoring and the obtained data is used to determine trends in glucose metabolism. The FDA approved this product for the US market in 2016.
    • Contains a glucose sensor and a reader displaying the glucose data collected by the sensor.
    • Segal Lab is switching to this device partly because it offers greater user convenience by avoiding the finger pricking technique for obtaining analysis-blood.
    • Eran claims the device is at least as accurate as the company states, possibly even more accurate.
  • Fit Bit Charge: A device from the FitBit company was used in Segal Lab research to track and integrate lifestyle (sleep, meditation, exercise) into predictive algorithms for personalized nutrition recommendations.

Biomarkers

  • Post-Meal Glucose Response: Measuring blood glucose levels for the two hours following a meal.
    • The most important measured phenomena by Segal Lab and subsequently used by LabTwo for making nutrition predictions – are glucose spikes following a meal.
    • Glucose spikes are sudden rapid increases in blood glucose concentrations as a result from particular meal types, or more broadly a result of your diet.
    • Glucose spikes are associated with disease (e.g. diabetes and types of cancer). Thus, avoiding such responses is important for optimizing blood glucose metabolism.
    • Other times we have discussed post-meal glucose response is Episode 7 on optimizing ketogenic dieting and Episode 43 on continuous glucose monitoring.
  • Hemoglobin A1C: This is the most used marker for diagnosing diabetes. Its interpretative power is derived from the connection between glucose and hemoglobin – the protein in red blood cells (RBCs) which carries oxygen. Because RBCs live approximately 3 months, Hemoglobin A1C reflects the average blood glucose levels over this period.
    • The results are reported in percent (%). Higher levels of hemoglobin A1C indicate poorer control of blood glucose levels.
    • Prediabetic states range between 5.7 – 6.4% and diabetes is diagnosed above 6.5%. Optimum HbA1c levels are likely below 5%.
    • A caveat: Depending on your diet, your RBCs can have a shorter or longer lifetime. Since HbA1C measures glucose accumulation having RBCs with a longer lifetime than average leads to higher HbA1C readings despite average blood glucose being low. For example, Damien’s blood glucose is typically under 100mg/dL at any time point even after many meals due to his ketogenic diet. His HbA1C has ranged between 5.1% and 5.3% during this time however low carb diets are assumed to lead to longer RBC lifetimes. Higher carb diets are typically assumed to have average RBC lifetime.
    • Both guests share the opinion that collecting HbA1C and other blood marker data is not useful for making nutrition predictions once you have microbiome sequencing data. This is because sequencing provides sufficient data when combined with an algorithm to predict an individual’s glucose metabolism and provide personalized nutrition recommendations.

Other People, Books & Resources

Organizations

  • DNA Genotek: A Canadian company supplying microbiome collection kits for DayTwo analysis. After extensive testing, DayTwo concluded that DNA Genotek offers the best state of the art technology requiring no freezing or timing. The end result is the ability to preserve stool sample in the Day0 condition for greatest result objectivity.
  • Mayo Clinic: LabTwo cooperates with the Mayo Clinic aimed at repeating the trial in Israel at the Weizmann Institute on an American population. The aim is to obtain more data and to optimize the predictive algorithm for blood sugar response to the US population. While the trial will last for a while, LabTwo is currently able to make precise predictions for US users and the data from the trial will be used to work on similar targeted future goals.
  • FDA: The US Food and Drug Administration has placed a diabetic label on CGM technology. Thus experimenting using CGM devices with individuals is not allowed, unless diabetes diagnosis has been previously established in the test participants. LabTwo partnered with the Mayo Clinic and have successfully designed a trial including CGM devices which was approved by the Mayo Clinic institutional review board (IRB) – essentially an internal ethics committee.

People

  • Dr. Saleyha Ahsan: She traveled to Israel to take part in the study on personalized nutrition at the Weizmann Institute. Afterward, this was covered in an episode of the BBC Two Trust me I’m a Doctor show.

Other

Full Interview Transcript

Click Here to Read Transcript

(00:05:43) [Damien Blenkinsopp]: Welcome to both Eran and Lihi Segal onto the call. Thank you both very much for joining us.

So I just wanted to jump straight into your research on the glucose response, and all of the other stuff you’ve been doing in the last couple of years really because it’s all kind of related. Why did you focus on the blood glucose topic in particular?

[Eran Segal]: That’s a really good question. When we started a few years ago, we wanted to take a science-based approach to nutrition.

We thought very hard about that problem, and what we should examine. And if you think of the most common approaches in most studies in nutrition they usually consist of some dietary intervention, and then they look at weight loss, or they look at a change in some marker of a disease. And that’s great because ultimately these are the parameters that we’d like to have an effect on.

But, the challenge we found with this approach is that it then takes weeks or months for these parameters to change. You know, a parameter that measures your diabetes level, or weight. And at the end of this, you get a single measure. It takes weeks or months to change, and that measure is affected by multiple things that happen to you during those weeks or months. Both the diet intervention that you give, but also many other factors unrelated, which can be then confounding to what you’re measuring.

So, we thought that maybe one of the reasons that it’s very hard to do nutritional research, and why many researchers are failing, is because they’re looking at this single measure effected by many things. So we didn’t want to go that way. Even if we see an effect, you’re not sure you can attribute it to the diet, and if you don’t see an effect it’s very hard to troubleshoot what went wrong.

So we thought very hard about this, and that led us to look at glucose levels. More specifically, the glucose levels after a meal, what’s called the postprandial glucose response, or post-meal glucose response.

So by that, what I mean is what your blood glucose levels look like in the two hours after you eat a meal, which we can also quantify using the area under the glucose curve into a single measure representing the response that you had to that meal.

[Damien Blenkinsopp]: Right, so that’s like the total area under the curve is the total amount of glucose that was in your bloodstream during that area of time.

[Eran Segal]: Yeah, you can think of that as an approximation. I’ll tell you in a moment what we really are hoping that this is actually measuring, but that’s quantifiable into a single measure. But now we have to think about three aspects, or three features of this that really led us to conclude that this is what we want to follow.

So in a nutshell, what they are is that we were convinced by all the existing literature that this post-meal glucose response is really key to weight management. It’s really key to disease – diabetes, but not only diabetes, I’ll talk about those.

Finally, and not least importantly, that it’s very easy to measure and it’s something that, not within weeks or months but within a week, we can obtain not one, but even 50 quantitative measures of healthy nutrition in a single individual.

So first, why is it important for weight loss and weight management? This is very basic, and there’s been a lot of literature on this.

When we eat – and I’m talking about healthy people, even people who are glucose intolerant, but let’s say not insulin dependent Type I diabetics. When we eat, our body digests carbohydrates in the meal and releases them into the bloodstream.

After that, there is a response of the body by secretion of insulin, whose job is to lower the glucose levels. But in addition, what insulin signals, also, is it signals the cells to uptake the sugar that’s floating around in our blood.

And then excess sugar is converted into fat for storage because it initially is converted into storage of glycogen, but our stores of glycogen are highly limited. So very fast the remainder will be stored as fat. And this is actually known as one of the primary mechanisms by which we gain weight. In other words, this action of insulin.

So, in a sense, we would have liked to even measure directly at a continuous rate insulin, but that’s technically not possible. But in healthy people – and there’s been lots of research – by measuring glucose levels you’re actually looking at a proxy for a measurement of insulin.

And there’s been work showing, for example, that if you eat a meal that spikes your glucose levels compared to a meal that does not, then after a meal that does not you have more oxidation of fat, more burning of fat.

So the connection to weight loss is very well established. There’s also a lot of literature looking at very low-carb diets, which I think as a dietary regiment it’s incompatible with life for most people. But if you look at some of the studies when you eat a low-carb diet your glucose levels are low, and in general, those have the most beneficial effect on weight loss.

So that’s item number one why we focused on blood glucose levels because it’s very important for weight loss and management. The second is disease, and the most obvious is, of course, diabetes.

In fact, diabetes is diagnosed and defined by glucose levels. It’s defined in two or three different measures; either by the hemoglobin A1C, which measures your average glucose over a period of three months or by the glucose levels that you have two hours after you eat a meal. So something very similar to what we’re measuring.

And so, of course, you directly are playing with and improving the measures by which you diagnose diabetes. By that we can manage better the disease; manage it better in pre-diabetics, even possibly reverse it in this population. And, of course, for all the people with normal glycemic levels, we can prevent or delay the onset of diabetes.

So that’s one area where it’s important, but then separate from diabetes there’s been a lot of links to cardiovascular disease, to cancer. So in cancer, this is known as the Warburg effect. We know this for 90 years that cancer cells have a very different metabolism that much more heavily relies on glucose.

And so the thought is that by limiting the amount of glucose that you provide, you deferentially affect the growth of cancer cells compared to normal cells. And there’s been associations in the literature between blood glucose levels and cancer.

There are also been associations to overall mortality. There’s one paper that tracked over 2000 people for 30 years showing that if you responded more highly to a glucose challenge 30 years ago, you’ll live longer, basically. So there’s been links to many diseases, and so we’re very confident that it also has a strong association to disease.

And the final point is what I made before that because of the technologies with continuous glucose monitors we can now really in a single week measure 50 quantitative measures of healthy nutrition. And they’re quantitative of health nutrition because of the two points I made before.

[Damien Blenkinsopp]: So you felt that it was basically the continuous glucose monitor was a game changer because you’d be able to gather a lot more data quickly, and eliminate somebody’s potential variables coming in from the longer term studies which you can avoid.

[Eran Segal]: Absolutely. So if you think about it, we actually focused on examining the direct effect, one of the ways by which food directly affects you, and this is your glucose levels.

And from everything I mentioned before, we also believed that this is really a very critical clinical marker for weight loss and disease.

(00:13:30) [Damien Blenkinsopp]: Right. Okay, great. So you focused on the post glucose response to meals specifically, but you did mention Hemoglobin A1C. Is that something else you tracked and you found useful in these studies?

[Eran Segal]: So that’s something that we measured. We found it useful for predicting how different people respond to different foods, but it’s nothing something that you measure as a direct effect of a meal.

It’s one of those single parameters that takes many weeks to change that, again, would be very hard to develop a dietary regiment that would affect that directly because of all the confounders that I mentioned before.

So in fact, glucose levels is, as far as we know, the only reliable quantitative measure that is really super relevant that we could track, and that’s why we focused on it.

(00:14:17) [Damien Blenkinsopp]: Right. And you mentioned the area under the curve is the part that you’re interested in. So I’m guessing that you’re looking at a benchmark to what’s okay, and what goes too high in terms of that area.

You said to me when I tried to give an analogy to explain that to the audience that it wasn’t quite right. How would you explain the utility of that?

[Eran Segal]: We can just say that it’s basically looking at your glucose response and it’s quantifying how much you had spikes for glucose levels after the meal. And these spikes, as I mentioned before, is what is strongly linked to everything else.

(00:14:53) [Damien Blenkinsopp]: Right. Thank you very much. How did you find the continuous monitoring technology? Did you use a specific device, and how sensitive or accurate did you find it? There’s various monitors out.

We’ve spoken about these before, and I know people that have been using them for diabetes management and so on. So I’m just interested in your opinion on where that technology is right now, if research can be improved maybe later as it advances, or is it already as good as it’s going to get.

[Eran Segal]: So I think it was very good for our purposes. Not without problems, but I think even finger pricking is problematic, and can be variable. But, there’s also progress.

There’s a recent device by Abbot that we are now shifting to using because it’s more convenient, mainly. It’s probably as accurate, possibly even with higher accuracy – that’s what the company claims. But it’s just much more convenient, and it doesn’t require the finger pricking anymore.

But overall, they definitely capture the trends. I will say that when we measure responses to 50,000 meals you really have a very large data set, and you can afford to have some inaccuracies here and there, which all the technologies have. And still you correct for that in the algorithms.

(00:16:10) [Damien Blenkinsopp]: Great, thank you for that. Moving on a bit to what you discovered is actually driving these blood sugar regulation changes. What are the examples of the most unexpected things that you saw in the data?

[Eran Segal]: Are you talking about the factors that affect it, or even just before the surprising responses that people had?

[Damien Blenkinsopp]: I’m interested in both. If we start with what you saw that maybe you weren’t expecting, and then what you think drove that, or what you discovered drove that.

[Eran Segal]: So the first key result of the study was – and this was initially very surprising – we saw that when you give different people the exact same meal, they have very, very different responses. And this is in contrast if you eat the same meal on two different days, which is what we’ve tested on an unprecedented scale of 1000 people. This is 7000 different meals standardized that we provided.

When you eat the same meal on two different days your response is going to be very similar, but when you and I will eat the same food, our responses will be dramatically different. You can eat bread and have zero response, and I can eat bread and have a higher response than what I would have if I even ate pure sugar. So it was really all over the place.

And this was even before talking about our solution, this was very surprising. And we realized also that it has a lot of implications.

Because if we realize, again, the importance of blood glucose levels to our health and weight, then what it directly means is that general dietary recommendations are always, no matter what they are, going to have limited utility. Because for any single food that we tested, we had people who had a high response and others that had a low response.

So you can’t really make a general recommendation about food. Now there are trends. There are foods that lower glucose levels on average, for some people. And that is known; it’s what’s called the glycemic index.

I think you even touched upon that in your questions. And we also saw that in the data. So whatever foods have been reported with lower glycemic index on average they have lower responses also in our data. But if you look at all those numbers that go into making that average, they’re all over the place.

[Damien Blenkinsopp]: So there isn’t a cluster around the mean, it’s widespread.

[Eran Segal]: Exactly. It’s very spread across it. And when you measure enough people the means will be significantly different, but there is a wide spread across the means.

Meaning that we can take ice cream, for example, which on average induced relatively low glucose levels, and we can take rice, which on average, induced high glucose levels, but you will still find people that respond more highly to ice cream than to rice.

(00:18:49) [Damien Blenkinsopp]: So it’s quite surprising in those terms. So, in terms of what you’ve found or discovered that drove that. I know you tested for a lot of different things. What sort of things did you also test for in order to try and find the pattern of what was driving this?

[Eran Segal]: So we looked at many different things. We looked at body measures, anthropometries, height, weight, waist for instance and so on. We looked at several metabolic parameters in blood. We looked at questionnaires.

So we had a medical background in food frequency and lifestyle questionnaires. And the most novel component that we integrated into the study is the microbiome. So we measured all of those. In fact I will say that we found an association, a strong correlation, between variability and the response to food in all of these different groups of parameters that we measure.

And then the next step was to take all of these parameters and integrate them into rules, or an algorithm, that basically given your inputs to all of these factors, which vary from person to person, we would be able to predict how you would respond to each and every single food or food combination or complex meals.

And we showed that that actually works very well, and predicts personalized responses with very high accuracy. In fact, the accuracy that we think is even feasible because, even when you eat the same meal on different days, I mentioned your response is going to be very similar, but it’s not going to be identical.

So there is some inherent biological variability, and our predictive power is approaching that variability.

(00:20:30) [Damien Blenkinsopp]: Okay, great. The microbiome was the novel part of this. What exactly did you look at? Because there’s a few different approaches to looking at the microbiome right now.

What were you looking at and trying to map with it?

[Eran Segal]: So we looked at the most comprehensive in terms of resolution, which is just doing shotgun sequencing. So that’s basically sequencing the entire content of what we find in a stool sample. That mostly consists of bacteria, but this type of sequencing is really the highest resolution.

It allows us to identify individual genes in the bacterial composition, of which there are several millions in each and every one of us. It allows us to identify not just species, but also specific strains of bacteria.

And so there are many of these different factors that we integrated together, and used them in the algorithm.

[Damien Blenkinsopp]: Great. Is that cost prohibitive verses some of the other technologies that are used out there?

So you have the 16S, which is just looking at one part which some of the projects like uBiome are using right now to enable them to serve many consumers and make it a lower cost so people can afford it right now. Are the costs much higher for what you were doing?

[Eran Segal]: So first of all, for 16S, I will say that we didn’t want to go in that direction because science-wise I don’t think we would have gotten as predictive power.

And in fact we even showed that to ourselves in the study because it doesn’t have the resolution, and in many cases it doesn’t allow you to go below even the genus level of bacteria. So you can have the pathogenic E. coli or non-pathogenic E. coli will have identical 16S; you won’t know what’s in there. Just to give an example.

So we went for the shotgun sequencing. It is indeed much more expensive. If you talk to researchers they’ll tell you that it’s way more expensive.

I will say that what we have been working on in our labs for many years prior to this study, and then as part of the study, is to optimize this process very extensively using automation and using robotics.

We’ve substantially reduced the cost; it is still significantly more expensive than 16S. But I think our margins of error are much smaller than other researchers, and this is probably also why we were able to profile at that level.

(00:22:53) [Damien Blenkinsopp]: Okay, great. So, in terms of the microbiome – because we’re talking a lot about the microbiome and the other factors – is there a stronger weighting of the variability? Are there variants associated more with the microbiome, or are there some other factors that are really important?

The other thing that is interesting is the microbiome actually does change, and we’re trying to change it and improve it and so on in many clinical situations now. Whereas your height, age aren’t changeable.

So if you could give me a bit of background on what you found is the biggest weighting there, and maybe which is most actionable?

[Eran Segal]: Those are two very good questions.

Related to what is most important, every component that I mentioned before we can show has significant predictive power. Now of course, in terms of predictive power, some of these components are somewhat redundant with each other.

So for example we found that when you add the microbiome and some other components, then we can do without all of the blood tests, and in fact we don’t need them at all for the predictive power. They add really something negligible.

Of course we think that blood parameters are predictive; it’s just that in the context of many other parameters, they’re somewhat redundant because they can be explained and correlated with several other parameters. And so likewise with the microbiome we found that actually unlike blood, in every context that we apply the algorithm, the microbiome always had a significant contribution to the prediction.

I will say though, that of course the microbiome has the most significant contribution when you add it by itself. As soon as you add more and more parameters, this is expected. It’s marginal contribution. And also, I believe this is an area where with additional research we can dramatically improve in the future.

We already have started this process because we have a lot more information and a lot of smarter ways by which we can handle this data, which is not true for BMI, weight, blood parameters, which are very limited in the amount of information they have.

[Damien Blenkinsopp]: Right, because there is basically truckloads of data we’re going to be taking out of our microbiomes, because there’s so much in there.

[Eran Segal]: And when we and others continue to research and identify key genes in the microbiomes that are helping in the breakdown of certain products, production of different metabolites that affect us, and we know better how to zoom in on different features, we’ll be able to improve the predictive power from it.

(00:25:25) [Damien Blenkinsopp]: Great. So in terms of the level, you mentioned that the technology that you’re using goes right down to the strain level, and the species, and genus, and so on. But where do you see the patterns?

Is it on the genus level, the species level? Is it just one species that can completely change how we respond? Or is it at a very high level like bacteroides, or something like that?

[Eran Segal]: So there are significant associations on all levels.

And I can say that it’s not a single species that is really dominating. We actually have this in our paper; we have many different features from the microbiome each make a contribution to the overall prediction, but together there’s dozens of these features. Together they make a significant contribution.

[Damien Blenkinsopp]: Right. It’s really a multifactorial analysis.

[Eran Segal]: Yeah.

(00:26:10) [Damien Blenkinsopp]: Okay. You did a paper before 2014 on the artificial sweeteners, which also got a lot of coverage. That was interesting also.

And in that one I believe it was the high bacteroides and the lower clostridiales which showed that you had a higher propensity to gain weight, wasn’t it? Rather than just blood glucose regulation.

[Eran Segal]: Yeah. So yes, we did see an overall effect there. But also there we developed an algorithm that could predict susceptibility, in that case, to consumption of artificial sweeteners. And that was also multifactorial basically using dimensionality reduction of essentially all the species that we had in the sample.

(00:26:53) [Damien Blenkinsopp]: So the most recent paper you are looking at is also looking at regaining weight after dieting.

For example, if you go on a diet and there’s this typical yo-yo effect where someone goes on a diet and they just regain it all back. I’m wondering is that related to the microbiome or what’s going on? So if you could relate what you’ve been looking at there and what you found?

[Eran Segal]: Yeah.

So we study many different aspects of the microbiome as it relates to our health. And this is another study where we studied another very basic phenomena, the yo-yo diet that you mentioned. And what we showed there is actually that even after you complete a diet and you lose weight, your microbiome doesn’t go back to what it was.

So it’s very well known that as you gain weight your microbiome changes, and what we showed is after you lose weight your microbiome doesn’t revert back to the original state. And that memory, if you will, of the microbiome is in fact sufficient to induce and enhance weight gain once you stop the diet.

So I would say it’s another work further establishing the causal link, and providing more insights into mechanisms by which the microbiome plays a key role in our health, and specifically with respect to metabolic states and diseases; in this case relapsing obesity.

[Damien Blenkinsopp]: In that study did you find any mechanisms? Is it specific species? I think you were talking about metabolites in there as well.

[Eran Segal]: Yes. So this work was in fact work in animal models; this was work in mice. And the advantage of is that we can really go deeper into mechanisms, unlike in humans where it’s much harder.

And so there, we also did a metabolomic profiling, and we identified metabolites that were missing after you lose the weight. And when we administered these molecules back, we in fact were able to cure the mice of the phenomena of relapsing obesity.

[Damien Blenkinsopp]: Wow.

[Eran Segal]: And more important we actually showed that these metabolites in fact regulate genes in the host, in the mouse, and they regulate genes that affect energy expenditure. So these mice, when they have less of these metabolites which are broken down by bacteria, when the bacteria break them down, these mice are going to have less energy expenditure and therefore more weight gain.

[Damien Blenkinsopp]: Wow. So I guess you don’t understand why that energy expenditure is going on. There’s probably quite a complex downstream process that follows.

[Eran Segal]: Right. That’s quite complex, but we also had some insights in the paper as to that as well, and we found some genes that regulate that process in brown fat tissue that are directly affected by these molecules. And these molecules are made less available because the bacteria in mice that had a previous history of obesity, in fact, were breaking down and taking away these molecules more.

[Damien Blenkinsopp]: Wow, so it’s actually the introduction of new bacteria for the weight gainers, which is taking away these substrates.

[Eran Segal]: So in this case, it was metabolites. So there are specific metabolites that are broken down by bacteria, which we showed here, we call that post-biotics as opposed to pre-biotics.

[Damien Blenkinsopp]: Right, by adding the bacteria that’s missing or making taking away the ones that are causing the problem.

(00:30:17) [Eran Segal]: Yeah. Those can be technically more challenging in some cases, but in general yes.

I also want to relate to, you asked me before about the stability, or how much the microbiome changes. And we have several studies on that; in fact, some are not even published. What we find is in fact the microbiome is actually much more stable, perhaps, than most people think.

So in fact your microbiome, unless there is very dramatic change in health or weight, is probably going to be very stable even across many years. We have data on that. And what I mean by stable, it means you will still look more similar to yourself even after following some dietary interventions, at least in the short term, than you will to other people.

Now, having said that, we also found that short term dietary interventions in fact do change the microbiome, also in consistent ways, across different people. So while you’ll still remain in the neighborhood of what your microbiome is, still some functions will go up, some will go down. Those can be consistent across multiple people who consume the same type of dietary intervention.

[Damien Blenkinsopp]: Right.

Just as a takeaway from that, do you think the microbiome is going to be an important area of work? Basically learning how to modify it, push it in another direction in order to solve things like weight gain, blood glucose regulation. Is that your hope?

[Eran Segal]: Absolutely.

So the more we find causal effects for the microbiome on our health and weight the more this should be a target for intervention. But of course that will require further studies to understand what is casual and also how to change it.

And I do believe that with – and this has also been shown – that with long-term changes in diet, you will in fact achieve changes in the microbiome. But with short term dietary intervention the changes will be consistent, but they will be more subtle and you’ll still remain in your own neighborhood.

And what that means in terms of the research that we did, it means the algorithm is going to give you essentially the same predictions, even in a very stable fashion, across even some small, short term dietary interventions because your microbiome is essentially going to be very much the same.

[Damien Blenkinsopp]: Right. So if I test one month, and then I test six months later after doing a series of interventions – maybe not too intense, something like courses of antibiotics, things like that might be more intense.

[Eran Segal]: Antibiotics is probably a different story. That can have a dramatic effect.

I’m talking about even if you change your diet for a few months, your microbiome is not going to change a lot. If you maintain a very different diet after a prolonged period of time – I can’t give you exact numbers, but a long time – then you will see change.

And at some point, those changes may be large enough you may want to test yourself to make some modifications to the diet. But, for a very long period of time, without dramatic interventions it should stay pretty much the same.

[Damien Blenkinsopp]: It might be interesting if you do a course of antibiotics, because people have to from time to time, to redo the test and see what it predicts afterwords. Maybe some of the food responses are going to be different.

[Eran Segal]: Absolutely. And I think after antibiotics you will have very significant changes, and those could affect the prediction.

(00:33:37) [Damien Blenkinsopp]: Yeah. So the last thing, just going back to the artificial sweeteners we spoke about. Because they did see that those had an impact on the microbiome over time.

Do you think smaller things like that, basically micronutrients or small fibers, not necessarily macronutrient profiles, but those kind of things could have longer term impacts on the diet?

[Eran Segal]: Absolutely. I would say some of them could even have bigger effects than macronutrients. So fiber, for example, is something that is digested solely by our gut bacteria, so definitely could, and this is known, have alternations and will overtime have sustained effects. So yeah, absolutely.

I think the way we think about it now, and even drugs. We and others have shown that the drugs that you take actually also affect your microbiome. Any substance that you intake, although depending on the substance, might just go through your gastrointestinal track, meet the trillions of bacteria that are there.

They have 100 times more genes than we do. They could definitely break down these products, they could convert it into other products. I would think of it right now, anything that you intake could definitely affect your microbiome.

(00:34:50) [Damien Blenkinsopp]: Yeah. Alright. Thank you very much for that. Just a last few things.

A lot of people take xylitol and stevia. It wasn’t in your original study, and I was just wondering if you knew anything about that. Because the other ones, aspartame, saccharine, and there was another.

[Eran Segal]: Sucralose.

[Damien Blenkinsopp]: Sucralose. Yeah. It was a bit of a negative view on them in terms of what they were doing to the microbiome. Have you got any information or did you see anything on the other two?

[Eran Segal]: We are studying those now.

[Damien Blenkinsopp]: Great.

Eran thank you so much for your time. It was really useful.

[Eran Segal]: Okay, great.

(00:35:19) [Damien Blenkinsopp]: Excellent. Okay, Lihi, let’s talk about DayTwo and what you’re doing there.

So basically you’re taking the work done by Eran and his co-researchers and you’ve been turning that into this algorithm service to help optimize people’s diets. Could you give me a bit of an overview, how you look at it? What the company’s doing and how you see it going forward over the next year or so?

[Lihi Segal]: Yeah, so we licensed the technology in an exclusive way about a year ago, in the summer of 2015.

And then what we’ve been doing since then with the help of both scientists, because our founders are scientists and they’re on the management team and very deeply involved in the company. And so there’s a lot of hand-holding in that sense on the scientific level as well.

But what we’ve been doing, we built a team up of machine learning experts in DayTwo and also developers, and we really dove into the algorithm.

As you heard, on the research level the first thing they took 30 metrics in the blood, they did the microbiome, both 16S and the full shotgun. What we really tried to do is once we have all the results is really look into the algorithm and see what is that minimum set of features that we need, and write it to consumer. We don’t want to send them to get anything that is redundant.

So looking into that features into the algorithm, and looking to see what we really need, how to commercialize this. So we went through a kind of learning period when we’re looking to see how we define the product, what do we need. Do we need to freeze your stool? Do we need to send you to a doctor to get blood tests, yes or no?

And where we ended up is by looking at a really minimum set; because as you heard Professor Segal say, the microbiome was very significant in any constellation that they took, and made other things redundant. So really where we ended up with on the product side is that it’s all online, almost.

So you come online and you fill in a lot of questions – not a lot, I think a 10 minute questionnaire. But, of course it has to do with your anthropometrics and your food preferences and your medical history. Any information you just fill in your questionnaire. And then we mail home a kit; just a box. In that box there is a small tube and you take a stool sample at home.

So we use DNA Genotek as our supplier of the kit. If you know them, they’re out of Canada. This is really kind of state of the art microbiome collection kit. You don’t have to freeze it, you literally just take it when you can, when it fits you. You don’t have to time it. It’s there, you take it, and then you just mail it back to us by regular mail.

[Damien Blenkinsopp]: Is it a quick swab, or are you actually taking a sample?

[Lihi Segal]: We tested a bunch of other alternatives as well, but this company really gave us the most stabilized microbiome in extreme temperatures.

It’s really important for us to stabilize it and then send it through the mail. And you don’t have to freeze it and all that. So it made it much easier on the consumer side, and it’s also very important scientifically to get the microbiome at the state it was as it was collected in Day Zero.

So we did a lot of trial specifically on that to see that what the company claims is actually right. And so we send you this kit, you mail it back to us, and then we sequence it.

We chose to sequence, as Eran said, on a full shotgun basis because we found that that resolution rate gets us the prediction into a higher level and a very good level. So we decided to do that despite the higher costs that it has.

But again, we try to put a product on the market that is very good; it’s good scientifically, we don’t really cut the corners there. So although the cost is still higher, we do expect it to go down a scale, both on the full shotgun basis and the kits.

And then what we do is give you a mobile application. So you get a personalized mobile app that you download, and it’s tailored just for you. And it gives you three things initially.

It gives you a microbiome report, because we did it and we have it. Not all our users are going to love it, but a lot of them may be curious to open it up and see. And so there’s a lot of information there.

We’re giving you your top food and meal recommendations. So what that means is that we really look into different categories. You have your top breakfast, your top lunch, your top dinner, your top fast food, because even when you eat fast food once in a while you can still choose healthier fast food than others.

We’re really trying to bring this into your day-to-day and make little changes and not turn your world upside down. And then there’s whatever alternatives with pasta, alternatives with rice. That’s really general.

And we’re really giving you your top A+ meals and scores all the way to your worst list, which has up to C-. So we’re trying to educate you through that stage. You could always go to see what your top breakfast is, what your top lunch, and all that, but then you also have the ability to search.

If we didn’t say something that you eat and you want to know what your score is, you just search for it in our database. In the US we are based on a database of MyNetDiary. So we have 400,000 different foods that are US based foods.

In Israel we are have a different database that has Israeli foods in it. So people can really find what they eat in there.

[Damien Blenkinsopp]: Right, so these are actually branded products you can buy. Is that what you’re saying?

[Lihi Segal]: Yeah, there are a lot of branded there as well, but there’s also, for example, an apple without skin.

[Damien Blenkinsopp]: Okay.

[Lihi Segal]: You also get your just general food as well, but you would find your specific brand of whatever, yogurt, that you’re eating in the specific territory. And then, so that’s the second thing. The third thing is the search and also a build your own meal kind of possibility.

So the whole point here is that we’re not scoring nutrients. We’re not saying carbs or proteins, and we’re not even going into a family of pasta versus rice. It’s very different if you eat a pasta with cream sauce or a pasta with meatballs, or you eat a pasta with macaroni and cheese.

You have to be able to score complex meals, and that is where our kind of secret sauce is, we’re really looking at your personalized response to these complex meals. And so you can just search for those meals if you want. If you’re cooking or if you’re sitting in a restaurant and you’re able to get your scores on the foods that you’re eating.

(00:42:00)[Damien Blenkinsopp]: Yeah. So just to clarify, this is just focusing on glucose management? So lowering…

[Lihi Segal]: Right. So what we aim to do is balance your blood sugar levels. So when you go on and you eat your A+ or A- foods and you eat that on a consistent basis, and you keep portion control.

So it’s not a kind of blank check to eat as much ice cream or drink as much beer as you want, unfortunately. But it does allow you some flexibility with foods that are surprising. Things you thought were unhealthy, all the sudden you understand you can eat them. And vice versa, so it’s surprising in both ways.

And then if you eat that consistently then yes, you’re going to see that we’re helping you balance your blood sugar levels.

And as Eran mentioned, balancing your blood sugar levels has an importance both in minimizing the risk for diseases of all kinds. Even as a healthy person, you don’t have diabetes but it is really important to keep your stable blood sugar levels. And also the whole thing about weight loss.

It helps you, it encourages weight loss in that sense. So you need to have a restrictive diet; you can’t eat whatever you want and think that you’re going to lose weight with this. But it does help you lose weight, it helps control your hunger, it helps control your cravings. And so it really helps you to plan and choose your foods right. That’s what we’re aiming to do.

(00:43:25) [Damien Blenkinsopp]: Okay, great. So, just to be clear. In terms of the inputs, it’s mostly filling in a questionnaire. Is there any other test apart from the microbiome sample? Or is that just the only one that they need to do?

[Lihi Segal]: No, the basic thing is that we need the microbiome and we need your questionnaire.

Now if you do have addition information, if you have your HBA1C levels then we’ll be happy to take them in. If you have more blood tests it’s always good to take in. But it’s not as significant enough so we’ll say you have to do it.

[Damien Blenkinsopp]: Yeah.

[Lihi Segal]: But on a general level, as much information as you’re willing to give us, it will always help, yes.

[Damien Blenkinsopp]: So in your algorithm, it will just take that into account as well?

[Lihi Segal]: Yes.

[Damien Blenkinsopp]: It’s just that in terms of the cost, you don’t want to add to the cost or be inconvenient.

[Lihi Segal]: Again, as Eran mentioned, it becomes redundant at some point.

And so if you have it, great, but we don’t want to get people – the cost is not that much for an HBA1C, it costs like 20 dollars in the US today. So that’s not really the issue.

It’s more just this is the basic package; you send it home, you send it back. But as we’re looking at our future products and as we interact with you throughout your day, the app is going to allow you in future versions to report to us what you ate.

And we have a lot of insight on your sleep and on your exercise. That was not published, but we have it in the data, and they haven’t published that data. He didn’t mention it, but in the research they actually had people logging in their foods, but also their sleep and also their meditations and their exercise. They had a Fitbit on everyone.

So there’s a lot of insight that we’re going to be able to give you. And when to eat your biggest meal, because people have a certain rhythm and that’s personalized as well. So when would be preferred to have a large meal of the day. In the US usually it’s dinner. In Israel sometimes it’s lunch, sometimes it’s dinner.

Certain foods that you should eat at certain times of day. So we can really interact with you over time if we have more information on how you slept last night and how much fiber you had in the past 24 hours. There’s a lot of things that go into the algorithm that, if we don’t have them, fine, but if we do it can even help us give you better results.

[Damien Blenkinsopp]: So you’re integrating these lifestyle factors as well into the computations to tell people when to eat. That’s great.

[Lihi Segal]: Your stress levels, all that.

(00:45:52) [Damien Blenkinsopp]: So I was wondering, are you able to tell the status of someone?

Say I’m glucose intolerant to an extent already, when you get the data from people without getting the HBA1C, for example, are you going to be able to know this person’s going to have to be more careful? Is any of that kind of information coming out?

[Lihi Segal]: We’re not at any point a diagnostic company, so whatever we see we will not tell you.

[Damien Blenkinsopp]: Oh, okay.

[Lihi Segal]: We don’t do health assessments on you. We’re giving you your recommendations under a predictive model.

And for example if we find things that we think you should know, then we would probably say maybe you should see your doctor, or take these results to your doctor or something like that. We would never go into actually giving you any medical advice.

(00:46:35) [Damien Blenkinsopp]: Right. The same usual thing. There’s a lot of blood glucose dis-regulation that goes on way before you get to diabetes, as Eran was saying.

So I’m just sort of interested from an algorithm perspective. I know you’re not going to publish it because there’s a medical borderline there that you don’t want to go near, but I was just interested from an algorithm perspective – can it tell how far you are along that line? Because everyone’s got a little intolerance. I’m just curious, does it offer any information?

[Lihi Segal]: I can’t.

[Damien Blenkinsopp]: Okay, fine.

[Lihi Segal]: I can’t answer that question.

But as Eran mentioned, we’re looking into on the road map for DayTwo that’s not just for the people who want to buy it right now but we are looking into various things we can do with the data that we have, the data we collect, and the things that we learn. And of course diagnostics and therapeutics are a part of that whole agenda.

And so there’s insight that we’re looking into and collecting, and can very well come out with additional products that are related.

[Damien Blenkinsopp]: So as a first stage it’s basically a food recommendation engine as the output, and of course your microbiome data.

Do you have an idea of what type of microbiome data is going to be given? I know we talked about uBiome, for instance, in the past. We had Rob Knight from some of the other tests.

We’ve looked at a few different ones in the past. Have you got an idea yet, or are there pictures or anything of what it’s going to look like in terms of the data you provide for the microbiome?

[Lihi Segal]: I can definitely go back and send you some information about how it’s going to look, more or less.

[Damien Blenkinsopp]: Alright, cool.

[Lihi Segal]: But we’re trying to go into a lot of detail. Again, we’re doing full shotgun so we have additional insight. We’re not at just a very high level; we are looking into specific types of bacteria and trying to link them. We’re looking at studies and just general information about them.

Again, we have to be a little bit careful and not tell you anything that you may be alarmed with, or if you think that you have this and you’re going to be Type II or anything like that. So of course we’re being careful in the way that we present it. But there’s a lot of interesting information.

We’re also looking to do this in a very cool way that’s going to be, at least on the web – on the mobile it’s going to be a little flatter – when you sign into your web, there’s a report that’s going to be very interactive. You can dive in and go all the way down to the strain level, and then come up. So it’s going to be really cool in that sense.

[Damien Blenkinsopp]: So is there going to be, basically are you going to give all of that data?

My audience tends to be on the high quantitative side, so some of them tend to be people who download the data and start playing around with it in Excel. So will you have that kind of data?

With uBiome, for example, they have two aspects of that. They have the raw data they provide for you to download, and then you can put it into software to actually interpret yourself, like biometrician software.

And then they give you graphs which are basically summarized. So there’s not all of that information there, it’s a bit different, and it’s according to their perspective. So in comparison, what will you provide?

[Lihi Segal]: No, I don’t know to tell you that we’re going to give you all of the raw data. We probably could, but we haven’t finalized that down to the core of it. But again, we have it.

We’re going to have, as I said, the report and the very interactive tool so you can explore it. And the infographics is really cool. People are just playing here with it when they’re too tired to code. So they go and start planning that. But we could also provide the raw data, for sure.

Again, I think our users as opposed to uBiome users, uBiome users are mainly people who purchased it because they were curious about the microbiome. Our users, most of them, if I need to kind of guess or what I see, the microbiome is what gets them to say, oh this is really interesting.

This is personalized for me, I have my personalized microbiome; these people are scientific based, it’s not just that somebody came up with a diet based on my blood type, there’s science here. I don’t think that a lot of them are going to be very interested in downloading the file of the microbiome and things with it.

But we could definitely allow that, or be able to do that, if we see that there’s a need for that from our users.

(00:50:58) [Damien Blenkinsopp]: Yeah, cool. Alright. I saw there was a mention of a Mayo study on your site?

[Lihi Segal]: Where did you see that mentioned, by the way? I’m trying to figure out how did that get to you. We didn’t publish…

[Damien Blenkinsopp]: Well I don’t know, I think it was just mentioned. Oh, I know where I found it.

I was looking through your FAQ and there were some directions for Mayo study people on how to find the information.

There’s a leak there.

[Lihi Segal]:L: No, it’s not a secret by far.

We are recruiting people in the Mayo clinic now, and DayTwo is all over it. We just didn’t issue the press release saying that yet. But that’s been approved and it’s on it’s way as well.

So, what we’re doing, I’m happy to share, it’s no secret. But what we’re doing with the Mayo clinic is a clinical trial that is very similar to the clinical trial that The Weizmann Institute has done in Israel.

And so we’re recruiting 500 people and going through the same process of putting exactly the same device that was used in the trial in Israel and giving them test foods that are American foods, like a bagel and cereal, and really having them log their foods and providing all that information, and a lot of blood tests. So we’re really replicating the trial.

We’re just going to do that because we wanted to make sure we’re providing relevant recommendations after we have a basic cohort of US people. It doesn’t have to be the entire 500 completed, but we just, as the Israeli one was all Israeli, with Israeli microbiome and Israeli food, we just wanted to make sure that we’re able to calibrate the algorithm and it also works on a US based population with US foods and all that.

So we’ve already kicked that off. It’s a great collaboration for us to do this with the Mayo clinic, obviously. So we’ve already connected people. If any of your users are Rochester or Minnesota based people they can go and be part of that clinical trial.

[Damien Blenkinsopp]: Right. And it will be literally a copy of the other study so they could look at the other study to see what it would entail as well.

[Lihi Segal]: Right. There’s a bit of new information there as well. So that’s the reason we’re doing that. And also to start a collaboration with the Mayo clinic for other things as well.

(00:53:14) [Damien Blenkinsopp]: Great. Do you have a timeline for that? In terms of when you might get results eventually?

[Lihi Segal]: The timeline for US, it’s opened for pre-order. I know you probably entered through the UK, so you didn’t see that, because it’s IP based.

But if you were in the US you would see a pre-order. If you were in Israel, you could also buy and start getting it. So we started selling in Israel already.

The US is open on a pre-order basis, and we’re going to start shipping kits out to people in the beginning of 2017.

[Damien Blenkinsopp]: Okay.

[Lihi Segal]: It’s just around the corner.

[Damien Blenkinsopp]: Okay. So there are people already using this service in Israel, and it’s functioning.

[Lihi Segal]: In Israel we started the whole process of getting the evaluation, the kits, out to people and getting them back and sequencing them. We’re just starting to get, we’re in the final stage of getting the application finalized, and then getting the recommendations for people.

But there are a lot of people already who are using it because they got recommendations, whether from the Weizmann Institute Study or through us.

They’re not using the fancy application with the ‘Build Your Own Meal’, but the results and all of that have been around and have been used. Actually the BBC had a great show – I don’t know if you’ve seen it.

[Damien Blenkinsopp]: No.

[Lihi Segal]: The BBC has a show called ‘Trust Me, I’m A Doctor’.

[Damien Blenkinsopp]: I don’t watch TV here, unfortunately.

[Lihi Segal]: Oh, okay. So anyway, ‘Trust Me, I’m a Doctor’, it’s a doctor that has a show and she features clinical trials. And so she actually participates in the clinical trials that she features on her show.

So after the publication itself, she approached the scientists. She came to Israel with her colleague and was profiled and went though it, got food recommendations. Then she went back home and only ate what she was supposed to eat, lost weight and felt great, her energy levels [were up].

She was all psyched about it, and featured it on the BBC in a great show. I’ll send you the links so if you want you can see them.

[Damien Blenkinsopp]: Yes, please.

[Lihi Segal]: So there’s a lot of people who are using it, but outside of the clinical trial setting as well.

[Damien Blenkinsopp]: Okay, great. So it’s already getting around.

[Lihi Segal]: It’s getting contracts. Yes, we see the results are there.

(00:55:23) [Damien Blenkinsopp]: Yeah. Okay, so in terms of just how it’s going to be available, you’re only shipping to the US. So is no one in Europe is going to be able to do this?

[Lihi Segal]: Well, soon. We get a lot of approach on our support.

After the show was aired there was like 10,000 people hitting the website. So we know that there’s a lot of people interested. And we really want to go into selling in the UK as well. We’re just trying to be [safe], being a start up and not to jump too far ahead.

[Damien Blenkinsopp]: One thing at a time.

[Lihi Segal]: Right. So we did Israel because otherwise people will kill us here if we don’t bring it home. But we didn’t even translate it into Hebrew, it sold in English.

And we’re opening in the US because it’s an important market to start in. But we have concrete plans to get into Europe in 2017. So, soon. At least in the English speaking countries.

Really, logistically it just means that we need to get this box to people, but it’s not that simple. We will need a local database of food. So there’s some work on the server side to give you your foods and the database that fits you. We don’t think we’re probably going to need a trial to do that.

So in terms of the microbiome what we see is that the changes are not that [significant]. So there’s changes in the territories in the microbiome, but they’re probably not that apart compared to where the recommendations are. So you and I are very different in the way the algorithm predicts for us.

The microbiome is different, but it’s not that different. Anyway, it works on people. It could work on the US even without the Mayo trial.

[Damien Blenkinsopp]: So it sounds like that’s a validation effort.

[Lihi Segal]: Right, exactly.

[Damien Blenkinsopp]: I haven’t looked at studies of comparison of different countries and their microbiomes. There are some?

[Lihi Segal]: There are, if you look at the [57:12 check, unclear] that they have their graph there. So these show the US and there’s overlaps between the US, Europe, and Israel.

There are differences as well, but the differences, the way it reflects it in the algorithm is not that significant. So it works.

(00:57:33) [Damien Blenkinsopp]: Do you know when the Mayo trial, how long that’s going on for?

[Lihi Segal]: Oh, the Mayo trial will take a while. But we don’t need to complete the trial before we’re able to give recommendations. So we just need to validate it in a smaller group. But we’re there collecting data.

It’s more, you know in the US you can’t put a continuous glucose monitor on people at all if you’re not diabetic. Except under IRB kind of trial setting. So on a consumer level we couldn’t find any provider that would allow us to put continuous glucose monitors on healthy human beings without prescriptions. It’s a diabetic label from the FDA.

So we don’t have the device, and in order to really collect that data in the US we need to have a clinical trial set up and get the appropriate IRB and all that. So part of the whole doing of the Mayo clinic is because we just want more data, relevant data with glucose monitors and logging of food.

So we don’t need that to continue to start operating. I don’t even want to stop it after 500, so we’re talking about opening Arizona as a site, and Florida as a site. It’s really good just for our internal research purposes to continue to get more data.

(00:58:53) [Damien Blenkinsopp]: One quick question. I’ve noticed that Arizona comes up a lot in lab testing. I’m just wondering, as you brought it up just then, is there any reason?

[Lihi Segal]: Because Mayo has a site there. So when I’m collaborating with Mayo clinic, they have additional sites other than Rochester, Minnesota. So they’re thinking of expanding this to there and I’m more than happy to get more data.

[Damien Blenkinsopp]: I was just on holiday in Arizona and I just noticed that there are a lot of lab testing companies there.

[Lihi Segal]: It’s probably due to relevant man power and cheap, and something like that.

[Damien Blenkinsopp]: I think there’s maybe some state regulations or something that make it a little bit easier. Something like that also.

[Lihi Segal]: But again, when you sell outside of Arizona then you’re going to have to comply with the state laws anyway. So I’m not sure if that’s going to help you. But I don’t really know.

(00:59:41) [Damien Blenkinsopp]: So right now for the US is it $299 for the pre-order?

[Lihi Segal]: The price is going to be $399 but we’re opening up at $299, that’s a pre-order discount. But once we stop reordering, we’re probably going to go up to $399.

In Israel it’s 500 dollars, but we’re also doing a premium product in Israel; we’re giving continuous glucose monitors to people in Israel. So we’re giving them a fancy report on their blood sugar levels and all kinds of other stuff. We can because the device that I talked about in Israel you can put it on humans that are not sick.

[Damien Blenkinsopp]: Right, wow. That sounds like quite a service. If someone would pay 1000 dollars or more…

[Lihi Segal]: No, no, 500.

[Damien Blenkinsopp]: Oh, and they’re getting that premium service with the glucose monitor?

[Lihi Segal]: Yeah. It’s a lot, 500 dollars. It’s just more expensive than the US because of the continuous glucose monitor that we’re putting on.

[Damien Blenkinsopp]: They’re quite expensive, those things.

[Lihi Segal]: Well, they cost a few hundred. I guess in the UK it’s about 80 Euros. And then the reader and then the patch cost a little bit more.

[Damien Blenkinsopp]: I looked into getting one for myself; not for medical reasons, just to play around with.

[Lihi Segal]: Abbott Freestyle. Just take the Abbott Freestyle Libre. Just look for it. Freestyle Libre and then just order it online. And I think it costs 100 Euros or something.

[Damien Blenkinsopp]: Okay. And it’s got consumables on it too.

[Lihi Segal]: And then you have a patch. You get a round patch that you put on for two weeks. It’s good for two weeks. And then you have a reader.

[Damien Blenkinsopp]: And this is the one that Eran was talking about earlier that they’ve started using.

[Lihi Segal]: Right. So you can get that online.

We bought a bunch of them online ourselves in the UK before we found it in Israel. And once we found it here in Israel we decided to go with this product that we can also collect from people their blood sugar managements and give them all the fancy reports on all that. So it’s cool.

[Damien Blenkinsopp]: Yeah, it sounds quite exciting what you’re doing in Israel, because you’ve got more flexibility there. Are you publishing anything, maybe a bit later, about that on your customer base?

[Lihi Segal]: Not yet.

[Damien Blenkinsopp]: Okay.

(1:01:51) Is there anything we haven’t covered about the service, that we’ve missed?

[Lihi Segal]: Yeah. I think that this is kind of our direct to consumer approach. So we’re selling to you directly, but what we’re really working on is partnerships. Because what we really believe is that the way you’re going to use this is also very personalized.

Some people, the fact that we give them a fancy application that’s really cool and has a report on it and teaches them what to eat and what not to eat. There’s going to be a diet planner at some point on this. So you can really be independent in the way you manage your food.

For some people that’s going to be great, but some people really need more support. So maybe they go to Weight Watchers or they use other weight management services. And once you know as a user that there’s specific recommendations for you that are personalized for you, you really can’t tolerate generalized information anymore.

I’m saying this for myself. I go to this Weight Watchers group – it’s not Weight Watchers, it’s a local Israeli group. But I can’t hear her say to me, you should eat pretzels as a snack. 100 calories of pretzels are your snack. I’ve been doing that for 15 years, and then I found that it was my number 1 spiking snack.

And I moved to a different, totally different corn-based snack that was much better for me if I’m eating that 100 calorie snack already. So I’m snacking on that.

And what we’re thinking of doing is really opening an API with a lot of services. And so you as a user can share your information with your doctor, or with your nutritionist, or with your weight management group. Or when you take out food you want to be able to get a score. You want to log in, connect to…

[Damien Blenkinsopp]: So you could plug into a meal delivery site.

[Lihi Segal]: Think of this. Let’s say you’re ordering take-out of your food. We do this every day at lunch, just because in Israel is how it works.

And so I want to log in and connect with my DayTwo account, into that service, then get a menu and my score, A, or B. I’m already in a great restaurant, I’m eating food or I’m taking it out, I want to be able to get a score and choose right.

In the US specifically there’s a lot of employer wellness programs. All of those wellness programs provide nutritional advice, but it’s generalized. I, as a user, want my personalized advice to go with me.

So, that’s kind of the partnerships that we’re doing. Some will bring us customers, some we will bring our customers to them. And we’re building a marketplace around this.

So literally, think of that that we’re not competing with anyone. That’s the strategy that we built. We want to enable anyone who wants to use this personalized service to use it in their application and services.

[Damien Blenkinsopp]: Great, to make the information more widely available.

Lihi, it sounds great. I’m sure there are insurance companies and so on who would be interested in that as well. I know they’re getting more interested in these wellness programs.

[Lihi Segal]: Of course.

[Damien Blenkinsopp]: Okay well thank you very much for your time today. I really appreciated it.

[Lihi Segal]: Sure. Thank you so much.

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Recent investigations have shown supplements to not always contain what they say they do. Or at other times to have unwanted contaminants such as heavy metals. Learn to use 3rd party lab testing to select supplements that contain the active ingredients needed to provide the results you seek.

Sometimes on this show, we discuss using supplements as tools to get desired results. Examples in past episodes included curcumin, activated charcoal, NT factor, Greens powder, oxaloacetate and many others.

I’ve been aware for a long time that not all supplement products are equal in quality. For instance, if they actually contain as much of the active ingredients as the label says on them, or if they are contaminated with heavy metals or pesticides, for example.

Last year this issue was given more publicity when the New York State Attorney General’s office investigated supplements found at GNC, Target, Walmart and Walgreens, and sent ‘Cease and Desist’ letters to each for some of their supplements that neither contained the active ingredients, and at times contained other undesirable ingredients that weren’t listed on the labels.

The unfortunate takeaway is if you truly want the results from supplements — so if we talk about results that can be achieved through a supplement on this show – then you can’t just take it for granted and buy any supplement. You have to make sure they contain what you want and don’t contain what you don’t want.

In practice, how do we do that? I’ve been using a lab service for a few years now that tests and reports on the quality of supplement products. So I can select the products that will achieve the results while minimizing the cost. Sometimes you don’t need to buy the most expensive brand to get the best quality, which is kind of cool.

The service was ConsumerLab.com, which is a subscription service, so unfortunately, you have to pay. However, the good news is that an open alternative is now available that has been publishing extensive lab testing data on popular supplement categories.

That company is Labdoor.com. If you have the internet available it will probably be useful to check out the rankings the company is publishing while listening to this episode to see what the end result is, and what they’re actually publishing.

“I think there are categories where 70 percent of products fail, there are categories like creatine where 10 percent or fewer products fail. And then there’s kind of the in-between zones where, with fish oil, about a quarter of the products have rancidity [fat oxidation] issues. And so we’re filtering that, and that’s a part of our [supplements testing] purity score.”
– Neil Thanedar

Today’s guest is Neil Thanedar, CEO and Founder of Labdoor.com, and Founder of Avomeen Analytical Services, which is a company that specializes in product lab analytics to see what they are composed of. Labdoor is now four years in the making and sets to start growing at a faster pace and covering more supplement categories now that they’ve got some sort of funding behind them.

In this interview, Neil walks us through the types of analysis they run on supplements to understand their quality and some of the most interesting and useful results they found in the supplement markets. It features highlights, such as we shouldn’t really be trusting user reviews that you find on the internet on places such as Amazon – because there doesn’t seem to be much of a correlation. And there are other big similar takeaways, which, I’m sure, goes against what we’ve all been doing.

itunes quantified body

What You’ll Learn

  • Neil’s research interests and orientation towards quality control supplement testing (3:57).
  • Labdoor is a spin-off business, diversifying lab testing services compared to what’s offered by Avomeen (5:40).
  • Labdoor and Avomeen are split in leadership between Neil and his father (7:50).
  • A consumer-aligned model and efforts to eliminate bias in producing objective information (8:03).
  • The major quality control issues with dietary supplements (10:04).
  • Defining supplement quality and criteria used for rating supplements (11:13).
  • The technologies used for testing supplements and the science behind interpreting results (12:19).
  • Customizing supplement ranking formulas and tailoring results to individual customers, ex. vegan or child categories (18:54).
  • Establishing accuracy in nutrient analysis and maximizing trust in results (20:25).
  • How Labdoor manages an active role as part of the supplement industry (22:54).
  • Dealing with testing newer or complex composition supplement products, where research is still accumulating (25:05).
  • Consumer demands and targeting of testing results to differing audiences (27:15).
  • Labdoor’s role in supporting an informed market (29:21).
  • Overview of tested categories of supplements (33:10).
  • Discovering products and prioritizing particular supplements testing (39:15).
  • A severe lack of price correlation in the supplement industry (40:58).
  • Cooperating with companies when Labdoor testing does not confirm producer certificate of analysis testing results (42:08).
  • Labdoor’s plans for reaching out to manufacturers more proactively (47:23).
  • The potential of re-testing for capturing trends in the supplement industry and increasing confidence in obtained data (48:30).
  • Case studies and key takeaways for particular categories of supplements (52:19).
  • Little brand correlation in same category products and guidelines for choosing supplements (54:21).
  • Caveats for non-scientific approaches towards choosing supplements (57:20).
  • Future prospects of wide-spread product testing aimed at empowering consumers to make science-based health decisions (1:01:44).
  • Reasons for re-organizing the supplement market, such that the best products are making the highest sales (1:03:59).
  • Scientific or practical business assumptions which Neil has changed his mind about (1:06:06).
  • The biomarkers Neil tracks on a routine basis to monitor and improve his health, longevity, and performance (1:08:21).
  • Recommended self-experiments for improving mental performance (1:14:07).
  • The best ways to discover the field of supplement testing (1:15:55).
  • How you can best connect with Neil or find out more about Labdoor (1:18:54).
  • Neil’s request for you – The Quantified Body audience (1:20:32).

Thank Neil Thanedar on Twitter for this interview.
Click Here to let him know you enjoyed the show!

Neil Thanedar, LabDoor

  • Avomeen: A chemical analysis lab specialized in failure analysis work (when products go wrong). Initially, it was started by Neil but is now run by his father – a scientist continuing his work and research in his retirement years.
  • Labdoor: A company currently run by Neil focused on providing scientifically-backed analysis and ranking of dietary supplement products. The company offers objective information on supplements and aims to empower people to make informed decisions. Check out Labdoor’s supplement rankings.
  • Labdoor’s Facebook & Reddit: The two fastest ways for you to reach out to Labdoor. Hundreds of questions have already been answered on these forums and Neil hopes new ones will spark lively debates on topics across the field.
  • Neil’s Twitter: Where Neil shares his ideas about testing and his opinions on how Labdoor touches other industries.

Recommended Self-Experiment

  • Tracking Time: Keep track of how you spend time for 10 days in a row with an app such as Hours. You should discover many useful takeaways such as areas where you waste the most time or activities you should cut. Neil suggests repeating approximately every 6 months to track improvements and optimize over time.

Tools & Tactics

Supplementation

  • B Complex: It contains Vitamin B12 – a molecule which is used in the metabolism of every cell and acts in DNA synthesis and regulation. B complex also contains folate which is needed for DNA repair and proper DNA methylation – see episode 5 with Ben Lynch. This product contains the active forms of B vitamins increasing their bioavailability.
  • Curcumin BCM95: The active ingredient of turmeric, also found in limited amounts in Ginger. Curcumin is a potent anti-inflammatory and cancer preventative molecule. Previously we have discussed this supplement in the context of lowering oxidative stress or inflammation in episode 4 with Cheryl Burdette and episode 25 with Josh Fessel.
  • Activated Charcoal: This is a medical-grade purified product which is highly absorbent of toxins. It promotes a healthy digestive track and improves brain functionality. Taking activated charcoal reduces the body’s toxic burden – a subject discussed in episode 23 with Kara Fitzgerald. This is a lower cost (value for money) Activated Charcoal option.
  • NT Factor EnergyLipids: A blend derived from soy lecithin extract specifically. This product is formulated and used for supporting memory and cognitive function. There’s also an NT Factor Energy Wafers option which is a chewable product packaged in pieces.
  • Greens Powder: A mix of alkalizing green foods, antioxidant rich fruits, and support herbs. This product is used as a dose of whole food nutrition – essentially aiming to supply a healthy background of nutrients.
  • Oxaloacetate (Aging Formula): A metabolite of the Krebs Cycle which improves blood sugar regulation, improves energy levels, and increase endurance. Previously we discussed oxaloacetate as an anti-aging supplement in episode 30 with Alan Cash and in the context of blood glucose regulation in episode 22 with Bob Troia.
  • Fish Oil: This supplement is useful against inflammation. Fish oil can be used post workout sessions or if inflammation is part of a disease state. Labdoor tests EPA and DHA content (beneficial Omega 3 fatty acids) in fish oil supplements. According to their data, often there are products which contain 50% Omega 3 instead of the labeled 90%.
  • Lypo-Spheric Vitamin C: These are liposome encapsulated vitamin C tablets and this maximizes the bioavailability of the active component. Previously we have discussed Vitamin C and its potential for preventing colds in a timely manner by tracking Heart Rate Variability (HRV) in episode 41 with Marco Altini.
  • Calcium: This supplement is aimed at improving the composition of bones. Calcium also plays a key role in muscle contraction thus this mineral supports neuromuscular health. The major benefit of calcium is lowering the risk of developing osteoporosis.
  • Magnesium : This mineral in supplement form is used to support nerve, heart and muscle functionality. See episode 17 with Dr. Carolyn Dean for testing and fixing magnesium deficiency.
  • Zinc: An essential mineral which plays a role in many enzymatic functions. Zinc supports immune system function and is an important component of the body’s antioxidant systems.
  • Creatine Monohydrate: This product is targeted for using after workouts to aid in the recovery process. Approximately 5-10% of these products are faulty, according to Labdoor supplement testing results data.
  • Garcinia Cambogia: A small fruit traditionally used to enhance the culinary experience of a meal and as an aid to weight loss. Garcinia cambogia was the worst category recorded by Labdoor. Up to 70% of products in this category do not actually contain the active ingredient (defined as less than 10% of the labeled ingredient quantity).
  • Ginseng: This supplement is effective for mood, immunity, and cognition. Examining the ginsenoside content is important in these products because Ginseng quantity is different from the active ingredient. This causes consistency problems because extraction processes differ. Neil advises patience before purchasing these supplements and, of course, waiting for Labdoor’s data on particular products.

Diet & Nutrition

  • Protein Bars: In the future, Labdoor plans to take on testing food beverages. For example, increasingly protein bars are marketed as a meal replacement, thus approaching the supplement (or functional food) category. Eventually, even well-known products such as a McDonald’s Big Mac, a Chipotle burrito, or liquid beverages such as Pepsi could be tested.
  • Baby Formula: Manufactured food products targeted for feeding infants under 12 months of age. Often, these are manufactured using methods similar to those used for the production of supplements.

Tracking

Labs Tests

  • Liquid Chromatography: Chromatography is a diverse set of laboratory techniques for the separation of mixtures. Detecting the concentration of specific substances out of a whole is key for objective supplement testing results. In liquid chromatography, the mixture is turned into a liquid phase which moves through a column or plane (solid phases used for detection). Individual chemicals can be detected based on a constant property, ex. by affinity for the solid phase coating material.
  • Gas Chromatography: This method is used for analyzing compounds that can be vaporized without decomposition. In vaporized form, chemicals travel through a column at different speeds and reach the detection surface at different times – known as retention time. This is a constant for individual types of chemicals and is the principle behind detecting particular types of chemicals in gas chromatography.
  • Mass Spectrometry: Mass Spec or MS as it is known is becoming increasingly popular for analysis of all types of samples from testosterone and other body metabolites or proteins to understanding the composition of any material.In a typical MS procedure, the sample is initially ionized by bombarding it with electrons. These ions are then accelerated by subjecting them to an electric or magnetic field. Individual substances are detected according to their mass-to-charge ratio. Ions of the same mass-to-charge ratio undergo the same amount of deflection on the detection surface. This is transferred into information about concentration.

    Liquid / Gas Chromatography is often used as a pre-analytical method for preparing isolated sets of chemical subgroups, before digging deeper using mass spectrometry to obtain accurate supplement testing results.

Apps

  • Headspace: A meditation, or mindful awareness, training app. It is useful for improving mental performance, to relieve anxiety, and increase endurance.
  • Lucid: An app focused on mental training for professional athletes.
  • Hours: An app used for tracking activities throughout the day, thus mapping time expenditure. This is useful for improving mental performance. Because tracking itself can be time-consuming, Damien suggests undertaking focused projects – one lasting a few weeks before moving to the next.

Other People, Books & Resources

Organizations

  • ConsumerLab: A company offering supplement testing service. Damien used ConsumerLab Reports until Labdoor appeared on the market and started offering supplement testing free of charge.
  • Thorne Research: A company manufacturing dietary supplements, separated in programs tailored towards health categories, ex. cardiovascular or immune support. Their products are usually sold through doctors, thus Labdoor has missed these in their initial supplement testing categories.
  • Life Extension: A manufacturing company producing supplements including vitamins, minerals, herbs, or hormones.
  • Elysium: A relatively new company gaining ground in the supplement industry, partly due to their science-strict operational and marketing model. Elysium is sponsored via venture capitalism investments – a business model different from Labdoor’s.

People

  • Gary Vaynerchuk: Recognized by Neil as an important voice in the understanding the link between marketing and consumer trust.

Other

  • Yelp: Neil draws a parallel between Labdoor and Yelp – a service specialized for ranking business of different categories ex. restaurants or shopping venues. This comparison demonstrates that Labdoor requires customer and manufacturer feedback to grow its business and to accomplish more ambitious challenges.

Full Interview Transcript

Click Here to Read Transcript
[Damien Blenkinsopp]: Neil, thank you so much for joining us.

[Neil Thanedar]: Yeah, absolutely. Thanks for having me.

[Damien Blenkinsopp]: You’re in a pretty niche area. There have been a couple of companies around which have been testing supplement products for a while. And of course there’s been a fair amount of news over the last year or so talking about the high variability in supplement quality, and whether we’re getting what we want.

So I was just interested in how you got into this whole area. Where did this start for you?

[Neil Thanedar]: Yeah, absolutely. I grew up in research, I grew up in science. My dad’s a Ph.D. Chemist. When I was two years old he quit his job as a researcher and started his own lab. And it was just him for a couple of months, and he slowly grew that lab all the way up until I was in college. So he had retired by the time I was in college.

When I was trying to figure out what I wanted to do with my career, the first thing I really wanted to do is, I had really thought about biotechnology or inventing new medicines. And those had been the first things I had thought of. And throughout the process, I found out that the existing process, the existing medicines and supplements just weren’t clean; they weren’t safe. And so I jumped right back into the same industry that my dad did, which is quality control.

And so right out of college I started a lab. It was a chemical analysis lab called Avomeen. We did product development and failure analysis work. We figured out for manufactures when something went very wrong: a pill had a black dot on it, your baseboards were yellowing, there was an odd smell coming from a multivitamin. Any sort of something going wrong, the company would come to us, we would do all of the testing required to figure out what they should go and fix.

(00:05:40) [Damien Blenkinsopp]: You just mentioned baseboards. What are baseboards?

[Neil Thanedar]: Literally the baseboards like in the floor, that connect the floor to the carpet. That little white strip? That’s actually a product that we did once. The white boards were turning yellow as soon as they were installed.

[Damien Blenkinsopp]: So you actually started from analyzing a broader spectrum of products, not just dietary products.

[Neil Thanedar]: Yeah. It was anything from that to household cleaners to a sunscreen to a multivitamin to even pharmaceuticals. Generic versus brand name medication.

And so we were doing it, but we were doing it in a very reactive way and we were doing it for manufacturers. And really one day I just had the idea that really we should do the opposite business.
What if we could, instead of being reactive we could be very proactive. We could go into a Walgreens or CVS and buy every product off the shelf and pretest it. So you would already know if it was good or bad. And if something failed, you would know ahead of time.

At this point, I had — as kind of a back-story — my dad had come in and started working with me to come out of retirement. He was starting to work at Avomeen. And so what I decided was I really felt like LabDoor needed its own focus. And so we kind of split up, and he went and he’s taking care of Avomeen now, and I fully run LabDoor.

So this was, for me it was a new way to work in the business. I kind of just jumped into the industry expecting it to be like it always was, and then just one day being the new person. I was just like, hey this is weird, why don’t we just start by testing everything?

(00:07:15) [Damien Blenkinsopp]: Cool. So how long has Avomeen been around?

[Neil Thanedar]: So that company has been around for about seven years now. And LabDoor has been around for just over four. It’s been all LabDoor for me for the last four years.

[Damien Blenkinsopp]: Okay. Cool. It’s very interesting. So it’s always good to see a family business. Your father’s kind of proud of you for carrying it on, the whole research lab area.

[Neil Thanedar]: Yeah, it’s so interesting. We always talked about it, but it was never something he asked me to do. It was just always interesting to me. And I think the science is so fascinating, when you figure out exactly what’s inside something. You get to break things down and you get to reverse engineer, it’s just fun.

The problem in the industry is really just, how do you get paid. Consumers need to see the data but they’re not going to pay ahead of time. It’s really just paying for this testing that’s the hard part.

(00:08:03) [Damien Blenkinsopp]: Right, yeah. So I guess you’ve got a slight advantage because Avomeen is associated with you, but how does LabDoor get paid so that you can do this for everyone else? Because the information is available for free, right?

[Neil Thanedar]: Yes. And so, what we want to do is do all the testing ahead of time and help you have all the data to make the research decision. And then what we’re finding out is that people, the next thing you’re doing is buying. And so if we just affiliate links down, we’ve got 10 percent of the conversion. And that really is most of the business.

And I think it’s what we, we love that kind of alignment with the consumer. So you’ve got the sense of I don’t get paid unless you actually find something you like. If you return it, we lose the commission. It’s this whole process where we can really be performance based.

And it’s also something where it’s sustainable. Every single day, there’s going to be tens of thousands of people who shop this site. They’re going to buy stuff, and that’s going to support the next round of testing.

[Damien Blenkinsopp]: Right. And I’m guessing it doesn’t matter what they buy. Are you putting Amazon links on most of the stuff?

[Neil Thanedar]: Yeah. So it’s really easy to put it on every single product. And we get some debate about this. The D and F products have affiliate links on them too.

[Damien Blenkinsopp]: The DN…

[Neil Thanedar]: The D and F. So it’s A through F. Every single product has the link.

[Damien Blenkinsopp]: Right. Well, I think that’s the way to go because you’re unbiased.

You’re not there to promote one product versus another. It’s just that you provide your objective information, and if someone buys something from using the information on your site to make that decision, you get a commission. But like you say, you’ve put a few links on the worst products and the best products, so there’s no official bias there.

I bring that up because there are some sites out there on the web which have been out there for quite a long time, and I’m sure people are aware or these – which are basically just affiliate review sites. And they have their number one product where they are getting paid, and all the others they are not getting paid. And obviously, they are just trying to cash in there.

But yours is a professional company without the bias.

(00:10:04) [Damien Blenkinsopp] Okay, so let’s talk about supplement quality to actually understand what the issues are. What is the context for us first? Why should people be interested or worried about dietary supplement quality?

[Neil Thanedar]: I think there are two parts of it.

I think the first part is actually that there are some products that legitimately have problems. They’re either massively under-dosing — and that’s maybe a third of the products that we see. So the active ingredient isn’t there, there are some sort of heavy metals or purity issues. And that might be the D or F grade products on the site.

And then there’s really this other group of products that you should worry about quality-wise — I would say the B and C products — where they’re just not highly concentrated. Maybe there’s some famous brand that you’ve always heard of, but like the fish oil is 50 percent Omega 3 instead of 90 percent Omega 3. Or the protein powder is 40 percent protein instead of 80 percent protein. And those are kind of the B and C products.

So those are the two things that you have to worry about: are you not getting what you paid for or are you really being cheated? These are the two types of quality control issues that we really find on a regular basis.

(00:11:13) [Damien Blenkinsopp]: Right. These are the most common things. How would you describe supplement quality? Because I know you’ve got your own kind of internal rating system, where you look through a whole bunch of different criteria.

[Neil Thanedar]: Yeah, I think what we really want to do is start by, it’s really kind of rewarding active ingredient quality and quantity, and starting to penalize for the negative inactive ingredients. And so, as much as possible it’s very, the calculations we try to be as intuitive as possible with it.

The number one factor is going to be the concentration of active ingredient. So it’s going to be the Omega 3 concentration in fish oil or the protein concentration in protein powder. Next, we’ll look at the quality of the active ingredient. We’ll look at the EPA and DHA in fish oil, we’ll look at the amino acid profile in protein.

We’ll look at label accuracy. So we’ll look at how those numbers compare to the label. And we’ll look at purity. We’ll look at mercury and PCBs in fish oil. We’ll look at arsenic, lead, and heavy metals in protein powder. And that’s really it. I think we want to try to look at purity and potency and figure out, ‘Does it work?’ and ‘Is it safe?’.

(00:12:19) [Damien Blenkinsopp]: Great. Thank you for that. So, how do we go about testing these things? What kind of technologies are you using to look at the supplements?

[Neil Thanedar]: Yeah, so it’s really kind of classic analytical chemistry. So we’re looking at chromatography and spectroscopy, like an HPLC or a GC-MS, ICP-MS.

[Damien Blenkinsopp]: Okay. Could you quickly describe that? I know what you’re talking about, but I think these are terms that the majority of people don’t really understand.

I look at chromatography as basically splitting things apart so that you can look at them. And then spectroscopy as actually doing the analysis. I don’t know if you’ve got a better way to explain it.

[Neil Thanedar]: So yeah, we’re basically separating, identify ingredients, and we’re figuring out their quantities. So an HPLC could actually look at anything from caffeine content or a kind of vitamin content, or it could even look at something like sunscreen content and look at the different sunscreen ingredients.

What we’d like to do, and I think this is a big part of our process, is if we can get a couple of HPLCs in the building and really ramp up our testing in supplements, that will allow us to start experimenting with other types of products that we could test.

And so really we’re looking at, in any of those machines, is we have standards of the ingredients. What are the best quality ingredients supposed to look like? You can run that through an HPLC and you’ll get a curve. Then you can run the product through the HPCL and get a curve and you can see the difference.

[Damien Blenkinsopp]: Great. So, when you say HPLC, what does that stand for again?

[Neil Thanedar]: It’s a High-Performance Liquid Chromatography.

[Damien Blenkinsopp]: Okay. Right, for separating things out.

[Neil Thanedar]: So yeah. I think those are the things where we’re not inventing, really. That’s not our, I mean there are a lot of scientific start-ups out on the market that are truly on the frontier of science. I think a lot of the work we do, there are new methods every year and things are advancing, but for the most part, it’s an established industry.

The testing part is established. I think the part that we’re trying to work on is – how can we test thousands of products. How does it get to a point where we test thousands of products?

[Damien Blenkinsopp]: I guess that’s primarily about cost?

[Neil Thanedar]: Yeah, it’s a chicken and egg problem, right? Because we’ve got to do the testing before you show up. So we need to, there’s kind of a constant process of kind of testing a little bit, add one more category, bring money back into the business.

And that cycle is really important to us. And the cycles are going faster at this point. We want to be at a point where we can test, instead of 25 products a month, 50 or 100 or 150 products a month.

[Damien Blenkinsopp]: So, with the approach to testing that you use, do you have to say what you’re looking for? Or does it actually show up, everything that is in the substance? So do you have to pre-decide that I’m looking for mercury, for example, or will you pick up other things in that process?

[Neil Thanedar]: You’re looking for specific ingredients.

[Damien Blenkinsopp]: Okay.

[Neil Thanedar]: So that’s the HPLC where you would look at caffeine versus a caffeine standard.

[Damien Blenkinsopp]: Yeah.

[Neil Thanedar]: And I think that’s the part that we haven’t quite, these ideas, these magical devices where you scan your food and it tells you every ingredient simultaneously. That’s truly on the frontier; that’s not science that exists today.

So we’d love to have more information on it. Until then there is, at some level, brute force work being done here. And at some level, we’ve got established panels of ingredients we can look for.

So you can look at all of the heavy metals at once, or you can look for a whole set of carcinogens at once. There’s a whole set of banned substances that you can all do in one scan. There are certain things that we’ve set up, and with everything else, there is a bit of brute force work. Especially with the active ingredients.

[Damien Blenkinsopp]: So when you say brute force, what does that mean?

[Neil Thanedar]: So you would have to, for example, for a multivitamin you would have to separate every individual vitamin out of there and test them each individually. And it might even be as far as vitamin A is going to be in the product in three or four different forms. So you would have to test each of the four forms of vitamin A individually.

That’s when I start thinking about, that’s truly where we start getting into reverse engineering for active ingredients. Where you need to get down to that individual level because we want our calculations to take that into account. We want to have, if different vitamins A forms have different bio-availabilities, we want to use that as part of the calculation.

[Damien Blenkinsopp]: So I guess in your process of trying to understand each new area, you plan a new category. For example, fish oil you’ve done, but then you come across something else so you’re like okay, maybe this is a growing supplement or something that people are getting more interested in so we’ll attack this category now.

I guess, first of all, you’re looking at some research to kind of see what the issues are, what kind of things you want to look at. And then you have these standard things, like carcinogens and metals that I’m guessing you’re looking for in most things, just because… I guess if something is made in China, the odds that it could have some metals in it, that’s one of the big concerns.

[Neil Thanedar]: It’s even beyond that. I think, well also almost every supply chain is global at this point. So we just test everything for heavy metals off the top. So those are certain things where it’s just automatic. An ICP-MS is expensive, but it gets a lot of use.

Whereas something like each individual ingredient, I think we have to make a decision on [what to test]. For example, with protein powders, we started with a very simple analysis. We started with just a [unclear 0:17:35], nitrogen analysis. So we were just looking at the total nitrogen content. And then we started looking at total amino acid content, and then we started looking a pre-amino acid content, subtracting pre-amino acid content out.

So there’s a whole range of how we get to the final data. I think the work’s never done because the next thing we’d want to do in protein is get into are there specific amino acid ratio [that are] more bio-available. So could we build into the calculations a system that scores the amino acids? That’s something that we would be interested in doing.

So at some level, there’s this constant improvement that has to happen. Many of the products on our site we’ve tested only once, because we test on a yearly basis and it’s the first year. That’s another thing that’s going to improve the data. So year two or year three, we’re going to get more data, we’re going to see is there any batch to batch, year to year variation.

So all of that stuff is part of our expansion process. It’s part of our growing process where it’s why we purposefully limited it to 25 products per month. That was our case, and we can hold to that. And we can consistently deliver that kind of quality, but we’re not going to go in and say, hey look we have 100,000 products on our site. It’s just not possible to do.

(00:18:54) [Damien Blenkinsopp]: Right, it’s not feasible. It sounds like you’re going to be on a learning curve. Say you did protein like two years ago, you do it another year and you’re like, you know what, last time we learned this, so we can integrate that and we can look for that this time, and that’s going to be important for the new formula.

Is that the process you’re going for with some of the main supplements?

[Neil Thanedar]: Yes. And it’s also, you get a lot of consumer feedback after that, because we might build our quality rankings based on usually very quantitative, what we talked about. Very quantitative factors like concentration.

But then what we need to figure out, and what we’d love to add, is more types of rankings. So there are other reasons or other ways for people to make a decision. And so we used to just have one set of rankings, and we found out that some people weren’t buying the number one.

And we said, hey, why do people not buy the number one? Oh, there are some people who are vegan so that’s not their number one. So we added a vegan filter. Some people were buying products for kids, and so we added a children filter. People were buying by value, so we added a value ranking that’s completely separate value ranking.

And I think in a perfect world, there would be, you could take a test where we would just know who you were, and your perfect LabDoor rankings would show up. And they would be perfectly customized to you. We’re on that lifelong path of getting to the point where we can perfectly customize it to you.

And quality and value and kind of vegan and sugar-free; we’re hitting the major ones right now. And then it just keeps getting better and better.

(00:20:25) [Damien Blenkinsopp]: Excellent. And so how accurate is the volume aspect? So you can identify and say that fish oil has DHA in it, or it’s non-oxidized. But how do you understand the actual amounts of this, and how accurate is that?

[Neil Thanedar]: So we’re looking at percentages.

So if you look at a fish oil capsule, it’s anywhere from 10 percent of that capsule is Omega 3, to 90 percent is Omega 3. If you tested the same product again that was at 90, you might see it at 92 or 88.

There might be a little bit of a variation there between tests, but you’ve got a good sense. The product that tested at 90 versus the product that tested at 80, there is a clear separation there.

[Damien Blenkinsopp]: Sure. So what is the swing, and is that, I mean that could be just due to each capsule, right?

[Neil Thanedar]: We’re taking an average of at least 10 plus capsules. So we’re getting a little bit of a range there.

It’s that kind of a range, so maybe in the 2-5 percent range. Sometimes in certain categories with many ingredients sometimes you see a 10 percent variance. But these things are pretty consistent. Once you put that first test out, you have good data.

And I think that 10 percent variance off of the label; the labels are often very inaccurate as well. So the labels tend to be more than 10 percent inaccurate. So I think what we want to do is as soon as we put that first data point there, you’ve already got better data than you had before.

And now our job is to go in and solidify that. And so there’s a constant tradeoff between ‘do we go to a new product’ or ‘do we test the old product again?’

[Damien Blenkinsopp]: Right. So when you’re taking the average, are you taking, say from one bottle you’re taking like 10 capsules or are you trying several bottles? How do you approach that?

[Neil Thanedar]: No, so we’ll want to take it all of it from the same lot. So we’ll try to buy three or four bottles and have it be the same lot.

And so then we might need 50 to 100 total samples because you might be 10 per test or similar. So you will end up using about 100 of those capsules in a round, and save the other 300 just in case a company comes back and questions the data, we need to retest. All of these kinds of things, so it’s important for us to do.

So we’ve got a decent range there. And I think what we found out is these companies are generally doing between two to four major batches of product a year. If you grab any one of those products off the shelf, you get really close on that first test. And then everything after that, we just have to test every year.

(00:22:54) [Damien Blenkinsopp]: Right. So you’ve mentioned lots and batch. Are they the same thing?

[Neil Thanedar]: So I think a lot of people would think, I mean there might be multiple lots in a batch. So it’s a little bit of manufacturing lingo.

I think we are starting out, so that’s part of our learning curve as well. We’re trying to get more into how manufacturers work, and how that side of the industry works because I think we jumped in just totally as consumers. And we were just like how can we figure out how to make this data out.

And then what we found out was there’s different, I mean from the industry there are companies complaining about, hey you’re sharing our proprietary blend. Don’t do that. Or, that data is wrong, or our data shows something else. Our internal lab says something else. And there’s a lot of that.

And in the early days I think we almost didn’t have the time to handle all of the information at once, and if we had to focus on one thing it would be consumers. We’d want to focus on the people who are taking the products. But now I think, as we step back and get a little more organized, we’re starting to figure those things out.

How do you talk to companies, how do you manage the system, how do you figure out and return that data back to the manufacturer? If we find something, can we alert them? I think we want to do a better job with that, we want to do a better job of being a part of the entire industry, instead of being this kind of renegade on the side.

[Damien Blenkinsopp]: Right. Do you get a lot of manufacturers reaching out proactively to you then? Has that happened a lot?

[Neil Thanedar]: It’s a slow, steady pace. There might be a manufacturer a month or something who will come out.

And I think there’s a whole range of them. I think the majority of the complains are honestly like A- companies who…

[Damien Blenkinsopp]: Right. The one’s who really care.

[Neil Thanedar]: Yeah, they really care. “I’m number 8 and I want to be number 1, and here’s why.” And there’s literally 20 reasons why, and five studies attached. And we love that; that’s wonderful. If you do that, our scientists will read all of those studies and we’ll talk about it over a meeting and it’ll be interesting to us.

And if you can convince us, [great]. That’s one of the big things that the protein manufacturers are trying to argue, add an amino acid scoring system. And maybe the ranking will shift a little bit. I don’t think it’ll do very much, but there might be a few products that fall out.

(00:25:05) [Damien Blenkinsopp]: Yeah. So I guess there’s the other subject that some of these products have been around for a long time. So protein is pretty well standardized as a market, and fish oil as well. But of course, then you have some of the newer supplements.

Those must be a bit more challenging because the research can still be evolving, in what the active ingredients are. “We’re not 100 percent sure, but we think it’s this one” kind of stuff.

[Neil Thanedar]: That’s a tough one. I think that is a lot more in our calculations. So the testing is much more straightforward.

So the nice thing is, even if we’re testing a nootropic or something, there would be specific ingredients where even if the clinical research hadn’t completely proven that that ingredient works or not, we could 100 percent know whether it’s there or not. We could at least know that.

[Damien Blenkinsopp]: Right. Because the first thing you’re doing is you’re just comparing the label. The label says it has this, and actually, it has something a little bit different in it. So it’s an easy comparison to start with.

[Neil Thanedar]: That’s easier. The part that we need to figure out, and sometimes we’re staggering that. We might really focus first on the ingredients that have really clear claims.

And now we’re kind of, we are getting more and more into specialty products now. So we are now ramping into testing B complex in glutamine and all of the joint support.

So now we’re going into things that have more complexity or variety. We’re starting to unpack our old categories. So now protein is going to have protein bars, and protein shakes. There’s going to be new categories.

[Damien Blenkinsopp]: I mean, a protein bar tends to be pretty complex in its makeup, right? It has all sort of ingredients.

[Neil Thanedar]: We want to figure out the protein quality in the protein bars because that’s such an important thing. We’ll start testing vegan Omega 3s in the next couple of months.

So it is that kind of constant process of expanding the existing categories, getting into new categories, and then doing the research on the fly. And we’re finding that in some places there’s not good research.

When you test an ingredient, and you have all the data and then, it’s garcinia cambogia and there’s no great evidence that says that it works. And in many cases, we still try to plug that data into our rankings, and you get like in our garcinia rankings, there’s not a single A grade product on the ranking. Because there’s just not enough efficacy in the calculation to get the score up.

(00:27:15) [Damien Blenkinsopp]: Right. So you have five criteria. [First is] label accuracy, which is very straightforward for you guys, you basically just compare. Then you have product purity. What is that exactly?

[Neil Thanedar]: We’re just looking at the heavy metals and contaminants versus upper limits.

[Damien Blenkinsopp]: Okay, great. And then the nutritional value, would that fit more into what we were just discussing about garcinia cambogia? How would you say that?

[Neil Thanedar]: Garcinia cambogia. No, nutritional I would think like the RDAs or daily values of the macronutrients.

So that’s what we’re looking at. We’re working on all of these names, and we’ll have to figure out exactly what they are.

[Damien Blenkinsopp]: Yeah.

[Neil Thanedar]: But I think nutritional value, I pour it over the daily value type stuff.

[Damien Blenkinsopp]:Okay, so you compare there. And then you’ve got ingredient safety.

[Neil Thanedar]: So I’m looking at the quality of the inactive ingredients. So what’s the safety risk of the inactive ingredients?

[Damien Blenkinsopp]: Okay. So if people don’t like aspartame or something in their pills, there you go. And then projected efficacy, would that be going back to our other discussion right now, as in is this really an active molecule?

[Neil Thanedar]: Yeah. So that’s concentration of active ingredient and the quality of the active ingredient.

[Damien Blenkinsopp]: Okay, cool.

Just so people know when they go to your site what they’re looking at and how to navigate it properly. So it makes a lot more sense and they understand where things are at, and how these things are based over time. And obviously, the label accuracy is the thing that they can trust the most from the get-go.

[Neil Thanedar]: It’s really interesting, and I think we look at it that we want to have different people weigh it different ways. That’s another part of our learning curve.

Some people want to be entirely efficacy focused. So it’s just like, give me my active ingredient. And I think that’s really important to people. “I want a 95% pure Omega 3.” And some people are very focused on purity, and purity is the only thing that matters to them. And they’d almost rather take a placebo that’s pure.

And then there’s a group of people who are all about honesty and label accuracy. And I think what we want to do is we have our own weighing system, and I think we’d love that as part of the personalization process.

We’d love to have a process where you put in your own weights for what you think is most important, and the rankings change based on that.

(00:29:21) [Damien Blenkinsopp]: Great. A lot of people in the supplement industry have certificates of analysis from the manufacturers. Is this something you get from the companies?

I guess you’re not reaching out to all of these guys, you’re just kind of buying up the products.

[Neil Thanedar]: No, it’s really a retail process for us. It’s an independent purchase.

The A- people will send us their certificate of analysis. And that’s fine. Anytime we’re working with manufacturers and there’s science going back and forth, we’re in a good place.

[Damien Blenkinsopp]: Yeah, cool. So their certificate of analysis is basically the same kind of analysis or something similar, to say what’s in it, that they’ve had done either by their manufacturer or themselves or a third party lab normally. And then they can compare it to yours and say hey, I want to be A+.

[Neil Thanedar]: Yeah, and sometimes it’s the other way. Actually, more often it is a request for a certificate of analysis from us because they want to go to their supplier and complain.

[Damien Blenkinsopp]: Ah, interesting. So do you think they’ve got false certificates of analysis? Or they just didn’t…

[Neil Thanedar]: Well there’s just so many moving parts in any of these supply chains. So if you’re making a multivitamin you might be sourcing 30, 40, 50 ingredients. And so if you see the LabDoor report and two are off, you know which supplier that is and you can go find out.

And that’s something that’s really interesting data that could help the supply chain and manufacturers. And honestly, we just haven’t found a way to package that data back up. It’s just that we’ve always purely focused on how to get the data first to consumers.

And as we build up more and more data, as we start seeing trends and see more years of data, that will be another type of business that I think would be interesting for us. Because that’s important to us; I think we’d want to be more and more integrated over time.

I could see a place where maybe LabDoor does all of those types of certifications. Instead of an Organic certification and a Gluten certification and the Tested for Sports certification all being different companies. LabDoor is going to have to do all that testing anyway. So if we could somehow say look we’ve already done the testing, here’s the certification, that could be a really interesting thing for us.

We’ll look at every part of the industry in every way that we can help. That’s part of the expansion process, it’s part of how we learn, how we grow, how we provide more value.

[Damien Blenkinsopp]: And now just to consumers but, like you say, to the manufacturers and the suppliers to improve the supply chain in general. Because it’s not necessarily the brand owners.

He could design a great product and he could ask a manufacturer depending on his due diligence, and [unclear 0:31:59] just to pick up on these things. And the testing given to him might not be his fault, but it’s not exactly what he wanted in the first place.

[Neil Thanedar]: Yeah, I think it’s between that and there are so many things that they’re focusing on. And I think that we want to be the place where if you’re a manufacturer, just focus on making the best product. We’ll help show it to consumers; don’t spend money on marketing, spend money on quality ingredients.

And we’ll give you the data you need. It’s really transparent; we’re really transparent with the A- people about what it takes to get to an A. And we’ll do that with everyone else.

Every company knows, obviously, the reason I’m losing to the number one guy is they have twice as much Omega 3 per gram as I do. Now I know that it’s going to be three times more expensive for me to increase my Omega 3 concentration. But that’s a tradeoff, and they’re going to have to make that equation.

And we would love it if LabDoor was driving so much sales to the high concentration folks that the math eventually worked out, that you should just make higher quality products.

[Damien Blenkinsopp]: Right, because you’ve provided more information into the market, and more people are making informed decisions, and thus it becomes more in their interest to raise the quality because their sales volume increases based on it.

(00:33:10) [Damien Blenkinsopp]: So what types of supplements have you looked at so far, and as an overview how have you found the general quality of supplements to be? Was it what you expected? Especially based on the articles that all came out last year about testing Walmart, CVS Pharmacy and places like that. There were a lot of issues that were brought up then.

[Neil Thanedar]: I think, well there are a couple of things. So one, we’re about to release glutamine, which will be our 20th category. So if you go to LabDoor.com/rankings, you will see the 19 rankings we have done so far.

So it is more than just protein and fish oil, there’s multivitamins, prenatals. We’ve also looked at vitamin C and D, calcium, magnesium, and zinc. We’re trying to go through category by category of the most popular.

And so under that list of the top 20 are the next 50 that we’re looking at. And those, really, consumers go in and vote on what they want to see next.

[Damien Blenkinsopp]: Oh. So you’ll do that, if people are like, “Yeah, I want this reviewed.”

[Neil Thanedar]: Yeah. LabDoor.com/rankings.

[Damien Blenkinsopp]: Okay, and they can vote for something new that they want ranked.

[Neil Thanedar]: Yup. And so there’s a whole bunch of categories in there. We’re just trying to grab them as quickly as possible.

So some of the most popular ones on there like glutamine and B complex and glucosamine are already in the lab. We’re already working on them. And just keep voting. Basically, you’ll get an email when that category is available.

What I’m going to try to do is over the next year or so finish those 50 categories. Really go through and say hey, in the supplement industry you can really come up with any major product and LabDoor will have it. Have at least one set of data on it. Just enough to get you in.

And I think once we do that and really get the lab fully up and running and instead of 25 products a month we really should be doing 100 plus product per month. That’s when I would say maybe we’ll look at other categories.

Maybe we’ll look at food and beverage, maybe we’ll look at meal replacement. I mean, we’re already kind of there. Protein bars are already starting to touch meal replacement and functional foods. Even baby products, like baby food and baby formula, are really on the edge of being a supplement; they’re manufactured in very much the same way.

And so any of those types of things we’d love to be in places where you feel like there’s some uncertainty. If you feel like, I don’t know what I’m buying, that’s enough for LabDoor to jump in.

It doesn’t necessarily need to be the supplement industry where you get data every week saying something goes wrong. I think it’s even a case where you are buying baby formula and you have no idea what’s in it. At any point where there’s any of that kind of insecurity, you should look to places like LabDoor to get some science and data, and make that decision with more backing.

I actually don’t think that the, I want to try to make sure that the supplement industry doesn’t get all negative stories. Really that’s where it’s starting to go, it’s really kind of pushing it to a lot of negative stories. And that’s not really our market. You’ll see that LabDoor is not the person driving a lot of those stories.

[Damien Blenkinsopp]: Sure. I mean, what do you think of the market? You’ve got the data on nearly 20 categories now. Where would you say it’s at? If you had to explain in objective terms, where is supplement quality currently at?

[Neil Thanedar]: I think there are about three even groups of companies.

There are a third that are doing a really great job. And those are basically the A products in the market.
There is a third that are like the B and C products that are just not worth it for the money. And those are usually the guys using brand or marketing to sell products. And then you’ve got the D and F…

[Damien Blenkinsopp]: When you say brand or marketing, could you give an example of that, maybe naming a specific company? But what does that mean to you? Brand or marketing?

[Neil Thanedar]: These are companies that I’ve literally looked at some of these companies that have, first the head of R&D works for the head of marketing in a lot of these companies.

You’ll see these companies haven’t made significant investments in R and D but are spending 20, 30, 40 percent of their budget or more on marketing. And these are companies that are truly spending more on marketing as a percentage of revenue than they are on the products themselves.

And you see that in the data. And those become the B and C products that are actually usually, more expensive than the A products. We’re finding that there’s really no correlation between price and quality. There’s just none in this market.

There are people who are in the middle group who are just medium quality for high price.

[Damien Blenkinsopp]: Right. So you’ve got some products which are brand driven. They’re a premium brand and have put a lot of good marketing behind it, but actually, the product doesn’t back it up.

[Neil Thanedar]: Yeah, that’s the second third.

And I think the third is honestly the D and F grade products, where people are honestly cheating. There are, and it’s different by different categories.

Something as simple as a creatine product you usually don’t have to worry about as much. It’s just creatine in a bottle. There are fewer things that could go wrong. Those products, maybe 5 or 10 percent of products, have problems. But there are things like garcinia, 70 percent of products have problems.

[Damien Blenkinsopp]: Wow. So it really does vary a lot by [category].

So creatine has been around for a long time, and it’s extremely standardized. So I imagine there’s a bit of market development. There must be so many manufacturing facilities now that the technology is well standardized at creating creatine and everything, so it’s a little bit easier.

And it’s also something very straight forward. It’s not like it gets damaged easily, like fish oils and so on. So yeah, I guess each category can be quite different.

[Neil Thanedar]: Yeah, so each category is quite different. Overall, it’s about what we need to do is try to get people to the top third as much as possible. If we can do that, if we can really help you focus when you’re in the store.

Because that’s what’s happening in the store. There are 100 fish oils. And how are you picking with 100 fish oils? And I think that’s why the branded marketing thing works so well.

When there’re 100 fish oils, you see the brand you recognize and that just makes that purchase easier. And what we want to do is say, what if those 100 fish oils were instead ordered from one to 100 in some sort of other system based on science?

(00:39:15) [Damien Blenkinsopp]: Yeah, excellent. A couple of questions. I realize you probably don’t want to name companies, but I’m interested in the Trusted Science brands, the ones that look like they’re doing research and backing it up with content like Thorne Research, Life Extension. People tend to trust these kinds of brands.

I don’t know if you’ve looked at those types of brands. Not necessarily those guys, but similar ones which are putting out a fair amount of content on their sites, and they talk about their research. Do those tend to have reasonable quality?

[Neil Thanedar]: We haven’t tested as many of those yet, and I think the reason why is because our initial way of picking the most popular products by category was to use online best-seller lists. And the Thorne and the Life Extension are usually sold through doctors so we missed that in the first round.

[Damien Blenkinsopp]: Probably a bit more expensive for most people as well. That might be a smaller market.

[Neil Thanedar]: It’s more expensive and just in different channels.

We’d like to prove that. We’d love to test those products and see is there really a price and quality correlation there. Because otherwise, industry wide there is zero price correlation. And there are honestly categories on our site where literally the cheapest product in the category is the number one in quality.

[Damien Blenkinsopp]: Wow.

[Neil Thanedar]: It’s amazing. It doesn’t work [unclear 0:40:29] maybe in handbags or cosmetics. So these are the types of industry where that works, right?

[Damien Blenkinsopp]: Could you give us an example? Is that something like creatine? Where it’s very simple?

[Neil Thanedar]: It might have been creatine. It might have been something like creatine where the people who were really trying to jazz it up with the fancy box, and five artificial sweeteners and not enough creatine, those are the people who are expensive and at the bottom.

And vice versa; the people who just throw 100 percent creatine monohydrate in a bag do pretty well.

(00:40:58) [Damien Blenkinsopp]: Cool. Okay, so we talked about the price correlation, and that there isn’t much, which is interesting. You looked at online reviews from consumers on Amazon as well, I noticed just recently. What were your results there?

[Neil Thanedar]: Same thing. Zero correlation. And what we might need to figure out is they might be answering totally different questions. The user reviews might be totally answering the qualitative question, and we’re answering the quantitative question.

And first of all, there are certain categories of supplements, like a multivitamin for example, where other than pill size there isn’t that much qualitative that you need to worry about. You’re not taking a multivitamin like, oh I feel better today.

There’s not that much qualitative to do. These decisions should be more quantitative. They should be more scientific. And so the thing we try to talk about as much as possible is for most of these categories we should be letting user reviews go and really be focusing most of our energy on scientific reviews.

[Damien Blenkinsopp]: Yeah, well unfortunately, they’re not around everywhere. You’re working on it, but it can be hard to come by.

I used to use Consumer Lab Reports, which is the other company that was doing it. And then you guys came along, and it’s a free service versus a paid service, so it helps me out that way.

(00:42:08) [Damien Blenkinsopp]: What I want to bring up, I don’t know if you’ve seen this new company, which is kind of trying to position itself right at the top of the supplement industry which is Elysium?

[Neil Thanedar]: I’ve seen that, yes.

[Damien Blenkinsopp]: With their anti-aging. And they have a scientific board of directors.

So they’ve really tried to go more the scientific approach that we should be trusted, we’re using a pharmaceutical grade production process. We have a scientific board of advisers of some of the top scientists in this area in the world.

I found that was really interesting and really encouraging in terms of really taking a step up. And it’s got VC funding. So it’s a completely different business model, really.

And I guess it’s only been possible now because of the size of the market, where they can now have a VC driven model where they can go and get top scientific advisers on board, sometimes Nobel prize winning guys to be able to raise the standard a lot.

So, it would be interesting if you help with your work to promote that kind of activity as well.

[Neil Thanedar]: Absolutely. I feel like guys like that are the new generation of the Thorne and Pure Encapsulations. And there are more people like that. I think honest companies really try to do that not just in supplements but in cosmetics and household products.

So there are a lot of places where there’s renewed interest in that kind of high quality and direct to the consumer brand. And I think that fits really well with where LabDoor is. I think we want to, we need to get to a place where that product is in a category, versus the other people.

And that would be really interesting. There’s now food test on some of those same ingredients, for example. And there are a lot of generic manufacturers who have the same ingredients as Elysium does, but there’s an issue of do you trust the generic manufacturer.

[Damien Blenkinsopp]: It’s interesting, because I looked on Amazon, of course, for the ingredients — because they’re being transparent about the ingredients, which is another thing. Not all companies will tell you exactly what it is in the product.

Some companies you can ask them for their certificate of analysis. A lot of consumers don’t know that, but you can just contact them. And sometimes they’ll give it to you. It depends on their policy. And sometimes they’ll say sorry we don’t hand out that for propriety reasons. Or whatever.

So there are a fair number of certifications out there. I don’t know if you’ve looked at any of these. Sometimes we see these stamps on products and we don’t really know what’s behind them, a lot of the time. Have you looked at any of those?

[Neil Thanedar]: We’ve looked at it a little bit.

So, I think my general issue with certifications is there are many of them and consumers don’t really understand what they all mean. I worry that in a situation where if you give too much information, it’s an overload and actually doesn’t get paid attention to.

So that’s one of my issues with certifications. What we’d like to do at LabDoor is to try and figure out if there’s some way to get beyond a certification, beyond a pass/fail system and get to is the product really good.

Because there are two different parts to this. There’s the part where hey here are the third, or two thirds of the products that are bad. That’s fine, but I think our business is really dependent on can we help you make a good decision. Can we help you get into the good third?

And so what we need to do as much as possible is find that way of saying I’m just highlighting the good products. I think for us that’s really we have to keep focusing on it that way. And so I want to, as much as possible I would like that not to be certification based.

I think if we wanted to say, look it’s not about whether it’s organic or not, it’s about what’s the quality of the product. And in many cases, just because it’s organic doesn’t mean it’s pure, in many cases, organic products can catch a lot of heavy metals.

[Damien Blenkinsopp]: Yeah, that’s a good point.

[Neil Thanedar]: So all of those things we don’t want to get into, we don’t want to outsource the decision to that single certification. That you really should be having your decision on a holistic approach to the product.

[Damien Blenkinsopp]: Yeah. I guess whether it’s organic or not, that’s kind of a philosophy. But at the end of the day, it’s the pesticide resides and the heavy metals that people are really interested in, a lot of the time.

[Neil Thanedar]: It’s very much like the filters, to me. So, if you want to have a vegan filter, or a sugar-free filter, or an organic filter, a non-GMO filter in your life I think that’s fine.

I think that’s just a fundamentally different decision criteria that’s almost like the quality and value ranking. We’ll let those things be, let them cross, and that is useful as a filtering tool.

[Damien Blenkinsopp]: Also, I think we kind of covered this, but have you come across instances where the certificates of analysis have been different to what you found?

[Neil Thanedar]: Yeah. What we’ll do is there’s a kind of a standard process.

So if we have our testing and our certificate of analysis, a company comes with their own, then we will go to a third party lab and we will get testing done there.

And the idea is basically if the grade goes up, we’ll pay for it. If the grade goes down, they pay for it. And that’s it, right? It’s just I think that is, we want to figure out a system where it’s just [fair].

I mean, at any given point we’re defending 700 products, and soon we’ll be defending thousands of products. And so we want to be able to say at some level we want to be the referee and we understand that not everything is going to be 100 percent perfect. And we’ll just be open to it.

And if you think that something is wrong, challenge us on it. And challenge us with scientific data with a certificate of analysis and look we’ll test it. We can always test more. That’s possible. The thing we can’t do is kind of get into shouting matches with companies.

(00:47:23) [Damien Blenkinsopp]: Yeah, sure. So in terms of, to give people an idea, how often does that come up? Does it come up a lot or is it relatively rare?

[Neil Thanedar]: I would say it’s less than five percent of the companies who will ever kind of come and talk to us.

And I think a lot of people indirectly come and talk to us. We’ll get emails from their customers complaining, or things like that. There are all kinds of side things.

I think it’s something where there are some very passionate people on the manufacturing side of the industry, and I think we’ve tried to be really open with it. I think it’s important for us to actually be talking to more of the industry.

I actually should be going – and I’ll do more of this — is going and travel, spend time at supply side conferences, where people are actually talking to the manufacturers. I need to do that. And I think that’s something that as we get bigger I should be talking to half or more of the industry.

Because I think if LabDoor’s data gets back to the companies, it’s going to be good for the industry. It’ll have rapid feedback. You’ll have feedback from consumers and from the lab. Both of those things are incredibly valuable for manufacturers, and it’ll make the products better.

(00:48:30) [Damien Blenkinsopp]: So we’re talking about the technologies you’re using are relatively standardized now. They’ve been around quite a long time. I think they’re currently getting better in terms of cost, right? They’re expected to get cheaper over the next years. That was just a training I was at recently.

But I was just wondering if you think there’s some variability. So say if they did come with another certificate of analysis and then you went to a third party lab, how much variance does there tend to be between labs?

Because just in my own testing, I test a lot of different things, and there’s a fair amount of variability between the labs, unfortunately. We’re still in the middle of a kind of, I guess it’s mostly the processes and ironing out all of these things, and some of the technologies are getting more mature over time and more stable.

For these particular technologies, how stable would you say they are in the accuracy?

[Neil Thanedar]: You’re getting good data out of it.

I think even in a situation where there’s a 10 percent lab-to lab-variation, firstly there are different labs and I think [with] the labs we use we’re seeing some 10 percent variation. And in many cases, we were talking about 2-5 percent batch-to-batch variation.

So even different labs, different product in a different batch, we’re seeing pretty similar results. And that’s just some of these products, and it’s with the established companies. The thing that we’re finding is there are some companies where the product is vastly different, from category to category. There are certain things where I worry less about that.

I think what we need to do is build repeat testing into the model. Because any sort of calculation like this the confidence goes way up when you get the second, third and fourth test. So I think that’s where we’re at right now.

The first test is good data, and it’s important for consumers to get it. And then every other test, the second, third, or fourth, you get a lot of increase in confidence, and then you just have to be consistent. Then you have to get on your yearly or every-other-year basis, and we’ll be humming along normally.

And so I think for us, LabDoor Year 5 out of a 10-year process of really kind of stabilizing everything and having a fully operational machine. And then we’d want it to just automatically test products.

Like every month people request new products, we test it. We’re automatically getting into new categories, we’re automatically maybe thinking about new ways to rank products, we’re getting deeper and deeper into personalization. But it’s a very, it’ll be a very consistent improvement process.

[Damien Blenkinsopp]: Have you got plans to retest any categories yet? Or are you doing your first retest with any category yet this coming year, or is it going to be a little way off yet?

[Neil Thanedar]: No, I think, well yeah, we’ll be doing retesting. I think we’ll get multivitamins retested next year. There will be whole categories.

We want to be, in 2017 if we can get to the point where we are not just, we’re marking the dates on when we tested it last and predicting when we’re going to test it next. And really as much as possible, say the popular categories are every year, the less popular every two years.

And again, just like everything, we can start shrinking those things because right now we’re on basically two-year testing cycles. And we want to push everything to yearly testing cycles.

And it would be great to say that LabDoor 2016 protein data is this and 2017 protein is this, and let’s see the trend of which brands have been consistently at the top and consistently at the bottom. Those are all things that it is about, we need more lab capacity. We need more testing.

We’re going out and we’ve raised venture capital. And so that’s a big part of this process and a big part of the reason why we think we can do 100 products a month next year instead of 25 products per month. That’s a big part of that too.

That’s how we’re going to get there. We’re going to have to get there 100 products a month at a time. We’re not going to be able to download the database of 100,000 products because that doesn’t exist.

[Damien Blenkinsopp]: Yeah. It’s step by step. You’re building lab capacity basically over time and trying to make sure it’s monetized. So it’s a step by step process. Great.

(00:52:19) [Damien Blenkinsopp]: Now let’s talk about some specific case studies from some of the more interesting takeaways. What have been some of the worst lab results you’ve seen in categories?

[Neil Thanedar]: I mean, the garcinia cambogia was still the worst category we ever saw. There were fully 70 percent of the products that did not have the labeled active ingredient.

[Damien Blenkinsopp]: So they had zero, had nothing?

[Neil Thanedar]: No, they had less than their quantity, but they had…well we’re talking about 10 percent or less than the label claimed, that kind of thing. For most of those products. To the point where it’s essentially nothing.

And what that is is that was a lot of fly-by-night, they are usually selling on Amazon. This is something where you can just spin up a brand out of nowhere, white label it, throw it onto Amazon and there’s no check. There’s nothing between you.

And then theoretically, there are user reviews between you and that product, but then these companies buy user reviews too. And so that’s it, there’s literally nothing between you and this product hitting the market.

And so we’ve seen, the cool thing is you go and look at a lot of those affiliate links and they’re broken, which means that the products have come off of Amazon, so not being sold anymore. And so there’s some sort of cat and mouse game there.

I’m sure some of them have spun up and made new products, and we’re going to have to go chase those down. But at least in some of those cases, we’re seeing that they’re gone, they’re not there anymore. And I think in those cases we do our job, when we show people what’s right and wrong. I think we’ve done a good job.

I think there are categories like that where 70 percent of products fail, there are categories like creatine where 10 percent or fewer products fail. And then there’s kind of the in-between zones where with fish oil you’ve got about a quarter of the products have rancidity issues. And so we’re filtering that, and that’s part of purity; that’s a part of our purity score.

So we’re seeing in different categories there are issues, but I think in the other categories they’re more like, hey there’s this like, half of the products that you need to avoid. Or there’s 30 percent of products or 10 percent of products you need to avoid. It’s still worth checking. Right?

In any of these situations, it’s still worth checking, but that’s the range we’re at. Somewhere between 10 and 70 percent you’ve got to worry about.

(00:54:21) [Damien Blenkinsopp]: Excellent. So, as you were talking there, I kind of took some guidelines or rules away from the situations you brought up.

Do you have any guidelines in your mind from the research you’ve done so far, on like if there is no data, having been through your research process, have you seen any patterns where you’re like, okay instead I’d use this heuristic to decide which product to buy, if I don’t have access to the data right now.

[Neil Thanedar]: We’re not seeing very much brand correlation. There’s not a ton of brand correlation.

One thing we find is that companies that only make one or two things do really well. So like a company that specializes in probiotics does a really good job in probiotics, but actually has a B- multivitamin or something. Those types of things happen a lot.

And so you have a protein specialist or the creatine specialist that does really well there; fish oil is the same way. So think about that. I think that might be one thing to think about, people who are specialists.

And then really other than that, send us the link on LabDoor and we will add it to our site. I think we need to test those products. We’ve had the luxury I think a little bit of kind of growing quietly. I think a lot of people are just learning about us five years later.

And we did that on purpose. And we did that very, kind of fundamentally we said we’re going to just focus on one category. We won’t go to the press saying, hey LabDoor is this great company, we’ll say hey look at LabDoor’s fish oil data, or look at LabDoor’s Vitamin C data. Look at LabDoor’s multivitamin data.

That part of it I think we’ve been focused on just, come listen to us about what we know. We’ll be an expert in certain things. We’ll be a destination in one category at a time.

And now I think we’re at a point where we need to move faster. And I think that’s why we’ve gone and raised more money. We are kind of going in and buying HPLCs and bringing them into the building. We’re buying auto-samplers. All this kind of stuff to make things go faster.

And so at this point, if you can find things that are specialty products and you trust them, take them. Otherwise, I’m really at the point where I’m waiting. I’m actually saying, well I’m thinking about taking curcumin, but I’ll wait six months until LabDoor tests it.

I might be in that process, I think because I know curcumin is going to be one of many other categories that are going to be… You’ve got an extract that certain companies, certain products are going to really pull a lot of heavy metals out of that extract. There are different extraction processes.

[Damien Blenkinsopp]: Yeah. There are some like that which are going to be challenging, for sure. Because it comes from turmeric, and turmeric can come from all sorts of places. So you can tell that one is going to be a complex one.

[Neil Thanedar]: And that reminds me of something like Ginseng, where the ginsenoside content you can look at. Ginseng is different than the active ingredient, and so you’re not always getting the same extraction. And it’s not consistent. And so in cases like that, I would basically say wait. And that’s how I do it. I wait until LabDoor has some data.

[Damien Blenkinsopp]: And you’ve got the inside guide to that. Okay. Great.

(00:57:20) [Damien Blenkinsopp]: The other heuristic I was thinking of was you were talking — because I’ve seen this a lot in Amazon — is you have these one product wonder companies, where they basically just make one product. And I think they just pop up.

There’s a new fat loss supplement that they just kind of jump on board. And you see that this company otherwise doesn’t seem to be anywhere or doing anything, but it’s just made this one product. Even it’s website sometimes isn’t great.

But on Amazon they’ve got thousands of reviews, and sometimes they’re at the top of the category. And you’re like what’s going on here? And often they’re giving away products for reviews, and they’re using a whole bunch of marketing tactics to establish themselves there.

But if you look a bit more into the company they don’t have a strong background and they’re just going to come and go. So that’s one of the things I’ve also noticed a little bit that might be worth thinking about.

[Neil Thanedar]: Yeah, we see those a lot too. I think LabDoor is really meant to replace heuristics with kind of a scientific method as much as possible. And I think that’s just really what, bringing us all the way back to the beginning, it’s really what motivated the idea of LabDoor at the beginning.

It was just the idea of imagining standing in a Walgreens with 100 options, and how are you making that decision? You’re going to use the heuristic, you’re going to use… If you were buying wine you would buy the second cheapest. There’s all these goofy heuristics that you can use. Maybe you buy the cheapest, maybe you buy the house brand, maybe you buy the famous brand, you buy the most expensive.

Everyone’s got their system. And we are kind of just consistently finding that any one of these heuristics has no correlation to the scientific data. So you really just have to keep coming back to the data to make your decision.

[Damien Blenkinsopp]: It’ll be interesting at some point for you to publish which heuristics were the worst in correlation.

[Neil Thanedar]: Oh man, I’d love that. That’s a great one.

I think we mess with this all the time, and I think this is another thing that we’d love to do more at LabDoor is get outside of just the testing that we have to do to grow the site. If we’re able to test 100 or 150 products we might have some leeway to take 10 or 20 or 50 products and just say, hey you want us to test a Chipotle burrito or a McDonald’s BigMac, we’ll do that too. Just because it’s interesting to us.

Or we might want to get into talking about user reviews. We might want to talk about trying to figure out a system to verify user reviews, or figure out whether…

Maybe actually teach people about these correlations. Teach people that there’s really no correlation between price and quality. So you shouldn’t use price. There’s no correlation between user reviews and quality in these categories.

And you should really think about what kind of products are experienced based products, where 10 minutes after you finished your meal you know whether it was good or not. And which products are truly scientific products.

[Damien Blenkinsopp]: And which are just subjects of experience. Someone’s just like, oh yeah I kind of like the brand and I bought it and I really enjoy the brand.

[Neil Thanedar]: Yeah. And so we really want to make, we have to figure that out. And I think that is such a — I mean we did that in VC meetings.

We literally, I was walking to the elevator after one of these VC meetings of an investor who said no. And he said, “You know the entire history of the universe, marketing has won.”

[Damien Blenkinsopp]: Marketing will find a way.

[Neil Thanedar]: And I said look, maybe we will. And we’ve kind of thought about that, and we said look maybe we just need to market the science better. We need to figure out ways to make the data easier to understand. We need to go, and that’s part of our team.

And so I think we’ll do that. We’ll find easier ways to teach this. Maybe we’ll redo the Pepsi challenge. And you redo the Pepsi challenge and you talk about, hey, there were problems with the Pepsi challenge. First, Pepsi was running the Pepsi challenge, and there are some credibility issues there.

And all of these things, and you can teach people through very simple systems that they already understand. “Hey this is how you’re currently making decisions, and this is how you are currently being marketed to and here’s how you should be marketed to. You should be marketed to based on science, based on the data, based on transparency and objectivity.”

[Damien Blenkinsopp]: I think the fact that Elysium and other companies like that are now showing up is showing that there is something changing.

Of course, marketing is always going to be important but I think some of this authoritative input is starting to become a lot more important, and trust. You see it across the markets, and there’s a lot of people talking about it. And so Gary Vaynerchuk and I, some of these people — I don’t know if you’ve ever heard of him.

[Neil Thanedar]: Yeah. Yeah, yeah.

(01:01:44) [Damien Blenkinsopp]: Yeah. But I think they’ve definitely got a point about trust for authority, and so on. And it’s going to become bigger and bigger. What are you looking forward to in this space? Are there going to be changes in technology which are going to help you over the next five or even 10 years do a better job of this? What are you looking forward to in this space?

[Neil Thanedar]: I honestly think it’s, for us, it’s as simple as getting 10 times bigger. I think if we get 10 times bigger every part of the system makes sense for us. And I think that’s what we’re trying to figure out.

We just got to 15 employees. This is a pretty tight unit here. And we need to go, as we grow from 10 to 100 employees here, and these are going to be mostly science and technology folks, those are the structures right now where we’ll be able to unpack some of these jobs. People who are doing five or six or seven jobs will be just doing one.

And we’ll be able to add some redundancy, we’ll be able to add more testing, we’ll be able to go faster. And really we’ll be able to, the spool engine will be running where, well really the old categories are paying for the new categories. All of that stuff needs to happen.

And as we grow, as we do that, I think this is where I see LabDoor becoming a more and more mainstream brand over the next 5, 10 years. And I want to have, very much like more experienced products like restaurants, you don’t buy without checking Yelp.

I think you really want to say for scientific products, for medical products, for health products, you don’t buy without checking LabDoor.

[Damien Blenkinsopp]: Where you want a functional benefit, you’re looking for this functional benefit.

[Neil Thanedar]: Does it work if it’s fake? Then, the more you think about that, you make so many decisions like that.

I just did this with a household cleaner. I was thinking about buying this Method cleaner versus this Honest company cleaner versus this Clorox cleaner. Does the green cleaner work? Does that organic certification matter?

You’ve got all the same problems. Is there anything toxic in this? I’m going to breathe this in, I might eat it. You’ve got all the same problems as you do with a supplement, and you make that decision even more casually than you do with a supplement because there’s even less data.

And we have to get into more and more of these categories. And I need it to be in a place where maybe I have your whole profile, I know exactly what you’re allergic to, I know exactly what your preferences are and I’m helping you in the entire drug store to make quality decisions.

(01:03:59) [Damien Blenkinsopp]: For a little case study there, I’ve been testing a whole bunch of pesticides and heavy metals and so on.

One of the more unique and interesting things I came out with in my samples was really really high atrazine mercapturate. Which was interesting because it’s been banned in the EU where I’ve spent some time since 2004 I think.

And so mine was off the chart; it was like 96th percentile. So I was hunting around trying to figure out where this stuff was coming from.

[Neil Thanedar]: Wow.

[Damien Blenkinsopp]: And I recently, I’ve been keto since January and so I started using different oils. One of them was macadamia oil, and it just happens to come from Australia where atrazine isn’t banned.

And I’m guessing [it’s out] because I’ve stopped that now. I looked into the research and it’s very probable that that’s where it came from. So I’m guessing that will be gone from my system the next time I test.

But yeah, just to say that this isn’t a theory. It happens and if you test your own body samples you can come up with stuff, and you’re like, “Whoa, I’m eating something toxic and I had no idea, didn’t even think about it.”

And I’m one of the guys who tests a lot more and thinks more about this stuff than most people. So if I’m getting that kind of effect, I figure most people are getting more of an effect than me.

[Neil Thanedar]: Absolutely. It’s so important to check. And I think, there’s too much. I hear too many of these stories.

Whenever you see that new negative supplement story, I think what happens is people withdraw and they become less likely to buy. Or they become more attached to their existing purchases. They stick to their existing brands.

And I think both of those kinds of withdrawing motions are wrong; you actually should go out and get more data. But the problem is it becomes this thing where there’s a lot of negativity and you don’t want to go out and get more data.

And so I think what we want to do with LabDoor is say look, well focus you on the best products. We’ll focus you on the A grade products, and let’s make it a good story. Let’s focus sales in the market, let’s put 100,000 of people a month and let’s focus them on the best products in the market.

Let’s reward companies for doing a good job and making a great product. And let’s see if there’s something really positive that we can do. Can we really reorganize the market to where the best quality products are making the most sales?

(01:06:06) [Damien Blenkinsopp]: Alright, so this could be a more challenging question, I guess. Just because some people wonder about this, but it can be really interesting what comes out of it.

Is there anything you’ve changed your mind about in the last few years in the testing area, or in supplements in general? Is there an underlying assumption of how you go about things, or what you’ve been thinking, that you’ve kind of turned on its head?

[Neil Thanedar]: There’s been a couple. I think one of them was really, we’ve kind of gone in two different directions with the data. We started with very technical, these long reports.

And then we went all the way in the other direction with this A through F grade, which was very simple, and the rankings were very simple. And we definitely needed to do that because I think that’s really what helped people actually use LabDoor.

And what we’ll probably do is slowly taper it. Our idea is to do every version of it. We’ve actually thought about this idea, we used to think of that as a fight between more data or less data. And I think the answer is actually all of the above, but we need to organize it.

So first you see the A, and the A breaks down into five categories. And those five categories break down into this data. And so what we’re trying to do, as much as possible, is everything. This is the point where we used to get into these fights of more or less, and I think the right answer is everything. And that’s one of the big things we’ve learned.

I think the bigger one, in terms of my mind changing, was really — we talked about it a little bit earlier — the manufacturers. I think I used to just be 100 percent consumer focused, and just said this is all about being the consumer watchdog.

And it still is about being the consumer watchdog, but more importantly, we are a marketplace that’s organizing these decisions for consumers. And so I think when it really comes down to it, our job is connecting consumers to the best companies and the best products.

And if that connection then makes us really good, and it’s not… The thing where we show people that there’s a bad product on the market is part of our job, but it’s not the core job.

And I think that was the thing that we switched. We came out there kind of guns blazing wanting to try and find the bad stuff, and increasingly we’re realizing that our job is just to find the good stuff.

(01:08:21) [Damien Blenkinsopp]: Okay. I’d like to hear a little bit more about you.

Do you look at improving your body and use of tracking? You’ve kind of already given us a couple of takeaways, but is there anything you track in terms of metrics or biomarkers or anything like that? For yourself?

[Neil Thanedar]: So these days my biggest focus is very, really into mental performance.

So I have a tracker of my major daily tasks that I do. And then I have a time tracker, where I’m measuring how much time I’m spending in a day learning versus planning versus training versus communicating versus executing in the business.

And so I’m separating my time and I’ve been using that to figure out… And I’m using that for optimization right now. For example, I’m noticing that as our company scales, I’m just noticing more push from executing to communicating. I’m seeing that switch, and really communicating is starting to become the more dominant mode.

And so I think for me between that and between more… I really like Headspace and Lucid, which are two mental training apps. Lucid is more focused on almost professional athletes. It might be more of strength training for your mind. Whereas I think something like Headspace might be more about conditioning, and it’s more about the endurance of kind of long-term training.

And so really that’s been my focus. In terms of my physical health, it’s really simple. I have Vitamin D and Fish Oil that I take every day, and protein and creatine that I take after workouts, and that’s really my base stock. There’s not really much that I’m doing.

There are, after that I’m curious about a lot of different ingredients that I’m waiting for us to test. I used to be a wrestler for many years, so I have achy knees. And so I’ve always been looking for joint supportive curcumin products. So that’s been something that’s really curious to me.

I really have been curious about nootropics and different kind of mental [supplements]. I’d love to see more caffeine plus thiamin plus other ingredient research. Try to figure out ways where LabDoor can get better at thinking about synergies between ingredients.

Those are things where it’s almost like we need to figure it out. We need to figure out the science before we can do the ranking, but those are the types of things we’re figuring out. And I think if we did that I would love to experiment more into the nootropics side, if I could get it right.

And so that’s how I track, but I think the last two or three years have been very mental focused. I feel like maybe the 10 years before that, between sports and through college I was so focused on all my physical numbers. And every since LabDoor especially it’s been very focused on my mental output.

[Damien Blenkinsopp]: Great. So that time tracking thing that you’ve done, are you tracking every minute of your day with an app in your phone or something? How do you do it?

[Neil Thanedar]: Yeah, so it’s an app called Hours. So all you have to do is turn it on in the morning, and then you switch it between different tasks. I don’t switch it between things too often, so it might only be five or ten total transitions per day. It measures it over time.

That’s really the most zoomed out version of it, and I try to do these things in sprints. So it reminds me the same thing of calorie tracking. I got a really great recommendation from a dietician once that said, “Track every calorie for 10 days and then stop.”

And that’s basically the same thing I’m going to do with this tracking. I’ve been doing it for seven days; I’ll do it for 10 every quarter or every six months, something like that. And I would come back to it and make sure.

The Headspace or Lucid I’m actually doing that at least, Headspace at least 3 times a week, mental training at least 5 times a week. So those I’m actually getting into the gyms, so to say, and getting my work in. But the really detailed tracking I try as much as possible to limit into specific sections.

[Damien Blenkinsopp]: Yeah. Tracking can be time-consuming. That’s the way I found it, to be more beneficial as well, basically doing what I call projects.

I do a project for a couple of weeks or something, make an adjustment. Hopefully, an action or something comes out of it and then move on to the next.

Actually, a lot of my friends have also done the time tracking thing. I did it for about 3 months, many many years ago. I learned so much about where my time was going, and I made adjustments on an every day basis. I haven’t gone back to it; maybe I should go back to it at this point, because who knows what’s happened now.

Did you get any, what are your big takeaways so far in the seven days? Do you make any changes, like, “Wow, I’m spending a lot of time there”?

[Neil Thanedar]: One thing that was initially bothering me that I felt like I wasn’t spending enough of my time actually executing.

And I think it actually taught me that when I was actually tracking what I was doing with that time instead, I was realizing that it was a lot of casual, like grab someone for 10 minutes and talk to them about something specific that we’d want to improve. And that was really high-value time.

And I was scared to do it because I felt like sitting at my desk writing emails seems much more productive. So I think that was really what it is. And I think so much of the mental training and kind of this work was actually just kind of confidence that you’re doing the right thing.

This is kind of just bringing the calm down, and kind of just bringing yourself into your zone as much as possible, and just feeling like… Just getting your priorities right.

I think that was the other thing. I had my priorities right and I was worried about it. And I think that’s why the 10 days really works because it’s just a nice check in. And if you feel like you’re doing a good job, or in the time like now that’s a bit of a transition, you can make a move.

(01:14:07) [Damien Blenkinsopp]: Great. Great. If you were to recommend one experiment someone should try to improve any aspects of their body, like mental performance or whatever you would think to have the biggest payoff, or likely to have a payoff, what would it be?

[Neil Thanedar]: I’m going to make sales for this mental training.

I came up with a system where also I think part of habit forming is attaching it to something. Attaching it to something where your new habit is attached to something that you do a lot.

And I think, one thing I noticed was I always get into moments where I’ll work for an hour or two, and then I’ll get up and want to pace or something. And then I’ll come back and sit down.

And so what I did is I said the first time, I noticed that the trigger for the pacing was something like I would get agitated or I had been working for too long. That’s the trigger. It feels negative, something negative is that trigger.

And what I attached it to is that first time I felt that kind of, I need to get up off my desk and go somewhere else, the first time of the day I felt that I would take my mental training app and do a 10 minute session. In that moment where I’m frustrated and agitated, I would take that moment.

And there are a couple of magical things. First, every single day of my life I have an agitated moment, so I always train. And it reminds me that when I’m agitated, it calms me down and then I get back. So it’s like a positive rep.

And any time I can turn that, you try to take a negative rep and turn it into a positive rep it’s always a huge improvement. Because it does a [unclear 1:15:35]. And so I’m trying, as much as possible, to focus on the atomic unit of the habit, and just getting it right each time.

[Damien Blenkinsopp]: Cool. Thanks for that. This is really interesting. Basically attaching it to something that happens to you all the time. And that you want to get rid of. So you’ve got that trigger, and you just turn it around.

(01:15:55) [Damien Blenkinsopp]: Okay. Where should, I mean we probably already know, but where should someone look to learn more about this topic from you?

Are there any good books or presentations on testing? Is there any more information if they want to geek out on this?

[Neil Thanedar]: The thing you want to do, I mean obviously for anything testing related go to LabDoor.com/rankings, that’s where we’re going to do all the voting. So to vote for things, I think that really helps us. Send us emails or Twitter or Facebook messages and tell us what you want us to test and we’ll test it.

Everything after that I think what we’d really like to do, and I think I really want to focus on people knowing that there are good supplements in every category. These things are safe. This market is safe. And it really is a matter of just doing your research.

And I think as much as possible if we can push and we can get into a sense where we’re focused on the research, and we’re buying based on science, that’s really what’s going to drive this. The more and more people who buy through LabDoor, if I can go to a company and they know that 20 percent of their sales are from LabDoor, that starts becoming a thing where, hey this is one of my major sales channels.

And that’s going to happen. And I think right now we might be in the 5 or 10 percent range for some companies. And we’re growing. And in some companies, it’s in different ranges.

And we want to get that up, and we want people to pressure themselves to focus more on science. To really make these decisions the right way. And I think it will pull up. I think the whole industry will come up and we will all get better products, and we’ll all be healthier out of it.

[Damien Blenkinsopp]: So when they go to your website, are there more details on what you’re doing? If some of the guys are listening to this today and they want to understand better what you’re doing, are there any resources on your website or anything they could look at?

[Neil Thanedar]: So, that’s honestly something we’re not doing a great job of right now.

So there’s some stuff on our site. If you go to LabDoor.com, it’ll explain how we make money, a little more detail to explain what labs we use and things like that. It even, on our top bar, it will say how we grade. So if you want to click there and get deeper into what the five grades mean, that’s something that we can do as well.

But I think the thing that we want to do this year, over the next 12 or 18 months a big focus for us will be bringing people into the lab. Can we do experiments for you? If anyone had a question or just wanted to do an experiment, I’d want to be able to do that more. I want to be able to bring cameras into the lab more.

All of that stuff, I want people to ask those questions. We’re working through YouTube right now. We’re trying to, we have a new studio that I’m standing in now that we’re trying to [use] to answer questions as much as possible.

And so I think for us, as much as possible it’s just being as transparent as possible, and doing Podcasts like this. Just talking to people. I think the first four or five years we needed to be quiet and do our work as much as possible.

And this is we’re just doing that transition point where we might step out, look up, and say hey people come look at this. We’ve got something here.

(01:18:54) [Damien Blenkinsopp]: Excellent. How can people best connect with you? Either you or the company?

[Neil Thanedar]: Facebook and Reddit are the two fastest ways that people get to us.

So if you want to talk to the company it’s just Facebook.com/LabDoor, or our Reddit user is just LabDoor and we’ve answered hundreds of questions on there. And sometimes that sparks lively debate, and we love that. The idea of why should certain rankings matter? Why does label accuracy versus projected efficacy, the weightings. It gets really into the details. That’s a really interesting way to do that.

I’m on twitter if you want to find me at Neil Thanedar. On Twitter, you’ll find I’m using talking about LabDoor or different things, like my ideas about testing. I think as we grow I started to think more and more about how LabDoor touches other industries.

While at the core we’re this scientific lab, there’s a big part of us that is a technology start-up. There’s a big part of us that is an online media company. At some level we’re journalists. And so as it unpacks, as we get deeper and deeper into LabDoor, my interests of what LabDoor can have kind of expanded.

So if you have any ideas about what we should test next or what, hey you should grade it differently, or you should think about LabDoor in a different way, I love thinking about that. I love dissecting what are the moving parts in any sort of industry. Not just ours, in any industry or business, it is fascinating to me.

So unpacking those is always so interesting. So yeah, ask me questions about that, happy to chat forever about stuff like that.

(01:20:32) [Damien Blenkinsopp]: Excellent. Thanks, that’s great. Do you have anything to ask or request from my audience? Anything specific?

[Neil Thanedar]: It really is, never buy supplements without checking LabDoor. Use our affiliate links, help support LabDoor’s business. And if there’s anyone that you know that, just help spread the word at this point.

I think we are right in that phase where I mean Yelp is really only 15 or 20 years old at this point. It took them a good 5 or 10 years to establish that brand. And that’s really that zone that we’re in right now, where we’re going from this ugg start to this trusted rating agency.

And part of that, most of that, is really going to be people telling their friends about LabDoor, and saying once you try it, you trust it and you keep using it. That’s really our business, and we’re going to grow as fast as people help us grow.

And so as much as possible, if there’s any way that your folks can share the word, we’d love that.

[Damien Blenkinsopp]: Okay. Thank you.

Neil, thanks for your time. It’s been a really great interview. I really learned a lot about the whole testing situation, and where it’s at. So it’s going to be really useful for everyone.

[Neil Thanedar]: Yeah, absolutely. Thanks for having me.

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Micronutrient status is a foundation of health, performance and chronic disease minimization. This episode looks at how to optimize fat soluble micronutrients status.

In this episode we look at ensuring micronutrient status. Ensuring your body has the building blocks it needs to do what it needs to do. This is an important lever to increasing your health span and current functionality and performance.

Previously we discussed micronutrient status with a focus on magnesium in episode 17 with Dr. Carolyn Dean.

This episode is about fat-soluble micronutrients including vitamin A, D and K. I personally look at micronutrient status as a foundational piece to get covered first. It is easier to do than most things and has wide ranging impacts thus it’s a good place to start.

Something else I wish to highlight for you to pay attention to in today’s episode is looking at the body as a set of dynamic systems. Typically we think we just have to raise one value into an optimum range with blood work or labs or so on.

However, as you will learn today, even with respect to basic vitamins it is often not that simple. It can be personally nuanced (different for each person). There are interplays between different markers to consider, thus the benefits of looking at several markers at one time, which we have discussed before. For instance, making use of a panel to get a realistic picture, by looking at several markers which point out one aspect of functionality in your body.

You focus on vitamin K but you may not realize what’s ultimately missing is something upstream that’s allowing vitamin K to fulfill its function. Just throwing vitamin K at the system isn’t going to do anything. It’s really important that we continually improve our understanding about how to figure out what the weakest link in the chain is because we’re always going to get the biggest benefit from fixing what’s missing.

– Chris Masterjohn

Today’s guest is Chris Masterjohn. He has a PhD in Nutritional Sciences and he is currently Assistant Professor of Health and Nutrition Sciences at Brooklyn College, part of the city university of New York.

In the last five years Chris has been responsible for originating influential ideas and papers on the fat-soluble vitamins A, D and K. The importance of their role in the body and addressing that status, the status of these micronutrients to promote health.

If you follow the Paleo, Ancestral Health or Western A Price Foundation communities it would be difficult to not have already come across some of his work. Chris now has both a podcast as well as his own blog named The Daily Lipid, where he covers his ideas and research on optimum nutrition. His podcast is both technically detailed and has a lot of practical takeaways. I highly recommend you also check that out.

The episode highlights, biomarkers, and links to the apps, devices and labs and everything else mentioned are below. Enjoy the show and let me know what you think in the comments!

itunes quantified body

What You’ll Learn

  • How Chris developed interest in researching fat soluble micronutrients (4:16).
  • The health issues our guest was better enabled to resolve by studying fat soluble micronutrients (6:30).
  • Chris primarily researches vitamins A, D, and K all of which are tightly connected in a functional physiological network (7:56).
  • Vitamins are integral parts of a broad system which can be optimized, as opposed to individual separate nutrients (9:32).
  • Examples of how molecular mechanisms involving micronutrients are inter-dependent in regulating a range of functions (10:28).
  • Focusing on improving the most deficient part of an interconnected nutrient system – thus bring about the greatest benefit (15:08).
  • Different diseases often share common root causes, involving lack of micronutrients or improper distribution in the body (17:00).
  • The science of interpreting vitamin K deficiency in children and young people (19:30).
  • The differences between vitamin K1 and K2 in managing risks factors for various health issues (27:02).
  • Pharmacological doses of vitamin K2 and how these are tested and used (28:44).
  • It is preferable to take vitamin K in doses close to the range of maximal concentrations obtainable from food intake (29:29).
  • Micronutrients have independent functions including regulation of gene expression – thus leading to biological complexity (30:13).
  • How the body manages vitamin K when faced with deficient supplies (34:00).
  • Variation of micronutrient intake from various diets and caveats for analyzing outcomes of specific diets (36:00).
  • Managing a healthy micronutrient system with various types of diets (42:28).
  • Testing, supplementing, and understanding the factors influencing vitamin D in complex physiological systems (43:48).
  • Maintaining balanced vitamin intake by diversifying food types and lifestyle changes (49:49).
  • Why adding fermented foods is the optimal strategy for properly managing vitamin K2 intake (52:50).
  • Subscribing to local farms and weekly auto delivery of groceries (54:20).
  • Strategy for maintaining variability in consuming vegetables by weekly rotations (54:52).
  • Parathyroid Hormone (PTH) is a more specific marker of inadequacy in the body’s calcium-vitamin D economy, compared to 25(OH) vitamin D (56:39).
  • Deriving conclusions regarding nutrient intake based on ‘shotgun’ genetic analysis is tricky; often sufficient scientific evidence is lacking (1:02:08).
  • Vitamin A testing and how deficiency influences impaired eye vision (01:07:10).
  • Making nutrient test ranges actionable and novel biomarkers (1:08:52).
  • A Dutch company offers testing specifically for the inactive form of Matrix Gla protein (MGP), as of yet only via research-purpose contracts with clinicians (1:13:02).
  • The broader context in understanding testing for Vitamin K2 deficiency (1:14:16).
  • What projects are the main focus of Chris’s current work (1:15:27).
  • Using of high dose fish oil in resolving inflammation issues (1:18:24).
  • What Chris has changed his mind about in the last few years (1:19:26).
  • What biomarkers Chris tracks on a routine basis to improve his health and performance (1:20:38).
  • The legal aspects of drawing larger amounts of blood from consenting adults, or yourself at home (1:24:26).
  • Chris’s recommendations for routine monitoring of our health (1:25:49).
  • Discovering more about Chris and keeping up with his work (1:29:23).

Thank Chris Masterjohn on Twitter for this interview.
Click Here to let him know you enjoyed the show!

Chris Masterjohn (Ph.D), The Daily Lipid Blog

Recommended Self-Experiment

  1. Tool/ Tactic: Improve your body composition by becoming more aware of your caloric intake. Chris believes is a high impact lever for most people, and will likely have downstream benefits for insulin sensitivity and the other systems discussed in this episode.
  2. Tracking: Build a habit of tracking your waist circumference, your body weight and keeping a food log with an app like MyFitnessPal.

Tools & Tactics

Diet & Nutrition

  • Vitamin AThe physiologically active form of vitamin A is retinol which occurs only in animal foods. However red, orange, yellow, and green colored vegetables are rich in carotenoids – precursors to retinol. To maintain your vitamin A at recommended daily allowance (RDA), one serving of liver per week covers vitamin A nutritional requirement. Liver cod oil is also a rich source.
  • Vitamin K: The general population obtains Vitamin K primarily via cheese and egg yolk consumption. Vitamin K2 is a sub-type of vit K found in animal products and fermented foods. Vitamin K1 is found in green-leafy plant foods. Vitamin K2 is more effective at activating your body’s vitamin K-dependent protective system. The richest source of vitamin K2 is natto, a fermented soy food popular in east Japan. You can use the natto bacteria to prepare homemade fermented vegetables as a good source of vitamin K2.
  • Vitamin D: Different foods contain varying amounts of particular nutrients. A fish’s liver tends to be high in vitamin D and A for instance. The same is not the case for terrestrial animals’ liver meat – because terrestrials store vitamin D primarily in blood and not the liver. You can compensate for not eating traditional sources of Vitamin D (such as fish), by increasing sunshine exposure. Eating UVB irradiated mushrooms is also a rich source of vitamin D.
  • Variety In Dieting: Adding different foods to your diet, such that steady levels of necessary vitamins can be achieved. This can be done by week-to-week rotations of food types.
  • Thrive Market: An online service for ordering groceries ex. for weekly auto-delivery. Subscribing to local farms is another useful tip for increasing productivity in diversifying your diet.
  • Vegetarian / Vegan: A vegetarian diet excludes meat by focusing on plants for food. In addition to excluding all meat products, a vegan diet usually also excludes all animal products, such as cheese and eggs. Genetic compatibility with diet types plays is important for vitamin nutrition. For example, common genetic polymorphisms, dietary and metabolic factors influence body’s ability to convert carotenoids to retinol. Note: Both Damien and Chris experienced exaggerated symptoms of tooth decay during vegan dieting – indicating insufficiency in calcium flow to bone tissue including the teeth.
  • Paleo: A diet focused on foods which paleolithic humans might likely have eaten. It is based on the idea that modern diseases result from a mismatch between our evolutionary and current-day environments (including dieting style). Whether paleo effectively supports your micronutrient system depends on defining the diet. A paleo diet based on restricting foods (often similar to an average American diet except grains, legumes and dairy) is not sufficient. Paying attention to organ meats is a solution because these are rich in fat-soluble nutrients.
  • KetogenicA high fat, moderate protein and low carbohydrate diet. Metabolism is altered so that ketones are used instead of glucose for fuel. See episode 7 with Jimmy Moore for detailed discussion on the benefits of this dietary approach. Carbon dioxide is required for the functionality of vitamin K. Given that carbohydrates produce up to 50% more carbon dioxide than fats do, you must must maintain minimal necessary carbohydrate intake – especially with ketogenic dieting.

Supplementation

  • Targeted Reason: Most-often supplementing an individual vitamin is not necessary solely based on a low result. Upstream factors often influence the functionality of a particular nutrient on a systemic level. Have a targeted reason for supplementing, start with conservative doses, and titrate to higher levels based on response.
  • Vitamin K Pharmacological Doses: Vitamin K supplementation has been shown to be more effective than osteoporosis drugs in reducing the risk of bone fracture. The adequate intake level for vitamin K is set at 90 μg/day for women and 120 μg/day for men. In trials involving very high vitamin K intake (ex. 500mcg doses), it remains unknown whether the effects seen at such pharmacological doses are already achieved with much lower doses. For example, the initial 45mg of the dose might be sufficient to cause equal effects.
  • High Dose Fish Oil: Fish oil rich in EPA has been found to be counterproductive in balancing the inflammatory effects of omega 6-fatty acids. Other interactions alter EPA influence in resolving inflammation pathways. Damien promises to include the topic of resolving inflammation by using high dose fish oil, because this is specific to him.

Tracking

Micronutrient System

  • The System: Consists of vitamin A, D, and E – collectively known as the fat-soluble vitamins. These micronutrients are absorbed in fat and stored in tissues, for example in the liver. The system demonstrates multilayered biological complexity. Understanding the interdependence of vitamin-regulated physiological mechanisms is key to taking action and optimizing micronutrient status.
  • Reference Ranges: In general for fat-soluble micronutrients, Chris prefers people to remain in the middle of a range compared to the lower range portion. Damien argues that it is worthwhile to be in the top third of most ranges, because the general population is characterized with non-optimal health.

Biomarkers

  • Matrix Gla Protein (MGP): A vitamin K-dependent protein which regulates calcium flow. MGP continually removes calcium from arteries (where calcium is a risk factor for plaque formation and cardiovascular disease) and moves it into bone tissue (where calcium is needed for proper bone metabolism and preventing osteoporosis). Quantifying MGP in its activated form is not a useful biomarker for vitamin K status.
  • desphospho-uncarboxylated Matrix Gla protein: This is the inactivated form of MGP and serves as a useful biomarker for vitamin K status. If inactive MGP levels are measured high, this indicates poor supply of vitamin K specifically in blood vessels. Currently this marker is not available in the US.
  • % of Carboxylated Osteocalcin: Osteocalcin binds and moves calcium into bone tissue. Similar to MGP, vitamin K is required to carboxylate osteocalcin – thus enabling calcium binding. Carboxylated osteocalcin levels alone are not useful in determining vitamin K status in blood. Instead the percent of carboxylated osteocalcin is a useful marker – encompassing micronutrient functionality in calcium flow. For example, if vitamin K supplementation produces a notable increase of % carboxylated osteocalcin, this indicates operating in a range of inadequate vitamin K. For a more in depth look, see this article on osteocalcin by Chris on the Weston Price blog.
  • Serum Retinol (Vitamin A): The most effective way to quantify your vitamin A status is to measure the active form of this nutrient – known as retinol. Low retinol levels indicate vitamin A deficiency. The reference range for retinol is based on the role of vitamin A in supporting night vision. The lower end of this range is approximately a concentration at which you can see during night time without symptoms of distorted vision.
  • 25-OH Vitamin D: The most common marker for measuring vitamin D is a downstream metabolite of vitamin D known as 25-OH vitamin D. The Vitamin D Council suggests an optimum level of 50 ng/mL of 25(OH) vitamin D. Chris also suggest that vitamin D optimal ranges are downward of 60 ng/mL 25(OH) vitamin D.
  • Parathyroid Hormone (PTH): A hormone produced by the parathyroid gland in response to changes in calcium blood levels. Compared to 25(OH) vitamin D, PTH is more specific for detecting inadequacy in the calcium-vitamin D system. Deficiency in vitamin D or calcium results in chronically active PTH production (high serum levels). From this perspective, remaining in the lower half of the PTH range (~30pg/mL) is optimal for a functional vitamin D-calcium system.
  • Ferritin: Serum ferritin acts as a buffer against iron deficiency and iron overload. Ferritin levels have a direct correlation with the total amount of iron stored in the body. Chris has a genetic predisposition for hemochromatosis, a condition in which too much iron builds up in the body causing toxicity. By optimizing his blood donation schedule, Chris maintains ferritin levels at around 150 ng/mL. The reference range for ferritin has an upper limit of 500 ng/mL.

Lab Tests

  • Amino Diagnostic Systems: A company working on gaining FDA approval for a test aimed at measuring the inactive form of MGP protein. Therefore, this test in still not available in the US.
  • VitaK: A company based in the Netherlands which offers testing for the dephosphorylated inactive form of MGP protein. However, they offer this test only to clinicians and for research purposes.
  • Quest Diagnostics: Testing of both serum retinol and serum vitamin A palmitate – the main form of serum retinyl ester. A formula for testing vitamin A overdose includes measuring levels of serum retinol and retinol palmitate in fasting state. If serum retinyl esters are greater than 10% of the sum of the values obtained from both tests, then this indicates liver vitamin A overload.
  • 23andMe: The largest personalized genetics company offering testing directly to customers. While health analysis data is no longer provided in 23andMe reports, the obtained data can be used with other gene analytics services. Chris discovered a predisposition for his iron overload condition via 23andme testing. Also see episode 5 with Dr. Ben Lynch featuring the use of such data in optimizing methylation.
  • SpectraCellDamien took this test in 2012 (see full report here) – the report did show a slight vitamin K2 deficiency at the time, which is one of the items he took action on by looking into Chris Masterjohn’s work at that time. Chris disagrees with the micronutrient testing SpectraCell report because it leads to conflicting conclusions. For example, there is very little scientific evidence that nutrient levels inside immune system blood cells.

Devices and Apps

  • MyFitnessPal App: A free application for tracking calorie intake and energy use, including a large database of foods and exercises. A useful tool for optimizing diet and improving fitness. Initial experiments can be tracking weight / waist circumference or keeping a food log to deduce your body composition. The app also integrates with other fitness devices and apps, such as the Fitbit and Withings which we have discussed before. See episode 24 with Troy Angrignon for the value of wearable devices or episode 32 with Paul Abramson on the potential of self-tracking in medicine.

Other People, Books & Resources

People

  • Weston Price: A researcher who documented the nutritional transition that occurred in many different cultures across the globe. He concluded physical degradation as a result of the switch from traditional diets to modern refined foods diets. Chris notes that traditional diets put strong emphasis on nutrient dense animal foods which supplied fat soluble vitamins.
  • Dr. Bruce Ames: A scientist whose major accomplishment is the Triage Theory. In summary, when the supply of nutrients is compromised, the body prioritizes vitamin K usage for acute survival needs over investing in long term health. When vitamin K is marginally inadequate, the liver gets top priority to activate blood clotting factors. Meanwhile the bones, blood vessels and other vitamin K-dependent systems perform with reduced functionality. This is a valuable tool for understanding the functioning and optimizing the vitamin K system.

Organizations

Books

  • Nutrition and Physical DegenerationA book by Weston Price on the micronutrient system, focused centrally on tooth decay. Chris found it useful for understanding the roles vitamins play in bringing about a protective effect on teeth.

Other

Full Interview Transcript

Click Here to Read Transcript
(00:04:16)[Damien Blenkinsopp]: Chris, thank you so much for joining the show.

[Chris Masterjohn]: It’s great to be here Damien. Thank you for having me.

[Damien Blenkinsopp]: I just want to get a little bit of an introduction from you, so that the audience that hasn’t come across you already, although I expect most of them already have, can get a bit of an idea where you’ve came from and how you got into what you do.

[Chris Masterjohn]: Sure, I have a Ph.D in Nutritional Sciences and I’m currently assistant professor of Health and Nutrition Sciences at Brooklyn College, in Brooklyn New York. I had always been interested in nutrition, at least since my teenage years but I sort of got set along my current path when I went vegan for awhile and didn’t have very good health outcomes on it.

I actually really improved my health a lot when I learned about Weston Price who studied, at an opportune time in the 1930’s, and documented the nutritional transition that occurred in many different cultures across the globe from traditional diet to diets of modern refined foods and documented the physical degeneration that took place there.

What struck me from that, that really provided a lot of utility to me at the time, was that in traditional diets that were associated with great health there was a really strong emphasis on nutrient dense animal foods that supplied fat soluble vitamins.

So in learning that and implementing principles that helped turn my health around I became very interested in the fat-soluble vitamins, and that’s why studying vitamins A, D, and K, which is one of my passions and current focus of research, has been something that I’ve been so interested in.

Over the course of, even leading up into graduate school, I had done a lot of work trying to understand the interactions between the fat-soluble vitamins and I published a hypothesis paper about that. When I was in graduate school I actually studied energy metabolism and glycation and antioxidant defense, but then in my postdoctorate at University of Illinois at Urbana-Champaign and now at Brooklyn College, I’m moving back into studying the fat-soluble vitamins.

(00:06:30) [Damien Blenkinsopp]: Excellent, thank you for very much for that. I’m curious, what kind of health issues did you have and you found resolved through this journey?

[Chris Masterjohn]: Most of what I experienced was an aggravation of existing predispositions. As an example, as a child I had been fairly predisposed to tooth decay, when I was vegan this became very exaggerated. So, in one single trip to the dentist I found out that I had over a dozen cavities and I needed two root canals. I had had digestive problems since I was a baby but when I was vegan they became much worse to the point where they were really interfering with my day-to-day function.

I had been predisposed toward anxiety probably at least since my early to mid-teens, but the anxiety and panic disorder really became strong and really started interfering with my day-to-day function when I was a vegan.

And Weston Price’s work actually focused centrally on tooth decay so when I was reading his magnum opus, “Nutrition and Physical Degeneration” I was most interested in, “How can I fix my tooth decay?” What really surprised me was that my mental health was completely revolutionized without me even trying to fix it once I started to incorporating nutrient dense animal foods into my diet.

(00:07:56) [Damien Blenkinsopp]: Very interesting. I had a similar experience I did vegan, for not as long as you probably, I think I did about four months but it was around that time also I started getting tooth issues. I started having all these fillings and so on, so it’s interesting. Maybe that happens to a lot of people and of course today I’m doing much better. I don’t really need to go to the dentist that much these days, so that’s cool.

I wanted to jump into this whole area of fat-soluble micronutrients, which you’ve done a hell-of-a lot of work in, and your work is very well known for this area. Would you say, first of all, just to isolate what we’re talking about, when you say, “fat-soluble micronutrients” what area you talking about? Is it the A, D, and K or a little bit broader? How would you categorize that?

[Chris Masterjohn]: The fat-soluble vitamins there are four of them, they are A, D, E and K. In my research I have also done a lot of research into the antioxidant defense system and I view vitamin E as a functional part of that system.

When I was in graduate school my work was very closely related to vitamin E, but I view vitamins A, D, and K as being involved in a functional network together where there is a whole set of specific physiological functions that those three vitamins cooperate together in, in a way that vitamin E is not as closely aligned with that system. So, most of the work when I refer to the fat-soluble vitamins, technically that includes vitamin E, but more often than not I’m referring to A, D and K.

(00:09:32) [Damien Blenkinsopp]: Right. I find it really interesting, because I noticed when I was doing preparation for this that you talk about it as a system, because a lot of people think of vitamins as separate things but it seems the way you look at it is it’s a system. You look at this whole systemic level and when you’re optimizing or improving it you have to look at it from that broad perspective. Is that correct?

[Chris Masterjohn]: Absolutely. I think that most scientists who actively think about this sort of thing would agree that during the course of the 20th century we did a really good job of breaking things down into fragments and we did not do a very good job putting them back together again.

So the task that lies before us in the 21st century is to take all of this fragmentation and all of this very granular knowledge that we’ve obtained about specific things and then figure out how they fit together in systems. I think that is the frontier of science right now.

(00:10:28) [Damien Blenkinsopp]: Yeah, it’s exciting stuff. If you were to describe this as a system, is there anything else you’d add in, beyond what you’ve already said about it, which gives people the overview of that whole system? Not to get into too much detail, but to get the highlights. Is there anything to add?

[Chris Masterjohn]: Yeah, absolutely. I think biological complexity is kind of like an onion, you peel away one layer and then as soon as you look beyond that layer you come across another layer, you come across another layer, and you come across another layer. To take an illustrative example of how some of these things would fit together into a system lets just take one specific protein.

Matrix Gla Protein or MGP is a vitamin K-dependent protein that’s responsible for putting calcium into our bones and teeth where it primarily belongs and preventing it from going into the places that it doesn’t belong, like the the soft tissues, particularly the blood vessels or the kidneys, where it would contribute to vascular disease or kidney stones.

Now you take this one protein. We call it a vitamin K-dependent protein because vitamin K is necessary to activate it and give it that ability to control calcium, but how do we get it in the first place?

Well vitamins A and D are responsible for telling the cell to make that protein but vitamins A and D can’t do that on their own, because to strip away to the next layer, when vitamins A and D tell the cell to do something they do it because they are metabolized into signaling compounds that then bind to a receptor that then binds to DNA and controls the degree to which genes are expressed.

When they bind to their receptor, the only way the receptor can bind to the DNA is because there are interlocking finger structures that fit together, kind of like if you were to clasp your own fingers together in your hand and you imagine that one set of fingers from the left hand is the receptor and the other set of fingers from the right hand is the DNA.

They fit together basically just like that, but what’s responsible for the finger shapes is the coordination by zinc. So, if you don’t have the zinc there, you can have vitamin A there, you can have vitamin D there and they can bind to the receptor but the receptor won’t bind to the DNA and the function won’t be carried out. So zinc is clearly important there.

Then you could take magnesium. I almost think that trying to get granular about all the specific things that magnesium does would cause you to underestimate its roles, because if you just take two of the roles magnesium plays and ignore all of the other specific enzymes it activates — magnesium is necessary to activate the enzymes that are involved in translating genes into proteins.

So imagine that vitamins A and D, with the help of zinc, are binding to the DNA and telling the DNA to be expressed. If magnesium isn’t there that compromises the ability to synthesize those specific proteins as well as every other protein in the body. Magnesium also plays other roles in regulating the distribution of calcium that would ultimately allow MGP to fulfill the function we were talking about before.

To take another example, carbon dioxide is necessary for the process because when vitamin K activates MGP, what it does is by taking carbon dioxide and adding that to the protein. And that addition of carbon dioxide is actually what allows that protein to start controlling the distribution of calcium.

Carbon dioxide is produced primarily during energy metabolism and that means that supplying that carbon dioxide is dependent on your metabolic rate but also the macronutrient mix in the diet plays a role as well. For example, carbohydrates produce fifty percent more carbon dioxide than fats do. So getting adequate carbohydrates is important.

So I just peeled the layer back to the third layer. I’m sure that we could keep going and ultimately if you just keep peeling it back and peeling it back what you find is that everything is interdependent with everything.

But what I have tried to do in my writing is: we can’t make any use of the information if we don’t simplify it and try to develop a working paradigm to talk about it and to understand it. I think that it’s necessary to have that top layer of the onion where we focus in on some of the key points, or otherwise it would just be information overload and we wouldn’t really be able to do anything with it.

(00:15:08)[Damien Blenkinsopp]: Absolutely. I’m hoping my processing and learning and things like that will eventually be able to get around that and actually understand all of these complex systems. It’s kind of obvious that it’s going to be beyond human level of understanding just because there are so many moving parts and it’s a dynamic system. You change one thing and something else is going to get distorted.

Is it safe to say that anything that would be deficient? Say, it could be one of the vitamins or some of those associated micronutrient minerals you mentioned, like magnesium or zinc, could distort the system and therefore get an output you’re not looking for?

[Chris Masterjohn]: Absolutely. That is one of the reasons why it’s so difficult to really answer questions about what’s going on in many cases. Because you can say, “I’m prone to tooth decay or I’m prone to… my children tend to have a narrow palate.” And you can say, “Well, vitamin K dependent proteins should be necessary to broaden the palate and to supply mineralization to the teeth.”

So, you focus on vitamin K but you may not realize what’s ultimately missing is something upstream that’s allowing vitamin K to fulfill its function. Just throwing vitamin K at the system isn’t going to do anything.

It’s really important that we continually improve our understanding about how to figure out what the weakest link in the chain is because we’re always going to get the biggest benefit from fixing what’s missing. If we take something that’s 80-90% good and we make that 95% then that’s going to be relatively little benefit, but spending the time to figure out what might be really missing at 20%, moving that up to 80% could provide huge effects.

(00:17:00) [Damien Blenkinsopp]: Yeah. Would you say of the things you’ve looked at, this system of vitamin D, K and A is basically a high impact lever for changing health scenarios because you feel like deficiency of any of these can affect a lot of systems in our body?

[Chris Masterjohn]: Yes, I do. If you look at some of the most common diseases that we would be concerned about you can see, particularly with heart disease, fat-soluble vitamins likely play a very vital role in protecting arteries from calcification. Calcification of arterial plaque is one of the driving forces of that plaque which eventually leads to a heart attack or an ischemic stroke. That’s a major concern.

We see a correlation between heart disease and kidney disease and osteoporosis. All of that can be grouped under this general malfunction of putting calcium where it’s supposed to be. If calcium is going into the kidneys and into the blood vessels and it’s not going into the bones.

The wrong way to approach that is to send the person to the bone doctor to look at the bones, send the person to the heart doctor to look at the heart, and send the person to the kidney doctor to look at the kidney.

That may be necessary to manage the disease process but what we want to be doing is figuring out, “What are the commonalities here?” and “What is the central defect in this system that’s contributing to all of these different things?”. That can very easily be explained by a malfunction of the fat-soluble vitamin dependent system of putting calcium where it does belong and keeping it out of where it doesn’t belong.

If you take that out of the area of the elderly and you put it into the area of children then you will see similar things where attaining proper growth and not just getting tall, but also having a broad dental palate that fits all of your teeth, and so on and so forth. All of those aspects of growth are also powerfully affected by fat-soluble vitamins.

Although there is some controversy over how you would interpret the data it does seem, to the degree that we’ve measured it, that there is a very high prevalence of poorly activated vitamin K dependent proteins in children when they’re in their growth phase. So I would say from the cradle to the grave it seems like there is, within the context of modern civilization, there seems to be this lifelong deficit in this system.

(00:19:30)[Damien Blenkinsopp]: Interesting. You’re basically saying it’s pretty common and there are a number of issues you think are quite common through society which are affected by this? Can you give us any example? Are there any studies? Or what kind of evidence is there to show how prevalent this kind of deficiency or these kinds of problems in this system is?

[Chris Masterjohn]: I want to take a step back and say there are two versions of this story. One is the clean version and that’s what I’ve been delivering you so far. That version is the version where you can make a strong case where this is true.

There is another version of this story that gets very dirty, and that is that when we try to assess the prevalence of these issues it becomes very sticky because we’re always learning more and more about how to interpret blood markers.

And if we are honest, that has to force us to continually revise how we’re interpreting those blood markers. We could get into the topic of testing of vitamin D status, which is wildly controversial, but let’s stay on vitamin K for a moment.

One of the ways we could look at vitamin K status in children is to look at the percentage of osteocalcin that is carboxylated. Osteocalcin is a protein that’s made by bone cells and carboxylation is the process where by vitamin K activates that protein to allow it to bind to calcium.

Now through most of the 20th century into the 1970’s no one knew about osteocalcin. Through that whole time we just saw vitamin K we though it was important to blood clotting and nothing else. Then the new era, over the ensuing decades the vitamin K research communities started developing a body of literature around osteocalcin. Then the phase after the 90’s where they started producing reviews that other people could read and this idea became popularized.

Up through the end of the 20th century and into the really recent years in the last decade, what emerged out of osteocalcin research was this idea that under-carboxylated osteocalcin is a marker of vitamin K deficiency because if vitamin K carboxylates osteocalcin then if you are adequate in vitamin K then all of your osteocalcin should be carboxylated.

That seemed totally logical and totally rational. There are multiple studies, I can’t site the exact figures off the top of my head, but what we can do is put links to the studies in the show notes if you would like, for the podcast. But there are multiple studies showing that in children the percentage of osteocalcin that is under-carboxylated could quite often reach sixty or seventy percent.

What this looks like with this simple interpretation of osteocalcin, is that children have massive vitamin K deficiency because two-thirds of their osteocalcin is not being activated by vitamin K. Now what has emerged more recently in the last decade is that we now know that vitamin K is needed to carboxylate osteocalcin so that it can bind to the extracellular mineralized matrix of bone. But during the process of bone resorption that osteocalcin, after it had already been carboxylated, will be decarboxylated and released into the serum.

Not only that, but that under-carboxylated osteocalcin that’s released into the serum is actually a beneficial hormone that acts on, in males, on the testes to increase testosterone production; and in males and females, it acts on adipose tissue and possibly multiple other tissues to increase insulin sensitivity and it acts on the pancreas to increase insulin output. But what that increased insulin output occurs in the context of being very sensitive to the insulin.

So overall it causes a very radical increase in metabolic health. And I would say that no one really knows why this system has evolved the way it does, but you could speculate that it might be a way to link to bone resorption to the anabolic affects of insulin and testosterone.

So you would want bone resorption to be tied to bone growth and if you’re in a process of greater bone remodeling then perhaps the resorption causes osteocalcin to be released into the serum and then provide an anabolic stimulus to help rebuild that bone. That’s just speculation.

What isn’t speculation is that this causes a real challenge to interpreting, “What does it mean that such a high percentage of osteocalcin is under-carboxylated in children?” Does it mean that the children are not getting enough vitamin K?

Or does it mean because those children are engaging in a rapid period of bone growth, that their bones are just producing more of this hormone in order to provide a greater anabolic stimulus, which is exactly what they should need as growing children? Or is it both?

I actually am of the opinion that it’s both, [for] several reasons. One, is that whenever you take someone who has a considerable percentage of under-carboxylated osteocalcin in their blood and you give them vitamin K supplements, you increase the carboxylation status. That seems to provide some proof of principle that they are operating in some range of inadequate vitamin K.

But also, if you look at the fracture rate of children. Growing children actually reach a point during puberty where their fracture rate is equal to elderly people who are starting to have their bones deteriorate. So I believe that probably both of these things are true.

And although under-carboxylated osteocalcin is not a clear, clean, straight-forward marker of vitamin K adequacy; I do think the data overall suggests that children’s bones are growing faster than the mineralization of those bones can keep up with.

I think the reason that the fracture risk temporarily increases is because: imagine that you’re stretching a rubber band. If you are stretching that you are putting pressure on the system and it can break. So you are expanding the bone matrix and you are not at the same rate mineralizing it.

That’s like stretching out that system too thin and in that case you temporarily undergo this position of greater fracture risk, until the bones can eventually keep up. Because eventually you stop growing and then if you just get a little bit more mineral at a time you can eventually fix the problem you created during the time period of rapid growth.

I will say that my working paradigm is that this system is inadequate but I don’t want to give the impression that it’s incontrovertible. I also don’t want to give the impression that, just to be clear, it’s equally controvertible if someone is going to take the opposite position. This is a reasonable debate.

(00:27:02)[Damien Blenkinsopp]: Right. There are two ways to look at it. If you were trying to resolve that — if you did a controlled study through the teenage years, with families where they were getting more vitamin K, getting more nutrients from the system, versus the other, some kind of study like that. Would it help resolve and potentially give us the answers?

[Chris Masterjohn]: That’s another line of evidence that we actually do have. There are multiple observational studies that suggest that higher vitamin K2 intakes. To clarify vitamin K2 is a specific form of vitamin K that is found in animal products and fermented foods, as opposed to vitamin K1 that’s found in green-leafy plant foods. Vitamin K2 is more effective at activating the systems that we’ve been talking about than vitamin K1 is.

If you look at vitamin K2 intakes, observationally people who are in the highest — depending on the study, tertile, or quartile, or whatever they looked at — intakes of vitamin K are likely to have better bone mineralization, a lower risk of heart disease and blood vessel calcification and also, we didn’t even get into this, a lower risk of multiple different types of cancer.

There are cases, to my knowledge I don’t know of a study showing that in children you can reverse that increase in the fracture risk during that period with vitamin K supplementation but there are some, multiple, successful vitamin K interventions in elderly where very high doses, possibly pharmacological doses used in Japan, caused a dramatic decrease in osteoporosis risk that was more effective than osteoporosis drugs.

(00:28:44)[Damien Blenkinsopp]: What would be a pharmacological dose?

[Chris Masterjohn]: If you look at what you’re going to get from food, the highest intakes of vitamin K2 tend to be topping out at 200mcg a day. Most people would not be getting that, but you could find that among people who are eating whole foods. In the Japanese trials they were using 45mg, a microgram is a thousandth of a gram. You’re talking about orders of magnitude higher than what you could get from food.

But no one has tested lower doses of vitamin K. So with the osteoporosis trials, it’s sort of this question, “Was it the first 500mcg that caused the decrease in risk and the rest was just chafe?” Or do you actually need 45mg to cause that effect.

(00:29:29)[Damien Blenkinsopp]: It takes a while to find the minimal effective dose. I’m guessing vitamin K2 isn’t toxic at high doses?

[Chris Masterjohn]: In those Japanese trials there were no reported adverse effects. Anecdotally I have talked to some people who seem to be hypersensitive to vitamin K and seem to anecdotally have negative experiences from supplementation.

I think there is reason to speculate that it would be preferable to keep vitamin K in doses closer to the maximum of what you can get from natural whole foods, because there are some biochemical effects that you could reasonable construe as negative, when you get into really high doses.

(00:30:13)[Damien Blenkinsopp]: Great, thanks. You just mentioned cancer. I guess we didn’t really go through the complete list of things of issues you think could be associated with this system. Are there others that we haven’t mentioned which you would see as commonly or with a high potential associated with this system and a deficiency?

[Chris Masterjohn]: When I’m looking at vitamins A, D, and K in a functional network, I think the system where that really stands out is the system of calcium distribution. When you start talking about cancer it gets a little bit less clear how they interact.

Vitamins A and D are involved in the expression of numerous genes that are not coding for vitamin K dependent proteins. They have independent affects, where vitamin A does something and vitamin D doesn’t do and vice versa, but there are also genes that are regulated cooperatively by vitamins A and D that don’t relate to vitamin K.

In addition to that, although the best characterized function of vitamin K is to activate proteins by adding carbon dioxide to them or that carboxylation process that we were talking about before.

One of the things that for a long time that we could speculate about was, “Why is it that that process occurs in one part of the cell and we actually find most of the vitamin K in the nucleus and the mitochondria?” What we’re finding out now is that vitamin K also plays a role in energy metabolism. Vitamin K also plays a role in gene expression and so on and so forth.

When you start thinking about gene expression then anything that is a failure of the cell to behave in a way that that cell should behave, suddenly becomes a candidate risk of a deficit in that system.

For example, Autoimmune conditions makes a lot of sense to look at when you’re thinking about at vitamins A and D. I don’t know of any studies that have shown when vitamins A and D are given together in humans, will do anything positive in type I diabetes.

But I do know of at least one study where they showed when you take pancreatic stem cells you can regenerate the insulin producing cells that are being lost in type I diabetes by providing the active signaling compounds that are made from vitamins A and D together in those cells. Does that translate into a human affect? I don’t know, but that’s one possible candidate risk that we can be looking at.

When you’re looking at vitamin K, probably the most compelling study was one where they looked at liver cancer in women who are at very high risk and I believe — it’s been awhile since I’ve looked at it — but I believe the risk was caused by the existence of viral cirrhosis. That showed that the incidence of cancer in a controlled trial, that vitamin K supplementation virtually obliterated the rate of cancer, like lowered it by over 80%.

There are also multiple other cancer related endpoints that could be related to vitamin K because we have cell studies where we can say, “Okay, we can drop vitamin K in this specific form on the cell, and this is what it does.” Most of that has not translated into human outcomes.

And most of it has not really — so little is known about the mechanism. When I was telling you about how A, D and K interact to regulate this calcium distribution system; we have a lot more understanding, mechanistically, of how that system operates. I suspect that there are a lot of interactions between nutrients that we could eventually uncover when looking at autoimmune conditions or cancer, but we just don’t have the mechanistic basis to understand it at that level yet.

(00:34:00)[Damien Blenkinsopp]: Thank you for that clarification. It sounds pretty broad spectrum. If you’re thinking about tackling this and are in any of those spots we were just describing it might be worth looking at this because it’s not something really hard to fix or address either. I was just wondering, because you were just talking about cancer, if you’ve looked at the work of Dr. Bruce Ames and his triage theory? And if you think that’s something that could be playing a role there?

[Chris Masterjohn]: Yes. Not exhaustively, but I think with respect to vitamin K metabolism that Ames’ triage theory is pretty well known. I actually know about it from studying vitamin K and I suspect that if you were to talk to leading vitamin K researchers probably most would consider it a very valuable tool in understanding vitamin K metabolism.

If you look at triage theory in that sense the implications of that are — So triage theory is the idea that the body is going to prioritize acute survival needs over investment in long term health when the supply of nutrients in compromised.

In the case of vitamin K what we see is that if that you are marginally inadequate in vitamin K then your liver seems to get top priority to activate blood clotting factors and the bones and blood vessels and all these other systems that are dependent on vitamin K, lose out.

That’s the rational decision of the body saying, “Look, if I get cut and bleed to death that’s much more of an imminent risk than if twenty or thirty years down the road I get arterial plaque, or a heart attack, or a stroke, or osteoporosis with this slow degeneration of the bone matrix.”

So I think there is pretty good evidence that the body does prioritize vitamin K that way and I think it’s almost become standard, in the field, to use that as a working framework to try to understand how that prioritization occurs.

(00:36:08)[Damien Blenkinsopp]: Thank you. I’m always interested how different ideas overlap and where people’s work is using similar frameworks and so on.

I think in my audience people are actually using a variety of different diets. They could be doing whole foods, vegan, paleo, keto, or maybe something a bit more standard. It might be hard to answer this question, but how relevant do you think it is to each of those groups, more or less? Are some of them going to be better positioned to not have a deficiency than others and some, like you were talking about vegan earlier, are potentially going to be more at risk?

[Chris Masterjohn]: One of the issues that comes up here is genetic polymorphisms. One of the areas in which we are starting to get a lot of research in is in the ability to derive vitamin A from plant foods.

So the physiological form of vitamin A, meaning the form that we need in our bodies to fulfill the functions we’ve been talking about, is retinol. It only occurs in animal foods, whereas red, orange, yellow and green vegetables are rich in carotenoids which can act as precursors to retinol.

Since 2012 we’ve been accumulating a small body of evidence showing that there are very common genetic polymorphisms that strongly affect the ability to convert carotenoids to retinol. In addition to the genetic effects there are also a huge number of dietary and metabolic factors that also affect that conversion.

I can list those if you want me to. But even if you were optimize the dozen factors that can affect that conversion rate you may be just be stuck with poor genetics in terms of the ability to convert carotenoids to retinol.

My suspicion is that in vegans, one of the determinants of whether someone is going to do well or not do well on that diet is: what are their genetics like for the ability to derive vitamin A from plant foods? And because this is so dependent on genetics and metabolic health and other dietary factors there’s no saying that a vegan will become deficient in vitamin A.

But I think people who are going to be vegan have to be conscious of how they’re going to respond to that because if they fall into that category of poor derivation of vitamin A from plant foods, then that would likely be a weak spot for them.

A vegan also wouldn’t be eating fish or traditional sources of vitamin D but they could compensate for that by getting sunshine. People can also take vitamin D supplements and I think it could be debatable to whether this is the best choice, but there are also UVB irradiated mushrooms that are on the market as a food source of vitamin D.

For vitamin K I would say that that also would tend to be limiting on a vegan diet, and that’s not because you can’t get it. In fact, by far and away the best source of vitamin K2 in terms of quantity is natto, which is a fermented soy food which is popular in eastern Japan.

But the fact of the matter is when you look at the general population most of the people are getting most of their vitamin K2 from egg yolks and cheese. So if you take out egg yolks and cheese and you don’t put in natto to compensate for that, you’re going to have a huge drop in your vitamin K2 intake. I think that could be very significant.

So in the case of the vegan, for vitamin D and K, it’s really a matter of properly designing the diet in order to compensate for those changes. With respect to vitamin A there is also an element of, “Is your constitution really well matched to this diet?” If it’s not, then you need to either rethink the dietary strategy or you need to supplement with vitamin A.

I think if you look at paleo and keto, it kind of depends on what foods are being incorporated. Some people define paleo based on what foods it’s restricting. Other people might define paleo more based on the theoretical framework: that much of modern disease is caused by a mismatch between our environment and our evolutionary environment.

People who are thinking of it more like that are more likely to say, “How were our ancestors eating?”, They were getting nose to tail and they were getting all the organ meats when they killed an animal.”

I think if someone is doing paleo and they’re doing that then they’re going to be in a much better position than if they’re eating what the standard average American is eating, or average person in modern society are eating, minus the grains, legumes and diary. Just taking those foods out is not at all going to guarantee you good nutritional status, but paying attention to the organ meats will.

Most people, back in the day, paleo tended to be equated with low-carb. Nowadays there is a greater diversity of approaches towards carbohydrates. Keto obviously is low carb.

It is important to recognize that carbohydrates do play a role in supporting the system. Like I was saying before, it results in greater carbon dioxide production, that would be relevant. Carbohydrates also supports greater thyroid status and thyroid hormone helps cooperate to produce vitamin K-dependent proteins just like vitamins A and D do.

Also, vitamin K, you use it one time and you have recycle it. And recycling vitamin K is dependent on NADPH. NADPH is a form of niacin that carries energy from glucose to a variety of other systems. So the glucose is ultimately supplying the energy to recycle vitamin K.

When you look at all of those things, I think there is a grey area there where you want to be careful that you’re monitoring the health outcomes on a ketogenic diet. Because, to be honest, I don’t think anyone has really studied, “How does a ketogenic diet affect the carboxylation of matrix Gla protein?” Or anything like that. You can speculate there are a lot of things you want to be careful of, but ultimately what we need is more research to look at the actual outcomes on those diets.

(00:42:28)[Damien Blenkinsopp]: Right. It sounds like no matter which situation you are in you have to be cognizant of this. As you were saying, people are doing lots of different paleo diets, and it’s the same for keto as well. Some people will be eating primarily cheeses and diary and things like that, and others will be more focused on the meat. I think there is quite a wide variety.

It sounds like you have quite a few principles which can cut across all of these areas and, no matter which diet you’re following, could potentially resolve this system if you keep to those rules? It’s kind of independent of any of these diets.

[Chris Masterjohn]: Yeah, to a degree. You could even broaden that to other diets. So what is the diet that most greatly restricts egg yolks and cheese? It’s the, “I’m trying to be healthy diet.”
You don’t have to be paleo, or keto, or vegan to restrict egg yolks and cheese. You just need to trust the system and be health conscious.

[Damien Blenkinsopp]: Right. Absolutely.

[Chris Masterjohn]: That’s the message: to be heart healthy you get rid of foods that are high in saturated fat and cholesterol. The hell with nutrients, that’s been the prevailing approach to health consciousness. I think this is an under appreciated system that cuts across all of these diets and people really need to pay attention to it.

(00:43:48)[Damien Blenkinsopp]: Excellent. Thank you.

When I was doing preparation for this I was looking at one of your presentations that was really good on YouTube, it went through all of this area. In that, you established some principles behind optimizing this area, or this system. And you already brought up some of them that are important, like genetics, that can play a role in this.

It would be good to cover a few of these to give people an idea of the system. I think there are some misunderstandings. When it comes to vitamin D for example. For many years we’ve just been thinking, “Okay, I have low vitamin D compared to other vitamin D count says. I have to take a supplement to raise it.” Where I think what you’re saying is it’s quite a bit more complex than that, and that doesn’t necessarily help you.

[Chris Masterjohn]: Well that’s true. That’s not only true because of the other interacting factors, but it’s also true because 25-OHD which has been promoted as a specific marker for vitamin D nutritional status, isn’t one.

It is very true that if someone is low in vitamin D status their 25-OHD status will be low and if you supplement them with vitamin D or restore nutritional status it will rise. That is true. And yes it’s useful as a marker of vitamin D nutritional status, but there are also numerous other things that are both good things and bad things, that can affect 25-OHD.

For example, calcium deficiency can lower it because you’re using more vitamin D at a greater rate. Vitamin A supplementation could potentially lower it because you’re increasing utilization of vitamin D to fulfill cooperative functions that they’re needed for together. There are genetic differences that just make some people metabolize it to the active form at a higher rate and that seems to be associated with better health outcomes.

One of the things that I have been advocating especially recently to better understand 25-OHD as a marker of vitamin D nutritional status is to look at parathyroid hormone, or PTH. This is a test that you could very easily ask your doctor for. It is not difficult to get.

But the reference range for PTH is based on diagnosing parathyroid disorders, so it’s sort of not useful for this. But if you look at the rationale for putting the cut-off of vitamin D adequacy at a certain 25-OHD, it’s actually because on a population level that 25-OHD is associated with maximal suppression of parathyroid hormone.

The parathyroid gland is the resident expert within the human body and your individual calcium-vitamin D economy and PTH output increases in direct response to that economy of vitamin D and calcium being inadequate.

Instead of saying on a population level, “This much 25-OHD on average is associated with maximal suppression of parathyroid hormone.” We can take the same mainstream conventional principle and apply it to the individual by looking at, “Is that individual’s PTH maximally suppressed or not?”

My tentative conclusions about this are if you look at PTH you want it to be in the lower half of the reference range. That’s basically thirty, in picagrams per milliliter, seems to be the sweet spot, thirty or below.

If someone’s at thirty-five I don’t know if that’s concerning. But when it’s forty, or it’s fifty or it’s sixty I think that is a very good corroborating sign that that persons’ body perceives itself to be inadequate in vitamin D. I think that can really help us get a more nuanced and sophisticated approach to looking at that. That’s one thing that I would mention.

Also, as we’ve been talking about, you add vitamin D to this system and it needs the other cooperating nutrients to fulfill those roles. One of the problem points here is — Let’s take, “What is the prevalence of low serum retinol in the population?”

Well it’s really low like two or three percent of people have serum retinol below the reference range. So everyone says, “Well people are a lot more likely to get too much vitamin A than not enough.” So they tell everyone to avoid vitamin A.

Then people come in and say, “Lets ten fold increase your vitamin D intake.” Now all of the sudden you are taking that person, if you’re 10x-ing their vitamin D exposure, you’re taking them out of that original population and putting them into a totally different population of “10x vitamin D” status. In that case, what is happening to your vitamin A status?

I think there are a lot of reasons to be concerned that all of the sudden vitamin A intake becomes very relevant to most people when you move them into that high dose vitamin D supplementation. I think that if you’re going to tweak this system it’s really important that you pay attention to the whole system and not just take one element and blast it out of the system hoping that the one element is going to turn things around.

The most important principle of that is even if you’re going to supplement, first of all, have a targeted reason for the supplementation. Be conservative about the dose and titrate it up to higher doses based on how you’re responding to it, if needed. Also be very careful that the background diet is supplying all of those extra nutrients.

If you’re going to supplement with vitamin D, be conservative about it. But also, get your liver once a week, get your daily egg yolks in, get your fermented foods in, get this background supply of nutrients up to par so if you do perturb the system the rest of those factors make the system robust and it can handle the changes that you’re putting into it.

(00:49:49)[Damien Blenkinsopp]: Definitely balance versus saturation of one micronutrient. You’re saying [to] get a good background of foods there. Is one of the principles behind that, that foods tend to be naturally balanced in these nutrients? If you look at liver, it’s got vitamin A and D combined. It comes from a body so you’d think it wouldn’t be completely out of whack with the needs of a body.

[Chris Masterjohn]: I actually don’t think that’s true. If you take a fish’s liver then fish liver tends to be high in vitamin A and D, but that’s not true if you take a terrestrial animal’s liver. That’s because mammals, we store vitamin D primarily in the blood and not in the liver. So our metabolism is a little bit different that a fish’s metabolism.

If you were using the blood in the animal and you were using the kidneys in the animal and you were truly eating the whole animal, that would probably balance out. But it’s not necessarily true that you can say, “My substitute for eating nose to tail is that I will eat liver once a week.” That’s not necessarily doing you any favors with respect to vitamin D.

What it is doing is it’s making you robust to any problems with your derivation of vitamin A from plant foods. Lets take the person who really is terrible at making that conversion. If they eat one serving of liver once a week, [then] they’re meeting the RDA through vitamin A.

You can debate what is the optimal level of vitamin A intake and is it higher than the RDA or not, but if you take that liver out and they aren’t good at getting vitamin A from plant foods, what other foods besides liver or cod liver oil is going to bring that person up par? Nothing.

What you’re doing by doing that is not — the liver isn’t going to magically make the whole balance of the diet. Even if you were to catalog all the potential polymorphisms you have in the enzyme that makes that conversion you’d kind of get stuck no where because every time a new study comes out we identify these new polymorphisms.

So you really have no idea what your conversion is, at all, unless you subject yourself to a randomized cross over study where you’re undergoing multiple diets and collecting data on it, and no one does that. So just including liver in the diet, you can put that question to rest. You don’t really have to care about that conversion if you make that one step.

When it comes to vitamin D you need to get regular sun exposure. That’s not the only reason to go out in the sun. Include some fatty fish, include some pastured egg yolks, get outdoors. That in most cases, in the absence of some constitutional or disease issue, for most people covering those bases covers vitamin D.

Get your egg yolks in, get your fermented foods in, get your leafy greens in. For most people who don’t have a specific vitamin K related problem, just getting the diversity of vitamin K rich foods in covers the bases.

(00:52:50)[Damien Blenkinsopp]: When you say fermented foods, you mentioned natto earlier. Are there other ones you recommend?

[Chris Masterjohn]: Honestly, for the average person cheese is going to the be most potent one if not on their list. Part of the issue is that it depends on the bacteria. If you take the natto bacteria and you make homemade fermented vegetables with it instead of fermented soybeans my understanding is that would be a pretty good source of vitamin K2.

By contrast, if you are eating, say sauerkraut, you are getting some vitamin K2 from that and that’s good but it’s incomprehensibly less than what you would get from natto. Even if you just compare sauerkraut and cheese together, cheese is way ahead of sauerkraut.

I think diversification is the best strategy here. You can micromanage it and you can look at the table and log your K2 intake everyday. But if you want to be practical about it and you don’t want to be spending exorbitant amounts of time thinking about it and managing it, then I think what you do is you say, “Okay fermented foods in general, but particularly cheese and also egg yolks are convenience sources. If I just rotate these in my diet on a regular basis and don’t think about it too much then that secures a baseline level of adequacy.”

[Damien Blenkinsopp]: So variety is a big principle here.

[Chris Masterjohn]: Yeah. The more you restrict your diet the more you need to micromanage it.

(00:54:20)[Damien Blenkinsopp]: In terms of productivity, I think you do this as well. You basically do auto-order. I have local farms I subscribe to. You fill out the stuff you want and it gets auto-delivered every week, so I don’t have to think about it.

On the other hand that means I’m probably not getting the maximum variety because I’m always getting over delivered with food if I was trying to maximize the variety. I don’t know if you, in terms of productivity, if that’s something you deal with? I think you use Thrive Market right?

[Chris Masterjohn]: I do.

(00:54:52)[Damien Blenkinsopp]: In terms of variety do you kind of switch yours up? Have a look at your list and just change it each week or do you leave it on auto?

[Chris Masterjohn]: I actually don’t auto subscribe to things like that, although the way that I deal with it is actually pretty close because I mostly have mobile apps where I just tap, tap, tap, tap, tap on the things that I’ve been ordering recently and it’s that simple.

A lot of the ways that I deal with variety is to deal with it on a week-to-week rotation basis. To take an example, I find trying to get variety in within a day or from one day to the next is extremely taxing. It’s not only taxing mentally on trying to think about what I’m trying to put together but it’s also taxing on my ability to not throw food away, because getting that variety in would mean that I would have to over order things.

I try to get a variety of green leafy vegetables in, but what that means is that on a given week kale will be my cooked vegetable that goes into a big batch of starches that I just take out of the refrigerator and reheat in two minutes each time I use them. And I will get a box of some type of leafy green that I would eat raw and I’ll just eat platefuls of that.

But the next week I will switch out the kale for a different green vegetable that I make cooked and I will switch out whatever those raw leafy greens were, for a different one. So I get my variety in more on a week-to-week basis where I’m rotating different types of similar things into my diet rather than within a day or from day-to-day.

(00:56:39)[Damien Blenkinsopp]: Excellent. Thank you for that. I like to make sure the information is practical. I will probably have to change mine up based on that.

I wanted to go back to the testing, this is a quants show at the end of the day, a lot of the time. When you were talking about the PTH earlier that was basically a downstream marker of vitamin D, kind of like an indirect measure versus a direct measure where you’re looking directly at the blood, D-3 to 25-OHD. Is that a typical strategy you’d take for this area if you were — I think it would be interesting to find if you think it’s actually worth testing in this area because I know in some areas it’s not that useful at times.

So first of all, is it useful to start looking at testing in this area if it’s a concern of yours? And second, is a downstream strategy often best versus going for the direct ones, similar to the D-3 in the other areas?

[Chris Masterjohn]: Well, no one uses the direct strategy with vitamin D. If you consume vitamin D you consume it as vitamin D and measuring vitamin D in your blood is virtually useless as a marker of nutritional status. Everyone is using the indirect strategy of measuring 25-OHD which is a downstream metabolite of vitamin D.

The issue is, in every case, when you’re looking at a biomarker for anything the questions that you’re asking are: is it sensitive? And is it specific? Quite often we may think that something is specific then when our understanding of it increasingly evolves we need to revise that.

I think that PTH is a more specific marker of inadequacy in the calcium-vitamin D economy than 25-OHD is. One of the ways to think about this on an intuitive level is: what is the parathyroid gland doing? It is continuously monitoring the vitamin D-calcium economy using sensors of receptors that sense the concentration of calcium in the blood.

If you have serum calcium dip for even a millisecond the parathyroid gland will sense it. And on a scale of less than a fraction of a second it will respond to that and carry out a downstream cascade of events that will start operating within seconds and basically finish operating within minutes to normalize serum calcium.

If you take someone who is consistently deficient in vitamin D or calcium; what you wind up with is that person will have a higher level of PTH because that PTH is being chronically activated to compensate for that deficiency.

If you’re to compare PTH and 25-OHD. I’m not going to argue that PTH is a hundred percent perfectly specific but it adds a lot interpretive power to the 25-OHD. To take an example of one of the confounding factors, if we look at people from different ancestries we will see that there seems to be differences in how they metabolize vitamin D.

People of white/European ancestry actually seem to be outliers in the amount of 25-OHD they need circulating in their blood to maximally suppress parathyroid hormone. Now remember, when we set the benchmark for, “What is an adequate 25-OHD?”, that is set on the basis of maximally suppressing PTH. That is the benchmark that is accepted.

I’m not advocating a different principle. I’m advocating individualizing the principle. If you take someone who is African-American or someone who has Inuit ancestry, probably if you take someone who has Asian ancestry and you compare that to someone who has white/European ancestry you will see that on average they will have lower 25-OHD.

But they will also have higher levels of calcitriol, which is the fully active hormonal form of vitamin D. They will also have lower levels of PTH. If you trace that further what you’ll find is that there are genetic polymorphisms that are more prevalent in those populations that trace to different ways of metabolizing vitamin D.

One of the ways to interpret that is: different populations are adapted to different levels of 25-OHD needed to maximally suppress PTH. One of the problems with that is that’s just on average. If I take the average of white girls and black girls in Oklahoma then on average all those things that I just said will be true of those groups.

But then when you take the group and you separate them into individuals, the genetics aren’t separated into those two groups perfectly. Some of the African-American girls will have the genes that are more prevalent among the white girls and vice versa. In order to actually treat the individual you can’t just define them by their group.

In that case, what better way to do that than to actually look at whether PTH is maximally suppressed in that person? I think all you’re doing is taking the conventional standard strategy and saying, “Is this actually operating the way we’re saying it should operate in this particular person?”

(01:02:08)[Damien Blenkinsopp]: It’s a great reminder that you have to look at this on a personal level for a lot of things, just as you’ve talked about these complexities.

It reminds me a bit of methylation. I’m sure you’ve looked at methylation a bit, but with all of the polymorphisms and everything, people react completely different to supplementation and when you’re trying to tackle that. It sounds exactly the same with this.

In terms of other tests that I’ve come across, one of them is SpectraCell, the micronutrient testing they have. I don’t know if you’ve looked at that and if you’ve thought it’s useful? It has vitamin K2 and K1 I believe, if I remember from memory.

[Chris Masterjohn]: I do not like SpectraCell. Unless they have radically changed how they do it in the last couple of years, I haven’t looked at a recent SpectraCell report, but I basically disagree with the entire principle behind the SpectraCell report. I also think that it generates pretty bizarre conclusions as well.

I will say that, I don’t want to sound like I’m singling out SpectraCell. I would say it’s generally true of all of the shotgun approaches to practically anything, even genetic polymorphisms. You can take your 23andMe data and run it through various software or web apps that will give you back a report that will give you ridiculously conflicting practical conclusions like, “You have this polymorphism, so take methyl-B12. You have that polymorphism, so avoid methyl-B12.”

I think that’s an inevitable consequence of trying to do too much at once. I think it is possible to do many things at once and I think we’re eventually heading towards that area, it’s just that you can’t sacrifice the integrity of the methodology in order to get more stuff.

In the case of SpectraCell, and I don’t know if they’ve changed this in recent years, but at least a couple years ago when I was looking at SpectraCell reports what they were doing was taking lymphocyte concentrations of these different nutrients. One of the problems with that is that there is practically zero research on that.

Take for example vitamin D. There are thousands of studies that span tens of thousands of people looking at 25-OHD levels. There are at least hundreds, if not thousands of useful studies that are worth looking at in terms of, “How does it correlate with disease risk? How does it correlate with metabolic factors?” and so on and so forth.

And by contrast we don’t have a lot of data on, “How do white blood cell concentrations of vitamin D correlate with these factors?” Although there are huge limitations to interpreting 25-OHD that I was just describing for you, the only reason I even know about those limitations is because there is so much research on it.

With leukocyte concentrations of vitamin D I can’t tell you what those limitations are because we don’t have a huge body of literature assessing its usefulness. But I can tell you is that there is no particular positive reason to assume that is a useful marker.

I can also tell you that I had a consulting client who was taking vitamin D supplements, who had really high 25-OHD and a really low leukocyte concentrations of vitamin D. SpectraCell told him to take more vitamin D.

By any accepted definition he should have been, if anything, cutting back on his vitamin D. What does it mean that his leukocyte vitamin D concentrations were low? To be honest, I have no idea. I don’t know what it means, but neither does SpectraCell.

[Damien Blenkinsopp]: As you were saying it could be some of the things like genetic polymorphisms, people are just different that way. All of these things that aren’t uncovered because there’s no research.

[Chris Masterjohn]: Also leukocytes are a part of the immune system and the immune system uses these things and profoundly affects their metabolism. One of the things we know is that one of the reasons that you can have low 25-OHD is because of inflammatory activation.

Even for example in the recovery for surgery the immune response that is involved in tissue repair will cause a pretty large drop in 25-OHD acutely in that sense. And probably it’s true of chronic inflammation as well.

So one of the things that you want to ask is: Why does a leukocyte decide to concentrate vitamin D and does it decide to do that some times and not others? And does that leukocyte concentration of vitamin D have a lot more to do with what that leukocyte is deciding what to do because of the context of immune signaling in that person and not nutritional status of vitamin D? That’s a question of, we need research studies.

Ideally research studies come before you start practically applying tests rather than after. The ideal time to say, we tested this, now you should go out and do this is when we have a lot of information about what that means. Not so we can ten or twenty years later hope to get some information about it.

(01:07:10)[Damien Blenkinsopp]: Absolutely. Thank you for that.

Are there any other tests that you’ve come across in this area, either bad or good? Ones you don’t think are worthwhile doing or anything good?

[Chris Masterjohn]: Specifically on vitamin D or across the board?

[Damien Blenkinsopp]: Yeah, the whole fat-soluble.

[Chris Masterjohn]: Yeah, a few others that stick out. First of all, for vitamin A status the most useful measure is serum retinol. Serum retinol does not perfectly correlate with vitamin A status but it will tend to be low if you are running low on vitamin A and in general the reference range is pretty good on that.

The reference range if you just get a Quest report for serum — I will warn you it should be called serum retinol and at least Quest Diagnostics calls it serum vitamin A, but in any case it’s the same test. The reference range for that is based on the role of vitamin A in supporting night vision. If you are within the reference range that should preclude virtually all cases of impaired night vision as a result of vitamin A deficiency.

Now, I think there are some big question marks over whether that is actually the most sensitive marker of adequacy? I will tell you from my personal experience, I had some pretty severe eye related signs that indicated to me that I was vitamin A deficient. I made a very intensive effort to improve my vitamin A status over the course of the week.

After I did that, I was still resolving my vitamin A status, but I have my serum retinol tested and it was towards the bottom of the reference range, but it wasn’t below it. You probably don’t want to be operating at the bottom of the reference range.

(01:08:52)[Damien Blenkinsopp]: I think one of the baseline rules that we’ve spoken about before on this show is like if you’re in the top third for a lot of these standard reference ranges because the normal population tends to have a fair amount of chronic illness and non-optimal health. Is that a rule you could take for this test?

[Chris Masterjohn]: I’m not quite sure about that, but I will say I would prefer to be in the middle than on the bottom. I don’t want to encourage people who are in the middle to get up to the top third, but I would say if you’re towards the bottom you should definitely try to get towards the middle.

If you’re at the top sixty or seventy percent, I’m not going to recommend you get down to the middle. The data isn’t really that clear, but you want to keep your distance from the bottom of the reference range in my opinion.

I will also say that in rats, I can’t remember if it was rats or mice, but there was a recent paper that came out that showed that obesity compromises tissue vitamin A status. I shouldn’t say tissue, tissue besides the blood. The blood is a tissue.

But it compromises vitamin A status in many tissues without decreasing serum retinol. So there are caveats that we are just starting to learn about with these tests. I would say in general serum retinol, despite potential limitations, is very useful to have.

I want to say one more thing about vitamin A. If you’re concerned you’re getting too much vitamin A there’s a good formula to use. That is to get your fasting serum retinol and your fasting serum retinyl esters tested.

I know that Quest Diagnostics actually calls these two tests serum vitamin A and serum vitamin A palmitate. That means retinol palmitate which is the predominate retinyl ester. This has to be fasting. If in the fasting state you add those two values together and your serum retinyl esters are greater than ten percent of the sum of the two values then that is an indication that your liver is overloaded with vitamin A and you either need to cut back or you need to correct some backup in your metabolism.

It could, for example, if someone has fatty liver disease that will compromise their liver’s vitamin A storage, then that could play a role in it. If you are lean and healthy with good body composition, the most reasonable interpretation of that would be that you’re overloading your liver with vitamin A.

With vitamin K, I am not happy with any test that’s currently available, at all. I do not think it’s useful to look at leukocyte vitamin K concentrations. I don’t think it’s useful to look at plasma serum or red blood cell concentrations.

What I [do think] would be useful is the carboxylation status of osteocalcin. I don’t remember which lab it is, but last I looked the only lab that was offering this gave you under-carboxylated osteocalcin without giving you, “What is the percentage of the total osteocalcin that’s carboxylated.” Just looking at total under-carboxylated osteocalcin is not useful.

On the horizon there is a company called Amino Diagnostic Systems that two or three years ago told me they were trying to develop a test for desphospho-uncarboxylated Matrix Gla protein, or DCUCMGP which put simply is the inactivated form of MGP. That’s the protein that protects soft tissues from calcification and helps direct calcium into bones and teeth.

If that’s high it’s a very good marker that you don’t have a very good supply of vitamin K to your blood vessels. They told me two or three years ago they told me they were hoping to get this test past FDA approval and I asked them this morning, in preparation for this show, if they’ve made any progress on that. They said, they’re working on it.

[Damien Blenkinsopp]: Wow, awesome.

(01:13:02)[Chris Masterjohn]: I think on the horizon we can eventually see the inactive form of MGP be a very useful marker of vitamin K status in the blood vessel. When that comes out I’m going to be super happy and tout it with fanfare all over the place. But right now nothing is available that isn’t a waste of money, in my opinion.

I will say also, that there’s a company based out of the Netherlands called VitaK. They offer testing of all of these things to people who form contracts with them. I do not know if they would form those contracts with clinicians who are testing it in patients. I do know that I was talking to a clinician who was doing clinical research and he was taking samples from patients to do a research study and he just sends them to them. They measure all this stuff and give the data back to him.

This is not going to be helpful for patients or for the average person but if there are any clinicians listening, they may be worth approaching about this to see if you can come to an arrangement with them to start collecting some clinical patient data.

(01:14:16)[Damien Blenkinsopp]: Awesome. That’s some amazing stuff there. You’ve obviously kept up to date with all of this stuff.

It’s great to hear about the SpectraCell. I did SpectraCell about three years ago and so it would have been the same test you looked at. It had some stuff like K2 deficiency. There wasn’t actually that much that come of it for me. Nothing really interesting.

[Chris Masterjohn]: Just to add one thing. I had someone who had the same result and they said because K2 was deficient they should supplement with vitamin K1 because it’s a precursor to K2. And all of the evidence indicates that humans tend to be relatively poor converters of K1 to K2. So that’s just one more example of how the data is not translated well into practical recommendations in those shotgun tests.

[Damien Blenkinsopp]: I would say with tests, a lot of the lab tests, they have these recommendations which, if you look at organic acids or a lot of different tests, are spit out through an algorithm based on a marker being low or something. I think most people say not to look at those. Just as a general rule across most tests because it’s not very useful. It’s not taken in context of what else is going on.

[Chris Masterjohn]: Right, but there is no reason that that’s not doable. I hope that we will be moving forward into an area where that aspect of that testing can be improved.

(01:15:27)[Damien Blenkinsopp]: Yeah, it would be awesome if it could eventually be automated.

So this has been great. So much great information. I’d love to know what you’re up to right now. Is there some current research, some questions you’re trying to answer? What’s sort of top-of-mind for you right now?

[Chris Masterjohn]: Right now my top priority is putting together a special report that I will be selling once it’s out, on a very practical guide about how to resolve chronic inflammation using essential fatty acids. One of the things that I think has been profoundly misunderstood since at least the 1990’s, is how the inflammatory process works and how it’s resolved.

Many of the things that have traditionally come out of the outdated 1990’s framework, like take high-dose fish oil to inhibit the inflammatory effects omega-6. Or particularly, take non-steroidal anti-inflammatory drugs to inhibit the inflammatory actions of omega-6 are possibilly down right backwards.

So what I’m trying to do is put together a really practical approach to what is the minimal effective dose for a healthy person of different fatty acids, and in different disease states what is that effective dose? What are the factors that could actually be distorting a metabolism that could be fixed? And things like that.

That’s the sort of the longer term project I’m working on. Some of the more immediate things I’m working on are I just started my own podcast, The Daily Lipid. Anyone can search for that in their favorite podcast app. I’m upping my social media game. I finally got back into tweeting. I finally got active on Instagram and most recently I’ve joined Snapchat.

I’m doing some useful content on Snapchat. A lot of the things I hope to eventually put into permanent content I’m snapping as I’m thinking about them. For example, yesterday I snapped a video tutorial about how people who have gotten their 23andMe post-FDA debacle can despite “No Alzheimer’s” report still hack the system to still get their APOE genetics and stuff like that.

Eventually that will become a YouTube video that’s part of a blogpost, but that could be a month down the road. This way, you follow me on Snapchat and you get these cool little things as I’m thinking about them. That sums up what I’m up to at the moment.

I’m also lining up some potential interesting research for the fall academic year. I’m playing with a couple ideas and I am not ready to really say for sure what I’m going to be doing but with the right amount of help I may actually start looking at how vitamin A and genetic polymorphisms and sleep disorders relate in student populations. If that pans out that will be pretty exciting.

(01:18:24)[Damien Blenkinsopp]: Thank you. I’m really interested in the inflammation stuff actually because I’ve actually taken high dose fish oil to resolve some inflammation but we’ll talk about it later because it’s very specific to me. Not necessarily everyone who’s done that. Maybe you know something about it.

[Chris Masterjohn]: There is value to the fatty acids in fish oil it’s just that if you are effectively resolving inflammation then it’s probably through a very different mechanism than what’s been traditionally touted as the mechanism.

[Damien Blenkinsopp]: You’re saying the Omega-6 vs the Omega-3 mechanism?

[Chris Masterjohn]: I mean what the Omega-3 fatty acids are actually doing there. The traditional idea has been that the EPAH should inhibit our arachidonic metabolism and what we’re finding out now is that’s counterproductive. There are other mechanisms where omega-3 fatty acids come into play. But actually understanding why also provides insight into: what kind of dose should we use? What should we take it with? What’s the best way to optimize the process?

[Damien Blenkinsopp]: It sounds very interesting. Maybe we can have you back on the show later whenever that comes out because inflammation is a big topic right now.

[Chris Masterjohn]: For sure

(01:19:26)[Damien Blenkinsopp]: You know what would be really interesting? Is there anything that you’ve changed your mind about in the last few years?

[Chris Masterjohn]: Change my mind about? There’s probably a whole bunch of things. One thing that I’ve changed my mind about that really relates to the stuff we’ve been talking about here today is 25-OHD status.

When I first started looking at vitamin A, D, K interactions I kind of focused all of my critical analysis into those interactions and took for granted what a lot of the vocal vitamin D community was saying about, “You want to have fifty to sixty nanograms per milliliter, 25-OHD” I’ve really revised that downward as I’ve started to applying the same critical analysis to that particular issue.

Moving outside of that, I was never really an advocate of low-carb diets per se. But I think that I did buy in to a lot the theoretical framework of low-carb approaches even though I figured, “I’m lean so I don’t have to worry about that, etc, etc.” I’ve sort of become a little bit more critical of the low-carbohydrate approach to a lot of issues and trying to build a bit more of an appreciation of carbohydrates recently. That’s an unrelated thing that I’ve changed my mind about.

(01:20:38)[Damien Blenkinsopp]: It’s always very interesting to see people going back on stuff. It’s very important to be able to go back on decisions and change your mind. As you’re saying, it’s all developing all the time. It’s hard to stay on one topic and be sure of it.

Is there anything that you track in terms of metrics or biomarkers, for your body on a routine basis? And why?

[Chris Masterjohn]: I try to take the information one at a time because I feel like I could track everything but then I would probably get lost in the information. Also, in the last year I’ve been recovering from “workaholic syndrome” where I was not tracking anything because I was consumed with the work that I was doing.

I’m trying to gently move into targeting the highly specific things that I know I need to track. For me, one of the things I was tracking over the last few months was my protein intake and my caloric intake and I wound up losing thirty pounds and a pretty hefty amount of body fat that I’m pretty happy with, over the course of a few months.

I’ve kind of moved on from that but still actually track my calories most days because I’m trying to strategically move into fat loss and into gentle muscle building without much fat gain, so that’s something that I continue to track. That’s kind of partly a health thing, partly a vanity thing.

One thing that’s much more straight out health related is my iron status. I am homozygous for the relatively common allele that interferes with the hemochromatosis related pathway. It’s thought that it only causes hemochromatosis when it’s paired with a more severe allele. I just have two of the minor ones, but that puts me in the top three percent of dysfunctional iron absorption in the population.

Theoretically I shouldn’t get diagnosable hemochromatosis. But what I find is that if I do not give blood regularly my serum ferritin is high-ish, but no where near even the middle of the reference range, so maybe it’s 150. A lot of people say it should be lower than that, but the reference range says that if it’s under 500 it’s fine.

What I find is that my transferrin saturation starts getting out of the upper end of the reference range and my unbound iron binding capacity starts getting out of the bottom of the reference range. That means that relative to my capacity to deal with the iron, my iron is being overloaded and that increases the risk of free iron running around, that can contribute to oxidative stress in my body. I actually think that that has a huge impact on my metabolism.

I discovered this slowly over the course of several years. Before I knew I had these genetics and before I had ever tested my iron what I noticed was when I was a guinea pig in my doctoral lab and people would take my blood, I would always feel better.

One of the best responses I ever felt was when I was a guinea pig for a pharmacokinetic study where my lab mate put a catheter in me so she could take twelve blood draws in a single day. Then a thirteenth blood draw the next morning and I felt awesome.

That was when I started thinking about it but then it was a year or two after when I got the 23andMe and that showed me I had those alleles and that motivated me go out and measure my iron status. Once I got a full iron panel that’s when I really put it all together.

With balancing work and life it’s been difficult to maintain a regular schedule of blood donation. That’s my number one health priority right now, is just trying to stay on top of donating blood every eight weeks. And next time around I think I’m going to try my first double red cell donation, so we’ll see how that goes.

(01:24:26)[Damien Blenkinsopp]: Cool. Is it legal to do that at home? Because just recently I’ve been basically forced to get my own blood samples at home because I’m traveling sometimes. And in the UK sometimes sending stuff to the US because the tests are over there.

[Chris Masterjohn]: Oh, for testing?

[Damien Blenkinsopp]: Yeah well you could take more blood out. That’s why I was wondering if there was a legal repercussions?

[Chris Masterjohn]: I honestly have no idea. I know that if you were a student in the high school the teacher would be legally bound to report that. But for a consenting adult that knows what they’re doing, I don’t know why that would be illegal, but I am not a legal expert.

[Damien Blenkinsopp]: Yeah, I guess they’ve never thought to do a rule about it. Probably, I guess they’ve never given the number of people.

[Chris Masterjohn]: When I was in grad school – the rules in Connecticut, they differ state-by-state, were anyone who gets properly trained can take blood. People would just practice on themselves just to get practice. I don’t know.

[Damien Blenkinsopp]: This iron error sounds like something you’re going to have to monitor.

[Chris Masterjohn]: For sure. Right now, I have a sense of how often I need to do it but it’s definitely something that after a few times I’m going to monitor and try to get a precise idea of how many times I need to donate to bring it down to the level that I want.

(01:25:49)[Damien Blenkinsopp]: Excellent. Very interesting.

It’s funny how the number of people I interview on this show that end up with something like this, a very specific thing that they found out about themselves that they then begin to start monitoring very routinely. It starts to make me think that everyone in the world has one specific thing, just for diversity, that a little bit out of whack. Once they look into the numbers a little bit they’ve discovered there’s this one strange thing. It just seems it comes up more than it should.

If you were to recommend one experiment someone should try to improve their body, whether it’s for health benefits, performance, or longevity with the biggest payoff, what would that be and how should they track it to understand it?

[Chris Masterjohn]: Do you mean in terms of measuring something or in terms of intervening without having any data about it?

[Damien Blenkinsopp]: Just taking some kind of action. Ideally having some kind of way of knowing that it’s actually successful. Or it could be something in your opinion where you say, “98% of people, if they do this it’s going to be beneficial in some way.”

[Chris Masterjohn]: For the very reason that you just said, I suspect that there isn’t one thing that 98% percent of people can do and have it equally payoff among them because they all have one particular weak thing to work on.

I would say, to be honest, if we’re talking about the general population, then I think that biggest payoff would be a self-experiment to find a sustainable way to modify your body composition. A few things that I would toy with would be protein intake and habit formation.

I think you have to look at your self and your individual psychological traits. I will say that for me tracking my calories with MyFitnessPal is one of the most effective things that I’ve ever tracked because I always had a problem where if I didn’t eat enough food I would have insomnia from it. Because of not tracking my calories I would constantly overshoot in order to preempt any possibility of not falling asleep because I didn’t eat enough food.

I was always eating a little bit more food than I needed. I was able to titrate my caloric intake to the sweet spot that allowed me consistent weight loss but also to optimize my sleep. Had I not been tracking calories there is no way I would have found that sweet spot.

I don’t want to make a blanket recommendation that everyone track calories, but I do think that, maybe this isn’t true for your audience because everyone so is on top of tracking everything, but if I were to go out to the general public for sure, I would say that self-experimenting, if you track waist circumference, and body weight to get some insight into your body composition and you keep a food log, and experiment with: is there a specific set of very simply habits?

Or actually tracking calories and serving sizes and those things that can come together to produce a consistent movement in a positive direction with body composition is where I think the biggest payoff would be because there are so many downstream metabolic dysfunctions from carrying the wrong mix of fat in the wrong places in your body.

Even the systems we were talking about today, normalizing your insulin sensitivity and your thyroid hormone and all that stuff that can come from managing your body composition can make the fat-soluble vitamins work much more effectively than they would otherwise. That’s what I would give.

(01:29:23)[Damien Blenkinsopp]: Thank you, that’s a great takeaway. This pretty much winds it up. You’ve mentioned your podcast, your podcast is great. You started it recently and it’s extremely detailed. If you guys listening today enjoyed this talk, there is even more detailed stuff on the podcast which is The Daily Lipid.

Is there any specific other requests? We already mentioned your Snapchat, I saw you’re on there, and some others. Is that the easiest way for people to connect with you? Facebook, Twitter?

[Chris Masterjohn]: If you want to follow consistently everything that I get, I think the best way to do that is to go to my blog, blog.cholesterol-and-health.com. If you subscribe by email or to the RSS feed there, you will get all of my long-form content that way. Anything that I write, any of my podcasts and so on and so forth.

Definitely I would say I’d love to have you following my Twitter, Snapchat and Instagram, but of course that’s kind of a different way of following me. When people follow someone on Snapchat or Twitter they don’t see everything that they put out. They stream it at a given time and if something’s there they see it, if something’s not there they don’t.

On Facebook, one thing I’m trying to do consistently now is to do Facebook Live, once a week. When I do Facebook live that shows up in 150,000 to 300,000 people’s newsfeed. If I post something on Facebook it shows up at something like 500 people’s newsfeed. You can follow me on Facebook but if you do that probably what you will actually see in your newsfeed is my Facebook Live Q&A sessions, so check those out as well.

[Damien Blenkinsopp]: Cool, thanks so much for what you do Chris. It’s been a great conversation with awesome details. Thank you so much for your time.

[Chris Masterjohn]:Yeah. It’s great to be here. Thank you so much, Damien.

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Ketone bodies, whether gained from fasting, keto diets, MCTs or exogenous ketones have many potential applications with benefits ranging from performance, to health, to longevity and mitigating symptoms and risks of certain diseases.

There is growing evidence that ketone bodies, whether they come from fasting, keto diets, MCTs or exogenous ketones have potential applications across many areas from longevity to performance, to health and mitigating some of the risks and symptoms of certain diseases like cancer and neurologically inclined deceases. As such the whole ketone body area is what I call a high leverage area due to the many potential upsides.

So I’ve personally been investing more time into experimenting in this area as the payoff for that effort, looks pretty promising. You’ll have noticed that I’ve done a fair amount of fasting and since late 2015, that also includes the exogenous ketones and playing around with the ketogenic diet. More to come on my results with all of those in future episodes.

This interview is a very in depth look at many of the applications of ketone bodies and the nuances of their use in the body.

Ketones have a unique effect of being… anaplerotic… [This] helps to generate the bioenergetic intermediates [including] the Krebs cycle intermediates… to energize the brain when fuel flow is kind of low.
– Dominic D’Agostino

Today’s guest is Dominic D’Agostino. Dominic has something that I found relatively rare but makes for extremely valuable interviews. He has a combined prospective coming from both research and self-experimentation. He has a considerable amount of lab work and research specifically done into ketogenic diets, ketones, ketone driving supplements and a growing number of applications. And he has done a lot of his own self-experimentation for many years in this area.

Dominic is currently an associate professor in the Department of Molecular Pharmacology and Physiology at the University of South Florida, and he’s also a senior research scientist at the Institute for Human & Machine Cognition (IHMC). His research is focused on developing and testing ketogenic diets, ketone supplements, and amino acid formulations for a broad range of therapeutic and performance applications.

His laboratory uses in-vivo and in-vitro techniques to understand the physiological, cellular, and molecular mechanism of nutritional ketosis and supplement formulas. His current efforts are focused on evaluating different methods for inducing and sustaining nutritional ketosis and how this can be optimized to the specific individual and applications. So, we’ll see in today’s interview that there are a lot of nuances and it’s a bit more complex than just boosting your ketones.

Dominic’s research is supported by the Office of Naval Research, The Department of Defense, Support Supplement Companies, and Private Foundations.

Special Note: In the interest of full disclosure, since late 2015 I own a company (Ketosource.co.uk) that develops ketogenic and ketone driving supplements, foods and drinks for the UK.

The episode highlights, biomarkers, and links to the apps, devices and labs and everything else mentioned are below. Enjoy the show and let me know if you want more on this topic in the comments!

itunes quantified body

What You’ll Learn

  • Using exogenous ketones to mitigate some of the impairments of sleep deprivation (all nighters, or jetlag) (5:50).
  • How the stress response from scenarios like jetlag will kick you out of ketosis (and can be compensated for via exogenous ketones) (13:00).
  • Dominic’s background research and how his career has evolved to working on ketone bodies and ketogenic diets and their applications (14:50).
  • Recent research with mice that may indicate that ketosis reduces anxiety (17:00).
  • Screening a range of different naturally derived exogenous ketone agents for their therapeutic and performance benefits (18:40).
  • A once to twice per year fast or nutritional ketosis protocol for potentially activating a range of beneficial genes (37:50).
  • The press-pulse ketone body strategy for the management of cancer (40:40).
  • The benefits of the ketogenic diet for the management of epilepsy over the pharmaceutical alternatives (49:20).
  • Using the ketogenic diet to restore normal appetite regulation (50:15).
  • The various health, performance and longevity applications for ketone bodies (52:00).
  • Potentially reducing tremors in Parkinsons and Alzheimers with the use of ketone bodies (57:10).
  • Evaluating the legitimacy of recently raised safety and effectiveness concerns related to ketone salts and MCTs based on scientific facts and their track record over the last two decades (1:01:10).
  • How racemic exogenous ketones suppress glucose more effectively than non-racemic exogenous ketones (1:13:40).
  • Using MCT oil powder as a staple product for coffee, baking and protein shakes to boost the ketogenic profile of your diet (1:16:00).
  • Avoiding liquid meals in order to be able to elevate protein intake higher while remaining in ketosis (1:18:00).
  • What a typical ketogenic day looks like for Dominic in terms of blood ketone measurements from morning to evening and how he optimizes it (1:20:00).
  • How Dominic has identified his optimum ketone and Glucose-Ketone Index ranges for mental performance (1:21:00).
  • To standardize and control for your blood ketones and glucose you need to be fairly sedentary (1:34:10)
  • Dominic D’Agostino’s recommended self-experiment with the largest potential upside with the tactic to test and biomarkers to track (1:42:00).

Thank Dominic D’Agostino on Twitter for this interview.
Click Here to show him some appreciation for doing this interview!

Dominic D’Agostino

Recommended Self-Experiment

  1. Tool/ Tactic: Start Intermittent Fasting with fasting windows of 18 hours and eating windows of 6 hours each day. Dom recommends listening to Matt Mattson’s talk on IF before you start.
  2. Tracking: Get some baseline lab tests before you start the IF and again 3-4, and/or 6-8 weeks afterwards to see the positive impacts. Your lab tests should include fasting glucose, triglycerides and hs-CRP.

Tools & Tactics

Diet & Nutrition

  • Well Formulated Ketogenic Diet: The high fat, low carb, moderate protein diet that puts you into ketosis with typical blood ketones of between 0.5 and 3 mmol/L depending on execution and the person. Not suggested for children, teens or people in their 20s with good insulin sensitivity in general.
    Foods Dominic Makes Particular Use of:

    • Coconut Cream: Combines the fats with some of the fiber from the coconut flesh. Coconut cream is also known as Coconut Butter.
    • Ghee (Clarified Butter): Butter that has had the dairy proteins removed to leave solely the fats. As such it is considered dairy-free.
    • Wild Sardines
    • Sour Cream with Live Cultures: Didn’t find a link to this – if you know a good source please let me know in the comments.
  • Fasting Protocols

  • Intermittent Fasting: Sometimes referred to as short-term fasting due to the typical 16 hour to 20 hour fasting window. Dom noted that he has spoken to a fair number of high-performing CEOs doing this routinely recently.
  • Fat Fast: A modified intermittent fasting protocol whereby you restrict caloric intake in the fasting window (e.g. 18 hours of day) to some fats, exogenous ketones and/ or MCTs instead of a pure fast (no food or calories). Dom finds this method effective and that he tends to be less hungry going into the eating window (i.e. 6 hour window).
  • Periodic Fasting: Typically refers to fasts spread out by once per week or once per month. We’ve done past self-experiments on the once per month periodic fasting protocols via a 5 day fast, 10 day fast and fast-mimicking diet.

Supplementation & Drugs

Exogenous Ketones

Dominic’s lab has looked at a variety of exogenous ketone formulations in different scenarios and applications. Amongst their papers are included improved blood lipid profiles1 and non-toxic metabolic management of cancer2.

MCTs and C8 (Caprylic Acid)

  • Brain Octane: Pure Caprylic Acid (C8) from Bulletproof Nutrition.
  • Keto8: Pure Caprylic Acid (C8) oil from KetoSports.
  • Quest MCT Powder: MCT powder that Dom is using as one of his staples mixed into coffee for example.

Dominic’s Sleep Deprivation Effects Mitigation Cocktail

  • Exogenous ketone: Take your pick from one of the exo ketones listed above. Is beneficial to combine with MCTs such as C8 or MCT powder.
  • Caffeine: Needs no introduction – use coffee or your other favorite
  • Huperzine A: A nootropic herb used for cognitive enhancement via modification of acetylcholine levels.

Drugs

  • Metformin: A drug which is used to improve blood sugar regulation in diabetes. Researchers are looking at its wider applications with cancer treatment as it has been found to inhibit insulin secretion.
  • Ringer’s Lactate: The long term use of this racemic solution was noted as evidence as to the safety of racemic ketone salts.

Tech & Devices

  • Hyperbaric Oxygen Therapy: Increasing the amount of oxygen in the body with the use of a hyperbaric oxygen tank which uses air that is more highly saturated with oxygen and which is compressed. Dominic has worked on research with Doctor Thomas Seyfried looking at its application for cancer therapy in combination with ketogenic diets3.

Tracking

Biomarkers

    Glucose/ Ketone Metabolism

  • Glucose: Dom suggests aiming to keep values between 60 and 80mg/dl and that if you can maintain this all other biomarkers should be fine.
  • Glucose Tolerance (OGTT): The Oral Glucose Tolerance Test is a glucose challenge test whereby you take a certain number of grams (e.g. the typical standard is 75 or 100 grams) of glucose and test your body’s ability to regulate glucose and bring your blood glucose back into normal range over a certain time period (e.g. 2 or 4 hours). Dom used the OGTT to assess his insulin sensitivity – the more insulin sensitive you are the quicker your blood glucose returns to normal fasting levels e.g. between 60 and 80mg/dl optimally.
  • HOMA (Homeostatic Model Assessment): An alternative method to the OGTT used to assess insulin sensitivity/ insulin resistance.
  • Glucose-Ketone Index (GKI): This index was conceived by Thomas Seyfried and discussed in detail with him in episode 16. It assesses the weighting of the metabolism towards ketone vs. glucose. Lower values are ketone driven metabolisms and higher value (especially over 20) can be associated with heavy glucose metabolisms associated with chronic disease. Dom brought a new angle to this marker with an optimum everyday target he shoots for of between 2 to 4. Previously we discussed Thomas Seyfried’s recommendation of undertaking a 5 to 7 day therapeutic water fast once or more times per year targeting a GKI value under 1.
  • Lipids

  • Triglycerides: Dom believes this is the most important biomarker to watch. Optimum levels estimated as below 40mg/dl.
  • HDL: Higher HDL levels are said to be protective and beneficial. Dom’s value are around 90 mg/dl.
  • LDL: Dom believes keeping values in the normal to normal high reference range are perhaps optimal. This puts levels at approx. 80mg/dl to 110mg/dl. We previously discussed LDL in more depth in episode 7.
  • Other

  • hs-CRP (high sensitivity CRP): CRP (C-Reactive Protein) is a very common marker of inflammation that is used to assess cardiovascular risk amongst other things. It tends to drop on a ketogenic diet. Dom’s values have been between 0.1 and 0.2 since he quit dairy (Note: Damien’s levels are also at this level).
  • IGF-1: IGF-1 was discussed in more detail in our FMD episode. Dom’s IGF-1 values dropped significantly after quitting dairy.
  • Heart Rate: Typically heart rate is measured as the biomarker Resting Heart Rate (RHR) for standardization, which is an average of the beats per minute. See episode 1 to understand the use of RHR.
  • Blood Pressure: Optimum ranges are for systolic between 90 and 120 and dystolic 60 to 80 expressed as for example 110/70 mm Hg.

Lab Tests, Devices and Apps

Devices for Measuring Glucose & Ketones

The different approaches to measuring ketones provide different perspectives on your ketone metabolism. These can be looked at in terms of the ‘window of snapshot’ that they represent. Some methods have a snapshot of a longer duration, so provide more of an average reading, while others provide a direct status of that exact moment.

Moving from the more average-based value end of the scale to the more direct status end you have:

  1. Measuring ketones via the urine (via the ketone body acetoacetate) has the longest snapshot with it representing your ketone values over the last 5 to 6 hours.
  2. Measuring via the breath (the ketone body acetone) has a smaller snapshot window of the 2 hours leading up to the measurement.
  3. Measuring via the blood (via the ketone body beta hydroxybutyrate) provides you a snapshot of your ketone level at that exact moment.

The various devices available for glucose/ ketones testing and mentioend include:

  • Urine Ketone Strips: . Both hydration status and becoming keto-adapted interfere with the measurement values provided by this. Dominic recommends starting with urine test strips as they are the cheapest and effective until you get keto adapted.
  • Ketonix Breath Meter: Currently the only breath acetone meter. If you are moderate to high on this meter you are effectively in ketosis (i.e. typically over 0.5 mmol/L). Dom recommends this in particular for epilepsy since breath acetone has been correlated with seizure control.
  • Blood Glucose & Ketone Monitoring Systems
  • Precision Xtra: The most popular meter for testing blood glucose and ketones in the U.S. Has a broader reference range than the NOVA providing values for lower blood glucose levels instead of the LOW error.
  • Freestyle Optium Neo: Freestyle Optium Neo is the upcoming replacement for the PrecisionXtra, it comes from the same company and has similar functionality – the only difference in the meters seems to be a rebranding exercise.
  • Novamax Plus: Novamax Plus is a slightly cheaper meter with some greater accuracy and sensitivity concerns than the Precision Xtra or Freestyle Optium Neo.
  • Dexcom G5 CGM: A Continuous Glucose Monitor that Dom is about to start experimenting with for blood glucose optimization. Peter Attia has also been using this tracking device recently to optimize blood glucose regulation. We discussed continuous glucose monitoring and the devices available in episode 43

Other People, Books & Resources

Books

People

Researchers

Other Mentions

  • Tim Ferriss: Has been experimenting with the breathe hold extending effects of ketone bodies via ketogenic diet and exogenous ketones.
  • Ben Greenfield: Has been experimenting with using exogenous ketones for free-diving.

Organizations & Companies

Other

Full Interview Transcript

Click Here to Read Transcript
(05:32) [Damien Blenkinsopp]: Dom welcome to the show.

[Dominic D’Agostino]: Thanks for having me, Damien.

[Damien Blenkinsopp]: Yes, it’s great to connect. So you’re just back from a trip to Budapest and you just told me that you’re doing something to bypass the jet lag?

(05:42) [Dominic D’Agostino]: Yeah. Sometimes depending on circumstances I try to prioritize sleep and try to get between six to seven hours sometimes eight on the weekends if I can. But in the absence of sleep, I like to test certain things.

Usually happens once every month or two or I’m going to have to skip one night completely and have to get thrown right back into the fire of work again. I’m doing that now, and testing some different exogenous ketones in combination with caffeine and some Huperzine, and a few other little things in a stack formula that I’m working on.

It seems to be working because I’m functioning and I’ve been able to manage my tasks in a way that allows me to get stuff done.

[Damien Blenkinsopp]: So, this could be a new jet lag formula? Or if you want to keep going on sleep deprivation and work for a night or something…

[Dominic D’Agostino]: Yeah. So, inevitably people will come to the situation where they have to meet a deadline and stay up all night to get something. I don’t recommend doing it all the time because you can get burned out. There is no pill that you can take that will substitute for sleep.

But there are ways to extend your productivity and performance with two or three days of no sleep. I don’t like when those situations arise, but I worked on ways to mitigate some of the impairments that accompany that.

(07:13) [Damien Blenkinsopp]: That’s excellent, that sounds like another application for exogenous ketones I had not thought of. I know there are a whole bunch I want to discuss with you because it seems like there’s quite a few of them. So now if you want to work all night, they can help with that.

I’m tempted actually, what is the mechanism behind that specifically for sleep, is it just a pure energy thing or?

[Dominic D’Agostino]: As far as sleep? Mitigating sleep?

[Damien Blenkinsopp]: Why would exogenous ketones help with?

[Dominic D’Agostino]: Yeah, I think there are several ways that they can help. You can formulate things to provide energy to the brain. There’s various, what we call tricarboxylic acid cycle intermediates, including alpha-Ketoglutarate, creatine – is actually something that could be beneficial to the brain when energy reserves are low, and ketones have a unique effect of being anaplerotic. So if something is anaplerotic it helps to generate the bioenergetic intermediates which include the Krebs cycle or also called the TCA cycle intermediates.

Essentially just helping to energize the brain when fuel flow is low. Many of the TCA cycle intermediates are also precursors to neurotransmitters. For example, alpha-Ketoglutarate is a precursor to glutamate, and then from glutamate through glutamic acid decarboxylase we make GABA.

So, ensuring that we have efficient energy flow to the brain and sort of stimulating anaplerotic reactions and bioenergetic reactions we can replenish the neurotransmitters. Being in a state of ketosis too, can also be glycogen sparing.
I always had the opinion that when we sleep, part of the function of sleep not only restore neurotransmitters but to also restore brain glycogen levels.

Glycogen is actually stored in the astrocytes of the brain. Astrocytes are not just for support cells they have a really important function that pertains to glutamate recycling and sort of dynamic interactions with the synapses and recycling of neurotransmitters and restoring brain glycogen levels is a function when we sleep.

I think we need to look into this more but I have a theory that being in a state of strong ketosis could prevent some of the glycogen depletion that accompanies a normal day in a person that is normally sort of carbohydrate fed.

Where the brain is sucking massive amounts of glucose but if you’re ensuring that it gets a steady fuel flow of ketones it’s going to be glycogen sparing in that way. Sort of like what Jeff Volek is doing with the athletes and it showed in a recent metabolism paper, that being keto-fat adapted and keto-adapted can actually be very glycogen sparing. If you look at the muscles of lead athletes on a carbohydrate restriction, amazingly their glycogen stores are topped off in the muscles.

I think the same thing is happening, I see no reason why it wouldn’t happen in the brain. Our energy reserves in our brain tank, adenosine goes up, neurotransmitters are depleted – we want to sleep. Being in a state of ketosis can slow that process, and exogenous ketones can be a tool in a toolbox to help with that.

[Damien Blenkinsopp]: That’s really fascinating. It’s like the biochemistry of sleep, we’re getting tired and I think we understand on a very basic level but you’ve just broken down quite a few mechanisms which lead to us needing to sleep and how to counter them.

[Dominic D’Agostino]: Yeah, sleep is a really complicated subject. I did my Ph.D. in a pulmonary critical care department that was also a sleep lab. So I sat in on a lot of rounds and meetings with residents and fellows about the mechanics of sleep.

It’s just a fascinating subject, and something I’ll probably get more into research wise. But I do teach the medical students about obstructive sleep apnea and central sleep apnea, that’s some of the research that I did in my Ph.D.

(11:22) [Damien Blenkinsopp]: Excellent, and you’re on a keto-diet as well right still?

[Dominic D’Agostino]: Yeah. I maintain that but I also like to cycle a little bit because I think a lot of the therapeutic and performance enhancing benefits can be achieved with nutritional ketosis but I also think it’s good to have relative changes.

Not to stay on something all the time, but to adjust your macronutrients a little bit, and also maybe your calories a little bit, and occasionally fasting. These relative changes can produce some pretty good performance and therapeutic effects.

[Damien Blenkinsopp]: It’s kind of like exercise like promoting metabolic flexibility, is that where you’re coming from?

[Dominic D’Agostino]: Yeah, that was what I was going to say and relate it back to a hormetic effect where relative changes are good. For a while, I just stayed on the exact same ketogenic diet for a long time and I started adjusting and playing around with different supplements and I realized it’s good to sort of adjust the diet and even adjust your calorie levels sometimes. My life is variable, it kind of fits on with my lifestyle too.

[Damien Blenkinsopp]: I feel the same way. I’m probably doing the something a bit more varied these days. So, it’s just interesting, you said you are basically stacking exogenous ketones for sleep on top of your keto diet. Does that push your levels quite high?

[Dominic D’Agostino]: At least doubles or maybe triples where I would be. I have noticed in the past that if I just stick to my normal diet and I cross time zones. I’ve been in at least a dozen time zones for the last month and a half, two months.

When I do that and I miss a complete night of sleep, coming from Southeast Asia completely flips circadian. I realized that I get a stress response from that I think my cortisol goes up, my sympathetic nervous system can be activated. And I notice that can kick me out of ketosis a little bit or I’ll have levels that are — I would predict there would be much higher based on the macronutrient profile that I’m eating and even fasting.

So, I find that exogenous ketones can sort of help in those situations where I put my body into an unaccustomed stress.

(13:36) [Damien Blenkinsopp]: That’s very interesting. I’ve started to use some of the supplements, exogenous ketones for different scenarios a bit like that situation but we can talk about that later. So, I wanted to give people a background, would you say your focus area is ketones, ketogenic diet? Is that what you’d call your focus area of research?

[Dominic D’Agostino]: Yeah. I’m classically sort of trained as a neuroscientist. I did my PhD in something very specific, it’s patch clamp electrophysiology where you measure from individual neurons and you record the membrane potential, firing frequency input resistance of individual neurons, either in cell culture or in a brain slice, and studying pharmacology and the metabolic activity. I became very interested in observing fundamental neuronal activity.

I became very interested in the metabolism that was supporting that. I realized that the life that I was seeing on the amplifier of the oscilloscope, these neurons firing was completely a result of the electrochemical and the electrical gradients between the neurons, they’re like little batteries.

That was generated completely by the metabolic activity so cells they need to maintain negative 56 kilojoules per mole of energy and they will do anything to do that. Some substrates and some means of generating ATP are more efficient than others. In my early work, I was actually looking at lactate.

I was interested in Ringer’s lactate, so racemic Ringer’s lactate is actually used on the battlefield and also in surgery when people have a lot of massive blood loss. Lactate is extremely efficient fuel, and I studied hypoxia in the brain and ischemia, and I was interested in lactate for that. That got me interested in this whole idea of developing and testing metabolic substrates to preserve and enhance brain energy metabolism in the face of extreme environments.

Our work for the last decade has been funded by the military. So I’m interested in particular situations that would accompany military operations, like a navy seal using a closed circuit rebreather with high levels of oxygen. He’s susceptible to a limitation of his mission, would be oxygen toxicity seizures so the fundamental neuroscience that I learned in my Ph.D.

I applied that to developing and testing metabolic base therapies to preserve that cognitive function and metabolic resilience in the environmental extreme of high-pressure oxygen. That’s sort of a fun thing to do because there’s many ways to do it. I’m always looking for the next, or the optimal formula, of ketones and that’s why we don’t focus on any one particular exogenous ketones. We screen a variety of ketogenic agents or formulas of them to identify the one that’s most neuroprotective or anticonvulsant.

Now, we do cancer studies and we do wound healing, performance applications – and it might be a different ketone for different applications and we’re testing that now. In Budapest, we actually presented some really interesting work on anxiety. So if we induce a state of nutritional ketosis, the anxiety levels go down pretty significantly. In a rodent model, they’ll spend more time in like an open-arm of an elevated plus maze.

Perhaps that reduced anxiety can play a role in reducing seizures too, so it’s another variable that we need to look at. I probably went off on a tangent. My background was neuroscience and now I do what I would call a nutritional neuroscience or metabolic based sort of strategies to target neuronal processes and neuroprotection.

(17:43) [Damien Blenkinsopp]: How many years have you been doing this now?

[Dominic D’Agostino]: I started neuroscience research as an undergraduate in 1997. So, it’s going on about — 1996 or 1997 — so about 20 years now I’ve been into neuroscience research. The office of navy research, post-doctoral fellowship, was the first large grant money that I’ve got, and that was 10 years ago.

It took me about four years to recognize that the most potent strategy for oxygen toxicity for mitigating that, which I was being funded to do would be a ketogenic approach. Then the ketogenic diet at that time was recognized as something very obscure even just six years ago. So the funding agency really wanted a ketogenic diet in a pill per se.

In addition, to our ketogenic diet research which I feel is also very important we have developed these synthetic and actually naturally derived ketogenic agents to mimic the effects of fasting, the ketogenic diet, and also to further augment the therapeutic efficacy of the ketogenic diet. If the ketogenic diet can only get you to one to two millimolar, and we boost it in another one or two millimolar with exogenous ketones. We’ve realized that, that can be very beneficial.

Not everyone can follow a ketogenic diet including performance applications or for therapeutic purposes.

[Damien Blenkinsopp]: People find it quite hard. I don’t think it’s relatively complex to get into it. I speak to a lot of people who think they’re in ketosis but they’re not.

[Dominic D’Agostino]: Yeah, I do too.

(19:25) [Damien Blenkinsopp]: It’s a little bit tricky I think. So, alas comes the supplementation and so on which could make it easier. I think what’s really awesome about you, you self-experiment as well in addition to your research.

You’re always looking for this stuff and I know you’ve been on a keto diet for a long time, when did you start that?

[Dominic D’Agostino]: Yeah, that’s the fun part of this research that I’m really excited about. Well looking back, I did low-carb diets for a while because I was always into powerlifting, fitness, and nutrition. So, I would experiment, and I was under the impression that being on ketosis was bad.

When I did a low-carb diet or what I call the ketogenic diet, I remember smelling like ammonia. Because it was basically a very high protein, zero carb diet, with a normal amount of fat. Then I got educated I guess, being connected with the folks at John’s Hopkins who are using this on a clinical setting. I read the book by John Freeman and Eric Kossoff at John’s Hopkins, which is a great book, ‘The Ketogenic Diet’ for epilepsy and other disorders that’s out there.

There are one or more popular books on Amazon. I realized wow I didn’t know what a ketogenic diet was. I didn’t realize it has this fascinating history. You know written with Travis Christofferson, we wrote a three part of series on Robb Wolf’s blog about the ketogenic diet the history. When I actually got into the 4:1 ratio ketogenic diet, the John’s Hopkins which is like 90% fat.

And I transitioned into a state of nutritional ketosis, it was kind of difficult in the beginning. After about two or three weeks I adapted quite well and started realizing the neurological benefits. The appetite suppression was pretty extreme it was difficult for me to maintain my weight even.

(21:16) [Damien Blenkinsopp]: In terms of losing weight?

[Dominic D’Agostino]: Yeah, because my protein level was really high. I think I was getting probably 300 grams of protein a day which is really high. So, I had to drop that down to about 100 grams of protein a day to hit those macronutrient ratios.

Probably about 120 grams a day of protein, which was a relative change that was really low. When I reduced my protein to 1/3 but elevated my fat, and I still kept going to the gym. But at the time my academic career was sort of going full steam and I was in the gym less, but still making it once or twice a week.

My weights that I was handling on major exercises were maintained so I realized that being in a state of nutritional ketosis had a pretty profound anti-catabolic effect. So, I figured I’d be wasting away if I wasn’t getting my body all these protein. But I was amazed that I could eat.

I even started experimenting and went down to like 60 or 80 grams of protein a day. Even after a couple weeks and months I was able to still move the same weights.

So it really blew my mind that shifting the metabolic physiology to being more fat and keto-adapted had this sort of protein sparing anti-catabolic effect. Which makes sense if you look at it through like an evolutionary lens.

So if we stop eating and we didn’t make ketones to fuel this big, highly energetic organ in our head. If the ketones weren’t providing fuel for our brain we would liberate a lot of gluconeogenic amino acids from the skeletal muscle, and we would quickly waste away probably in a week or two, for a lean individual. That’s important to recognize in the context of using a ketogenic diet for a weight loss strategy and also for body composition.

For example, athletes that need to make weight which many sports do — wrestling, boxing, mixed martial arts – keeping that power to weight ratio is important. We think from the studies that we’ve done, we actually just got a study approved finally for publication yesterday showing elite level athletes or advanced lifters that the ketogenic diet is quite effective for body composition alterations and preserving strength and muscle strength and performance.

So that should be out pretty soon in general strength and conditioning. We realize that the ketogenic diet has far more applications than just pediatric epilepsy, which was it’s original application. We’ve probably studied about 10 different applications now in our lab.

(23:59) [Damien Blenkinsopp]: Excellent. So I wanted to run through some of those applications. First of all taking a step back because you mentioned lactate earlier. I think the majority of us assumes that glucose is the main metabolism. Then we learned about ketones and we think maybe there’re two substrates that we’re using for metabolism.

As I understand it, it’s a lot more complicated right? That we’re using a number of different fuels at any time?

[Dominic D’Agostino]: Yeah. I think the big ones for brain metabolism, which our laboratory originally focused on and now we’ve branched off, would be glucose would be the primary fuel for most people. Then ketones are sort of a backup fuel.

If you’re on a ketogenic diet, you’re running this hybrid engine and you’re using both fuels at the same time. With ketones probably the most efficient of the two. Then lactate too.

When we exercise, we mobilize a lot of lactate and put a lot of lactate back into the bloodstream through what’s called the Cori cycle. We convert that back to glucose and then replenish liver glycogen or muscle glycogen. But that lactate can also go past the blood brain barrier across which is called the monocarboxylic acid transporters and provide a source of energy for our brains.

Lactate metabolism in the brain can also occur under conditions of oxygen deprivation, so it may be beneficial. That was also an interest in my earlier work, using lactate to preserve bioenergetic processes in the absence of oxygen. What we call hypoxia or anoxia, which is a complete lack of oxygen.

Interestingly ketones can generate more ATP per oxygen molecule consumed. In a hypoxic situation, ketone metabolism may also be able to preserve the bioenergetic state of the brain. That’s something that we’re also looking into hypoxia and ischemia protection of the brain with various fuels, ketones, lactate preventing or an alternative substrate to glucose.

In certain situations, neuropathologies and even a hypoxia, stroke, a brain injury for traumatic brain injury can cause a quick impairment of glucose utilization of the brain. By internalization of the GLUT3 transporter and also inactivation or reduced activity of Pyruvate dehydrogenase complex, the PDH complex, can be impaired under certain conditions of brain injury. Even certain viruses that cause neuroinflammation can impair this rate-limiting step for glucose metabolism.

So, alternative energy substrates are a way to bypass that glucose block.

(26:37)[Damien Blenkinsopp]: It’s like a diversification strategy?

[Dominic D’Agostino]: It is, in diving we always talk about being redundance. You need a level of redundancy to ensure safety. I think the brain does that pretty nicely. So we achieve that with fasting.

We have an alternative energy substrates being utilized in the absence of glucose. It’s interesting to be able to delve into that and understand what happens during fasting in different states. From my perspective, it’s a fascinating field of research to develop naturally derived or synthetic agents that can mimic those processes.

(27:17)[Damien Blenkinsopp]: Right. Because we are on a ketogenic diet do we also use fatty acids directly for energy substrates or do they have to be turned into ketones first?

[Dominic D’Agostino]: Yeah. Hepatic gluconeogenesis will be in a state of fasting, completely dependent upon the liberation of fatty acids from adipose tissue. Fat mobilization is directly almost correlated to a ketone production in that fasted state.

Our heart can use fatty acids more efficiently than glucose – our heart is an awesome fat burner. The skeletal muscle is an awesome fat burner especially in the keto-fat adapted athlete, the liver, various organs can use fatty acids quite efficiently. The long-chain fatty acids do not readily cross the blood-brain barrier.

Short chain fatty acids do, and medium chain fatty acids can actually cross the blood-brain barrier. So, that was actually an interest of mine and we did some brain metabolomic studies where we took out the hippocampus of some rodent models that we looked at. We saw a high level of the C8 and the CA10 MCT that we administered to the animals.

I think if you look at the ratio between the blood levels and the brain levels. I think there was a kind of like a 1:5 ratio, so that wasn’t readily getting through but a lot of it was getting into the brain. Of course, the brain was metabolizing it.

Our numbers might have not correlated precisely in a 1:1 ratio in that way. But it’s clear that our body can use fatty acids as fuels, and it’s an incredible fuel for our mitochondria. Because it metabolized exclusively in the mitochondria through oxidative phosphorylation.

(29:03) I would say ketone molecules are I’d like to call water soluble fat molecules, sort of an excessive beta-oxidation or accelerated beta-oxidation in the liver, contributes to the accumulation of acetyl-CoA which drives ketone production, and hepatic ketogenesis. So the acetyl-CoA essentially condenses to form acetoacetate. Then beta-hydroxybutyrate and these spill into the bloodstream.

So it’s interesting that the liver is a massive ketone producer but it lacks certain enzymes that prevent the liver from using the ketones as an energy source so it lacks succinyl-CoA transferase for example.

So, the liver will produce massive amounts of ketones. Then dump it into the bloodstream primarily for our central nervous system to maintain energy flow to the brain, then the central nervous system, and probably the heart too. The liver is a greedy organ, if you fast and you eat, the amino acids and glucose will basically stay in the liver and the liver will take what it needs and put whatever is left into the bloodstream.

But with ketones since the liver does not metabolize ketones it puts them immediately in the bloodstream when it’s burning fat for energy. Looking at it through an evolutionary lens, that function is to ensure that our brain gets adequate fuel flow. In the absence of food, if our brain tanked because we’re hypoglycemic, we wouldn’t be able to hunt.

So, being very lucid and having our brains energized during a period of food deprivation ensure that our species survived. The humans that weren’t able to do that did not get on and live. I think we’re sort of hardwired in a way to function optimally when we’re in a fasted state and that’s important to recognize.

Also, in the context of a society that’s programmed to give three high carbohydrate feedings per day. The metabolic program that is activated during fasting is largely silenced because of the societal norms, associated with our macronutrient profile, but also our eating pattern which is frequent feedings throughout the day.

(31:22)[Damien Blenkinsopp]: Yeah. One of the reasons I ask this is because I’ve had some fear and scared feedback about fasting for instance, which is a bit more of an extreme situation like ketogenic diet normally. One of the things I did was publish some of my own information on YouTube and I got some crazy comments from people saying I was going to die because my glucose was low.

I think it was 3.3 millimolar or something about 54-55 mg/dL. My mother’s a nurse and she saw the numbers and she was quite shocked at the time as well. Everyone thinks that we’re driven solely by glucose metabolism that’s the only thing they look at. So I think it’s really interesting that we have several various fuels that we can be going on, turns out that the glucose isn’t that important.

Someone else just sent me the numbers recently and they were the lowest I’d ever seen, like I was doing a fast and she got 1.8 millimolar with her glucose. I don’t know if you’ve seen anything that low.

[Dominic D’Agostino]: I did. Well, when I fasted for a week I tried some strategies, I probably shouldn’t talk about it here.

[Damien Blenkinsopp]: Okay. In case someone else does it.

[Dominic D’Agostino]: Yeah. After fasting a week, I was staying around the mid-fifties to low fifty’s and occasionally I would dip into the high forty’s depending on my activity and things like that. I did some strategies — I’ll label it as “strategies” — to lower it down to a level that the meter didn’t read, so it just actually was flashing low.

The lowest my meter was able to read was 25 or 26 mg/dL. I assume 25 that’s the limit. I spent a good part of the day with it flashing low and unable to read. I was using the Nova Max meter, and I was using the Precision Xtra Meter and also using the Neo Meter, so I had three different meters and I was scrambling.

[Damien Blenkinsopp]: Is that the Freestyle Optium Neo?

[Dominic D’Agostino]: Yeah. The freestyle like a lower profile sort of meter than the Precision Xtra. So I had three different meters, and I was measuring and I was like, “Oh no I don’t even know what my glucose is. All I know it’s probably under 1 millimolar range.”

I was starting to feel a little bit — using different pharmacological strategies to lower it — but I realized that I was at a level that was universally fatal for everyone if I didn’t have my ketones elevated.

[Damien Blenkinsopp]: Right. But if you had been admitted to the hospital, they’ll put you on the emergency ward most probably if you walked in like that.

[Dominic D’Agostino]: Yeah. During this particular day, I was preparing for a lecture, I was writing a grant it was really a productive day. As I was working I was doing these things and I would do measurements and work for a little bit more and it just goes to show it was a very dramatic demonstration an alternative energy source.

For me, that has tremendous implications therapeutically for someone that’s experiencing insulin shock or a neurological disease with impaired glucose metabolism. So we worked very closely with the glucose transporter type 1 deficiency association. It’s a rare disease where the brain does not have glucose available due to deficiency of the GLUT1 transporter.

There are many different diseases like that. I was also inspired by the work of George Cahill, there was a study that was published in 1967. The first author was Oliver Owen and they fasted subjects for 40 days.

In another report that wasn’t originally published with the original report. I found it in another book they administered insulin, 29 IU of insulin they gave IV. In these fasted subject they lowered the glucose down to 1-2 millimolar and kept it down there.

[Damien Blenkinsopp]: So it’s like 35 mg/dL somewhere around there?

[Dominic D’Agostino]: It’s not even that it was about that 25 range that my meter couldn’t read. So one millimolar would be 18 mg/dL. That inspired me, I was thinking if these subjects can fast for 40 days I could do a week.

It’s about five years ago or so that’s when I did the week long fast and did some experiments on myself. One of the most interesting things that happened to me was my breath hold time. So at the time I was outside a lot.

I was in and out of the pool, taking short walks and trying to stay active, keep my mind off of food. Because the main challenge was just the pleasure of eating was not there. I was swimming I was under the pool and I realized, “Wow,I had been down for quite a while”, and I wasn’t gasping for air.

I got back up to the surface and my girlfriend was there at the time, now my wife, and I started testing my breath hold time. I was like, “Keep an eye on me.” Normally I could do over a minute about 90 seconds, but I was able to stay down for three to four minutes which is remarkable.

I don’t have any kind of specialized training. I’ve been wanting to take a freediver course. I know Ben Greenfield did and we exchanged emails when he was going through that because he was trying exogenous ketones. But I found that after one week of fasting, I had a profound prolongation of my breath hold time. I think that’s fascinating to me.

Fasting does definitely start to shut down your metabolism. I think my body temperature probably went down a degree or two so the metabolic demands just weren’t there. But I think our drive to breath has a lot to do with our CO2 sensitivity.

So there’s receptors in the ventral respiratory group and the ventral surface of the medulla that sense CO2 levels and drive the urge to breathe. We also have the carotid bodies, at the bifurcation of the common carotid artery that sends oxygen and CO2 and they also mitigate or they also play a role in the drive to breath.

I think there’re interesting mechanisms going on there. A desensitization in some way or in combination to just altering our metabolic physiology. I think that has some practical benefits for different sports, maybe military operations.

I want to study that a little bit further with adaptations that happen during fasting.

[Damien Blenkinsopp]: Yes, very interesting. I’m wanting to go and test that out with freediving.

[Dominic D’Agostino]: A number of other people have, I think I might have mentioned it once or twice very briefly, not as descriptive in other podcasts but other people went out there and did it.

I think Tim Ferriss did it. I’m not sure if he’d blogged about it yet but he sent me quite a few texts and emails just saying that dramatically enhanced his breath hold time. So, I’m pretty sure it’s a real phenomenon.

(38:15) [Damien Blenkinsopp]: Very cool, to kind of round that conversation off. I get these emails, like I said, some people are scared because they get injured in fasting particularly a very low glucose levels of 30-35mg/dL.

Do you think that’s something to be concerned about or is it absolutely no problem? Typically, they have ketones like six millimolar, somewhere around there at that stage?

[Dominic D’Agostino]: I wouldn’t recommend that for a long term sustainment of life. Because there are a lot of biological processes that require glucose: red blood cells, your kidney, certain immune cells, and even biosynthetic processes like the generation of certain neurotransmitters are in some part glucose dependent. I think it’s good to get into that level and I’m going out on a limb by saying this to be a mainstream sort of medical college.

I actually think it’s very good to be in a state of nutritional ketosis with sustained hypoglycemia for a period of time, and to do that at least once a year, preferably a couple of times a year. I think what really kicks on a genetic program that activates so many biological processes that I think could be protective from enhanced insulin sensitivity to autophagy, to activating a number of different genes. There’s certain ones obviously, ampakine is activated, mTOR is suppressed.

You put tremendous metabolic stress on glycolytic cancer cells or pre-cancer cells that we may have in our body, sort of an immune activation. I know Dr. Adrienne Scheck is doing some work with the ketogenic diet and she’s doing some elegant work on the immune activation, and from the gist of it and from other bodies of literature it supports the idea that the immune system becomes hyper-vigilant, to recognizing and attacking existing cancer cells when we put our bodies into the state of fasting.

Either prolong fasting or even the ketogenic diet. I think it’s good to do that sometimes. But say if you’re on the ketogenic diet all the time in the state of moderate ketosis and then you fast.

You probably won’t get the same benefits as a person who’s on a high carb diet and did a fast. It would be a lot harder for that person who is on a high carb diet to do a fast. It would be greater stress because it’s that relative change or that pulse.

Thomas Seyfried and I we’re going to work on, it was originally his idea. We talked a lot about this press pulse phenomenon for the metabolic management of cancer. The press would just be a mild state of nutritional ketosis and the pulse could be periodic fasting or some of the things that we’re interested in. Such as hyperbaric oxygen therapy that could be pulsed exogenous ketones to further allow for a greater hypoglycemic response.

Also, you could pulse various cancer-specific metabolic drugs like 2-deoxyglucose, or dichloroacetate, or 3- Bromo Pyruvate] could be used. The press would just be nutritional ketosis and that would metabolically compromise a lot of the highly glycolytic, which corresponds to highly aggressive cancer cells.

(41:41)[Damien Blenkinsopp]: When you say press that would be like something chronic that you’re doing?

[Dominic D’Agostino]: Yeah. We know that being in a state of nutritional ketosis causes suppression of the hormone insulin. The cancer cells that light up on a fluorodeoxyglucose PET scan, a FDG-PET scan. The PET [or PET-CT] scan is really the gold standard technique.

I would say when it’s coupled with the CT scan allows you to precisely locate where that hypermetabolic activity is. So the PET-CT is an incredible, gold standard tool to assess the location and aggressiveness of existing cancer cells. The greater the standardized values that are coming out, like 2.5 would be sort of the normalized value.

If you have a PET scan showing SUVs of a 100 or 250, those cancer cells are very aggressive.

[Damien Blenkinsopp]: So they show up as the big red and yellow blotches?

[Dominic D’Agostino]: Yes.

(42:47)[Damien Blenkinsopp]: Yeah, we spoke to Gene Fine on a previous episode he was talking about the PET scan.

[Dominic D’Agostino]: Oh yeah. Actually Dr. Fine, you probably know he did a study for 28 days. He did a study with a ketogenic diet and he selected patients based on their PET scans. The topic that I was going to touch on is that insulin suppression correlates with ketosis.

I think even the title of his paper didn’t even mention the ketogenic diet, it was something like insulin inhibition therapy can be used to target cancer. It didn’t even talk about the ketogenic diet. But if you read the paper, he basically used the ketogenic diet to suppress the hormone insulin as a therapy for managing these hard to treat cancers or people who have failed the standard of care.

So, that would be the press that I’m talking about. The ketogenic diet limits glucose availability to the cancer cells. It suppresses the hormone insulin which drives IGF-1, mTOR and other factors that cause cancer cell growth and proliferation. I don’t know if Dr. Fine talked about it, but he has a number of publications.

I was inspired by his work and I actually got us to look at exogenous ketones and the effect on cancer cells. We find that if you limit glucose, suppress the hormone insulin and elevate ketones, the ketones themselves have anti-cancer effects. So, we did a study, we published in the International Journal of Cancer.

The first author was my graduate student at the time, Dr. Angela Poff, she’s now a research associate following up on this work. We gave ketones to highly aggressive cancer cells that have a glioblastoma-like origin. When we grew the cancer cells in the presence of ketones, even in the presence of 25 millimolar glucose, it inhibited, it dramatically slowed down cancer growth and proliferation.

(44:47) We did a viability testing where we looked at live cells and dead cells and the ratios of that. We found significantly more dead cells when we grew the cancer cells with ketones even in the presence of glucose. The take home was that ketones were probably turning down or shutting off a lot of some of the glycolytic mechanisms and there’s previous reports suggesting that ketone metabolism can turn down glycolytic metabolism.

So, that would be the press.

[Damien Blenkinsopp]: It sounds like a signal even for the cancer cells?

[Dominic D’Agostino]: Yes.

[Damien Blenkinsopp]: For them to switch them off even if they can’t use the ketones?

[Dominic D’Agostino]: Yeah, we think so. Now, we need to mechanistically dissect those kind of signals that are happening with the ketones because they do high-level sciences. Our lab approaches things a little different. We don’t sort of identify a target and then work up from that.

We screen a lot of things at the top and find out what works. Then, once we found out what actually causes animals to live longer or produce a neuroprotective effect then we go and try to find the mechanism.

(46:00) [Damien Blenkinsopp]: That sounds like a little bit like the pharmaceutical drug research process where they screen many many molecules for doing something. Correct me if I’m wrong. It seems like maybe it’s an efficient process to find things that work by just screening a lot of things and then focusing on the things that are working.

[Dominic D’Agostino]: Okay. So, it’s a little different, with pharmaceutical companies they actually target a mechanism or a biological kind of process and enzyme.

[Damien Blenkinsopp]: So they’re all looking for an end result right?

[Dominic D’Agostino]: Yeah. We’re testing a bunch of things, we don’t even know how they work. We’re testing various ketogenic exogenous ketone formulas and we don’t even have the pharmacokinetic nailed down yet. We don’t even know specifically how they’re metabolized.

We feel that it’s really important to get this research done so we can get these therapeutic agents out there as fast as possible. We screen a lot in various agents, first in human or first in animal, and then we identify what works. But the mechanisms, the metabolism is incredibly complex.

What we find is that it’s not working through one particular mechanism, it’s many different mechanisms working in synergy. The ketogenic diet, you have an increase in the GABA to glutamate ratio or ATP production you have a greater bioenergetic potential of the mitochondria. You have more TCA cycle intermediates.

The list goes on and on. There’s a science paper showing that ketones beta-hydroxybutyrate is a HDAC inhibitor. We published a nature medicine paper showing that inhibits the NLRP3 inflammasome and that’s independent of metabolism.

(47:41)[Damien Blenkinsopp]: So it’s like a huge dynamic system? There’s no way you can see all of the mechanisms going on there? As you’re saying you looked for the end effects and then you started looking for the mechanisms.

All of these mechanisms that you just brought up and started piecing them together to see how it worked after you’ve got the end result that you wanted.

[Dominic D’Agostino]: Yeah. The important thing is that it works and then the secondary important thing is to find out the mechanism. Because once you do know the mechanism, if the majority of the therapeutic effects or performance enhancing effects are due to a particular mechanism, out of many mechanisms. Then we can tweak the molecule of the formula, the pharmacokinetics, to further enhance that particular mechanism.

Then we can go back and tweak the formula, or the molecule to make it hydrolyze faster or to increase the sustainment of it, or deliver it in a certain nanoparticle formula to a particular tissue or something like that.

(48:37)[Damien Blenkinsopp]: So we’ve already spoken about quite a variety of basic applications, benefits of ketone based metabolism, and ketones. Could you just go through the top ones in your mind, maybe the ones that we haven’t already covered? So I know a lot of people are focused on weight loss for instance.

[Dominic D’Agostino]: That probably goes back to what they call the ‘Banting diet’. That even predates some of the work that I first got attracted to in epilepsy. So, epilepsy that would be the big thing.

The ketogenic diet, the only thing that is used for standard of care in mainstream medicine is the management of epilepsy. I always harp on this too, the ketogenic diet is grossly underutilized as a tool for managing epilepsy because it works when drugs fail.

It works in about two-thirds of the population. Imagine the efficacy of it if it was the first line of therapy. If you have a child that’s two or three years old and you load them up with anti-convulsant drugs, we know that these anticonvulsant drugs cause developmental delays. It’s even more important in pediatric epilepsy, I think to start with the ketogenic diet.

I just like to throw that out there. We’ve already talked about epilepsy. So, epilepsy would be the big one and obviously weight loss. You have the original Banting diet. Then Atkins came out with what he said was his famous diet but it was really a playoff with the Banting diet. It allows for effortless weight loss because when you’re in a state of nutritional ketosis the ketones function to control appetite.

It prevents your appetite from controlling you. We don’t really know the mechanisms that regulate appetite control, are incredibly complex. But we think that the ketones are essentially telling the brain it’s in a fed state, that’s the simplistic way to put it.

(50:32)[Damien Blenkinsopp]: Okay. Ketones get converted back into fat? Because people know that you basically pee ketones out when you first get onto a keto diet. Is that one of the mechanisms also?

[Dominic D’Agostino]: Well, yeah. If you collect all the urine of someone that’s on a ketogenic diet and then you look at how many calories are there, it’s pretty marginal. I think Atkins even advertised, “Look you’re peeing out fat, you’re peeing out calories.”

But it only came down to like 50 to a 100 calories or something like that. I think the big effect, the metabolic advantage really, is not that you’re burning more calories. I think there’re different organizations out there that we’re trying to prove if there’s a metabolic advantage to being in ketosis.

I think the big advantage that we need to focus on is appetite regulation. Our current diet of processed carbohydrates contributes to appetite dysregulation. The ketogenic diet is very effective at restoring sort of normal appetite behavior because there’s no fluctuations in blood glucose.

If we’re on a carbohydrate based diet and we go hypoglycemic that’s going to trigger an intense craving for carbohydrate re-feed to re-establish that glycemia. That’s completely abolished on the ketogenic diet.

So when you’re on a well formulated ketogenic diet, the craving that you’d have with hypoglycemia is going to be significantly attenuated if not abolished. We talked about weight loss and type 2 diabetes pretty much every disorder out there. Let’s think cancer, even kidney failure, neurological diseases like Alzheimer’s disease and many other pathologies are sort of linked pathophysiologically to the metabolic dysregulation and also obesity type 2 diabetes.

If a diet does promote a healthy weight loss and sustainment of that weight loss, it’s going to be therapeutic for many other disorders. Some of the things that we study include Alzheimer’s disease, ALS, we have a really active cancer research program in the lab. I have two Ph.D. students right now studying.

One is looking at Metformin and other cancer-specific metabolic drugs but combining it with a ketogenic diet. His main thing is to locate drugs. But we think some drugs will synergize with the ketogenic diet.

In another project is looking at the ketogenic diet or exogenous ketones and branch chain amino acids to mitigate cancer cachexia, which is muscle loss or wasting, so we’re looking at that. Exercise performance we’re looking at that. The most recent data that I’m really excited about because of the pretty robust effect as far as some of the behavioral models that we use.

One particular model is the elevated plus maze which looks at anxiety. We found that being in a state of nutritional ketosis that was induced completely with exogenous ketones stimulates in the elevated plus maze which is like a rodent going out on a catwalk. You can go into a cave or come out into an open area where you’re on a plank and you’re elevated in the air.

It’s a very anxiety producing situation. In our rodent models validate as a very useful model. We’ll spend much more time on the open arm and less more time hiding in the cave. We think that has significant implications for military personnel with PTSD and anxiety in general, and a lot of depression too is also sort of a comorbidity there with anxiety, a lot of depression, and anxiety fueled.

[Damien Blenkinsopp]: You’re saying that they’re willing to go out walk on the plank, take that risk and feel comfortable with it?

[Dominic D’Agostino]: Yeah.

(54:28)[Damien Blenkinsopp]: Do you measure it by time spent on the plank?

[Dominic D’Agostino]: Yeah. Less anti-social behavior I guess. We set up this elevated plus maze and then we have a whole video imaging system above it. We keep the animals as low stress as possible.

We have the same person working with the animals so they’re not experiencing different smells, and things like that. The room is very very quiet. We pay attention to circadian, light on light off things.

There’s a lot of variables that need to be controlled and then we image them in the absence of ketones. We see how much time they’re like in the middle, in the open arm, closed arm and our video camera system sort of can track all that. We have various programs and algorithms that do all the calculations for various things.

We do a bunch of animals just on a standard high carb diet. Then what we’ve been doing is testing various ketogenic agents, or various exogenous ketone and ketone formulas that would be administered 30 minutes prior to being put in this elevated plus maze, and being there for a couple of hours. Then we’ll track all that information, it’s all done blinded.

We have one person who’s, usually two people part of the project that’s administering the agent. The person that does the analysis does not know what the animal is receiving. We’ve got a pretty robust effect with a few of the ketogenic agents on reducing this anxiety behavior.

That’s some new data that we just presented literally less than a week ago in Budapest. That’s what I’m just returning back now. So we want to follow up on that. We used one dose, we need to determine what would be the optimal dose.

There’s a lot of work that we still need to do to optimize that and maybe think about putting together a formula that could be beneficial for people.

(56:30)[Damien Blenkinsopp]: Very cool. One of the ones you didn’t mentioned is Parkinson’s, is that something?

[Dominic D’Agostino]: Yeah. There’s an earlier study I think that was done by Dr. Theodore B. VanItallie. Dr. VanItallie is like 96 years old. We still communicate on the phone and through Email.

He was one of the original ketogenic diet researchers. He did a small sort of pilot study showing that people with Parkinson’s disease can follow a ketogenic diet and that being in a state of nutritional ketosis reduced the tremors associated with Parkinson’s disease and prevented some of the symptoms. Not a cure, but it could help manage some of the symptoms associated with Parkinson’s disease.

There really hasn’t been a good follow-up study to that. I know there was a ketone ester that was developed at NIH and a study at Oxford. There was that group that had a clinical trial open. But I think they might have had some problems recruiting people into that clinical trial, that opened a few years ago.

I know there was a clinical trial looking at the effects of exogenous ketones on Parkinson’s disease. And if we weren’t tied up with so many other projects I would be jumping on that. Because I was able to observe on Alzheimer’s patients when they took a medium chain triglyceride supplement, or even exogenous ketones. They would have pretty dramatic tremors.

And some Parkinson’s disease-like symptoms can be manifested in people with Alzheimer’s, especially advanced Alzheimer’s. I was able to observe and also got feedback from caretakers that when they induced a state of nutritional ketosis it really rapidly stops the tremors associated with that. So, that needs to be followed up on.

The pharmaceutical industry dictates a lot of what studies are done. Because you need a strong financial backing on top of a university, or chain of universities that supports this kind of research. On top of a review board, an IRB, that will prove this kind of research using these nutritional metabolic substances. There are many hurdles that need to happen.

Then you have to recruit patients on top of that and convince them that it’s not a drug but it’s a nasty tasting food that could potentially benefit you. They were like — well, it’s easier for a child, a son or a daughter [who] is bringing in their mom who is typically in a situation — 80 or 90 years old.

They’re not going to want to try to formulate some nasty tasting shake to do that. It’s much easier to just give them a pill. These are some of the things you see, the feedback that you get from people who are trying to implement these kinds of nutritional protocols in patients.

There’s a lot of hurdles. A lot of people ask me, “Well, if it’s so effective, how come science is not using the ketogenic diet or exogenous ketones to treat all these disorders?” I could write a book on the reasons why, but nutritional research is so hard to do.

Because nutrition is really tied into the lifestyle thing, and getting institutional support, getting the expertise needed, ensuring that patients are following through and complying with the protocol. All of these things are hard to do. A supplement, in theory, is a lot easier but we’re at the very initial stages. Because these are just new entities that just developed.

(1:00:16)[Damien Blenkinsopp]: Right, it’s only two and a half years you’ve had the ketone salts for instance, and the esters a bit longer?

[Dominic D’Agostino]: A little bit more than that. I would say the ketone ester was actually developed probably about 20 years ago, if you look into the animal literature. Then they were dropped because it was thought that they’re very expensive to produce and they taste like jet fuel.

Some of the people that originally developed these things, like Henri Brunengraber. He’s like a hardcore metabolic physiologist-scientist who develops a lot of remarkable things. But he kind of drops it and moves on to the next thing.

There’s also sharing the chair of his department and running a billion other things at the same time. So, I dug up some of this research and realized, “Wow, why didn’t anyone follow up on this?” Then I saw some of the work that was funded by DARPA, showing that they were the secret project.

They were using these ketone esters for warfighter performance enhancement. I found some patents and some files on that. I was like, “Well, this is what I need to explore, for use of CNS oxygen toxicity.”

Not only can the ketones potentially mitigate the oxygen seizures but the ketogenic diet was super effective. Even independent of the ideology of the seizures that it tends to work which is really remarkable. But instead of giving an anti-convulsant drug to a warfighter, which can dull your senses and impair your physical and cognitive performance.

You could be giving an anti-convulsant neuroprotective substance that enhances the physical and cognitive performance. It seemed like a win-win situation. I’d rapidly grasped this idea and just went into this manic state of writing grants and writing proposals, and digging up all the research.

Then, I was calling my program officer and I was like, “You need to hear this information and what I’m going to tell you.” We actually had a little meeting at our university and he was like, “We have to do this.” He was very generous to fund some of the initial basic science proof of concept research that demonstrated the efficacy of this ketone ester in mitigating oxygen toxicity.

It worked better than anything we had ever tested or anybody had ever tested, even drug wise. That’s going back in 2009 or 2010. From there, I’m really in safety because I’m really scared about bringing something to market that could potentially harm someone. I know there has been some discussion out there about the quote and quote dangers of a racemic beta-hydroxybutyrate salt.

People need to recognize the difference between someone’s opinion and scientific fact. The scientific fact is that racemic beta-hydroxybutyrate salts have been used for decades for treating a disorder called MAD, Multiple acyl-CoA dehydrogenase deficiency. I get Emails from the patients or from the parents that are treating their kids with this, and it’s like a miracle for them.

I also get Emails from parents that are treating their kids with glucose transporter type 1 deficiency syndrome with a racemic beta-hydroxybutyrate (sodium beta-hydroxybutyrate), which is actually a prescription you can get in Europe.

But they’re also using these commercially available ketone salt products which would be the ones that you might be familiar with. There’s KetoCana from KetoSports, Pruvit makes Keto OS, Forever Green makes Ketopia. The Kegenix product which is the one I’m testing now. It’s a really excellent exogenous ketone product.

This idea which was talked about in various podcasts, I think in Bulletproof podcasts and Ben Greenfield’s that racemic sodium beta-hydroxybutyrate was dangerous and ineffective. It is an opinion and there’s no science to back it up.

If you go back and listen to the podcast you’ll hear the speaker actually reference no actual studies. So, it has an intellectual property supporting the non-racemic, so that needs to be acknowledged and appreciated.

What is appreciated from my end, the science backing up the efficacy and the safety are really profound – like I’ve said on expert panels to approve some of these molecules. And no toxicologist or physiologist could find any evidence that racemic, which is the DL version of beta-hydroxybutyrate, was dangerous in any way.

For example, if you’re a medical doctor or a combat doctor on the field and you’re treating soldiers that have a loss of blood or you’re in the emergency room just talking to the ER doctors, use the Ringer’s Lactate and that’s Racemic lactate.

So, L-lactate would be the natural lactate that you would find in your body. The DL would be in an enantiomer or a mirror image of that lactate. Both of the lactate molecules get metabolized to energy. So, the same things happen with ketones. So the D and the L version get metabolized to ATP, to energy.

A lot of the metabolism has been worked out with very elegant tracer based fate association studies by Dr. Brunengraber at Case Western. Lactate Ringer’s has been used in millions of combat troops and emergency rooms. If there was a danger to using a racemic metabolate, there would be a lot of dead bodies around – and that has not been the case.

Actually, it’s FDA approved, it’s widely used and accepted, and it was even studied the difference between L-lactate and Racemic lactate before it became a standard of care. Actually, it was looked into, and it had exact same effect.

So, if you use the Racemic versus the L-lactate have the same effect at preserving the metabolic activity of the tissues and being protective in that way. So, that needs to be acknowledged that when statements are made, that they could be an opinion and not validated by scientific facts.

The ketone supplements that are on the market now that I’m aware of are very safe and from feedback, they’re very effective. I don’t support any particular ketone supplement that’s out there. I’ve tested all of them and they tend to elevate my beta-hydroxybutyrate and the .5 – 1 millimolar range for one dose.

So, for me to really boost my ketone levels up, I have to take a packet and a half, or a dose and a half, which I can tolerate pretty well. But I think there’s a lot of room for improvement and the products that are out there.

I hope to work with these companies, hoping that they will fund research to support the further development and evolution of these products for different applications.

(1:07:30)[Damien Blenkinsopp]: Excellent. Thanks for going through that because that’s something I have my eye on as well and wanting to get some more facts. Something else that was thrown out, a couple of things was that the racemics were less efficient or were ineffective?

We also have all of the MCTs which people are using to kick up their ketones as well. We have the C8 and C10 of the MCTs, there’re various products around. Another statement that was said they were undesirable and you should avoid those as well unless you really had to take them.

For instance, if you have Parkinson’s it was okay to take them but otherwise you shouldn’t be really taking them. But a lot of people are taking these. Right now, there’s a bulletproof brain octane. I’m sure a lot of people are taking that.

KetoSports has got their own product that I’ve been taking for a long time personally. I don’t know if you have got any comments on that?

[Dominic D’Agostino]: Yeah. I study a lot of very expensive exogenous ketone products. But the more I look into medium change triglycerides, especially the C8 oil which is digested and assimilated much differently than long-chain fatty acids. When you consume it, it basically perfuses the liver.

I mean it goes right to the liver via hepatic portal circulation. It goes right through to liver and is burned as energy. So, they’re poorly astrophied, which means they’re not re-astrophied back and packaged into chylomicrons, like long-chain fatty acids.

Once they reach the liver, it’s basically an obligate oxidation. The medium chains are almost completely oxidized to ketone bodies. Some of them will spill into the bloodstream because we find them in the brain tissue and other tissues.

But it’s independent of the various transporters too. For the medium chain triglycerides to get into the mitochondria there’s various CPT-1, for example, is not needed to get the MCT into the mitochondria. So, they bypass a lot of these rate limiting steps.

And you consume them, it goes right to the liver, you generate a lot of beta-hydroxybutyrate and some of that gets into the bloodstream. So you have the combination of ketones and the medium chain triglycerides going right to the mitochondria. And that can be very therapeutic and beneficial for many different disorders.

You have to realize that the person making that statement that MCTs are dangerous or ineffective, has some underlying personal interests in advancing the commercialization of his particular exogenous ketone, and that needs to be appreciated and understood.

From our perspective, we’re interested in testing that particular ketone formulation and 20 other, and finding out the truth, finding out which is most effective, which is safe. When it comes to the racemic, and the statement that racemic beta-hydroxybutyrate is not as effective. We have not found that out to be the case.

Actually, the first ketone ester that we studied for oxygen toxicity was a monoester of the R-beta-hydroxybutyrate we have formulated. And that did not prevent CNS oxygen toxicity, which actually was very strange to me. But the more research I did I found out that you needed to elevate both the acetoacetate and beta-hydroxybutyrate in the blood to mimic some of what happens naturally, physiologically.

The acetoacetate through spontaneous decarboxylation to acetone, or maybe it has it’s own metabolic effect independently. The elevation of acetoacetate was absolutely critical. It also in the presence of beta-hydroxybutyrate but it was absolutely critical to elevating both ketone bodies to get the anti-convulsing effect.

We published that in the American Journal of Physiology and showed the pharmacokinetics and seizure work with that. So, we screened a lot of agents and found out the particular ketone ester that we found to be most effective was 1,3-Buntanediol acetoacetate diester]. So it was 1,3-Buntanediol that was racemic, so it would make racemic beta-hydroxybutyrate.

But even the non-physiological enantiomer gets broken down and converted to Acetyl-CoA and some of that goes back to the physiological enantiomer so it all gets broken down and metabolized similarly to Ringer’s Lactate which is used in millions of patients.

But the important thing about that particular molecule is that when it’s consumed orally it gets hydrolyzed and it rapidly liberates the acetoacetate. Then the 1,3-Buntanediol gets metabolized in the liver and elevates beta-hydroxybutyrate. So you have both ketone bodies elevated in the blood. We find that it’s absolutely critical to get a certain level of acetoacetate to get the anticonvulsant effect.

(1:12:30) One thing I didn’t talk about was Angelman Syndrome, which is characterized by impairment of motor function and also drug resistant seizures. It’s extremely effective in an animal model of Angelman Syndrome.

If you look at Angelman Syndrome and the ketogenic diet, you come across case reports showing that it basically puts Angelman syndrome patients into remission, at least for seizures. So, it’s highly efficient for that.

So, the first ketone ester we studied was this R in the enantiomer, the hydroxybutyrate, and it was not effective. So it was actually the racemic version of a ketone ester that was most efficacious.

But we’re interested in exploring all different pathologies and finding out which one. So, we have not found out that the R and enantiomer is any more efficacious for any other disorder than the racemic. I think that’s important to acknowledge.

We also found that medium chain triglycerides tend to formulate really well with this exogenous ketones. Not only are they carriers but we think they enhance the transport across membranes and they improve the pharmacokinetic profile, two of many of the ketones salts. So when it’s formulated with MCTs which have the nice advantage of also being ketogenic.

One of the benefits of racemic, the other enantiomer, so there’s D and L. The L-enantiomer tends to impact the liver in a way that reduces hepatic gluconeogenesis. So, you have this hypoglycemic effect that is very well characterized by our laboratory and other peoples laboratory.

[Damien Blenkinsopp]: So you’re saying that ketones go up and the glucose goes down?

[Dominic D’Agostino]: Yeah. It’s more pronounced with the racemic and we don’t know why that is.

(1:14:22)[Damien Blenkinsopp]: Is that beneficial to some of the applications more than others? Weight loss for example?

[Dominic D’Agostino]: Yeah for weight loss, maybe for seizures too. We know that reducing glycolytic metabolism can be beneficial for seizures but also for cancer. As I mentioned, we have pre-active cancer research program.

The lower we can get glucose or glucose response to a meal, the lower we can reduce that, the better therapeutic efficacy we think the agent will have. If we formulate the agent with food, so every time our animal models will eat the food they’re getting a dose of it.

Instead of injecting into the animal or ‘gavaging’ it in the mouth for our cancer studies, we actually take these ketogenic agents and formulate it to about 10 to 20 percent of the weight of the food. Then we count the macronutrient ratio, and then they eat it.

Every time they’re eating the food they’re getting a dose of ketones with the glucose. Because we do a lot of our studies formulating with a high carb diet. Because we want to find out the therapeutic effects of the particular agent and distinguish that between the ketogenic diet.

But we also published a study, about a year ago, where we formulated the ketogenic diet with the ketogenic agent. We did this with a ketone ester and found that it further enhanced the anti-cancer effect of ketogenic diet.

(1:15:48)[Damien Blenkinsopp]: Okay. I’ve got a few questions about this. There’s some MCT powders on the market which combine glucose. Me coming from a ketogenic perspective, that’s not something I want to take with the MCT powder. There’re other powders which don’t have the glucose.

Is there anything to think about or is it not really an issue? Because there’s this effect of the ketones pushing down the glucose anyway? Would it have zero effect? I haven’t tested it myself yet.

[Dominic D’Agostino]: Yeah, the MCT powders on the market like Quest Nutrition?

[Damien Blenkinsopp]: Not Quest, they don’t. It’s basically the generic ones. There’s this cheaper one, generic one, where they’ll put glucose syrup in it and some other glycemic ingredients.

[Dominic D’Agostino]: Yeah, with my interest in the ketogenic diet and staying in ketosis, I would rather get my carbohydrates from things like vegetables, salads, blueberries and dark chocolate. Basically encompasses my carb intake there. So I would avoid that.

A staple product that I use, I have it right by me right now is the Quest MCT oil powder. I did a little bit of beta testing for them as they brought that to market. We went back and forth, and I tested that a lot.

I consumed a lot of that and I did tons of the blood work and got to the point where I was really impressed with the product. There’s not too many products that I consider staple products, maybe about a half a dozen in total that I keep with me all the time.

That MCT oil powder is great, it’s very versatile. You could use it in baking, you could put in my coffee, you can add it to protein shakes to further boost the ketogenic profile of your shakes.

[Damien Blenkinsopp]: Do you take that with you? I take this stuff as well, I’ve got it right next to me as well in my coffee [unclear (1:17:32)]. What I was going to say is that you take that on top of your ketogenic diet?

But I think an interesting thing, I talk to people and they’re taking the exogenous ketones or the MCT powder as a normal diet, or the body builder’s diet where it’s high protein, and they’re not doing a keto diet.

Then there are other people who are interested in getting keto but finding it difficult. They’re using it to ease into the keto diet. So there’re a couple of different applications people use them for different things. I’m just wondering what you’re ideas are in those scenarios.

Dominic D’Agostino]: Yeah. If I put the Quest MCT oil into my coffee or shakes or things like that. I generally try to avoid liquid meals, because liquid meals digest totally different. The only liquid meal that I have would be my coffee, and I would put in some coconut oil and MCT on top of that.

Occasionally, I put in butter or coconut cream. I’ve been using coconut cream instead of full cream. The benefit is that I can elevate my protein a little bit more. I generally eat two meals a day now that I’m home and not traveling.

My meal in the evening is about twice the calorie count. So, I get about a third of my food calories in the morning and about two-thirds in the evening, but I get a lot of fat calories during the day I guess. Because I’ll make my coffee and whip it up and then bring it in a thermos, and drink that mostly in the morning. Then I’ll have a little kicker in the afternoon maybe.

That fat balm, I guess if you want to call it that and occasionally take some exogenous ketones too during the day, if I’m testing different products. It just adds to my total fat macronutrient ratio.

I probably get — with the coconut cream, the butter, and the MCT oil powder — probably get about an extra 100 grams of fat from that. So that allows me to eat a little less fat with my meal in the evening, and that makes it maybe a little bit more palatable because I could add some more protein.

On a typical schedule, I will do my physical activity in the evening. Then I’d like to couple that with a little bit higher protein intake.

(1:19:51)[Damien Blenkinsopp]: Right. So using the exogenous ketones or the MCTs to offset gluconeogenesis? Is that the idea?

[Dominic D’Agostino]: Yeah. This morning I had three or four eggs cooked in coconut oil. I usually have sardines, oysters, chicken, or steak from the night before. Then I’ll have a little bit of green vegetables cooked in fat, and that will be my breakfast.

It will be roughly under a thousand calories, somewhere around 800 – 1000. Then, I’ll get 1,500 – 2000 calories in the evening. During the day, I might even get an extra 500 – 1,000 just of fat or ketones.

I stay semi- fasted, so if I eat 6am or 7am I feel the best when my ketones get highest between like 3pm and 6 or 7pm.

(1:20:53)[Damien Blenkinsopp]: Okay what levels of ketones would you have then?

[Dominic D’Agostino]: I say high but it’s not really that high. In the morning when I wake up it’s maybe 1.0, sometimes .5 if I ate more blueberries or chocolate the night before. Right now, approaching noon, it would start to creep up about 1.5.

Then towards the end of my work day, I’m usually approaching about a 2.0 – 2.5 or somewhere around there. If I’m lucky I budget my time where I can go to the gym so I will be typically be working out. Then if I go home I’ll do some stuff, take my dog for a walk, do some sprints, and that’s when I feel most energetic – when I’m fasted, and in ketosis.

(1:21:40)[Damien Blenkinsopp]: Right, and you’re saying your blood ketones would be 2.5 or something like that and you’d feel that’s when you’re most energetic? Or you feel your best at that time?

[Dominic D’Agostino]: Yeah. I try to subjectively do this too. Basically, I would carry my meter, and I would be like, “When do I feel most energetic, and lucid?”. Then, I would measure my glucose and ketones at that point.

And I find that basically if my glucose is about 3.5 millimolar and my ketones are about 1.5 to 2.0 is when I personally feel the best, as far as energetic. So that would be a glucose-ketone index if we use the Thomas Seyfried’s calculation, of about 2.0. When you’re approaching 1.0, you’re starting to get into that therapeutic range.

But I think for all intensive purposes, for the normal person, if you keep between 2.0-4.0. It would be very abnormal for someone in a normal society to even approach that. If you’re hitting that then you’re doing really well.

You’re in an altered metabolic state. If you can sustain that, I think you’re going to get a lot of therapeutic and performance benefits from that.

[Damien Blenkinsopp]: So 2.0 – 4.0 in the GKI — glucose-ketone index — from Thomas Seyfried?

[Dominic D’Agostino]: Yeah.

(1:22:58)[Damien Blenkinsopp]: Which we covered in his episode in the past. Yeah, the only time I’ve got below 1.0 is when I’d be fasting. I’ve tracked full days as well, every half an hour I’ve tracked, it looks pretty similar to yours.

I’ve heard you say before that over 5.0 millimolar, in terms of ketones has some metabolic downsides. So, I was wondering about the ranges. Are there ranges that people shoot for between this 2.0 – 4.0 basically? You don’t really want to be lower?

Right? Say on the GKI, you don’t want to be going down to 1.0 unless you’re fasting or doing some pulse?

[Dominic D’Agostino]: Yeah, unless you’re really in a total fasted calorie restricted, deprived state, I think between 5.0 and 6.0. I think there was a report in a 60 day fast up to 8.0 millimolar. So that it may be beneficial there for just maintaining that energetic flow to the brain.

But if you’re on an isocaloric diet not calorie restricted. I think staying between 1.0 – 2.0 is probably good. If you’re mildly calorie restricted or maybe towards the end of an intermittent fasting, the fasting portion of an intermittent fasting day, approaching 3.0 may be optimal.

I based this upon thousands of blood measurements that I’ve taken and literally hundreds of blood measurements from other people. Between 1.0 – 3.0 millimolar I think is good. We’ve even seen it in animals, once you dose them up to about over 5.0 they start hyperventilating.

You create a mild metabolic acidosis that needs to be compensated for, so that you get the hyperventilation, they start getting even drunk and sedated, when you really start getting up there and has signs of ketoacidosis. In cases where they’re sedentary, that could be the reason. If you’re approaching 5.0 or 6.0 millimolar and you’re in an all-out sprint, you’re using that.

So maybe in the case of an athlete approaching the higher numbers could be beneficial if you train for that. But say you’re not trained for that and you dose up really high. Your body perceives it as a foreign acidic-metabolic substrate that has to neutralize, your bicarbonate compensates, and you have respiratory-renal compensation that needs to compensate for that.

I just had this discussion in metabolism and physiology with some people that I really respect. They were making the argument that anything above 4.0 or 5.0 is really going to be toxic to the body. I didn’t argue against that but we agreed upon — and there’s some pretty sharp minds in the room — anywhere between 1.0 – 3.0 was probably optimal.

As you know staying in 2.0 – 3.0 range is really hard to do with diet. But staying in a 1.0 range is pretty easy to do with a diet. I do a modified Atkins or modified ketogenic diet, and that’s pretty easy.

Then if I add a little bit of exogenous ketones or some C8 on top of that. I can easily boost that up to 2.0 – 2.5. I think that would give me a metabolic, performance, and cognitive advantage. I’m pretty sure about that.

So, that’s what’s exciting to me. So, not using exogenous ketones in the place of a low carb diet — but you might be able to do that too — I’m actually thinking about doing some experiment of getting off of my ketogenic diet for a period of time.

Not going super high carb but just being out of a state of nutritional ketosis and then adding supplements back in and then doing some blood work and see what happens there. I just haven’t got around to doing it because I enjoy eating ketogenic so much.

[Damien Blenkinsopp]: Right. Once you get into it for a while it’s like you don’t have to eat very often.

[Dominic D’Agostino]: It’s almost like I dread doing it.

(1:26:51)[Damien Blenkinsopp]: I was testing some of the supplements, the different supplements. I don’t think I didn’t do it very well. But what I was doing I was eating in the evening basically a high-carb meal lots of rice to put myself out of ketosis.

I did this for about a week and then tested different supplements in the morning. For the first reason, I don’t think it was a great control because I am basically keto-adapted now. I tend to pop straight back into ketosis relatively quickly.

I’d like your feedback on that whether it’s a decent control. Maybe I’m no good as a control because I’ve been just keto-adapted for a while and also may be I’d have to go for a few days ‘carbing’ it to make it a bit more realistic. What are your thoughts on that?

If you’re trying to do some normal, the first thing is, going back to your point about exogenous ketones. You’re saying like if someone just takes it straight off as some people are doing right now. They’ve been on a carb diet the whole time.

Then they can’t necessarily utilize those because they’re not keto or fat adapted. How long does that take? Should we be taking a lot of these when they haven’t really had that much exposure?

Do they have to take them over a period of a week or longer in order to start getting more benefits from taking them?

[Dominic D’Agostino]: Yeah, that’s a good question. Interestingly, we can use exogenous ketones even if we’re not keto-adapted at all, and that was our first study that we did for CNS oxygen toxicity. It was actually rats eating a standard rodent chow which is 60-70 percent carbohydrates.

We gave a single dose not even feeding it chronically, 30 minutes prior to doing a deep oxygen dive. It worked remarkably well and that really surprised me. So, taking a little bit of a step back, we use the R-enantiomer of the beta-hydroxybutyrate, and it didn’t work.

But then when we found out the ester that did work, that particular compound worked remarkably well. That kind of changed my thinking because I approached it with the understanding or the bias that you really need to be keto-adapted. But if you are adapted to burning fat and ketones for fuel, what has been shown is that you do up-regulate the transporters and the enzymes associated with ketone metabolism.

So, you will theoretically be deriving more benefit from exogenous ketones if you have been previously adapted to a ketogenic diet. I think from a practical standpoint, say you’re on a ketogenic diet and you choose to transition to eating carbs for some reason and then you throw ketones back in. Since you’re adapted to a ketogenic diet already, I think you’ll use those ketones more efficiently even by following a carbohydrate based diet.

We have some evidence to indicate that glucose disposal is enhanced in the presence of ketones. So, it may actually be enhancing insulin sensitivity. The glucose goes does, if you have animals eating a high carb diet and you bolus exogenous ketones, the glucose goes down remarkably low. Much more than you even get with something like Metformin.

What we don’t know why that’s happening, we want to look at the liver metabolimic profile. I think it could be influencing the liver in some way, and may be decreasing hepatic glucose output. Really it’s your liver that dictates your blood glucose, it’s all happening in the liver.

So, if you turn down gluconeogenesis in the liver, you would see a decrease in blood glucose. But also if you’re enhancing insulin sensitivity you would be facilitating glucose disposal and peripheral tissues with ketones. I know Dr. Richard Veech at the NIH has written about that and suggested that ketones actually do enhance glucose uptake and insulin sensitivity.

I get the question, what if you throw ketones on top of carbohydrates? What are the cells going to use? I think the cells will use what’s available to them and we know that the brain might not be able to use the certain types of fatty acids but they can use MCTs.

If you have glucose and ketones in the blood, your cells, your muscle cells, brain cells will be using both fuels. There’s some evidence that suggests that it will be using the glucose more efficiently in the presence of ketones. Because we know ketones can lower reactive oxygen species.

Excess ROS production can decrease insulin sensitivity and cause protein nucleic and lipid peroxidation that can inhibit glucose transporter processes. Even translocation of glucose transporters to the membrane or even PDH complex could be sensitive to the Redox state of the cell.

Ketones tend to normalize or prevent an oxidative environment that could potentially impair glucose transport and insulin sensitivity.

(1:31:56)[Damien Blenkinsopp]: There’s such a wealth of information in this area. It’s not like ketones are a panacea, but there’s just so many applications we’ve spoken about today, so I could go on talking to you for absolute forever. I’m conscious of your time also.

I wanted to round off of a bit of what you do more in terms of optimizing yourself and what you think is effective. For instance, in terms of blood ketones, you said you’re tracking your blood ketones. Have you used the other methods, the urine or the breath method?

The strips for the blood can be a little bit inaccessible in the UK, in the US sometimes, and also they are really expensive. The price varies. I’m sure you have your own ways of getting them but for everyone else it can be a little bit difficult, particularly in the UK I’ve found.

What do you think of the breath? There’s the Ketonix looking at the acetone instead. Do you think that correlates with the blood ketones, and it’s an okay way to try and optimize or not?

[Dominic D’Agostino]: Yeah, it’s a good question. I get this frequently. What I would say the breath, if you’re measuring moderate to high on a breath acetone meter you’re definitely in ketosis. I like it, and I wish it was more quantitative because I’m a numbers guy.

I think we’re all sort of what’s your number? There was like a ketone competition in the lab and my friends like, “You know what’s your ketones today?”. So we like numbers and I wish the unit could be designed.

I believe [unclear (1:33:20)] who’s working on a quantified meter. I like it, and I think it’s great for kids that are trying to manage their epilepsy because breath acetone has correlated with seizure control. So if you give this to a kid and he blows in it and he sees colors and he gets excited, I think that’s great.

It’s giving you a relative level but it’s not a precise level. But it’s also a snapshot of your level of ketosis over the last couple of hours. So your blood, beta-hydroxybutyrate can change.

I’m standing here in front of my desk and talking to you and relatively sedentary. But if I was to go and take a brisk walk on the other side of campus which I do occasionally to get things signed. I’ll come back and measure my ketones, and it’ll be cut in half.

It’ll go from two to one, or below one, just from brisk walk where it should be increased right? Because I should be mobilizing fat, I’m burning fat. But I’ve burnt those ketones for fuel during my movement.

(1:34:25)[Damien Blenkinsopp]: So then it goes into glycogen? I’ve seen this before and I didn’t understand it, that’s why I’m pretty curious.

[Dominic D’Agostino]: Well, it’s burned as fuel. Ketones are substrates, so they’re going to be burned up as fuel. And yes, you may mobilize glycogen from the liver so your glucose can actually go up. You might have some lactic acid from your muscles and through the Cori cycle goes back to the liver and you get some glucose in the blood.

The stress, the sympathetic nervous system from moving and running across traffic and navigating or whatever you do when you walk, that can contribute. What I really found that’s most important is you need to be completely calm and sedentary when you make these measurements to get accurate measurements to prevent the variability.

We have this issue with our rodent studies, we need to pull the food from them for about four to eight hours, to normalize the blood glucose. Because you have some that are nibbling on food, some that have gorged, others haven’t eaten. So the glucose is going to be all over.

To standardize and normalize glucose, you need to remove their food for a little bit and the numbers are tighter. The same thing applies for measuring ketones, especially blood ketones, you need to be fairly sedentary to do it. I really like the urine ketone strips, got a bad wrap, but I like the urine ketone strips.

They’re still used by John’s Hopkins. So, before you go spending a lot of money on getting ketone strips for the meter. You want to first confirm that you’re actually in ketosis on a urine strip.

If you’re registering 15 or 40 mg/dL on a ketone strip then it’s like, “Okay, at least if I take a blood measurement now. I’m going to register something on my blood meter and it’s going to be ‘I’m in ketosis’.” I remember the other meter, I think it’s the Novamax meter, would just give you this annoying, ‘low’, it won’t even read your number on it.

One person went out and bought a couple hundred hours worth of strips and have like 17 lows on there, and have come to find out you’re just eating too much protein or they think it’s okay to drink fruit juice. I forgot what the situation was.

Well first change your diet, then go out and get some urine ketone strips. Once you’re actually in ketosis on the urine strip then go back to the blood meter. And come to find that they tweaked their diet a little bit.

They did it until they were measuring ketones on the urine strip and they went to the blood meter, and bang they get 1.2 and they get all excited. So they could’ve saved a lot of money.

(1:37:04)[Damien Blenkinsopp]: Right. Because the urine gets a bad wrap, because it stops working once you get more keto-adapted. But when you’re first on a ketogenic diet and you’re trying to check that, that’s not going to happen. Right?

[Dominic D’Agostino]: Hydration state too, also plays a role, and less ketones will spill into the urine over time because you’ll conserve them as fuel. The transporters change a little bit. But if your hydration — if you’re drinking lots of water those people who carry water around with them and drinking.

Your urine ketones may register pretty low. Sometimes I wake up dehydrated and I would check my urine ketones will be quite high, whereas my blood ketones would be quite low. So, that’s just an indication of my hydration status.

It’s also a snapshot of what your ketones were over the last four, five, six hours because that urine is collecting in your bladder over time. So it’s sort of a snapshot of what’s happening through the course of the day, whereas your blood ketone is a snapshot of your ketone level at that point in time.

(1:38:04)[Damien Blenkinsopp]: Right, just a bit of information more about you and what you do these days? In terms of tracking things, it seems like you’ve tracked a lot yourself. Are there things that have stood out for you?

Overall, the time that you’ve tracked yourself and you found really useful insights from? Any quants or anything you’ve changed something you do in your life because of that?

[Dominic D’Agostino]: Yeah, I think initially when I started doing the ketogenic diet it was very dairy based. I was taking lots of creams, a stick or two. Two sticks of butter a day. So, I had a really high intake of dairy fat, probably about 200 plus grams of fat per day of dairy.

My LDL went up pretty high and my triglycerides went down a little bit but not really low. Then, I started replacing some of the dairy fat or the whole cream with coconut cream, and just using a little more coconut oil, getting more avocado in from my fats.

I still get dairy fat, by a sour cream that has live cultures in it. I’ll probably get about 50 to 70 grams of fat per day from dairy instead of like 250 grams of fat which I was getting initially. My lab test has improved. I guess you would say, I think my insulin sensitivity is better.

My glucose I can get lower glucose numbers now after eliminating some dairy. My triglycerides are really low now, they stay at 40s to 50s, I think it was 36 at one time. My HDL has improved and better and it’s really high, like 90 something.

My LDL went from really high to normal, but normal high. Now, which I think is completely normal and actually maybe even optimal. My IGF-1 levels are really low now compared to when I was on dairy.

I think dairy may have been contributing a little bit to some insulin resistance or maybe I was just getting a surplus amount of calories. My CRP levels also are the lowest now than they’ve ever been. I mean it’s like 0.1 or 0.2.

[Damien Blenkinsopp]: Right. Basically nothing, that’s the bottom of the range.

[Dominic D’Agostino]: Yeah, it’s like totally bombed out. I just feel better. If I eat a lot of dairy, I do wake up a little bit slightly congested, stuffy in my nose but it’s not bad.

I wouldn’t call it an allergies, and it could be due to allergies. But eliminating that has sort of helped, not eliminating, but reducing the amount of dairy. I don’t get in a whole lot of dairy protein. Maybe a slice of cheese here and there but I limit that. I limit casein. I don’t take away protein anymore.

The dairy that I get is primarily dairy fat. I was actually thinking about, I get very little butter, but I was going to switch to Ghee, and do some clarified butter. The triglycerides I would say for people to look at, for physiological biomarkers, your heart rate, blood pressure, sleep is an important one.

I wear the FitBit Charged. It’s really fun to look at my heart rate during the course of the day and in my sleep, and those sorts of things. I have a Dexcom that I’m going to put in. And I want to…

[Damien Blenkinsopp]: Is that the latest one? Is it the 4 or 5?

[Dominic D’Agostino]: Yeah.

[Damien Blenkinsopp]: I know Peter Attia is playing with that.

[Dominic D’Agostino]: Yeah, the 5 I think it is. So, I’ve just been traveling I just wanted to wait until I was put it in one spot and I can test it. I’m interested in trying that, and maybe working with some companies too, to do a glucose and ketone Dexcom.

I’m hoping to try that. That would definitely fit into your show. Yeah Quantified Self, and get some data for that, that would be good. As far as looking at physical biomarkers, you want to look at blood pressure, heart rates, sleep, and all these things improved when I got on a ketogenic diet.

I think there were various reasons for that. The lab test, the simple ones are probably the most beneficial ones. Triglycerides are the things that I look at the most. My HDL I think is important, and CRP, and of course your blood glucose. If you’re keeping glucose levels between 60 – 80, and doing that pretty much all the time.

Everything else is going to be good, that’s what I find.

(1:42:35)[Damien Blenkinsopp]: You said you did an insulin sensitivity, was that the homo or was it something else?

[Dominic D’Agostino]: No, I didn’t do that. I did the glucose tolerance.

[Damien Blenkinsopp]: Okay, the challenge.

[Dominic D’Agostino]: Yeah. I did like 50 grams, 75 and 100 grams I think. I think that was like over four hours, the 100-gram ones. Yeah, you drink the nasty Slurpee glucose and look at that. I’m extremely insulin sensitive. I dispose of glucose very fast.

I can also get a little bit of a hypoglycemic effect. If I’m on a ketogenic diet, and I go off of it. For example, I get some rice, sushi, or something like that, I will dip down into the low 50s and bounce back up again – very, very insulin sensitive.

(1:43:18)[Damien Blenkinsopp]: Thanks for that. If you were to recommend one experiment. I can guess what you’re going to say. So, we should try to improve the body whether it’s health performance longevity with the biggest payoff.

What would that be? How should they track it to make sure it’s getting that payoff?

[Dominic D’Agostino]: It depends on the person really. I don’t think low carb ketogenic diets are ideal for people in their teens or early 20s because they may be extremely insulin sensitive. I know I have tons of friends and I’ve even measured their glucose levels, and they’re great.

They stay pretty low, the glucose levels and they have adapted really well to a high carb diet. They wouldn’t want to do a ketogenic diet. So, maybe you’re expecting that kind of answer.

But, I think periodic fasting would be an important thing to do. I’ve been talking to some high-level CEO people and they tell me, “Well, I’ve been doing this anyway because I’m so busy. I wake up and I just work all day, and just go home and eat at night.”

But if your pattern of eating — like my patter of eating — I was obsessed with eating every two hours especially when I was really into lifting. I felt I had this preoccupation with food, preparing my meals, carrying it with me. I think it’s very liberating to not have to do that and to realize that your performance, energy levels, are not going to tank if you eat one meal a day.

If you were to do a short term fast, initially, and to do that every once in a while. I think, not only is very good for your metabolic health. I think it’s also good for your state of mind because it tells your body. It tells your mind that you don’t have to be sort of psychologically dependent upon food.

I would go five or six hours, and I’ll be like, “I’m starving I have to eat something.” I have been around people that are like that. My wife is kind of like that, she’s an incredible carb burner.

But if we’re traveling and she’s gone four to five hours without having a meal. I could see it in her mood and in everything. But that’s fine we’ll stop and get something to eat, and usually we’ll have coffee or something like that. But it’s interesting to see, and she sees it in me, “How could you go this long? Aren’t you hungry? What’s wrong with you?”.

She understands it now. She’s watched me do so many tricks and everything. If you’re not a big fan of being hungry. If you’re not a fan of having to eat every two or three hours because you’re hungry. I think doing some intermittent fasting would be a really good experiment for you to do.

I actually interviewed Mark Mattson at IHMC. So, I’m also a research scientist at Institute for Human and Machine Cognition. We interviewed Mattson, I think you did too for a podcast. He really went into the benefits of intermittent fasting and he’s at the National Institute of Health.

If you get a chance, he gave a brilliant lecture, presentation. If you go to IHMC lectures and look up Mark Mattson, he gave a great talk on this. He talks about all the health benefits.

If you do embark — if your listeners embark on [an] intermittent fasting experiment it would be interesting for them to track their blood glucose levels, their ketone levels, their triglycerides and their c-reactive protein. I think in each one of those biomarkers, if you want to call them that, will improve with intermittent fasting. I’ve seen it.

(1:46:51)[Damien Blenkinsopp]: You’re saying the 16-hour window or one day? Because you said short-fast, do you mean like a one day, 16, or 20 hours?

[Dominic D’Agostino]: Yeah. You could do every other day eating. But I think the easiest thing to do for most people would be, what I’d do if I do intermittent fasting maybe once or twice a week now. I eat two meals a day but like once or twice a week I’ll eat one meal a day, and it varies depending on what I’m doing and testing.

But it will be 18 hours of fasting and 6 hours of eating. Actually I get home late, so it ends being about 20 hours of fasting and four hours of eating. So, it will be 7pm – 11pm. I’ve done it [with] water and abstained from putting fat into my coffee.

I’ve also done what I would call ‘fat fast’, so I would put in some MCTs in my coffee and maybe get a ketone supplement during the day. I would still call that a fast because it’s basically non-glycemic.

[Damien Blenkinsopp]: Yeah, probably has very similar ketone and glucose effects.

[Dominic D’Agostino]: Yeah, I actually find that it’s optimal. So, I would call that a modified intermittent fasting protocol, where you would get in some fats and exogenous ketones during that fasting period. I’m a little less hungry once I go into that eating window.

I think that’s good too, so I tend to not over eat that much. My body is still strongly in a state of ketosis that has probably enhanced a bit with the supplementation. It tends to dampen my appetite a little bit so I’m not as ravenous.

But I don’t generally don’t get that ravenous anyway when I eat. But, I would experiment with that the intermittent fasting. I think it’s so easy to do. I mean intermittent fasting is easier to do than the ketogenic diet that’s what I find with people.

So, do some experiment, get some initial blood work, read up about it, listen to Mark Mattson’s talk on [the] IHMC website and you’ll find it there. I’m sure there’s a lot of blogs on the subject and do blood work before and three to four weeks after.

You’ll see pretty big effects, especially six and eight weeks after. You’ll see even bigger effects on your lipid profile and metabolic biomarkers.

(1:49:04)[Damien Blenkinsopp]: Excellent thank you so much for that, that’s a great one. Where would someone look to learn more about your topic? Are there any good books or presentations on the subject you’d recommend if they want to learn more about the whole subject of ketones and ketosis?

[Dominic D’Agostino]: One of the go to book that I would recommend is Jeff Volek’s ‘Art and Science of Low Carbohydrate Performance’. It’s a mandatory reading for students entering the lab just to get a hand on what the ketogenic diet is. The Ketogenic Diet Resource is a website maintained by a friend of mine, Ellen Davis, and I think has a lot of good information on it.

But I maintain a website to throw up links, compile links in there called ketonutrition.org. If you click on resources from the homepage, it will take you to dietary consultants, books, publications, list of podcasts, and lectures on there on a variety of subjects that hit on pretty much all the topics we’ve discussed. I probably need to get on there, but it’s relatively updated. I’ll probably update that in the next month or two.

Metabolic Optimization too, that’s a website that I started with Travis Christofferson who wrote the book ‘Tripping Over the Truth’ which is an excellent book that covers the metabolic theory of cancer. Travis and I maintain the website Metabolic Optimization, and we have Thomas Seyfried on.

We’ve had Adrienne Scheck, we’ve had Bruce Ames actually was our first guy. We’re going to line up a bunch of other speakers on metabolism so that’s another area where they can look up information on these topics.

[Damien Blenkinsopp]: Great, thanks for that. Are you active on Twitter? Where could people also connect with you and keep updated of what you’re at?

[Dominic D’Agostino]: I tried to post at Twitter maybe once or twice a week, not like super active. But on Facebook I post a little bit more. My page is maxed out, I got 500 or 5,000 people following me.

So I’ll probably create a more public page. But you could still follow me because I post things open to the public. I will post usually one or two studies per day, or podcasts or lectures per day on my Facebook page which should be very easy to find.

It’s always sort of topics relevant to the interests or the topics that we covered today. Sometimes I dual post on Twitter and Facebook, important things that pop up as far as studies and lectures and things like that.

(1:51:39)[Damien Blenkinsopp]: Excellent. Of course, we’ll put links to everything you’ve mentioned here in the short notes. Is there anyone besides yourself? You’ve already mentioned a few people, but was there any you would pull out and you would recommend if people wanted to learn more about the subject? Are there are some other people that you would recommend also?

[Dominic D’Agostino]: Yeah. My colleagues, there’s so many of them. I try to stay very active in collaboration. It’s really good for scientists to collaborate to help get their work out there. Also, to get other people to validate the findings that you did in the lab.

So, I know you’ve had Thomas Seyfried. He’s a great friend and colleague of mine. Adrienne Scheck is a fantastic scientist and a pioneer in ketogenic diets and moving the ketogenic diet into clinical trials at Barrow Neurological Institute.

There’s some of the mentors that even got me into this field — would be Dr. Eric Kossoff. He’s a neurologist at Johns Hopkins. He’s been a pioneer in using a ketogenic diet for kids with epilepsy, so look him up.

John Roe who’s a neuroscientist and pediatrician. He was originally at Barrow Neurological Institute and he was the first scientist I ever connected with to discuss this. The use of the ketogenic nutrition for oxygen toxicity.

Dr. Richard Veech he had a profound influence on me when I first got into this area of ketogenic diet and discovered exogenous ketones. It was his reviews on the subject. So if you look up on some of his reviews on ketones and the therapeutic effects of ketones, they’re really good.

Susan Masino has been really supportive of our work and she’s doing some really innovative work looking at the effects of the ketogenic diet on adenosine. Adenosine is a neuroprotective substance that’s elevated, has anti seizure, anti-convulsant, neuroprotective effects.

So, we actually have a lot of these speakers [who] will be coming to our Metabolic Therapeutics’s Conference which will be held either the last week in January or the first week in February. We had a number of speakers, we had Eugene Fine, Colin Champ, David Ludwig, David Diamond, he was a colleague of mine here at USF and [we] talked about cholesterol and statins.

We had Eric Kossoff, Adam Hartman, and a bunch of scientists. So, I would tell your listeners to go to the Metabolic Therapeutic’s website. We’re in the process now of sending out the invitation for speakers.

And pretty soon, I think we might have a preliminary site set up for that, but we’ll be updating that soon with all the different speakers and the topics that are going to be talked about. We really try to emphasize basic science, so you’re going to find lectures on neurophysiology, cancer biology, proteomics, tracer based metabolomics.

Performance — Jeff Volek will be there talking about performance. It will be a mix of things related to not just the ketogenic diet but metabolism in general.

[Damien Blenkinsopp]: Sounds fantastic so anyone can attend that?

[Dominic D’Agostino]: Anyone can attend that, yeah. We should have the registration going up soon. The problem that we had is that last year the venue was small. We wanted originally to keep it small, to cap it at about 250, but we had to turn so many people away.

So, this year we’re going to blow it up a little bit and probably have about maybe 600 – 700 people, hopefully in the same venue. But we’re going to get the whole hotel. You’re going to find a lot of great companies there that are producing these exogenous ketones.

So, Pruvit is going to be there, probably Forever Green, the company Kegenix – they make a great product that I’ve been testing recently during my travels. KetoSports hopefully will be there, and Quest Nutrition has a big footprint in our conference and they have been incredibly supportive of our work.

Scivation, who’s really the leader in branch chain amino acid supplements, will be there. Let me see, we have a lot of good sponsorship supporting this area of research. It’s really exciting to me that it’s becoming so popular it’s easy to find companies that are now emerging that are interested in developing products that can enhance nutritional ketosis.

So it’s fun to see a market for this evolving. They’re are creating products that I think will be very beneficial to patients even that are following nutritional ketosis for managing a disease process.

I do get Emails every single day from patients that are using these products that made a world of a difference. They couldn’t get into ketosis and once they did or their trial did, they started getting all these benefits from the ketones.

[Damien Blenkinsopp]: It’s a super exciting area, you’re very lucky to be right in the center of it.

[Dominic D’Agostino]: Yeah. I do feel lucky.

(1:56:48)[Damien Blenkinsopp]: Just as a quick anecdote, I gave some MCT powders and C8 to my mother because she has tremors. They have been getting worse over time, and they are so much better it seems. She was really surprised by that.

But it is an exciting area, they have so many crazy benefits, so broad compared to the other things we looked at. Which is one of the reasons I’ve covered it several times in different episodes, fasting, ketosis, all of these.

Whereas most topics I don’t cover in many episodes but this one has just so many applications, it’s just interesting. I think it’s worthwhile for people to learn more and more about it.

[Dominic D’Agostino]: Absolutely.

[Damien Blenkinsopp]: Dom, thank you so much for your time. I really appreciate it, we’ve covered such a wealth of topics. I know there’s so much more you could talk about. So, thanks very much for your time.

It’s been great talking to you.

[Dominic D’Agostino]: Thanks for having me Damien. I appreciate it.

References:

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Putting the body into ketosis and controlling blood glucose levels may prove to be effective therapy against certain cancers. This real case reveals one aggressive self-experimenter who used a combination of the ketogenic diet, fasting and other tools to control his epilepsy and send his brain cancer into remission.

This episode examines the ketogenic diet as a tool to fight against cancer. It is a follow up of the episodes on ketosis and fasting that we have done with Dr. Thomas Seyfried in episode 16, and Gene Fine in episode 36. You definitely should check those out for context before or after you dive into this one to fill in any gaps.

We are talking to someone who has actually used ketosis by a combination of ketogenic dieting and fasting as a therapy to fight his brain tumor. Our guest has gone through a variety of extreme approaches to ensure he remains in a high state of ketosis. In his case, his life depended on it. This episode is not just for those with cancer or epilepsy, but also for those interested in the benefits of the ketogenic diet. You can take some of the tools he used to improve your own state of ketosis if you are having trouble maintaining it.

[W]hen I have my blood tests . . . and [test] a number of markers for potential tumor progression, internally, I am actually much healthier than before I had cancer . . .
– Andrew Scarborough

I met Andrew Scarborough at a conference where he spoke about his experience with ketosis and its effect on his brain tumor. After being diagnosed with a type of malignant tumor called an Anaplastic Astrocytoma, Andrew underwent several months of unsuccessful chemo treatment. He decided to take his cancer treatment and management of his epilepsy into his own hands and to go the ketosis route. This decision was based in a small part on researching Thomas Seyfried’s work, which we will also discuss in the episode.

Fortunately, this decision has yielded very positive results for him, and his tumor has shrunk. In fact, it has disappeared from scans (seen below) and his doctors are now giving him the all clear. Andrew is now working with London-based hospitals to develop clinical trials for treating brain cancer patients using an optimized ketogenic diet.


Andrew's brain tumor before and after being on the ketogenic diet.

Andrew’s brain tumor before and after being on the ketogenic diet.


There are a lot of details in this podcast on how Andrew went about using the ketogenic diet, including the types of foods he ate, how he optimized the diet for his situation, the extreme measures he has taken, and how he has been able to keep up physical activity. We will talk about everything on his journey, including things like eating bugs and sheep’s brain, and quitting eating plant-based foods altogether.

The episode highlights, biomarkers, and links to the apps, devices and labs and everything else mentioned are below. Enjoy the show and let me know what you think in the comments!

itunes quantified body

What You’ll Learn

  • The beginning of Andrew’s brain cancer story (4:46).
  • Andrew is diagnosed with a grade 3 Anaplastic Astrocytoma (12:14).
  • After unsuccessful chemo treatment, Andrew devises a treatment using the ketogenic diet (19:19).
  • Using MRIs to visualize changes in the metabolic activity of the tumor due to the ketogenic diet (20:52).
  • Scans show complete remission since using the ketogenic diet (23:40).
  • Optimizing and maintaining the ketogenic diet for brain cancer management (26:40).
  • The biomarkers Andrew tracks to monitor the effects of the ketogenic diet (28:08).
  • The glucose-ketone index (29:13).
  • Andrew’s typical diet (32:58).
  • Maintaining a healthy 1:1 ratio of Omega-6 to Omega-3 (33:35).
  • The ketogenic foods Andrew eats (36:10).
  • Variations on the traditional ketogenic diet (41:30).
  • Supplementing the diet with insects (46:30).
  • Keeping up ketone levels and controlling seizure activity during exercise (50:16).
  • Andrew’s research on an optimized ketogenic diet for brain cancer patients (54:50).
  • More on Omega-6/Omega-3 ratios (59:15).
  • Limiting protein and fasting (1:00:32).
  • Using magnesium to prevent seizures during a fast (1:02:08).
  • Mimicking chemo naturally with diet (1:06:44).
  • The resources Andrew recommends for those facing cancer or epilepsy or interested in the ketogenic diet (1:11:47).
  • Andrew’s advice on what biomarkers to look at and where to start with the ketogenic diet (1:18:34).

Thank Andrew Scarborough on Twitter for this interview.
Click Here to let him know you enjoyed the show!

Andrew Scarborough

Tools & Tactics

Interventions

  • Hyperbaric Oxygen Therapy (HBOT): A therapy Dr. Seyfried believes may be beneficial to fight cancer but is relatively non-toxic in comparison to current treatment modalities (chemo and immuno-therapies). It exposes the body to higher levels of oxygen via having the person sit in a pressurized tank with higher oxygen concentrations. Andrew is adding this therapy to his current tools. Typically you visit centers that provide sessions inside hyperbaric oxygen tanks, however some new smaller and lower pressure HBOTs are now beginning to appear in the market that you can buy to use at home.

Supplementation

  • Ketosports KetoForce: KetoForce contains the endogenous ketone body beta-hydroxybutyrate (BHB) in sodium and potassium salt form. The compound BHB can be used as an energy source by the brain when blood glucose is low. Ingesting KetoForce raises the levels of blood ketones for 2.5-3.0 hours after ingestion. (Note: A similar product from the same company is Ketosports KetoCaNa). Andrew uses KetoForce to increase his ketone levels during gentle exercise.
  • Ancient Minerals Magnesium Spray: Most people with epilepsy have a magnesium deficiency. Magnesium supplementation has been used to reduce seizure activity in people with epilepsy. Andrew prepares his own magnesium chloride solution that he takes transdermally multiple times every day (about 230 mg per day) and during exercise, which can be a seizure trigger for him.
  • Curcumin BCM95: Curcumin is a derivative of turmeric which is an anti-inflammatory antioxidant and potentially has anti-cancer properties. Andrew takes Curcumin in tablet form with DHA because it increases the uptake of DHA to the brain.

Diet & Nutrition

  • Ketogenic Diets: The ketogenic diet is a low carb diet which raises the level of ketone bodies in the blood. Tumor cells are inefficient at processing ketone bodies for energy. The diet is commonly used to help control epilepsy in children.
  • Paleo Diet: A diet that mimics the nutrition of early hunter-gatherers, and consists of all lean meats and fish, fresh fruits, and non starchy vegetables.
  • Water Fasts: A water-only fast of at least 3 days and preferably 5 days is recommended by Dr. Seyfried as a tool to reduce cancer risk and to lower your glucose – ketone index to 1.0. They are the standard fast protocol used in most of the research studies looking at cancer inhibition or therapy for cancer patients. Learn more from Damien’s experience with a 5-day-water-fast.

Tracking

Biomarkers

  • Blood Glucose: A measure of the level of glucose in the blood at one point in time. Blood glucose is a biomarker for increased cancer risk. Therapies target reduction of blood glucose levels to limit cancer cell growth. Blood glucose levels vary throughout the day. Ideally levels should be kept below 100 mg/dL and below ~85mg/dL for fasting glucose. Andrew maintains his around 60-70 mg/dL.
  • Glucose – Ketone Index (GKI): The ratio between the concentration of glucose in the blood to ketone bodies in the blood. The calculation is Glucose (mmol)/ Ketone (mmol). Dr. Seyfried created the index as a better way to assess metabolic status. Therapeutic efficacy is considered best with index values approaching 1.0 or below. Patients with chronic disease like cancer have index values of 50 or more. Check out the episode with Thomas Seyfried here.
  • Cholesterol-HDL and LDL: The cholesterol biomarkers include lipoproteins and triglycerides which are found in the blood. There are standard markers that all doctors and labs will run, and some newer specialist labs that are more specific and accurate. There are two main types of lipoproteins, HDL and LDL. We covered these markers extensively in episode 7.
  • Omega-6/Omega-3 Ratio: Many Western diets are deficient in Omega-3 fatty acids, such as DHA, and have excess Omega-6 fatty acids. A high Omega-6/Omega-3 ratio promotes inflammation and the pathogenesis of many diseases, including cancer, whereas increased levels of Omega-3 (a low Omega-6/Omega-3 ratio of about 1) exert suppressive effects.
  • hs-CRP (high sensitivity C-reactive Protein): a marker for systematic inflammation that can be measured over a period of time to determine effectiveness of treatments such as the ketogenic diet. Ideally CRP levels should be <1 mg/L. High levels are associated with chronic inflammation, which is common in cancer and other chronic diseases.

Lab Tests, Devices and Apps

  • Glucometer: is a device used to measure the level of glucose in the blood. Andrew and Damien use the Freestyle Optium Neo Glucose/ Ketone meter. Andrew’s ketones and blood glucose levels hover around 65 mg/dl, which puts him somewhere around 0.6-0.8 on the Seyfried index. Check out episode 16 to learn more about the Seyfried Index.
  • Omega Blood Count: Measures the levels of Omega-6 and Omega-3 fatty acids in your blood. (Note: This test is only purchasable via offline retail stores such as pharmacies and health shops in the UK – an alternative test that Andrew recommends that you can buy online in US or UK is OmegaQuant.com)
  • Complete Lipid Panel: measures total cholesterol, triglyceride levels, HDL and LDL cholesterol, which are all found in the blood. High blood lipoprotein levels are associated with cancer.
  • Complete Blood Count: is a blood panel that measures the levels of the different cells in the blood. Numbers of the different types of cells vary depending on disease status and even between people. The test is often used to monitor cancer progression and treatment.
  • Magnetic Resonance Imaging (MRI): MRI scans use pulses of magnetic energy to visualize internal organs and structures. It can be used on almost any area of the body and provides information on tumors, bleeding, injuries, blood vessels, or infection. MRIs were used to monitor Andrew’s brain tumor.
  • Positron Emission Tomography (PET) scan: A PET scan is a functional imaging technique used to image body processes. A PET scan can be used to identify cancer presence and severity. A radioactive tracer, fluorodeoxyglucose, is used to tag cancerous cells so they can be visualized. Check out episode 36: Quantifying Cancer and Reexamining Which Cancers May be Inhibited by Fasts with Gene Fine to learn more about PET scans and cancer.

Other People, Books & Resources

People

  • Dr. Thomas N. Seyfried, PhD: University of Illinois, Urbana-Champaign. Dr. Seyfried’s research focuses on the mechanisms by which metabolic therapies manage chronic diseases like cancer, epilepsy, and neurodegenerative lipid storage dysfunctions. Check out Dr. Seyfried’s episode on “Water Fasts as Potential Tactic to Beat Cancer.”
  • Dr. Dominic D’Agostino, PhD: Assistant Professor in the Department of Molecular Pharmacology and Physiology at the University of South Florida Morsani College of Medicine, and a Senior Research Scientist at the Institute of Human and Machine Cognition. His research focuses on developing and testing nutritional and metabolic therapies for neurological disorders and cancer. His own website is Keto Nutrition
  • Dr. Colin Champ, MD: A board-certified radiation oncologist and Assistant Professor at the University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center. He is also board-certified in integrative medicine by the American Board of Integrative and Holistic Medicine. His focus is the role and effect diet and nutrition may have in cancer treatment.
  • Dr. Adrienne Scheck, PhD: An Associate Professor of Neurobiology at Barrow Neurological Institute. Her expertise is in neuro-oncology and her lab has been involved in investigating the effects of the ketogenic diet on brain cancer.

Organizations

Books

Other

  • Ketogenic Diet Resource: Andrew says this website has answers to just about all the questions you could have.
  • Clinicaltrials.gov: This site can provide you with information on clinical trials that are currently being done relating to the ketogenic diet and different cancers.

Full Interview Transcript

Click Here to Read Transcript

[Damien Blenkinsopp]: Andrew, welcome. Thank you so much for coming on the show.

[Andrew Scarborough]: Thank you for having me.

(04:39) [Damien Blenkinsopp]: Yes. You have quite an amazing story that a lot of people are very interested in hearing about. It’s always good to get the context of how this happened to you, and where it all started? Could you go into the beginning, how you made the discovery that you had this condition? How did it start?

[Andrew Scarborough]: Yes. I was studying a Master’s in Nutritional Therapy at the University of Westminster. This is before my diagnosis, and I was suffering from migraine headaches for a few months. Until suddenly I had lost my speech in February 2013, this was nearly 3 years ago now.

What I didn’t know at the time, that was my first partial seizure, and just being a man I carried on.

[Damien Blenkinsopp]: So to describe that, did you have difficulty saying words, or what exactly happened?

[Andrew Scarborough]: I went very dizzy, and then lost my speech completely for about five to six minutes, I was with a friend and we laughed about it because it was a bit strange. Because it was quite a cold day, it was February, I was just thinking when you get cold and shivering. You just stutter and loose — you struggle to speak, but it was a lot more serious than that.

I didn’t do anything about it. A couple of months later, I was experiencing very similar symptoms with pins and needles in my tongue and throat. To cut a long story short, I went on the train after a heavy gym workout. And, I felt like I actually have a lot of energy after the workout, even though I really struggled through it.

I just felt completely wiped out, even though it wasn’t the most difficult workout. I suffered more seizure activity afterwards, when I was getting on the train, very busy train actually in London to go home. And I devastatingly had a crushing headache, like my head was in a nutcracker.

The pressure was constantly building up, then I suffered a quite a traumatic brain hemorrhage, and grand mal seizure on the train, which wasn’t too pleasant, and the whole train stopped. I was rushed to hospital. There was so much blood in my brain that they didn’t know what to say, what actually was the cause.

As I was in hospital not knowing — feeling very confused not able to speak or walk at this point. I was given a CT scan and all that was shown was this massive blood in my brain. It looked like an explosion had gone off. I was still experiencing horrific grand mal seizures at this time, so I had things explained to me, and at the time, they were going in one ear and out the other, because I was so out of it.

That was quite a tough time from my family, and my first diagnosis was an AVM, which is an arteriovenous malformation. Because it looks so poor on the scans — because CT scans are quite ambiguous. All we could really see was just a tangle of blood vessels and arteries.

[Damien Blenkinsopp]: So, they thought it was an artery that had grown the wrong way, or you’d been born . . .

[Andrew Scarborough]: They saw it as being an unusual tangle of mess.

[Damien Blenkinsopp]: Okay, the arteries growing in the wrong way.

[Andrew Scarborough]: Yeah. They said, “No it’s not probably like that, it’s probably a Cavernous Hemangioma instead, which is a tangle of abnormal blood vessels, not tangled in the arteries.” Which is better because it was a bit less life-threatening, but I was given a number of misdiagnoses before. Eventually, I had an operation, because I was continually having these grand mal seizures that were starting to cause me cognitive difficulties, and my speech was getting worse, so I wasn’t able to speak at all at this stage.

(09:11) [Damien Blenkinsopp]: So, going back to the hemorrhage is that a stroke, is it the same as a stroke, or is it slightly different?

[Andrew Scarborough]: It’s very similar to a stroke, it was caused by the pressure of the tumor. Pushing against the side of my skull, and also it was between the speech movement area invading into the motor cortex, that’s why I had lost my speech completely. I had an operation not long after, in May 2013, to try and remove as much as possible, if this very vascular and invasive tumor, which was slightly larger than a size of a golf ball — but invading into the motor cortex area of my brain.

They couldn’t remove all of it because otherwise I would be completely paralyzed or dead. Because I was misdiagnosed, I should’ve had the operation awake but I was unconscious during it. The neurosurgeons said after, “Yeah we probably.”

If he has to do it again, he would have it awake so he could potentially get more out of it, but he couldn’t remove all of it because of where it was in the brain.

[Damien Blenkinsopp]: That’s interesting, what is the difference between you being unconscious and awake, are they able to get some feedback from you?

[Andrew Scarborough]: Yeah. You’re kept awake so they can monitor your responses, while they’re poking around in there to see what can be removed and what can’t, and what healthy brain tissue and what isn’t. One of the main issues with the brain surgery is it’s very difficult to distinguish what’s healthy tissue, and what’s the tumor.

[Damien Blenkinsopp]: So, this is what date now that you’ve had your surgery, and you’ve been given a clear diagnosis?

[Andrew Scarborough]: This point now? It’s two and a half years coming up to three.

[Damien Blenkinsopp]: Okay, it was a few months after your hemorrhage.

[Andrew Scarborough]: That was two months after that I’ve had the operation because they didn’t know what to do with me. There was a lot of blood in my brain, and if you think about a malignant brain tumor, it’s not a great thing if you’ve got a constant blood supply there — and it’s not a fantastic thing if you’ve had this thing that looks like an explosion in the brain, scattering around the cells, and blood everywhere. So, it just makes it more migratory, I guess if that’s the word.

More likely to spread into other areas, which is not ideal. I then had my pathology, finally, and it showed that the tumor was indeed extremely vascular. And there was still some significant scar tissue, as well as some slight enhancement there, but we didn’t know exactly what that was.

[Andrew Scarborough]: So you’re saying, is that a scan?

[Andrew Scarborough]: Yes, sorry.

[Damien Blenkinsopp]: Okay.

[Andrew Scarborough]: — This was the MRI scan after my operation.

[Damien Blenkinsopp]: Is that a straight MRI?

[Andrew Scarborough]: Yes, this was just a standard MRI, but I also had my pathology report from the amount of tumor that was able to be removed, and that came back as an Anaplastic Astrocytoma, which is a Grade 3 Astrocytoma — affecting the glial cells, the astrocytes in the brain, and quite important components of the brain. It’s not a great thing to have, particularly a high grade glioma, which is what mine was.

Brain tumors come in different gradings, so it’s like we’re staging how — with the brain it’s Grades 3 and 4 are highly malignant, and Grades 1 and 2 are slow growing. Grade 1 is typically a solid mass, that you can — if you can operate it can be curable. Even Grade 2s are known to come back, and do grow, but grow at a slower rate. But Grade 3 and 4 are the fastest growing, they grow quite fast. Mine was showing to be heterogeneous, it had quite a few Grade 3 cells in there.

[Damien Blenkinsopp]: Does that mean that it has different types of cancer cells there when you say heterogeneous?

[Andrew Scarborough]: Well, yeah. It showed numerous mutations. It’s very difficult to explain, but it showed that it wouldn’t be chemosensitive, it was negative for IDH1 which is a predictor of longest survival and chemosensitivity. It was also unmethylated for MGMT, which is a repair gene.

And that’s also — it’s not a good thing that it was unmethylated, so it was one of these gene mutations that they say is good to have for longer term survival. I also had tumor suppressor genes missing which again, with these Grade 3 tumors the timescale for survival is variable until it comes back. But in my case, I had just about the worse. It’s scenario terms with the pathology.

(14:33) [Damien Blenkinsopp]: So, did they give you a rough timeline, I guess at that point?

[Andrew Scarborough]: They said it was difficult to tell because of my age and the location of the tumor. Typically in that scenario, it’s around two years when it comes back, and that’s one of the best cases in that particular scenario. It’s a strange type of tumor because in a different scenario with different kind of pathology it can be up to five years or sometimes seven that it comes back.

It’s quite variable, but in my case it didn’t look so good, and I still had some scar tissue where there was lots of — healthy blood supply that could’ve had any enhancement that was present at the time, not great.

[Damien Blenkinsopp]: Must have been a shock, must have been a pretty big shock for you when that one came about.

[Andrew Scarborough]: Yeah, most definitely. I was told that even though my tumor was not chemosensitive that I should probably go ahead and have chemotherapy and radiotherapy, which I did for a short period because I was quite ignorant about it. I thought that it would potentially give me a bit more time.

But then once I’d looked into it I realized that it was only going to cause further mutations for me personally, and I didn’t want to see that. I started to learn my carbohydrate intake and go on a restrictive ketogenic diet after I’ve learned about it prior to my diagnosis, when I was studying a Master’s in Nutritional Therapy.

(16:17) [Damien Blenkinsopp]: Right, what was your lifestyle like before this all happened to you, and how old were you when this happened?

[Andrew Scarborough]: 27, 28. It’s difficult now thinking back, because my birthday’s at September 1, so I was 27 going on 28. It was two and half years ago and I’m 30 now.

[Damien Blenkinsopp]: So roughly 28 or 27.

[Andrew Scarborough]: Yeah. I was on a diet that I thought was healthy, so I was on a low fat, high carb with a complex carb diet, all whole foods, so I thought I was doing a good job, no processed food. I actually had quite a low body fat percentage and quite a high lean body mass. I thought I was very healthy, and I was very athletic.

I’d worked as a personal trainer for a few years. I was studying my Master’s in Nutritional Therapy and it was a shock to me that what I was learning in my undergraduate degree in Nutrition was completely useless, because I was learning all these new information that contradicted all the older information, but I was just learning about it. I thought it was interesting but it seemed to go against most of what I’ve studied for the past few years before that.

I thought I was healthy.

(17:44) [Damien Blenkinsopp]: When they gave you the diagnosis for the cancer —people at home are probably thinking, “Well is this one of those — metastasized, so it would spread to other parts of the body, or does it tend to stay concentrated?”

[Andrew Scarborough]: Yeah, well primary brain tumors typically just spread into the brain, which isn’t great because your brain is very useful. Apart from medulloblastoma, which can spread down the spinal fluid and into the central nervous system. It’s the central nervous system that can spread down the spine, and other also spread into the brain.

Mine is an astrocytoma, it would’ve just spread into the brain, and there can also be secondary tumors that come about as a response in the brain. It’s not a great type of tumor to have.

[Damien Blenkinsopp]: No, tumors are good ones to have, but it’s one of the nastier ones.

[Andrew Scarborough]: It’s the step down from glioblastoma, which is the most common type of brain cancer.

[Damien Blenkinsopp]: That always the worst, is the Type 4. . .

[Andrew Scarborough]: Yeah. I thought with my approach, with my own treatment strategy — I thought I have a little bit more time to play around with things and adjust to strict ketogenic diet. If I had a glioblastoma I would’ve pushed things a lot quicker. I did push things quite a lot, and I go to extremes with this diet and this approach.

(19:19) [Damien Blenkinsopp]: Yeah. Did you consider any other options? You said you took a little bit of chemo and radiotherapy —radiation, and pretty quickly you stopped, was that a couple of months?

[Andrew Scarborough]: I stopped after four months because I was proposed to have it for up to two years which is a long time, and I said no after a few months experiencing how horrible that was, and still having these horrible seizures. I thought, “Well, I want my quality of life to be good at least.” I stopped it, because my scans were still showing this enhancement.

I thought, “Well, we don’t know if that’s necrotic tissue or scar tissue, or if it’s the tumor activity.” But I thought that, because my tumor looked so glowing on the scan that it was potentially very responsive to carbohydrate restriction. So you do get some cancers that seem to use more glucose for energy, and you get some that actually use glutamine more for energy than glucose.

More or less they use both for energy, but because mine was so glowing up — lighting up like a Christmas tree I’d like to say, it showed that it was potentially more efficacious to just really cut down on the glucose, and see what was going to happen from that.

[Damien Blenkinsopp]: So these were all MRIs they were giving you?

[Andrew Scarborough]: Yeah, and interestingly even though it’s different from other cancers where you get a PET scan, and you can still see the enhancement there, on an MRI, that was interesting to me.

[Damien Blenkinsopp]: Do you know why that was? We spoke recently to Gene Fine who is talking about the PET scan, in the use of cancers. Do you know why you were able to see it quite clearly on the MRI in your case? Is that specific to brain cancers?

[Andrew Scarborough]: Yeah, I think from what I’ve seen in the literature it is, I don’t know exactly why that is. I guess it’s just you’re able to see the metabolic activity even with — I think it’s an iodine solution, not the good kind, the more radioactive iodine that they give you, rather than the supplemental iodine which you can get which is actually really good for hormonal control and certain cancers.

[Damien Blenkinsopp]: So, they give you an IV of that when you go to your MRI, so they can see more?

[Andrew Scarborough]: Yeah, that’s the contrast injection that they give you. Sometimes with PET scans, they do give you the — that shows up quite nicely with the contrast dye. I view my scan straight after I have them, so it’s interesting to view that.

[Damien Blenkinsopp]: Yeah. So I think its gadolinium, is that the contrast dye you’re talking about?

[Andrew Scarborough]: That’s one of them, but I don’t have that one from my scan, I have something else. I can’t remember exactly what it’s called, but I’ve had a few different kinds of scans. I’ve also had MRI spectroscopy which is a fascinating type of scan.

It works with lights, allowing you to see the microenvironment in the brain. And we’re looking at how the ketogenic diet is changing that environment within those biomarkers within the brain as I’m progressing. That’s really interesting to see.

(23:02) [Damien Blenkinsopp]: Yeah, so great. What kind of scans have you been having over time, and how frequently? And how have you seen the ketogenic diet impact that over time?

[Andrew Scarborough]: Well initially I had a standard MRI scans which were quite boring. The cancer cells, [unclear 23:19] was that wasn’t the best for brain cancer, even though it’s world-renowned for other cancers. At that time, I had the enhancement and significant scar tissue, and I had Hemosiderin, which is a blood staining, that was quite a lot of that showing on my scan.

Since then I’ve had progression in a way that I’ve been given a statement saying that I have a response, that I’ve achieved complete remission, and the enhancement is no longer present. I’ve also had significant healing of the scar tissue, and I’ve had vast improvement of my symptoms. So, I am completely off medication for epilepsy which I was told by five different neurologists — that I’d be crazy to even reduce the medication, and I should increase it because my seizure activity was so bad.

I’ve just had a linear progression of improvement in that respect, so I’m completely off medication for the epilepsy, and for that, I do a number of things which controls my seizure activity. And if I forget to do those things I instantly have seizures — it’s like being on a tightrope you have to keep up with doing all these things, I haven’t had a seizure in a long time. When I start to stop doing these things, or I slip up even a little bit I get an aura, which is a warning for me that I’m going to have a seizure.

I have emergency measures to reverse that, which I’ve devised myself largely. It’s interesting.

(25:07) [Damien Blenkinsopp]: Yeah, sounds very interesting, we’ll jump into that. So the epilepsy is a symptom, it’s driven by the hemorrhage that you had and some damage?

[Andrew Scarborough]: Yeah, and also it can provide these for an indicator of where you are with cancer with the brain. Particular with the temporal lobe epilepsy which is a typical response from a temporal lobe brain tumor. My tumor was between the temporal and frontal lobe, so I have three different types of seizures, which is fun.

Monitoring my symptoms and my seizure triggers, and my theories on what would resolve the seizures, not just the ketogenic diet but things I could do with the ketogenic diet to optimize it specifically for brain cancer management. I was able to work out what worked out most effectively for me personally and relate that to the literature as well. I was then able to go to my neurologist and say, “Well what do you think of this?”. And then when they said, “I think it’s absolutely ridiculous, there’re no science behind it.”

I was able to show the science behind it and my results. And then they could say, “Well that’s very interesting.” I’ve had success that they didn’t expect.

(26:42) [Damien Blenkinsopp]: That’s great. So when were you given the sign off, when they say, “Okay your scans are clear.” Did they say it’s in remission or do they say it’s clear?

[Andrew Scarborough]: With that kind of cancer it’s never deemed as curable and I don’t think it can be curable, but personally I think you can achieve and maintain complete remission, and maintain that status indefinitely. From close observation of the animal studies, when they come off the diet after they’ve achieved complete remission, same kind of cancers, that it comes back almost instantaneously. The unpublished human studies I know the same thing, the same occurrence.

I am very keen to stay on this very strict ketogenic diet, and I actually feel quite good on this. Internally, when I have my blood tests which I have a myriad of different blood tests just to see how I’m doing in terms of my general health. A number of markers for potential tumor progression. Internally I am actually much healthier than before I had cancer, which I find that kind of funny.

(28:08)[Damien Blenkinsopp]: So what kind of improvements have you seen, what are the biomarkers that stand out for you, the test results that have come back, and been useful?

[Andrew Scarborough]: The first thing I looked at was my vitamin D. When I was first diagnosed it was in a severely deficient range, and now it’s in the suboptimal range. People would say it’s too high now, it’s 200, and previously was 20.

I also have my triglycerides tested, I have my cholesterol done, and all those fun markers. I have a full blood count, my white blood cell count was pretty good, I can’t remember the exact figures. It’s actually better than before I had cancer, which is not typical even years after you had cancer, immunity can be compromised, so your white blood cell count is typically quite low, and I found that quite interesting.

(29:13) [Damien Blenkinsopp]: It’s great to hear about that progression. Let’s talk about the actual things that you’ve done in terms of where you started in your ketogenic diet, because I know that people said they’re ketogenic. Have you been tracking your blood ketones and blood glucose since the start? And have you seen how that’s changed as you’ve changed your diet?

[Andrew Scarborough]: Yeah. The first thing I did I went out and got a glucometer to measure my blood ketones and blood glucose, and I was comparing that to book cancerous [unclear 29:45] disease, and the glucose-ketone index that Thomas Seyfried devised and came up with, with his colleagues. I had a number of conversations with him about it, just over email, and I was amazed that he got back to me.

I found it very interesting, I started with trying to do the fast, to start with, to get me in ketosis quite quickly. But I realized with epilepsy that’s not a great idea. I had quite a few bad breakthrough seizures attempting that.

I decided not to try it that way, I decided to do it gradually and over time I managed to get into the therapeutic range within just a few weeks.

[Damien Blenkinsopp]: When you say therapeutic range what is that?

[Andrew Scarborough]: I was using the glucose-ketone index, which you use a ratio where you divide your blood ketones by the blood glucose, and you come up with a number, and you try and make sure that number is — I think it’s above one. I don’t measure it anymore in that way because I’m consistently in very deep ketosis with very low blood glucose, so I don’t have to do it anymore.

[Damien Blenkinsopp]: Yeah, we actually covered the index with Thomas Seyfried before. I think it’s a glucose divided by ketones, and there’s a couple of other little things you have to do in there, it’s not super straight forward. I put a spreadsheet up for some people who are asking, when he was talking to us he said it was under one.

So I guess that’s what you are aiming for and you seem to be saying you’ve gone…

[Andrew Scarborough]: Yeah at that time, that’s what I was aiming for, but now I’m consistently above 3.5, so I don’t have to worry about that so much.

[Damien Blenkinsopp]: Oh, in the glucose-ketone index?

[Andrew Scarborough]: Well my ketones are typically above 3.5, and the blood glucose is typically hovering around 3.5 — at the very least one to one.

[Damien Blenkinsopp]: Okay, so for the people at home, because in the US the blood glucose measurement isn’t millimolar. So you’re talking around in between 54 and 72 mg/dl, like 3-4 millimolar. I’m guessing you’re hovering around with the Seyfried Index somewhere around 0.6, 0.8.

So it’s well below one that’s what you’re saying because your ketones are so high.

[Andrew Scarborough]: Yeah. In the evenings it goes sky high, well the ketones go sky high, the glucose goes really low.

[Damien Blenkinsopp]: Do you mean from 5 o’clock onwards — it’s interesting because I saw that in some of my fast and some of my earlier experiments also.

[Andrew Scarborough]: Yeah. I guess it’s a hormonal thing that happens, and also because there’s that period of time where I only have typically two meals a day, that’s the in-between period, I guess where it goes that high. So that’s where I’ve unintentionally fasted for that period of time even though the diet’s mimicking fasting itself.

(32:58) [Damien Blenkinsopp]: What is a typical day look? What are you doing now, what is your typical day look like? I’m assuming at the moment you’ve got the most extreme version of your own program for this, is that correct?

[Andrew Scarborough]: Yeah. Typically I have 85% of fat and 15% protein in my diet, but over the last few days, I’ve experimented with 90% fat and 10% protein, and negligible carbs. Typically on my 85% and 15% protocol that I follow which is very similar to the animal studies, and quite similar to very strict ketogenic diet for children with epilepsy.

I restrict my calorie intake to 1,600 calories — calorie restriction is extremely important for brain cancer management. You probably discussed that with other people I’m guessing. What’s also important I think is the other things that I’m doing.

Personally, I think it’s very important to make sure you have correct therapeutic ratio — I like to call it of omega 3 and 6 in the blood, and I have at home testing kit for that which I send off to the lab every few months.

[Damien Blenkinsopp]: Okay, that’s interesting, is that a dry spot test?

[Andrew Scarborough]: Yeah, it is. You just have to collect quite a significant amount of blood, and it gives you a report back just saying what you’re ratios of omega 3 and 6 are in your blood.

[Damien Blenkinsopp]: Which lab are you using for that?

[Andrew Scarborough]: Well, the testing kit is by — if you go on Omegasense.com it comes up. There’s a center called the NutriCentre in London, and I just get it from there. It’s a pretty good test, very accurate.

[Damien Blenkinsopp]: Have you seen that change? This is actually the current levels ratio, it’s not like it’s your diet of the day like we were talking about — the blood glucose and the ketones which are changing all the time. It’s a more stable marker which is evolving over time, so you’re choosing for a range you want to keep it within.

[Andrew Scarborough]: I’m just trying to get us close to 1:1 ratio as possible, and I’ve experimented with a 2:1 and a 3:1 ratio in favor of omega 3 which is quite hard to do, but it’s very interesting. We know that omega 3 fatty acids exhibit neuroprotective properties and can represent a potential treatment for a variety of neurodegenerative diseases. It’s really interesting, we know that they are shown to be cytotoxic to tumor cells themselves.

Ideally, an optimal ketogenic diet for brain cancer should have, in my view a better ratio than omega 3 and 6. I think the standard ketogenic diets that are applied to humans at the moment are way to high in omega 6 which is inflammatory. I struggled when I was doing a standard ketogenic diet because of that.

[Damien Blenkinsopp]: What are you taking in order to raise your omega 3 levels? What are you doing in diet specifically?

[Andrew Scarborough]: Well, initially I was eating lots of brains because they are the best source of omega 3 that you could get, and that’s high in DHA, and one of the main fatty acids in the brain is DHA. The brain is 70% fat, and the rest is mostly water, it just makes sense to me to have in my diet mostly fat and water, that was my main reason for doing that.

We also know that the fatty acid composition of gliomas differs from that founding non-malignant brain tissue quite significantly. The reduction of glioma DHA content is really interesting to view — we know that in gliomas which is what my tumor was, and what a glioblastoma is as well. We know that they have significantly less DHA in and around them.

If we can increase that — the literature shows that it can have a very potent effect, particularly when on a ketogenic diet, in shrinking these tumors.

[Damien Blenkinsopp]: That’s great so you’re still eating brains today, is this a large part of your diet? What types of brains?

[Andrew Scarborough]: I was eating lamb’s brains, but, unfortunately, I’ve stopped eating them because of the very, very low risk of Scrapie which is like a CJD, a Mad Cow disease but the lamb form. Even though it’s a very small risk, and you probably have that same risk if you were to eat any infected tissue of that same animal, I just thought it would be a good idea to avoid it, which is a shame because it’s my favorite type of food on the ketogenic diet.

It’s a perfect ketogenic food, but my second most therapeutic ketogenic food that I found is sweetbreads which is the pancreas and the thymus gland of — in my case I get them from lambs again. I’ve done an experiment which is on YouTube, on my YouTube channel, just look at Andrew Scarborough, and look at my sweetbreads experiment, I’m testing the myoglobin of sweetbreads and it comes up very high on the glucometer for ketones.

When I test my blood after my postprandial blood glucose and my blood ketones after eating, my ketones shoot up very high, and the blood glucose stays more or less the same as before I started eating.

[Damien Blenkinsopp]: That’s interesting. Out of interest, how much do sweetbreads cost? Are they relatively cheap or expensive?

[Andrew Scarborough]: Well I mostly get them for free, sometimes I have to pay a pound for them.

[Damien Blenkinsopp]: Okay, so they are very cheap.

[Andrew Scarborough]: Yeah, because no one wants them.

[Damien Blenkinsopp]: Right that’s what I was thinking.

[Andrew Scarborough]: They’re incredibly nutrient dense, rich in trace minerals such as zinc and selenium, and they’re rich in protein, and omega 3 fatty acids. Like the brain, and like all the fish — the great source of omega 3. They also raise ketones very high.

[Damien Blenkinsopp]: Yeah, that’s very surprising. I don’t know if you’ve heard new supplement ranges which I’ve been playing around with it, exogenous ketones.

[Andrew Scarborough]: Yeah, I take those as well. I take KetoForce, mostly when I’m trying to do exercise because exercise is a huge seizure trigger for me. So yeah I play around with that.

[Damien Blenkinsopp]: It sounds like the sweetbreads are more effective than the KetoForce, KetoCaNa and the other ones.

[Andrew Scarborough]: Yeah. I actually made a supplement, a sludgy juice that the sweetbreads come in because I have them completely fresh straight after the animals are being slaughtered, well not straight after, but not long after, because they have to do a number of things just to make sure they are safe to eat. I made a supplement out of that and tested it, and it was very interesting the results, but it tasted absolutely foul.

[Damien Blenkinsopp]: Is that a downside of sweetbreads, they’re really awesome except they taste bad.

[Andrew Scarborough]: Yeah.

[Damien Blenkinsopp]: Okay.

[Andrew Scarborough]: It’s not the best tasting, you have to boil them for a long period of time, but they’re very nutrient dense and very effective.

[Damien Blenkinsopp]: How do you eat them? Have you got a quick recipe for the people at home, and they’re like, “Oh like a great thing to try out.” But if it tastes horrible is there some way to mask it.

[Andrew Scarborough]: The best thing to do is boil them for about an hour, that’s actually a short period of time typically for sweetbreads. Normally, it’s a lot longer. And then if you add tarragon to it, it actually compliments the flavor, and it actually tastes a lot nicer.

That’s one of the things I do, it goes well with tarragon. I just consume every bit of the animal, and I don’t have any carbohydrate so that’s how I get around possible nutrient deficiencies from not having any fruits and vegetables. And it allows me to not count carbohydrates, so it’s a Paleo-Ketogenic diet.

[Damien Blenkinsopp]: It’s a pure meat diet, right? Basically a pure carnivore?

[Andrew Scarborough]: Meat and fish, and fat, and that’s it.

(41:37) [Damien Blenkinsopp]: I do know there’s a little bit of story behind the reason — first you were on a ketogenic diet and you were doing more of a straight forward one with the coconut oil, and all of these kinds of things, what happened?

[Andrew Scarborough]: I noticed that with certain people with certain types of brain injury, your brain can be more sensitive to salicylates which are found in coconut oil, various vegetables and fruits, especially ones that have seeds. I wasn’t able to have avocados or any of the staple ketogenic foods that you have. I also couldn’t have dairy because I had a reaction to that, and I wouldn’t advise dairy anyway on a ketogenic diet for anyone with cancer let alone — brain cancer, because of IGF-1.

It just doesn’t make sense to me that there’re so many ketogenic diets for cancer management that have been based around dairy.

[Damien Blenkinsopp]: Right. There’s a lot of cheese, cheese is pushed quite hard…

[Andrew Scarborough]: Yeah, loads of cheese and double cream, and it’s not efficacious for me, even though I’m astounded that they get any results with these trans fat. And they do get some results, that’s encouraging for me on my — what I would call a more beneficial and effective ketogenic diet for this circumstance.

(43:06)[Damien Blenkinsopp]: Could you explain quickly the IGF-1, because there are people at home that are not quite up to speed on the IGF-1 and the dairy aspect of it. What’s the problem there?

[Andrew Scarborough]: It activates insulin-like growth factor and that can cause cancer cells to proliferate faster. One of the ways I get around that — I used to eat lots of butter, but because it’s more insulinogenic and it has milk proteins and casein. What I do is I have Ghee, which is clarified butter so the milk solids and the casein have been removed, and it’s much less insulinogenic and I actually get a much better blood ketone readings as a result as well compared to butter.

I find that interesting in itself, and we also know that compared to coconut oil, Ghee has much more omega 3 fatty acids, and coconut oil only has omega 6. If you’re basing a ketogenic diet around — just loads and loads of coconut oil which is just omega 6. Even though coconut oil is fantastic for achieving ketosis, I would advise it in moderate amounts if you can tolerate it because it’s really good.

I would say that making sure that you have enough omega 3 by having more animal fats is more beneficial in terms of the overall nutrient profile than just consuming tons of coconut oil.

(44:44) [Damien Blenkinsopp]: Right. You mentioned you eat all the parts of the animal, I’m guessing you mean all of the organs…

[Andrew Scarborough]: Yep.

[Damien Blenkinsopp]: Do you consume what you would call a variety of these? Do you try to cycle them, and the widest spectrum possible? So what other organs are you eating, are you literally eating all of the different organs on a rotation each week?

[Andrew Scarborough]: Yeah. Literally everything but mostly heart, because it’s very very cheap, it would cost me 60 pence at a time, and you get quite a substantial portion— because lamb hearts are quite fatty, there’s a huge chunk of fat on them. I can just eat them as they are, and I don’t need to add extra fat.

It’s a fantastic source of iron, zinc, selenium, B vitamins, folate, and it’s the best food source of coenzyme Q10. It’s funny how people pay an absolute fortune to get pills that have a coenzyme Q10, and I just get the best source that you could possibly get for 60 pence at a time.

[Damien Blenkinsopp]: There’s a psychological barrier about the taste, and it’s just what we’ve become used to really. I’m definitely nowhere near as far as you — I’ve been eating more organ meats and I’m trying to push it up, I just made another order today from a new company actually. I’m slowly building my way up, and it’s a taste I’m struggling with, recipes I think help with that, learning how to cook and deal with the different tastes, and just getting used to them.

[Andrew Scarborough]: Yeah. I actually did quite well to start with brains, they’re actually the most tolerable in terms of tastes because they just taste like creamy eggs.

[Damien Blenkinsopp]: Oh, I would’ve never thought that.

[Andrew Scarborough]: They taste like creamy salty eggs.

[Damien Blenkinsopp]: You just don’t look at them while you’re eating them.

[Andrew Scarborough]: No. And a number of things I do are just for entertainment, to keep the diet interesting, to make sure I have enough trace minerals. That’s why I added insects to my diet quite early on because anytime you eat the whole animal you’re getting a variety of nutrients. When you eat insects you’re consuming the whole animal — it just makes sense that it would be a beneficial thing to have.

[Damien Blenkinsopp]: How do you consume those? Because I know there are cricket bars out there in the US, how are you consuming insects?

[Andrew Scarborough]: What I do is I get the fattiest insects that are ketogenic, I get waxworms and super worms. Mostly insects that reptiles eat, I get them from a pet shop that sells them for reptiles now, I used to get them online.

[Damien Blenkinsopp]: Oh, man. Okay did you used to buy from [check 47:31 – Bug Grow], was that the specific brand — was that the only place you bought from?

[Andrew Scarborough]: Yeah, I tried a few, I tried silk worm, pupa as well — a few different insects have different medicinal properties, they’re in Chinese medicine. They’re really interesting in terms of the properties that they have. But we largely ignore that, mainly what I do now is I get them from the pet shop.

I just stick them in the freezer to kill them, and then I’ll give them a gentle wash and eat them …

[Damien Blenkinsopp]: You just eat them straight?

[Andrew Scarborough]: The problem, if you get them online is that they’ve been dehydrated and cooked so much that the nutrient profile isn’t as good as if you have them fresh after they’ve been wiggling about. I also grind them up and make my own flour after I’ve frozen them. That makes quite nice breads, I make a zero carb ketogenic bread which is very useful. People actually think it’s proper bread…

[Damien Blenkinsopp]: You don’t tell them right?

[Andrew Scarborough]: I’ve actually offered it to people without telling them, and they quite like it, and then I tell them what it is, and they want to punch me. But it’s actually surprisingly quite nice.

[Damien Blenkinsopp]: A quick story here, I was in Mexico 15 years ago and I went to Taxco. Anyway you go up into the mountains, into this old city and they were selling plastic bags full of live insects for eating. It’s something that we used to do — we don’t do in modern society. . .

[Andrew Scarborough]: If you look at anthropology, and how we evolved, it’s largely ignored especially with these Paleo diets — we evolved primarily eating a variety of insects, and in quite a large amount. It suggested that the man would go out and go hunting — would only about a 20% success rate catching these larger animals.

The woman would be mainly collecting insects for food. Seasonally they would collect nuts and berries, but it’s a fact in anthropological studies that we did consume a large amount of insects before we moved closer to the coast to eat fish, and that’s how our brains developed more. It’s an ignored fact.

(50:16)[Damien Blenkinsopp]: It’s really interesting, we’ll get there. There’ll be people writing books — maybe you, about the missing parts of the Paleo diet, Paleo upgraded. You did mention that, when you exercise you’re taking exogenous ketones, because of your epilepsy, why is that?

[Andrew Scarborough]: When I exercise my blood ketones go down, lower than my individual therapeutic reading for seizure control for me personally. I have to do that, and I also have to take another experimental treatment of mine which is proved effective, which I learned from the literature on epilepsy. It’s a magnesium chloride solution that I mix into water, and I have a specific amount that reverses auras.

An aura for me is when you have all symptoms that you’re about to have a more serious type of seizure. An aura is a partial seizure in itself.

[Damien Blenkinsopp]: Okay. Maybe you would loose your words a little bit?

[Andrew Scarborough]: I would get pins and needles in my mouth and throat, and I would feel very dizzy, and faint. I have this horrible feeling like I’m going to collapse and have a tonic-clonic seizure. When I take the magnesium solution that I take three times a day, it actually reverses that aura, it is a potent preventative measure that I found to control seizure activity extremely effectively.

People with any kind of epilepsy, their levels of magnesium drop very low, and there are certain types of the day that magnesium is at its lowest, and typically that’s when seizure threshold is also at its lowest. If we can control that, we can control seizures very effectively. Also, on a ketogenic diet, supplemental magnesium — particularly magnesium chloride are found most effective.

It acts as a natural statin, it has a beneficial effect not only on cholesterol, in a natural way not like a typical statin where it’s actually destroying that process, it’s working with your body to do it naturally. I find that it also controls blood glucose — it regulates blood glucose very effectively too. I see it as my replacement for my medication that I was on previously, and the medication interestingly actually causes magnesium deficiency as well as calcium deficiency, deficiency in vitamin B-12 and vitamin D.

[Damien Blenkinsopp]: Which medication where you on?

[Andrew Scarborough]: I was on the maximum dose of Levetiracetam, which the brand name is Keppra and Sodium Valproate the brand name for that is, Epilim. I was both on those and the highest possible amount that you could be on. You can imagine the side effects of that, and the nutrient deficiencies that caused were just quite substantial.

When you’re withdrawing from those drugs you could actually get breakthrough seizures if you don’t address those nutritional deficiencies, and those seizures can actually cause SUDEP — it’s shorthand for sudden unexpected death in epilepsy. I was told consistently that I was highly likely to have that if I was to — not only come off my medication which is what I eventually did but reduced the medication. I have to reduce that medication for a period of almost two years.

I had to do it very slowly, and adding these nutrients and trace elements so that I was not having these breakthrough seizures that were life-threatening. It was a difficult balance, but I achieved it.

(54:50) [Damien Blenkinsopp]: It makes it easier when you titrate down slowly, but still you’ve been courageous in pushing for all of these things when you’re getting this pushback which is saying it’s really dangerous. Just in terms of the exercise, how do you bump your ketones up – is it the KetoForce?

[Andrew Scarborough]: Yeah. I consume that throughout my workout but I tend to mostly just do quite a light bodyweight exercise because I don’t want to stress my body too much. Thomas Seyfried himself recommends that cancer patients don’t push themselves too much with exercise, because it just puts too much stress on the body and on the brain. Mostly I just go for long walks, in an area with lots of oxygen, and I’m actually going to start having hyperbaric oxygen therapy fairly soon.

I’m in discussions with a number of facilities about that, and I’m going to start doing case studies on patients. I’m actually working part-time at the moment with Imperial College London in Charing Cross Hospital, to start-up clinical trials hopefully next year with brain cancer patients using — what I would call an optimal ketogenic diet.

We’re looking at magnesium for these brain cancer patients, we’re looking at the omega 3 and 6 ratios in the blood, we’re looking at C-reactive protein as a marker for a systemic inflammation, and we’re able to measure that for over a period of time to see how that changes while on a ketogenic diet.

[Damien Blenkinsopp]: With cancer is that typically high the hs-CRP because of the inflammation, or is that just a. . .

[Andrew Scarborough]: Yeah. It’s typically higher than normal, but one of the main ideas of measuring that is to have a marker that you can measure over time. I’m a huge fan of testing and I know that even if these things have no effect on cancer, they have an effect on epilepsy and blood glucose management.

We know that these are prognostic factors and they’re also effective at managing epilepsy which many brain cancer patients have as a result. I’m very keen to start doing this in patients more, and I’m working very hard to do that.

[Damien Blenkinsopp]: It’s very exciting that you’re able to work in hospitals. This is starting next year you said, potentially?

[Andrew Scarborough]: Yes. It would also be featured in, New Scientist magazine early next year. My story and my approach will be featured, and that’s very exciting as well because it’s getting the message out there and we can then have the actual data on humans which is missing. It would be — as I’ve said before it will be efficacious.

We’ll be able to not just translate the diets that have been used for children with epilepsy which I don’t believe …

[Damien Blenkinsopp]: As good, as they could be?

[Andrew Scarborough]: I don’t think that they’re translatable for brain cancer patients because I think it’s just very different. For example, when I was on the standard type of ketogenic diet, they did include those ingredients. I developed symptoms that were similar to Temporal Arteritis, where my temporal arteries became so inflamed that I nearly went blind and I was prescribed steroids for it.

But instead of taking the steroids what I did is I looked at how much omega 6 I was taking in my diet, and even though my blood glucose and ketones looked fantastic, and the ketogenic diet is anti-inflammatory in itself. I was having these inflammatory responses which were only controlled and reversed when I re-addressed the balance of omega 3 and 6 ratios. That in itself is quite powerful.

(59:15)[Damien Blenkinsopp]: Interesting. Where did your omega 6 ratio start? We read studies where the standard American diet, for example, is you can get ratios of 20:1, 10:1 — quite far off.

[Andrew Scarborough]: I’ve read up to 40:1.

[Damien Blenkinsopp]: Were you not so bad because you said you had a reasonable — you were trying to have a reasonably healthy diet before. I wouldn’t expect you’d have the sad numbers.

[Andrew Scarborough]: Yes, prior to initiation of the diet, I would say I was most likely about a 10:1 ratio. But, on the ketogenic diet, it was probably quite similar actually because it was including lots of nuts, coconut oil, coconut milk, coconut cream, lots of vegetables that were high in omega 6. I just thought it could be done better — then I transferred on to what I like to call a, fishogenic diet.

I was consuming a lot more fish, and I felt instantly much better and then as I cut down on the vegetables – cut them out completely. I had an instant response where I can’t even remember the last time I had a headache, even a mild headache.

(60:32)[Damien Blenkinsopp]: Great to hear. I’m conscious of your time I know that you’re really busy currently. But there’re a couple of things — I do want to make sure we cover before you go. We didn’t speak about glutamine and I know that an important part you mentioned up front that’s something you had to restrict quite sharply. But how did you do that practically?

[Andrew Scarborough]: Well, the first thing I did was limit protein quite significantly, and I did a number of therapeutic fasts, and it wasn’t until then that I actually saw the greatest response in my MRI scans, in terms of the complete remission. One of the other things that’s quite effective is with the magnesium it has an effect on that as well. I need to find the study for that, but I can send it to you if you’re interested in reading it.

Another thing that I’m actually looking into for the long term is Metformin, because Metformin on a ketogenic diet has quite a potent effect. It has a number of mechanisms which I can’t remember all of them off the top of my head, but that’s one thing that I’m playing around at the moment. It gets an effect on MAMP and a few other things.

It’s quite hard to explain, it’s quite technical.

[Damien Blenkinsopp]: In terms of the fast, you said that’s when you really started seeing the effects, so that would mirror — we had Thomas Seyfried on here and he was talking about the importance of the fast. How many days — was that a pure water fast? Was it a seven or five day fast?

[Andrew Scarborough]: It’s interesting because I think that — when these researchers are talking about fasting for brain cancer patients particularly if they have epilepsy, what they fail to note is that there’s ionic changes that are happening in the brain when you’re doing these fasts. A patient with epilepsy can’t — especially if they have brain cancer in my opinion shouldn’t just do water-only fast.

I think that they need to do what I call, a ’magnesium fast’. When I fast I have my magnesium water solution that I make up myself, and that prevents me from having breakthrough seizures while I’m fasting because I have such low body fat percentage. My longest fast has only been nine days. I aimed for 10 but I couldn’t do more, I’ve done that a few times but I need to have my magnesium-chloride solution or I instantly have breakthrough seizures, not the good kind either.

I found out the hard way initially, but now it’s just the easiest thing that I do.

[Damien Blenkinsopp]: You’re taking specifically magnesium chloride, is that because it’s a spray kind or is it actually the magnesium chloride specifically — there’s something about the chloride which is helping?

[Andrew Scarborough]: It has something to do with hydrochloric acid and how you digest it. I’d say it’s more bioavailable and it seems to me to be just in my personal experiences that it seems to get the brain very quickly. The literature doesn’t actually say that, but personally, I found that — even though there is not much in the literature about that.

[Damien Blenkinsopp]: Are you buying a specific brand? We’ve talked about using magnesium spray transdermally, but I’m just wondering if you’re using one of those sprays? How much you’re taking of it?

[Andrew Scarborough]: It’s designed to be primarily used transdermally this particular type, and I just get it from a health food shop, it’s mainly people who do sports who take it, which is interesting and funny. I typically take about five sprays three times a day. I can’t remember exactly how much that is, for 10 sprays it’s 150 milligrams of magnesium.

It’s variable depending on how mixed up the solution is — typically around 230 milligrams in a day that I would take. If you consider our water is too high in calcium and not high enough in magnesium. It’s addressing that imbalance that we have, we know that we should have at least a 2:1 ratio of magnesium to calcium, that addresses that imbalance.

We know that in the mornings after we wake up, magnesium levels are lowest. Primarily take it in the morning, after waking up in the afternoon, and before I go to bed.

[Damien Blenkinsopp]: Have you checked your RBC magnesium levels?

[Andrew Scarborough]: I haven’t because I don’t think it’s an accurate measure. I just go by how I feel, and sometimes — I see the epilepsy as a blessing because everything to do with epilepsy with brain cancer is typically very similar to what would work for treating the cancer. If something is working for the epilepsy, you’ve got a pretty good idea that it’s beneficial for the cancer, and most of the things that I actually research about what helps in terms of my epilepsy, experimentally and otherwise.

I found incidentally that it has quite potent anti-cancer benefits as well. It’s really interesting the relationship. It’s quite empowering as well. What I would call spectacular results because I still can’t believe I’m not having these horrific seizures all the time without medication. It’s quite empowering to know that it’s potentially having the same benefit on the cancer.

(1:06:44)[Damien Blenkinsopp]: Yes, it’s pretty amazing your journey. I don’t know if you’ve come into contact with other people with similar stories to tell — I know that some other people who had cancer, you said, unfortunately, they’ve passed away — the ones you were relating to. But if you come across any other people who have been experimenting like yourself.

[Andrew Scarborough]: Yeah. I actually have a group of friends now who I came into contact with just through seeking out long-term survivors, and I have a group of long-term survivor friends who had glioblastoma many years ago, and now have no sign of disease. I have a group of friends with various other cancers who are still here now. They’ve mostly done a drug cocktail treatment on themselves, which is very interesting.

Personally, I wanted to try and copy that drug cocktail treatment but do it in a natural way just using diet.

[Damien Blenkinsopp]: When you say drug cocktail, is that chemo or is that more Metformin and things like that?

[Andrew Scarborough]: It’s more Metformin and statins, and phosphates, and various other DCA, and other very interesting drugs. Personally, the only one I’m considering is Metformin, and potentially a few others, but mainly Metformin and Curcumin which I take in tablet form with DHA because they work synergistically. Curcumin actually increases uptake of DHA to the brain.

Because we know that around these tumors, or where the tumor was – DHA is very low. We know that if you have Curcumin and DHA that’s a powerful combination. Curcumin is cytotoxic to the cells. We know that DHA is, and is essential for brain functioning.

[Damien Blenkinsopp]: You really have built a whole lot of armory against this — it sounds like you’re doing really well. On the Curcumin – there’s many forms available on the market today, you’re taking one of the bioavailable forms…

[Andrew Scarborough]: Yeah, it has piperine in it as well.

[Damien Blenkinsopp]: Okay.

[Andrew Scarborough]: It’s a component of black pepper. I have a number of strategies that I use, and I’m constantly optimizing my metabolic formula.

(1:09:14)[Damien Blenkinsopp]: Do you feel constant improvement? I don’t know if there are any symptoms because it seems like you’ve got most of it under control. Do you think you’re going to be able to repair your body, do you feel any signs of that in terms of potentially resolving the epilepsy?

Do you think this is more likely something that you’re just going to optimize and maintain so that it never bothers you, so you never get the actual symptoms?

[Andrew Scarborough]: As my brain has been visibly healing at a very fast rate on these scans while I’ve been utilizing this protocol, I’ve also found my symptoms have improved with that quite substantially as well. I had facial paresthesia constantly all throughout the day, everyday, and a number of other debilitating symptoms I couldn’t even go out and walk a few steps. The fatigue was horrendous as well.

Being able to do what I am now and this non-stop activity, and just doing so many different things, and having my seizure activity controlled in such a great way that’s much better than before — even before when I was doing all these things I was still getting more activity. I haven’t actually done that many more things if I compare to even just a few months ago. Definitely improving in quite a dramatic way, despite having to keep up with all these things.

It’s getting easier to control, to the point where I have days now that I have no symptoms at all, but if I get overconfident and I forget to have my magnesium drink or do something that’s just out of my routine, I’d definitely have more seizure activity coming. Even though it’s not to the degree that I used to have.

[Damien Blenkinsopp]: I guess really say why you’re saying epilepsy is a bit of a bonus for you because it’s early warning detection system for you…

[Andrew Scarborough]: Yeah.

[Damien Blenkinsopp]: — Whereas cancers can creep up on you and you won’t know unless you’re watching the scans and even the scans aren’t showing a small progression. So right now you can still have a small amount of cancer left, but you can’t see it. It does seem like a pretty nice little tool, even though it’s not nice to have it, in the longer term it sounds like it’s a beneficial thing for you.

[Andrew Scarborough]: Yeah, I can see it as beneficial now, I couldn’t before but it definitely is.

(1:11:47) [Damien Blenkinsopp]: Well Andrew this has been an amazing — it’s very inspiring episode today. I can really say that — I’m totally going to take some of the things that you have been trying and start testing them out myself. I would like to ask you — where to look first if they would like to learn about this topic if they’re facing cancer or epilepsy?

Are there good books or presentations on the subject, the first places to go to, to start learning themselves about this?

[Andrew Scarborough]: I would thoroughly recommend the book, Cancer as a Metabolic Disease by Thomas Seyfried. I think that’s a great starting point. For anyone starting a ketogenic diet I would recommend, Keto Clarity, that’s a good resource to use. I would also go to www.ketogenic-diet-resource.com — that has answers to just about all the questions that you could have.

For help to a dietician, if you live in the UK I would recommend the charity, Matthew’s Friends. In the US, I would recommend the Charlie Foundation which is the sister organization of Matthew’s Friends in the UK. It has recently started to see — it’s mainly brain cancer patients that they see because they get around with that by saying that they’re treating the epilepsy.

I would also go on Clinicaltrials.gov to see what clinical trials are happening globally to do with the ketogenic diet and different cancers.

[Damien Blenkinsopp]: Right, so if they’ll just search for a ketogenic diet on there…

[Andrew Scarborough]: Yeah, if they search for ketogenic diet and cancer on Clinicaltrials.gov they can see all of the clinical trials that are currently happening in terms of ketogenic diets for different cancers. It’s very exciting that more and more of these are popping up, and I hope to — I have a meeting on Thursday to discuss having proper official ketogenic diets, using the right approach in this country, and that’s really exciting new development.

[Damien Blenkinsopp]: Is that with the government, NHS or some other body that’s going to help promote it.

[Andrew Scarborough]: This is in conjunction with brain tumor research, they’re one of the very few cancer charities that actually are going all at it with this metabolic research, and they’re doing that with Imperial College London. It’s a small charity that’s doing this, it’s quite incredible what they are able to do being such a small organization.

[Damien Blenkinsopp]: It’s great they’re starting to be – some grounds building from the bottom and up.

[Andrew Scarborough]: Yeah, and I’m going to start-up my own individual research with a few of my lecturers at my university because I want to get these things happening much faster than if it’s going through clinical trial protocol. I want to do this myself with lower grade gliomas, so that we can see a long-term response to try and shrink these tumors hopefully, because they are not as aggressive, but, they still are incurable.

I want to see what effect that we can have on them rather than having to go through all the standard treatment to go through clinical trials. I think that’s very exciting going forward.

(1:15:25) [Damien Blenkinsopp]: That sounds really exciting, and I’m sure anyone who – maybe affected would be very interested to know more. What are the best ways for people to connect with you and learn about you, and keep up with you when you’re doing these things, they can stay up to date on them. Are you on Twitter, you mentioned you had a YouTube channel?

[Andrew Scarborough]: Yeah, my Twitter name is @ascarbs, and I’m on Facebook if people want to add me on there, Andrew Scarborough. I also am working on a website at the moment which is www.metabolictherapy.co.uk, and that has a holding page at the moment, but it should be live shortly. I have a YouTube channel, Andrew Scarborough, and I have a blog, My Brain Cancer Story that’s the title of it.

People search for Andrew Scarborough and My Brain Cancer Story, they should find it.

[Damien Blenkinsopp]: Excellent. We’ll put all those links on the show notes of course also, make sure all of that is there. Is there anyone besides yourself you’d recommend to learn more about the stuff that you mentioned, Thomas Seyfried, is there anyone else that people should look to?

[Andrew Scarborough]: I would look at the research by Dominic D’Agostino, also I would recommend Dr. Colin Champ, I’ve had various discussions with him online which are very interesting. He’s very interested in my approach and he is very unique, he’s a radiation oncologist who is very supportive of this metabolic treatment. Very similar to my oncologist who – it’s quite a rare thing to find – but it’s very encouraging.

There’s Dr. Adrienne Scheck, who I’m having a meeting with on Thursday she’s coming overseas from the Barrow Neurological Institute in the US, and she’s the one that does the rodent studies using the ketogenic diet. It’s great to be able to discuss with her.

(1:17:29) [Damien Blenkinsopp]: Great, great, thank you for those. Some quick items on your – just a personal approach on what you would advise people to get started with – are you still tracking any biomarkers, on a routine basis?

[Andrew Scarborough]: Only occasionally with MRI spectroscopy but we’ve stopped doing that now just because it looks a bit boring and nothing’s really changing. It all looks really good, that’s why we’re not monitoring it anymore.

[Damien Blenkinsopp]: So maybe once in every six months or once a year?

[Andrew Scarborough]: Yeah, just to keep an eye on it, but everything that you would expect to be elevated but would be a bad thing isn’t showing up – it sounds like a good thing. It’s very new research, we don’t know too much about it, but it’s very promising for the future.

Because if we can see these things before they show on the scan, in terms of enhancement or just showing in an obvious way then it’s – that can only be good for the patient really. Then we can intervene in a non-toxic way.

[Damien Blenkinsopp]: So if you were to recommend one experiment, basically you’ve done many experiments to get to this point – they’re not proven recommendations by doctors and so on. What would you recommend that someone with brain cancer or potential other cancer – what would be the first thing they should try, the biggest payoff from all of the things that you’ve mentioned, what should their first step be?

[Andrew Scarborough]: The first step should definitely be reducing carbohydrate intake. The second step would be reducing protein intake to maintenance levels, and therapeutic fasts are very important. But the main thing, I would say is the omega 3 to 6 ratio, I believe that they should be an omega 3 to 6 index, just like with the glucose-ketone index, and they should work together, as a synergistic therapy.

Because you could even argue the ratio of omega 3 to 6 is even more important than the ketones. I would also say, the magnesium is very important with that too, those three things. Therapeutic ketosis, the omega 3 to 6 ratio and the magnesium I would say are very important for brain cancer patients.

[Damien Blenkinsopp]: Great, thank you, that’s some great takeaways for people at home. Andrew, I’ve got to say this has been really amazing interview – it’s amazing all of the different avenues you’ve run-down and all of these different aspects that you found to improve your situation. I know it’s going to be an inspiring story for the audience.

Thank you very much for being on the show.

[Andrew Scarborough]: No problem, we did cover a lot but we got there in the end.

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