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
OFFERCost$89 per test$99 per test£274 ($379) per test$329 per test$781 per test$399/ year
Breadth of TestingGut, Mouth, Nose, Skin, GenitalsGutGut + DNA (+ Metabolomics/ Blood Markers)GutGut, Blood, Urine and Oral SwabsGut + Metabolism (blood glucose regulation) + Body dimensions
ServiceN/AN/AN/ANutritionist consultation includedN/AN/A
Geographies ServedInternationalInternationalUK & RussiaUS OnlyInternationalUS, UK & Canada
Year Started201220122017201720172017
TECHNOLOGY PLATFORMSequencing Type16S16S16SShotgunShotgunRNA
Information DepthFrom Phylum to GenusFrom Phylum to GenusFrom Phylum to GenusFrom Phylum to Species and StrainFrom Phylum to Species and StrainFrom Phylum to Species and Strain
Type of InformationMetagenomics
(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 SCOPECoverageBacteriaBacteriaBacteriaBacteriaBacteria, Viruses, Parasites and Fungi.Bacteria, Virus, Parasite and Fungi
BENCHMARKING DATA QUALITYBenchmark Data Quality/ ScopeLikely largest database currentlyN/AN/AThe 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 RECEIVEActionable vs. Informational?InformationalInformational: 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 RecommendationsN/AN/AHIGH: Includes reasing and study references for most recommendationsMEDIUM: Doesn't Explain Recommendations, but can assume comes from Weisman workHIGH: Discussion with researchers.LOW: No information given on which various inputs explain outputs or why
Raw DataYesYesNo (planning to add?)No
(but planning to add)
YesNo
(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)10? 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.11
  • GlycA: A novel biomarker useful for predicting predisposition to insulin resistance and Type 2 diabetes12, cardiovascular diseses13 and inflammation-driven diseases including cancer14. 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.15
  • 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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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 profiles16 and non-toxic metabolic management of cancer17.

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 diets18.

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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Most of us have non-optimal blood glucose regulation today.
The impact? Reduced performance, and reduced longevity. We wrongly assume that it’s only diabetics that are exposed to these issues. This episode explores using continuous glucose monitoring and other tech to optimize blood sugar through the eyes of a diabetic self-experimenter.

How can blood sugar regulation and dysregulation be  better understood? Certainly a lot of you are aware and concerned about these topics, if you haven’t already been tracking your blood glucose or your ketones through some of the self experiments we have previously done.

There are a lot of lessons on optimization in this area. Because it is such a serious issue today, there are a fair number of interviews coming up and talking about it.

Another aspect we look into is hacking medical devices. This means not waiting for the technology to arrive from big companies. We are talking about the DIY spirit that some people are taking towards technology. Rather than waiting for solutions to arrive from the market, they are making real use of technology today, right now.

We are also looking at open-loop and closed-loop system technologies. This is a different approach to using direct feedback to optimize ourselves, our biology. I hope you see that this as exciting as well and we will look at both of those scenarios in today’s blood sugar regulation area. And finally, of course, the value of n=1 experimentation as today’s guest is an n=1 experimenter.

This episode looks at blood sugar regulation through the lens of Diabetes. Now of course this is the main disease associated with blood sugar dysregulation, and this means that we’ll be looking at more of an extreme case. This can often be helpful, though, to finding really useful tools because when you are managing something like diabetes you have to take it a lot more seriously, and you have to manage it a lot more closely, and thus you learn more about it.

So today’s episode, even if you are not diabetic — I am sure there are a certain number of you out there, because it’s very common today — it will still be very useful. I found it incredibly useful myself. And one of the reasons for this is even if you are not Type 1 or Type 2 diabetic, you most probably have some level of blood sugar dysregulation; unless you’ve checked it, and you are at ease with that level.

What I am saying here is it may not be optimum. You may have suffered some metabolic damage along the way and your blood sugar doesn’t quite self-regulate as well as it could. If you wanted to test this yourself, you could do a simple blood glucose test and see what your post meal blood sugar is one and two hour after meals. So if it was over 120mg/dL, it may be something you need to look into further, as you may have accumulated some damage and you may be more towards the spectrum of diabetes, diabetes 2 most likely.

So today we’re going to learn from diabetes 1 management – the most challenging form of diabetes. What works for this is often applicable to your own blood sugar management optimization, and managing blood sugar dysregulation in general.

The power of [Continuous Glucose Management] is not necessarily giving the most accurate reading. It’s more the power of seeing the trend. So I know if I’m going up or down, or something is changing.
– Tim Omer

Today’s guest is Tim Omer. He is a guy in the UK who got frustrated with limitations and stresses of having to manage his own diabetes 1 condition, and he set out to fix it. He is an n=1 experimenter and has made a lot of progress in this area. He has really improved his own life through better information and levering the technologies that exist.

He is not isolated in this either. You will also learn in this episode about the community working to build a bionic pancreas. That is a closed-loop system, or potentially an open-loop system, which can manage insulin release automatically or semi-automatically.

So it is really set to replace the broken part of the body, the pancreas, going forward, which is pretty exciting stuff too. For example, you can learn more about this at #wearenotwaiting on Twitter.

I came across Tim through an article in the Guardian which talked about what he was up to, and his blog HypoDiabetic.co.uk where he talks about his journey and his updates.

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

  • Tim Omer’s personal motivation for monitoring blood sugar levels and his battle with type 1 Diabetes (05:57).
  • The basic summary of type 1 and 2 diabetes and on using insulin as therapy (06:56).
  • The effects of very high vs. low glucose levels and how diabetics optimize glucose levels (09:12).
  • Tim Omer’s realistic aim with diabetes management is to remain around the 100 mg/dL blood glucose level (12:57).
  • Long term management of blood glucose levels and sticking to healthy ranges (13:19).
  • Micromanaging diabetes – being proactive with lifestyle choices in order to avoid physiological and mental stress (14:31).
  • The difference in root causes behind the development Type 1 vs. Type 2 diabetes (20:13).
  • How switching to Paleo dieting helps increase insulin sensitivity and optimizes insulin therapy response (22:49).
  • Which are the long term risks of mis-managing diabetes (22:15).
  • Optimal ranges for blood ketone levels and avoiding toxic ketoacidosis in diabetes (26:51).
  • Defining a practical Paleo Diet and caveats with slow – release foods advertisements (29:21).
  • The advantages of switching from pin-prick devices to continuous glucose monitoring (30:39).
  • How CGM informs and empowers the patient in deciding on ways to regulate blood sugar levels (33:28).
  • How insulin pumps work and the benefits these devices offer (35:13).
  • Difficulties in obtaining CGM devices and overcoming initial psychological barriers of using such devices (38:02).
  • A comparison of major CGM devices on the market and user cost-reductions by hacking and re-engineering devices (41:48).
  • How the DIY community is advancing the use of devices and improving quality of life for diabetic patients (47:59).
  • Calibrating CGM devices to gain accurate and useful data for individuals (50:32).
  • Using CGM for detecting trends in blood glucose levels with consuming different food types (55:05).
  • Using open or closed – system devices capable of simultaneously tracking blood sugar levels and adequately administering insulin therapy (56:30).
  • The risks of being solely reliant on technology to treat diabetes and the need to self-engage in the process to achieve optimal positive outcomes (1:03:23).
  • Why the We Are Not Waiting community has taken diabetes treatment into their own hands? – explaining set goals and achieved progress (1:04:36).
  • How the artificial pancreas aims to replace the pancreas of diabetic patients and apps paving the way towards achieving this goal (1:05:46).
  • Undertaking medical and legal risks when participating in DIY biohacking devices and positive effects such movements have on the market (1:07:47).
  • Why the models for developing medical technology are outpaced by DIY communities and why feeling empowered as a patient matters in the social battle for obtaining medical devices, such as CGMs (1:11:51).
  • Tim’s number one recommendation for everyone involved in the field of medical devices and managing data to improve their lives (1:14:52).

Thank Tim Omer on Twitter for this interview.
Click Here to let him know you enjoyed the show!

Tim Omer, Hypo Diabetic Blog

  • The Guardian’s original article on Tim Omer: Describes the active role he is taking in using new technology to battle with his type 1 diabetes condition.
  • Hypo Diabetic Blog: Where Tim Omer talks about his journey and his updates.
  • Tim Omer’s Twitter
  • WeAreNotWaiting: A movement centered around a DIY approach to diabetes management instead of waiting for big companies to commercialize already tweaked – useful tools. It is a community led by diabetic patients and hackers aiming to make diabetes data and technology more accessible and actionable.

Biohacking CGM Devices

Tools & Tactics

Interventions

  • Insulin Therapy: There are two types of insulin injections most diabetic patients use. First, the body requires a background amount of insulin over a 24 h day. Thus patients take a slow-release form of insulin once or twice per day. Second, they use rapid acting insulin with meals such that it can accommodate for food coming into the system.

Tech

  • Insulin Pump: Insulin pumps deliver very minute levels of insulin over the course of a day, thus simplifying treatment and offering greater control. Essentially they simplify the background insulin aspect of therapy.
  • Bionic Pancreas: A closed-loop system, or potentially an open-loop system, which can manage insulin release automatically or semi-automatically. It integrates the insulin pump and continue glucose monitor technologies, so that insulin release responds to real-time data. Essentially, it is meant to serve as a real time replacement of the dysfunctional pancreas of diabetics.

Diet & Nutrition

  • Cheat Day: Cheat days are typically implemented as one day taken off from a diet per week to make the diet easier to follow. This style of dieting is also used by bodybuilders in an attempt to optimize metabolism and fat loss, and by Cyclic Ketogenic Dieters. Tim Ferriss’ The 4-Hour Body book recommended this tool within a Slow Carb Diet. Damien’s experience with this led to seeing high blood sugar levels throughout the entire day, ranging between 130-140 mg/dL. In his personal experience, these days were accompanied with headaches and attention deficit symptoms, adding up to reduced work productivity.
  • Paleo Diet: A diet that advocates eating whole-foods and restricts certain food types including high glycemic foods, grains, and dairy. The diet is low to moderate carbohydrate. Tim found that his insulin sensitivity doubled when he switched to a Paleo-based diet. This has helped him remain in optimal glucose level ranges for more prolonged periods.
  • Ketogenic Diet: 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. See episode 7 with Jimmy More for detailed discussion of the benefits of this dietary approach. This should not be confused with diabetic ketoacidosis (DKA) – a serious medical condition suffered only by diabetics when their insulin drops to near zero, and as a result ketones spike to abnormal levels (20 Mm plus). This situation does not occur for non-diabetics following a ketogenic diet.

Supplementation

  • Exogenous Ketones: A new range of supplements that increase blood ketones directly by providing beta-hydroxybutyrate (a ketone body). These supplements are being studied for and used to increase energy, performance and provide other health benefits. Damien remarked on their use. Read this article for a comprehensive explanation of exogenous ketones and their applications and see here for the list of currently available exogenous ketone products.

Tracking

Biomarkers

  • Blood Glucose: This is a simple measurement of the glucose (blood sugar) concentration in your system. It reflects the body’s ability to properly metabolize food and feed cells with essential energy – glucose molecules. Blood glucose levels usually range around 81 mg/dL (4.5 mmol – UK units). On the upper scale, you should aim to stay below 126 mg/dL (7 mmol), but this level is jumped several times every day. Damien notes that 120 mg/dL can often by hit post-meals, depending on what is eaten. As a diabetic patient, Tim aims to keep his blood glucose around the 100 mg/dL (that’s his target to aim for). Previously, we have covered measuring glucose, including fasting glucose as a biomarker, in Episode 22 with Bob Troia.
  • Blood Ketones: As a diabetic patient, testing for blood ketone levels is useful in determining whether your body is likely going into DKA state. For a diabetic, they monitor to ensure their Ketone levels stay below 11 mmol (which would indicate they are approaching Ketoacidosis). This is not the same as with a non-diabetic. For instance, Damien regularly see 8 mmol or higher during water fasts experiments, and specifically this was noted in his 10 day water fast. This is perfectly normal in that different context. Context matters. To understand the ketones values better, see Episode 7 with Jimmy Moore where we discussed measuring ketones in depth. 

Lab Tests, Devices and Apps

  • Pin-Prick Glucose Tracking Devices: The most popular and easily accessible devices for checking blood glucose (and ketones). While we’ve mostly covered these for use in tracking ketogenic diets, blood sugar optimization and fasting therapy these were originally developed for Diabetic patients. The majority of diabetic patients rely on these devices. 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
  • Dexcom Seven Plus: This CGM device has been retired and newer Dexcom devices are available on the market. It cost Tim around 400-500 pounds at the time when he bought it on eBay.
  • Dexcom G4: The CGM which Tim currently uses and one of the most popular on the market. A continuous glucose monitor containing a small sensor that measures glucose levels just underneath the skin. A transmitter then sends wireless data to a receiver which displays glucose trends. Tim has done extensive work on biohacking this device making it more user-friendly and actionable in managing diabetes.
  • xDrip Device & App: This system combines a small transistor device which allows for CGM data to be directly transferred to a phone or a smartwatch. Developed by Stephen Black and widely used in DIY biohacking circles.
  • Sony Smartwatch: Can be wirelessly linked for real-time access to information coming from a xDrip adapted with a Dexicom 4G device.
  • Medtronic 530G Insulin PumpA CGM device which is popular on the market and offers several unique tools, for example the Bolus Wizard calculator makes it easier to calculate mealtime insulin requirements.
  • Nightscout: This app allows parents to remotely monitor a child’s blood glucose levels. It links the Dexcom receiver, a little pager device, to a mobile phone and downloads CGM data readings every few minutes.

Other People, Books & Resources

Organizations

  • UK National Health Service (NHS): Tim discusses the difficulty of obtaining NHS – funded insulin pump devices, despite many more diabetic patients meeting recommended criteria. About 6% of diabetic persons have pumps in the UK.
  • National Institute for Care Excellence: This public organization provides guidelines for insulin pump therapy in the UK  – and on eligibility for getting a CGM device under the NHS healthcare system.
  • US Food and Drug Administration (FDA): Tim explains the complications of developing DIY diabetes management devices due to their sale being illegal under FDA guidelines.
  • Tidepool: A research company which has built a platform for diabetes data and apps that utilize data. Aiming to encourage others to build on this platform, the company uses a freely available open-source code.
  • Theranos: A company that has patented automated delivery of medicine, using sensing and delivering systems similar to the combination of a CGM and an insulin pump.

Full Interview Transcript

Click Here to Read Transcript

[00:05:57][Damien Blenkinsopp]: Tim, welcome to the show. Thank you so much for joining us.

[Tim Omer]: That’s okay. It’s a pleasure. Thank you for having me on.

[Damien Blenkinsopp]: Okay, so I want to dive straight into it. Why are you interested in monitoring your blood sugar? What is it about you personally that has motivated you to do this and is important to you?

[Tim Omer]: Well, obviously for me being a type 1 diabetic and knowing my blood sugar is very useful. I’m sure we’ll talk a bit more about diabetes itself in a moment, but the main reason why I went and got a CGM was the fact that I managed to acquire an insulin pump by the HS.

That insulin pump, I got that because I was going to go traveling, and it allowed me to have one type of insulin with me, but the insulin pump has a lot of configuration. Other people they choose own [unclear 00:06:41] as a diabetic insulin pump, therefore they must be cured.

It behaves like the pancreas. We couldn’t be further from the truth. You get an insulin pump, it’s just making your condition that much more complicated. But gives you that much more flexibility to manage your diabetes.

[00:06:56] [Damien Blenkinsopp]: Okay, so what’s the difference between an insulin pump, we’ll have to dive into diabetes now so people can understand the importance of all of this stuff, but let’s just talk about the insulin mechanism for a second here. So when you’re a diabetic, whether it is diabetes 1 or 2, you’re using insulin at times to help you stay in the right blood sugar zone. Is that correct?

[Tim Omer]: The basic summary, everyone has a pancreas. The pancreas produces insulin and in very simple terms insulin converts food you consume into energy. That is a very simple explanation of that. You have two types of diabetes, type 2 that you hear in the press and is generally in all the newspapers about the high costs of HS management, etc. It’s a real issue in the western world right now.

Type 2 is where you have a pancreas that is just not performing as well it could be. So generally you are still producing insulin, but not enough to sustain your lifestyle, and that’s mostly managed by diet and exercise and typically caused by a lack of decent diet and exercise. So that’s the majority of the diabetic world is type 2.

Now type 1 is where your pancreas basically packs in completely. You do not produce any insulin and to replace your pancreas, most diabetics go on to injections. There are two types of injections. There is rapid acting insulin so when I consume food I need to take the right amount of insulin for that food to accommodate the food coming in.

Also my body requires a background amount of insulin, a basal, so over 24 hours of slow releasing insulin, and that’s another injection that diabetics take once or twice a day. It gives a slow release of insulin.

[Damien Blenkinsopp]: Okay, so it’s two different types.

[Tim Omer]: That’s the two different types, correct. Again, for a diabetic type 1 it is a balancing act. How do I give myself enough insulin to cover what my body requires for the food I consume, but how do I avoid giving myself too much or I end up with a very low blood sugar levels if I give myself too much insulin which can result in you passing out, going into a coma, potentially death, or if you don’t take enough insulin, very high blood sugar levels, long-term complications associated with blindness, losing limbs, etc.

[00:09:12] [Damien Blenkinsopp]: Do you know what the rough values you are supposed to [be at], where are the extremes you are supposed to stay out of?

[Tim Omer]: So basically as a non diabetic you’re usually sitting around 4.5, I believe, I may be wrong here, a minimum of blood sugars or something, anyway, the number is 4.5. The 4.5 score. What it’s actually measuring is . . .

[Damien Blenkinsopp]: That is correct, it’s millimolar. These are actually UK measurements though, because a lot of people at home are used to the mg/dL so while you’re explaining that I’m going to look up an old calculator so we can translate this.

[Tim Omer]: Please do. That would be great to assist me on that. I say 4.5. Beyond that, I don’t really care much more. It’s just a number. So 4.5 is like the holy number, the holy grail I’m going after.

I don’t really want to go much below 4 for me as a person, so this does slightly change on every diabetic as well, but for me personally if I get below of 3.5, I start to suffer, my performance degrades, basically other people would associate it with being drunk. So as you go below 3.5 I suffer.

Anything I’d say below 2 or 1.5 we are entering real danger territory. Personally, I’ve been quite lucky. My blood sugars have gone quite low, as it does happen to all diabetics, and I’ve been okay, but it can be quite dangerous going that low.

On the upper scale, my aim is to stay below 7. Anything below 11 is acceptable now and then. You don’t really want to go much above 11. But throughout a day, you can jump between those two values multiple times. Type 1 diabetes is very much a real time situation and you feel the impact if you make a mistake pretty quickly.

[Damien Blenkinsopp]: Okay, for lovers of the metric system. I don’t know if we’re all going to move everything to metric one day, maybe. It would be really awesome if the world just used one system. So the values that Tim just gave out there, so the lower value was 1.5 millimolars so that’s what you want to stay out of if you don’t want to go into a coma is 27 mg/dL.

That’s pretty damn low, so for a comparison, when I was doing my fast, I was in a 55 mg/dL and I think I bottomed out around 50 mg/dL with very high ketones which is a different situation, so obviously another energy source supporting me. What you’re aiming for Tim was 4.5 millimolar, correct?

[Tim Omer]: Yes, that’s correct.

[Damien Blenkinsopp]: Yea, so that’s 81 mg/dL and I think we all know that’s a pretty good range. People talk about 75 to 80 as an ideal range there with diabetes 2 and just people in general. Then 7 was your upper range where you go to sometimes and you try and stay below. Is that right?

[Tim Omer]: Um-hum.

[Damien Blenkinsopp]: Yea. So that’s 126 mg/dL so it fits as well. After you’ve had a meal and so on, you expect it to go up to around that and then drive back down. So even when you’ve had a meal you’re still trying to stay roughly below that or just have that as a top upper limit of where you bounce up to.

[Tim Omer]: Well, in an ideal world you’ll always hitting your ideal number, but the reality is it’s just not possible. Even as a non diabetic you’re blood sugars going to spike, especially on the western diet what we are fed upon and believe to be good for us is generally quite bad for your blood sugar levels, hence increased type 2 diabetes.

[Damien Blenkinsopp]: Which we’re going to discuss soon.

[Tim Omer]: Oh yes, we can discuss more. As an example, I know we’re going to touch on this more, but my artificial pancreas app I’m using right now, so in the best, was it mg/dL?

[Damien Blenkinsopp]: Yes.

[Tim Omer]: That’s the first time I’ve ever had a break out of what that actually means. So high value, the system kicks in as at 125, the very low value that it kicks in to correct is 80 and in my target I’m trying around 100.

So that’s how my system is set up, so those are trigger points where it tries to do something. The other numbers, obviously those were extremes. You don’t want to get that high or that low.

[00:12:57] [Damien Blenkinsopp]: Right, right. So you’re aiming for a 100 because that’s a little bit different to some of the public knowledge out there.

[Tim Omer]: That is correct. It’s a realistic aim, should I say. In the UK formats, about 4.5, that is more non diabetic. If a diabetic can stay like that, that is a good day. Right now, I can tell you, I’m sitting at 106.

[Damien Blenkinsopp]: Okay.

[Tim Omer]: Quite nicely in my safety lines.

[00:13:19] [Damien Blenkinsopp]: Right, right. You feel pretty comfortable and you feel pretty good at that kind of blood sugar level?

[Tim Omer]: Yea. That’s something. The funny thing with diabetes, it’s not the number you’re sitting at, it’s how long you can sit at it.

So for example, if I look at my CGM now. Here’s a great example where the CGM is so useful. For the last 3-1/2 hours I’ve been quite close to around the 100 mark, so I feel quite stable. It’s when it starts jumping up and down is when you have a real problem.

Also, the danger associated with that, is you could get comfortable when your blood sugar is at 200. People do that. They get comfortable with higher and higher blood sugar levels. Therefore, they have to really struggle to bring them down.

[Damien Blenkinsopp]: If they go by feeling? Is that when they’re going by feeling more?

[Tim Omer]: That is correct, yea, and all diabetics do go by feeling. Unless you start losing that, it’s quite a danger. Even though it sounds like for a diabetic they feel comfortable with aiming for around 100, if they manage their blood sugars badly over a long period of time they will get used to it being higher than that, and therefore they’re comfortable at that level.

This is where you’re in real danger because diabetics themselves are very reluctant to lower it because they feel so rubbish by doing so. The explanation would be very easy, aim for 100, but the complications and the reality behind it is immensely complicated for the patient to manage.

[00:14:31] [Damien Blenkinsopp]: That’s really interesting because, I can tell you when I used to do cheat day dieting, so that would be basically eating clean six days a week and then one day a week I would eat crap, so I would eat coffees with sugar in them and donuts and whatever I felt like that day.

I would feel amazing that day. I would be so happy because obviously I am sure my blood sugar was up at 130 or 140 the whole day, and by the end of the day I would get horrible headaches and I would be ADD the whole day as well. That was the negative side effect. It wasn’t very good for performance or work.

I found it really hard to actually get anything done, but for hanging out with friends and just messing around and stuff like that, it would be great, or even go to the gym for that matter. That’s a good example to reflect on. Yes, people could get comfortable with being on a high blood sugar high all the time and then feel bad if they’re not in that zone.

[Tim Omer]: Everyone loves a sugar rush. That’s for sure. I’d say a positive side of diabetes, especially type 1, known as juvenile diabetes because just before puberty when they catch it, that’s quite common, though not always, but it does bring you up with a lifestyle of not being so used to sweet substances if you manage it correctly. That’s not always the case.

So that gave me the benefit to notice how high in sugar a lot of the western diet is and how to avoid it because my body’s never gotten used to having that high amount of sugar. We always have to try and keep that target area.

One that always makes me laugh actually is parents who give their children a bowl of sweets and fruit juice and then wonder why the kids go mental and start running up the walls. It’s because you just shoved them full of sugar and they going nuts. Is that not just the natural reaction?

[Damien Blenkinsopp]: Yea, I’ve seen crazy kids like that who were a real handful, and you’re putting them there in that biology zone. It’s your own fault for letting them have all that stuff.

And then they probably become even more naughty and such, so you sedate them. You say, “Oh, have some more sweets,” thinking it’s going to help.

[Tim Omer]: Yeah, exactly. So, sort of natural sugar and processed sugar, that’s the combination for an explosion, isn’t it? But again that’s the lack of education we generally have on our diets. As a diabetic, I can notice that a lot more. And it’s a lot more in my interest to watch those high-sugary food. Because I went to [16:44 unclear] I felt sick and horrible.

[Damien Blenkinsopp]: Right, yeah, because when you come down afterward. So the upper range there was 200 mg/dL, which is pretty crazy. I’ve never seen anything like that before. So when you were over that, what happens? Is it just causing damage over the longer term, or…

[Tim Omer]: Definitely, yeah. So from a long term perspective, anything above — for example, my sugar level is at 125 right now. That’s when you start saying, okay it’s starting to get a little bit too high let’s do something to correct it. At 200, obviously we’re entering danger territory there, areas you don’t want to be. You just feel sick, is the best way I can describe it. You just feel really sick. And the problem is not just that.

A lot of people don’t realize diabetes isn’t just the physical issues, it’s also mental. So if your blood sugar is running high, for example, [like that], you also have a frustration and stress associated with your body. Your body is letting you down, or you’ve made a mistake. There’s only one person to blame in these situations. Or, sometimes you just can’t find the cause.

Before I had a CGM, another good selling point for a CGM is you have those situations where you feel fine. Everything feels great, you go to check your blood sugars, and you find out you’re around the 200 block. And the level of frustration that you get hitting that is immense. So its all about how to process those situations or how do we get away. I don’t want to be told when there’s a problem, I want to be told when I’m approaching a potential issue. I need to be more reactive rather than…

[Damien Blenkinsopp]: You need to be more proactive than reactive. Like, oh I’m already in the 200 zone, and I want to get out of there.

[Tim Omer]: Exactly, and this escalates. So what happens then is you’re stressed, therefore insulin is one of the causes for you losing sensitivity. You’re stressed and that doesn’t help. You then start taking injections to try and lower it but your insulin sensitivity has gone. So therefore you start overdosing on insulin to try and fix it. Also there’s a delay between the insulin becoming active and taking effect in the body.

So you end up in a situation, as we’re humans we want to fix our situation now. So the reality is, you overdose on insulin, an hour later all the sudden your blood sugar goes crashing down, and that’s what makes you feel really bad, because you did a sudden change.

And then you have a thing called the rebound effect, where you go from being 200 all the way down to 20 within the space of 30 minutes. And then you end up doing the opposite: stuffing your face full of food, feeling really shit, feeling really rubbish. And then you rebound back up.

And this process, as I said it’s called the rebound effect, can take up to two days sometimes, of this constantly bouncing up and down, because you’re struggling to get control of your actual body’s blood sugars. I speak on behalf of other diabetics [but] I know for me, that can easily take two days where [I’m] trying to really gain control.

[Damien Blenkinsopp]: Yes. So really the situation you’re in is an extreme compared to most of the listeners today. It’s fair to say diabetes 1 is more extreme than diabetes 2, in terms of trying to manage it and control it and the importance of that.

[Tim Omer]: Yes.

[Damien Blenkinsopp]: You have to micromanage it more?

[Tim Omer]: You do. And type 2, you can only take tablets, it’s more lifestyle based. So if you adapt your lifestyle and get used to that lifestyle, then it’s easier. With type 1, it’s really [hard] because it can swing either way very quickly. Right now I’ve got very good blood sugars. In an hour, ask me again [and] it could be completely different. And that’s kind of the mental stress with diabetes; it’s not just physical, it’s very mental. It’s always constantly on your mind. And if you try to ignore it you’re not going to do yourself any favors in the long run.

[Damien Blenkinsopp]: Yeah, great.

[20:13] Okay let’s quickly cover our bases with diabetes. There’s two types of diabetes, and one of them, let’s talk about your situation first. Some people are born with this, and some people get it early in life. How do you get diabetes 1?

[Tim Omer]: There’s no real answer for getting Type 1 diabetes. They think it may be inherited, but again, look at a lot of families and that’s not been the case. But then again, if you look at more generations, a few generations before me, anyone with it would have died. It’s only been a kind of recent discovery, insulin.

So it’s typical around [or] just before puberty. You generally [do find] as a diabetic, more diabetics you meet, the more you realize you were diagnosed at a young age. Juvenile diabetes is the name for that is quite commonly named that. But we are seeing more and more older diabetics.

Now, whether that’s a result of lifestyle and therefore more people are getting affected by this at later an age, where it’s just circumstances, it just so happens to happen; there’s no real explanation there. But the percentage of Type 1 diabetics to Type 2, I wish I could give you a percentage, but it is minute. A minority of diabetics, as in something of like seven percent of all diabetics or something crazy like that.

[Damien Blenkinsopp]: Right, so it’s a lot rarer than diabetes 2, which has been growing over time. I don’t know if you know this, but has Type 1 kind of stayed stable while diabetes 2, which we say is due to lifestyle factors that you get this, has been growing over time?

[Tim Omer]: I’d hate to be quoted on that, but I’d generally say yes. As far as I’m aware, Type 1 diabetes I would say has been increasing. I think there is an effect, to a certain degree, of lifestyle. Maybe it’s a minute number, but Type 2 is the one that’s really on the increase. And it’s because our bodies are so good at processing the rubbish we give it, it’s only now later in life where people have been having a lifestyle of eating bad stuff does the body start to get to that point where it goes, right I’ve had enough. And the pancreas packs in — that’s my non-medical description. Let’s just be clear on that.

So for example, I had a good friend of mine, rings me up one day and he’s always been quite bad with his health — always eating pizzas, generally high processed carbohydrates, doesn’t exercise — and says to me, “Tim I’ve become Type 2.” And it’s like, congratulations you just decided to become a diabetic. I had no choice but to have this condition, stuck with it. You’ve actually chosen to become it. So you don’t have any sympathy.

And good for him, he [22:31 unclear], got into exercise, improved his diet, and now he’s not Type 2 diabetic anymore. So the difference between Type 1 and Type 2 is almost two different conditions. You know some people get insulted actually by the two conditions having the same name, because they can be so different.

[Damien Blenkinsopp]: Yeah, you just mentioned he reversed that situation.

[22:49]A lot of this is due to the pancreas not working so well, and in diabetes 1 is it an autoimmune issue, where actually the cells of the pancreas have got destroyed?

[Tim Omer]: That is correct, yeah. I believe that’s the case. It’s an autoimmune issue. So your body itself destroys the beta cells in your pancreas that actually produce the insulin. I would guess that’s the same for all Type 1s.

[Damien Blenkinsopp]: I’m mostly not sure what the Type 2 is. Because a lot of people can reverse it if they actively manage their lifestyle, get off…

[Tim Omer]: I believe Type 2 is generally the fact that your body is not accepting that insulin. So it could be that the pancreas is producing enough insulin, but your sensitivity — I have read a lot of things again I won’t be quoted — but it’s the sensitivity to insulin that can go.

So for example, I’ve generally had a healthy diet for most of my life [23:30 unclear]. But only in the last few years did I start looking into the right Paleo diets. And funnily enough, that’s actually more associated with gym than it was with Diabetes, because that’s not really taught with my condition. But when I moved to the Paleo diet, I found my insulin sensitivity doubled.

So it wasn’t the fact that, because I had less carbohydrates therefore I needed less insulin, correct. That does happen. But the insulin that I tookI was twice as sensitive to it.

[Damien Blenkinsopp]: Right. So before your diet was what, specifically, and what’s the time range we’re talking about here? So for most of your life your diet has been…

[Tim Omer]: So the majority of my life — I reckon less the last three years — so the majority of my life, for example, I had bowls of cereal in the morning, I would have a sandwich for lunch and typically boiled potatoes or rice or pasta, a main carbohydrate with dinner. I’d also have quite significant portions as well. I used to eat quite a lot.

And once I educated myself about the Paleo diet and the effects of those processed carbohydrates: one, I discovered I wasn’t hungry all the time by cutting back on those processed carbs I was more satisfied with less portions; and two, the amount of insulin I required dropped, clearly, so I had less carbs, but also the insulin I took I was twice as sensitive. So my body’s reaction to that insulin actually changed.

[Damien Blenkinsopp]: Yeah. You’d have to lower your doses over time, and you’d take them less frequently.

[Tim Omer]: Yeah. And, again I won’t be quoted, but there’s a lot of research right now going on about the effects of high insulin in the body and what it actually causes. So there’s a lot of things going on right now, discovering the effects of high insulin. And obviously all the non-diabetics out there do have unnatural high levels of insulin because of the diets that they’re eating. So the effect of this high amount of insulin in their system is now starting to be connected to other things.

[Damien Blenkinsopp]: You’re saying, I guess, health risks?

[Tim Omer]: That is correct.

[Damien Blenkinsopp]: So high insulin is probably not a good thing. Okay.

[25:15] We touched on the long term risks of this. We talked more about the acute risks, but the long term risks for a diabetic if you’re not managing your blood sugar within the zone as much, what kind of things [happen]? So we just say like high insulin, which obviously you’d be doing if you’ve got more variation. You’re bouncing around, you’re going to have to use high doses of insulin, and if you’re not on a Paleo diet, as you pointed out.

What kind of long term risks are there for higher blood sugar in general? So if you’re constantly around 120-140, does that do some kind of damage over the longer term? Does it affect your longevity?

[Tim Omer]: In a way it definitely does. The overall effect is that it damages the capillaries, and one of the first effects you notice of that is your sight. So you’ll start to lose your sight, basically. And I’ve known one or two people who’ve had the high blood sugar levels. Funny enough actually, these people were both females because high blood sugar levels help you lose weight and the result of that you actually end up partially sighted.

In the last few years, they’ve now started taking photographs of Type 1 diabetics eyes, the retina at the back, to see that damage. And even me, as a 20 year diabetic with reasonable control, not perfect, I’ve got the signs of a slight bit of damage. But that’s expected.

So basically it’s one of the first things to hit will be your eyesight, and then, god, I don’t really have a list of complications in front of me but all sorts of nasty things happen with blood sugar levels, you really do not want to encounter. Let alone just the day to day effect that it must be having on you system.

You also, in high blood sugar [levels], your body will produce ketones, so it’s kind of like a poison. You’re literally poisoning yourself if you have very high blood sugar levels over time.

[Damien Blenkinsopp]: Right.

[26:51] Just to jump in on that note, because there is a lot of talk on the internet on ketoacidosis, which is extremely high ketones. Do you know what range that is?

[Tim Omer]: Again, it would adjust slightly based on the diabetic, but it’s generally taught that anything above around the range of 11, in UK numbers. Above that, you should be checking for ketones.

[Damien Blenkinsopp]: Right. So that’s millimolar, and easy one this time since the US actually uses millimolar as well. And that’s the same as the numbers I’ve given out in previous podcasts. So we all get that one. Eleven, so that’s pretty damn high.

And so is that what happens when you have very low blood sugar? What kind of mechanism is driving high ketones for a diabetic?

[Tim Omer]: High blood sugar levels.

[Damien Blenkinsopp]: Oh high blood sugar gives you high ketones. That’s interesting.

[Tim Omer]: Yeah. So it’s generally taught that if your blood sugars are above 11, then you should be checking for ketones in your urine. Reality is that doesn’t really happen quite often. But the advice is if you do discover ketones in your urine is immediately go to Accident and Emergency. And it’s that critical that your body is poisoning itself.

[Damien Blenkinsopp]: What actually is happening there? Is it the pH of your blood changes? Do you know what the ketoacidosis refers to?

I don’t know myself. I do know that there’s a difference between, because there’s a lot of discussion on the internet, so I just want to make it very clear. I’ll have ketones when fasting at seven, or eight, it goes about as high as that. I could bump it up a little bit more if I took some exogenous ketones, like beta-hydroxybutyrate or some other products that are out now. But these are not dangerous conditions, basically. We don’t get the same impact on our blood and the same negative mechanism.

So I’m completely safe within those. Because a lot of people on the internet start talking about this. You go into ketosis, and they say, “Oh my god, that’s really dangerous, that’s what happens to diabetes.” It’s not at all the same thing, and it really comes down to the difference in these ranges again. Right? So seven, eight millimolar is fine, and when you’re pushing up there to 11 that’s when it becomes problematic.

[Tim Omer]: Yeah. So the Diabetes UK website ketoacidosis DKA diabetic is basically a severe lack of insulin, and the body cannot use glucose for energy, and the body starts breaking down other body tissues as an alternative energy source. So I don’t really want to read that [29:03 unclear].

[Damien Blenkinsopp]: So there’s actually a very different mechanism there. There’s something going on where your body is breaking you down and it’s creating this situation where you can’t absorb glucose anymore. So that’s not like when we fast or something like that. Just to make it clear. Or when we go on a ketogenic diet, a high fat diet, that’s not at all the same mechanism.

[29:21]So you’ve done a Paleo diet for a while, for three years now, did you say?

[Tim Omer]: Kind of, yes. I was traveling for a year so it was a struggle to do it then, but I do my best to have kind of a low processed carbohydrate diet. So, should we say 60% Paleo 40% normal would be realistic percentages.

[Damien Blenkinsopp]: Right. Do you have a lot of protein? Because I know Paleo these days, there’s a lot of differences in what people are doing. So when you say Paleo, it’s mostly you’re eliminating the grains and…

[Tim Omer]: Yeah, the majority I’m eliminating [is] grains and also eliminating white potatoes; I’ve switched now to sweet potatoes. Those sort of things. I’m not so much into dairy, to be fair. But without eating cereal, the main source of dairy kind of disappeared with that as well. So again, I don’t eat Paleo to the point where I walk into a restaurant and freak out, but I eat it to the point where I try and keep my diet as healthy as possible. The difference in cereal especially really makes a difference in blood sugar once you get rid of cereals in your diet.

[Damien Blenkinsopp]: So when you say cereals, is that oats or what types of cereals?

[Tim Omer]: Any breakfast cereal basically. Anything that is breakfast cereal is general a kind of grain based. So Weetabix used to be mine, [they] always raved on about how it has a slow release. And the reality as a diabetic, especially with a CGM, you look at CGM, it’s not slow release.

[30:39][Damien Blenkinsopp]: Great. So let’s dive into continuous glucose monitoring. What motivated you to start that? Because I assume it one point you were using pin-prick devices, and when did you make the switch?

[Tim Omer]: So yeah, as we were saying earlier I had acquired an insulin pump before I went traveling. One because I wanted that tech and two because it meant I only had to travel with one type of insulin so it made my life easier. With an insulin pump there’s a lot of functionality there so you can really tailor the background basal release of insulin over 24 hours. But how can you guess how much insulin you’ll need over that period if you don’t have a way to see what your blood sugars are over a period like that?

So the kind of NHS taught way, I believe, is kind of like, you have these days where you try your best to be as normal as possible, or miss breakfast and see what your blood sugar is [31:28 unclear]. It’s really difficult to try and get a life that boring. I actually did those tests and they suggest taking a blood sugar every two hours. But again, a lot can happen in two hours. So I can go high to low in minutes, let alone two hours.

So to have a real time reading of your blood sugar to help you calibrate your insulin pump, well I would dare say it’s almost impossible without the CGM. And that’s what drove me to get the CGM device.

[Damien Blenkinsopp]: Yeah, so a normal diabetic would do this every two hours, so say eight times a day or something like that. And obviously it’s not getting as fine a picture. So you mentioned a lifestyle impact there. You said you kind of have to have a boring lifestyle, you’re not able to do things because you’re not aware of where your blood sugar is going to be.

[Tim Omer]: You have to discover what your background insulin has to be. You have to, obviously, not disturbing your body in any amount, so one not consuming food, two not being too active, three not being very stressed. And then you try and have those periods of time, generally over a morning, lunch, or evening, overnight, have those periods of time where you can see what is your body doing? Is your blood sugar slowly creeping up, slowly creeping down? It gives you an indication of how much insulin you need per hour of that period.

Now, the reality of life, when do you get those quiet periods? I’ve been trying to do that calibration for the last three or four years, and have not been able to get those quiet periods in my life. So to do it via that mechanism of checking every few hours over that quiet period is really, really difficult.

So a CGM, it can give you that more real time information. So yes, it’s still beneficial to fast, yes it’s still beneficial to have those quiet days, but at least I know what’s happening in every five minute intervals.

So in those two hours if I’m finger pricking, I have no idea if I suddenly crashed and rebounded; I don’t know. It’s only two data points, I have no idea what’s happened. Also, if I do that test every few hours and I’m a five, what does that mean? Does that mean I’m going up, does it mean I’m going down? It’s a point in time value, it’s not really an indication of what the trend is. You know, where is your body kind of directing itself?

[33:28][Damien Blenkinsopp]: You mentioned there’s a number of things that you’re kind of looking at there, which I guess are things that you’ve learned; you said stress, activity, and food are the main inputs, what you’re thinking about when you’re thinking whether it’s going up or down.

Are these the main inputs? What have you kind of discovered from using a CGM over time? What things maybe are you surprised about? What kind of things is your blood sugar going up and down with that you’ve learned over time?

[Tim Omer]: It’s allowed me to understand what’s happening, and that in itself, even if there’s a problem, is incredibly valuable. It’s allowed me to notice when issues are potentially going to happen. So the general CGM, if you start going up high quickly or if you hit a threshold, while you still have hit that threshold at least the system can alarm you.

So you can deal with the issue. So in some ways it’s empowering the patient. As we described earlier, having a day where I feel fine, check my blood sugar and suddenly discover I’m 15 or 200, and oh no. I want a system that can at least assist me and take away some of that mental stress of constantly having to guess what’s actually happening.

[Damien Blenkinsopp]: Right. And that decision making, is it like taking away some of that having to think about it, so you can get on with other stuff in your life?

[Tim Omer]: Well not from a CGM perspective. In the artificial pancreas, yes. And we can come to that more in a second, but from the CGM, all the CGM does is give me more information.

So again, it’s like actually with a pump. Great, you have a pump, your Diabetes is cured. No, I have a pump my Diabetes is now that much more complicated, but I am now more empowered to deal with it. The same with CGM. It doesn’t cure my diabetes, it gives me more information. And what is more stressful, and for some people it’s too stressful; they get rid of the CGM. So it doesn’t help me manage my Diabetes, it gives me the information to help me make better judgment calls.

[35:13][Damien Blenkinsopp]: So, we’ve spoken about the insulin pump. Is that something you attach on you and it automatically injects you, versus having to do injections? You just kind of pump it and it injects you? How does that work? What’s the difference there?

[Tim Omer]: So what we described earlier, there are two types of insulin: one that happens over a long period of 24 hours, and the instant action one when you eat. So what the insulin pump does is it has one type of insulin inside it, and that’s the rapid action insulin. It has a profile on the pump, so ideally it can deliver very minute levels of insulin over the course of a day. And that level of insulin I can tailor the pump how much it gives me over that period.

So for example, a lot of diabetics have a thing called the dawn phenomenon, which basically means in the morning they have very high blood sugar levels. Unless somehow you can wake yourself up when that happens and inject yourself, you can’t manage it. With an insulin pump, you can at least tailor your profile to say deliver more insulin in this morning period to accommodate for the fact I know I have naturally high blood sugar levels. So that’s kind of one of the real powerful things with the insulin pump.

Second, obviously as we said as well, it gives boluses, so shots of insulin at any point in time. Just the same as taking an injection, just take a lump of insulin with the food you are eating. That in itself doesn’t sound like much, but let’s say for example you for a barbecue. What happens in a barbecue? You normally eat over a period of two or three hours. As a diabetic I’d have to be injecting myself constantly over that period.

With the insulin pump I can control it through the pump or the remote I have for it, and basically set it to give me an insulin injection now, another injection later. So I can kind of give myself the insulin as I might require it, and my lifestyle doesn’t have to be so controlled. I can be a bit more relaxed.

[Damien Blenkinsopp]: A bit more flexible.

[Tim Omer]: Exactly.

[Damien Blenkinsopp]: First of all, this sounds like it’s an implant, the insulin pump is an implant.

[Tim Omer]: Yeah you are correct. The insulin pump is a small pager device that has the insulin. It has a tube that comes out of that and goes to a cannula, like a little device that just sort of sits in my stomach. It sounds worse than it actually is.

[Damien Blenkinsopp]: That did sound quite bad the way you said it.

[Tim Omer]: But a cannula is kind of like a little plastic tube that goes into your stomach and you fire that in by a little device that just sort of smacks the skin and puts it in for me. And that stays on for about three days until I rotate to another site.

[Damien Blenkinsopp]: Okay, so you actually push it in yourself into a different area; so it doesn’t go in very deep?

[Tim Omer]: Yeah, correct. So I rotate the area myself. I have a special device; most insulin pumps will have this, it’s like an insertative device. What typically happens is it kind of fires it in, and the reason for that is the actual impact of it hitting your skin is kind of more distracting than the effect of the needle going inside you.

[Damien Blenkinsopp]: Right.

[Tim Omer]: But once you take the needle out, the only thing that’s left is a hollow tube. That’s, I think the ones I use are about 8mm long that go into the skin.

[Damien Blenkinsopp]: And then you can remove those tubes afterward when you go to a new site?

[Tim Omer]: You literally just peel it off. It’s like one of those things, the first few weeks you freak out…

[Damien Blenkinsopp]: As with everything.

[Tim Omer]: You almost go mad, and then suddenly you just get used to it.

[Damien Blenkinsopp]: Yeah, that’s the same with most stuff. Okay cool.

[38:02] So in terms of changes you’ve actually made, how long have you been using a continuous glucose monitor now?

[Tim Omer]: Permanently, actually only for the last six months, really. So the way I sourced my original CGM, I bought it secondhand off eBay in the US. Because I used one the NHS lent me for a week. They got all my data; I went and showed it to them, and they said, “Oh, we can’t really make much information from this, we need you to use it for longer.” So I said great let me have it for longer. “No, we can’t afford it.”

[Damien Blenkinsopp]: So why did they give it — I guess it’s just politics, I assume — but why give it to you for a week if they can’t use it?

[Tim Omer]: It’s generally down to costs. Diabetics on insulin pumps — I actually do have these numbers — from March 2013 there’s a survey, and I believe it’s about 6% of diabetics have pumps.

Getting an insulin pump is very difficult, you really have to hit a decent criteria. And even if you hit that criteria and NICE guidelines in your favor, if they don’t have funding you don’t get one. So to get a insulin pump itself is a challenge. The number of patients on CGMs, again the criteria for that is even tighter. It’s so tight I actually don’t know anyone who is on an NHS funded CGM.

[Damien Blenkinsopp]: Okay, so it’s very rare to be on a CGM.

[Tim Omer]: Very, very rare to be on one funded by the NHS. So the majority of people self-fund it in the UK — it’s different in the US with health insurance. So, with the frustration of only having the CGM for one week, and it being useless, in the US a new model came out and everyone started trying to flog their old models on eBay. eBay [couldn’t] quite take listings down quickly enough, because they weren’t allowed to sell medical devices. So I managed to nab one of these CGM devices, called the Dexcom Seven Plus.

A few weeks later it was in the post, and this device turned up in front of me with these two horrible looking needles that looked like something out of hell raiser. Out of date but still sterile. And I had to stick them in my stomach. So the whole process to do that, I have to say, was traumatic beyond belief, having to stick something inside you that you have no real medical guidance on. But that just goes to show the power and how useful day-to-day data is that I’m willing to take that risk.

[Damien Blenkinsopp]: So to cover the horror story part; if we think about the current technology that’s available in the market, Dexcom and others, currently is it the same situation where you have something quite horrific you have to plug into you? Or is it a little bit getting more friendly than that?

[Tim Omer]: Now I’m using the Dexcom G4 system. The process to stick the sensor in you is the same. It looks, honestly, more scary than it is. The process of actually sticking it in you is more scary than it generally is. But I’m guessing the process just isn’t natural. You don’t really want to be sticking needles in you. And and also you have to push to plunge it down, so you feel the sensation of it hitting your skin and going inside you.

So it’s all kind of, one of those things your gear yourself up for, you do it, and then say, “I don’t understand what the fuss was.”

[Damien Blenkinsopp]: Right, it’s more psychological.

[Tim Omer]: It definitely is, it’s definitely psychological for sure.

[Damien Blenkinsopp]: How deep does it go?

[Tim Omer]: Oh, good question. I’d say about, it goes in at an angle unlike the insulin pump cannula. There’s a bit of metal that’s left in there, and it goes in about a centimeter and a half I’d say. I think.

[Damien Blenkinsopp]: Okay at an angle, so it’s not going all…

[Tim Omer]: That’s true, but the problem I have is that I don’t have enough fat on my body; I’m quite lean, that’s annoying. So I can notice it a bit more, and sometimes it comes a bit too close to my muscle fibers.

The system is generally designed to go into your stomach, where it is more fatty, but the reality is you move your stomach a lot, and it therefore lasts a less amount of times. So I actually stick it in my upper arm.

[Damien Blenkinsopp]: Okay. So you have a choice where you [can put it]; it’s not specifically built and will only work on one part of the body. You can plug it on your upper arm and it will [work].

[Tim Omer]: It’s medically signed off to be in your stomach, for children I believe it can go on a thumb cheek. But it does definitely work elsewhere, yes.

[Damien Blenkinsopp]: Alright, excellent. Good, we’re past the horror story.

[41:48] Are there other makers? How many of these are on the market right now? What’s the cost of this? How much did you buy it for and how much would you buy these things for, brand new?

[Tim Omer]: So the main two players are the Medtronic and Dexcom in the UK market. There is another company who produces something similar called the FreeStyle system I think. I can’t remember what it’s called, but it’s very popular right now in the Diabetes circle. It actually works by NFC, near field communication. So it doesn’t give real time readings, but you can tap it for readings. And that’s an implant as well.

[Damien Blenkinsopp]: Yeah, I was actually looking at that one recently. It seemed like there were a lot of complaints. This is just from my reading around. There were a lot of complaints about it, and I was wondering if they put it off the market. Because I was looking at buying one and it seemed like it wasn’t available currently. So I was wondering if they were figuring of looking at it, because it seemed like a lot of people were having problems with it getting broken, basically, and having to return it.

[Tim Omer]: Well I have a lot of suspicions about the system, because it doesn’t quite calibrate as well. I don’t really quite understand how you do not have to calibrate it to a patient, I don’t get that. Also, that system only works by being tapped; it’s not in real time. So, I have a lot of questions in my head why. Do they know something’s not as accurate, or I don’t know.

[Damien Blenkinsopp]: So when you say it’s not in real time, you have to tap it every time you want to take a reading.

[Tim Omer]: Right. Like an Oyster card that you tap in on the Tube. You have to tap that with the reader and it gives you a reading. So it’s not as if like the Dexcom and Medtronic devices I have a pager in my bag and every five minutes it gets a reading. With the Libre system you have to tap it. Now I did speak to someone actually the other day and they did tell me they had done a recall because there had been some issues. So I would say your thoughts are correct there.

So I use the Dexcom G4 system, and it’s shall I dare say renown, it’s been one of the best on the market. The downside, as with all of these things, is obviously the cost. And a CGM it’s damn expensive. I have numbers on my blog, but the cost of the G4 at the time I did the blog page for the first year it’s just under 5000 pounds, and then after that it’s just under 4000 pounds. This is a really expensive system to maintain.

[Damien Blenkinsopp]: And are they consumables? What’s the base cost versus…

[Tim Omer]: Definitely is consumable, that’s how these things works. So you have the sensor that actually goes in your arm, that’s in theory only supposed to last a week, and then you rip it off and put up another one. That sensor costs about 60 pounds.

You then have a transmitter, which is a plastic thing that clips on top of the sensor and that broadcasts the actual reading every five minutes. And that’s a consumable that lasts approximately six months, maybe up to a year if you’re lucky. And then finally you actually have the receiver itself, it looks like a mini smart phone, that actually gets the readings.

So when I came back from traveling I wanted to start using my old Seven Plus CGM and I discovered that the transmitter, the little device that sits on top, the batteries had died. And when I researched the cost, it was — again, I can’t give exact numbers here but it isn’t cheap — something like 600 to 500 pounds for this transmitter. Where the cost of the batteries inside are no more than a couple of pounds.

So, personally I felt quite insulted by that. I wanted to use a medical device that’s helped me use my readings and clearly the markup on this was ridiculous. So the first thing I did was research the process actually how to access those batteries, and found other people who had done similar. I managed to cut the transmitter open by slicing the top off and popping the batteries out myself. So approximately five pounds later I had a device that would have cost me around 600. So the potential for savings were massive.

So this year when I wanted to move onto the G4 system, I can’t afford 5000 for the first year. I do not have this cash knocking around. But the actual community of diabetics, a lot had happened since I’d been traveling in 2014 and they all started to develop a lot of different ideas of how to access that data. And there’s an offshoot for this, a guy called Stephen Black developed a device called xDrip, which is like a little Tic-Tac box. And in it it basically has two circuit boards; one is a radio device that picks up RF frequency from the transmitter, and the second circuit board is a Bluetooth device that then relays it to your mobile. So you can actually get rid of the receiver for the system by using this device on your mobile phone.

[Damien Blenkinsopp]: So you’re using your mobile phone and this device.

[Tim Omer]: Yeah so you’re using this xDrip device, which looks like a little Tic-Tac box, and the xDrip mobile app. So by using those I don’t need to get the receiver, which itself is I think about 800 pounds to a 1000, something like that. So that was one cost down.

So the final tackle was the new G4 transmitter. There are people everywhere binning these every other day that are perfectly good devices, just the battery needed [to be] changed. So a few kind people donated their transmitters to me and I managed to, again following some other people’s guidance, managed to hack open and replace the batteries.

So for a really low cost I managed to get a G4 system where the impact was only me buying the sensors. So my consumables had gone down to just the sensors I wear. And if you’re tactical with the sensors, you can actually get up to three weeks to four weeks out of them, not just one week.

[Damien Blenkinsopp]: Yeah, and that’s because one part of that was you were lucky that there were a lot of people selling these on eBay at the time, the original Dexcom.

[Tim Omer]: Yeah the original one I bought on eBay that has end of life, so I was lucky to get that. And I paid about 400 or 500 pounds for that. And then moving to G4 system — I had to move to that system because the old one was being retired — I managed to get it working by a donated transmitter that I replaced the battery, building my own receiver with the xDrip stuff, and then still buying the retail sensors but making them last up to four weeks rather than one week.

[Damien Blenkinsopp]: Wow. That’s a hell of a cost reduction there.

[Tim Omer]: Massive. So, as we said earlier, the cost of the first year is roughly 5000. I brought that down to just over 1000 in the first year. So the saving was 3,500. So that’s massive.

[Damien Blenkinsopp]: And so other people could repeat this.

[Tim Omer]: Yes, definitely. Other people are doing similar, so I wasn’t the first person to discover any of this, really. I was the first to, or one of the first, shall we say, to actually go into the CGM world with the attitude, I do not want to buy a manufactured system. I need to get this to a point where it’s affordable. Or what’s the point I’m not able to use it.

[47:59][Damien Blenkinsopp]: Right. Is this called the DIY community?

[Tim Omer]: Yeah. In a very small nutshell, and I’m not going to do it justice, but the community We’re Not Waiting is a collection of basically diabetics or diabetic assistance — family members or hackers — all helping to make better use of the technology. And there’s two core projects that have come out of that, and they all revolve around individuals who wanted to better access their data. And therefore things came out of that.

One of them is called Nightscout, and that basically was originated from some parents who wanted to monitor their children remotely. So for example, say you’ve got your child on the Dexcom, they carry a little device in their bag and they wish to stay over a friends house for the first time. As a parent, you’re freaking out. You’ve constantly monitored this child from a young age, you have no way of knowing how they are.

So what they found was a process to link the Dexcom receiver, the little pager device, to a mobile phone [and] download the reading every few minutes. And once the patient had control of those readings on their phone they could do what they wanted with them. So what they did is develop a system called Nightscout and basically published it to a webpage. So this then blossomed into a community, where a lot of people are contributing towards it, and benefiting.

Then later on to Stephen Black who developed the xDrip app, the little Tic-Tac box I said that picks up a signal and pops on your mobile phone. So this was a wider solution. And what that allowed was first to not have things cabled together that’s just unreliable. They allowed you to take control of data on your mobile phone. And again, what would you want to do with that? Some people then published it to their website.

Stephen then developed an application that actually sends it to a smartwatch. So right now I’m sitting here with my smartwatch on, a Sony smartwatch that cost about 80 pounds, and I have my real time blood sugars on there. So rather than having a device in my bag or my back pocket that’s a pain in the ass to get out and check, something that I should be checking pretty much every 10-15 minutes to see what’s going on I now have on my wrist.

Now the quality of life improvement by just taking the data already produced and putting it somewhere more accessible for me is massive. I can’t even begin to describe the quality of life you get from that. Just having better access to your data. And that’s what the community discovered was if they could free that CGM data, then the patients can be creative in how they wish to visualize and view it.

[Damien Blenkinsopp]: Yeah. And it really has a big impact on their flexibility, and just their quality of life.

[50:32] So you mentioned that these things have to be calibrated. I understand that they’re not as accurate as a pinprick device, if you take the standard pinprick and then the strip that you use to assess your blood sugar. Are these not as accurate, or they can be as accurate? What are you dealing with there?

[Tim Omer]: The official term is they’re not. They definitely can be if calibrated correctly. And what I mean by calibration is every 12 hours you do have to prick your finger and draw blood and basically tell the CGM system what the reading is. And then it understands approximately whereabouts the reading it’s receiving, I believe it’s like your intravenous fluids, it reads it from there.

[Damien Blenkinsopp]: Yeah, rather than directly blood, yeah.

[Tim Omer]: Rather than direct blood, correct. So it calibrates it to that.

[Damien Blenkinsopp]: What have you found when you were doing it? Are you pricking yourself once per day or twice, morning and evening?

[Tim Omer]: So generally I’m pricking myself, if the system is functioning and I’m comfortable with it, then it will be once every 12 hours. Sometimes it’s up to three or four times every 12 hours because it’s very easy to miscalibrate. So for example, if my blood sugars are suddenly moving very quickly and I calibrate then, then the system becomes quite unreliable. It still has a decent trend; I can still see if I’m going up and down, but the reading it gives me will be off by a fair amount.

[Damien Blenkinsopp]: Well how much would that be? Is that…

[Tim Omer]: It really could be anything. So in a good day it would be, say, out by 1 unit, and this is the UK measurements I’m going here, by one unit roughly. And if it’s within one unit that’s generally classified as pretty damn good. I’d be quite happy. But it can be up to four if it’s been miscalibrated.

[Damien Blenkinsopp]: So we’re talking about eight milligrams per deciliter, or something like that, could be. Yeah, your one unit.

[Tim Omer]: So for a lot of people that freaks them out, but the power of the CGM is not necessarily giving the most accurate reading, it’s more the power of seeing the trend. So I know if I’m going up or down, or something is changing.

[Damien Blenkinsopp]: Or if you’re going up really quickly.

[Tim Omer]: Exactly, yeah. So don’t get me wrong, having a well calibrated device is amazing, but having one that’s not as good calibrated but still a lot of value in the system even though the numbers are slightly out. Now I know with a G4 system, I believe I’m correct in saying that, even if the system tells you something and you wish to act on it, the strict medical guidance is you still have to prick your finger. Because the system is not really designed to be a complete replacement.

[Damien Blenkinsopp]: I get you. So how do you use it? You personally. You make changes based on the trend you’re seeing?

[Tim Omer]: You have to be careful as well because there’s such a thing as over calibrating. As I said, with all these things there’s no right or wrong way, really it’s kind of a fine line balance.

So I personally, before the artificial pancreas stuff that I’ve worked on, I used the CGM more as information gathering. So are my blood sugars good when I think they are? Are they going down or up quickly? Is there something not right here? Is my carbohydrate to insulin ratio for my meal correct? Am I spiking too much after a meal?

The CGM is just like this constant feed of data and the limitation here is not the system — the system is very good — it’s the patient, because I’m just human. I can’t process that much data and understand what’s going on and benefit from it, and then configure my insulin pump to react, if need be to changes.

I’ve now gone from a point where I’ve had very little data and a lot of guessing to now where I am overloaded with data. I’m overloaded with CGM readings, I’m overloaded with the insulin pump that has more features than I could possible use. I’m overloaded by logging all my carbohydrates, my boluses, my exercise. I’m constantly producing all this data, but as an individual it’s mostly wasted.

[Damien Blenkinsopp]: I think it’s always important to come back, what do you actually look at now? If you kind of take a step back, what are the things you actually do look at now in terms of when you’re looking at it?

Is it you’re just looking for when it starts to rise quickly or drop quickly? Are those the main things that you’re taking into account? If you pull out a week’s data, what are the things that you notice and you think are interesting?

[Tim Omer]: So to be honest the only stuff I generally use it for is real time information. So what am I like now, where am I going, am I headed up or down? I’ve recently eaten and I feel pretty misjudged so I need to take more insulin. So it’s all real time that I benefit.

Now, this, again we can go on a whole long conversation here on historical data, but typically we’re lazy. I’m lazy; I can’t be bothered to look at my historical data. I struggle with dealing with the real time stuff rather than historical. But this is again, this is not an issue myself, this is an issue with the lack of usability of the technology around me. There should be ways to analyze that data for me and give me suggestions. And there are things in the community being worked on to benefit from that.

[55:05][Damien Blenkinsopp]: Right, so I guess that would be like looking at your diet and stuff. So I know that we spoke before about some things that you’ve noticed over time with respect to time to glucose change, and things like that we were speaking about. So one of the things we discussed last time was that nuts, one of the things you learned is when you eat nuts.

[Tim Omer]: Yeah, so that’s an interesting one and another great example, actually, of the benefits of CGM. For a few weeks I was noticing I was having very high blood sugar levels over night, and I couldn’t quite understand why. And over time I slowly realized I was consuming nuts before going to bed on those days. And nuts are high in protein and have a very slow release; they’re generally quite good. But, for me anyway, apparently they cause a spike in my blood sugars.

[Damien Blenkinsopp]: How long did that take? Was it over a few hours, or more?

[Tim Omer]: I think it was about two hours, actually. Or maybe less, maybe about an hour and a half. But it was very noticeable. And once you found the pattern it was easy to produce and easy to fix, because I could give myself insulin, but with my pump with insulin being delivered over an extended amount of time. So it was ready to kind of cope with that spike later.

And again, that’s another benefit of the CGM, the fact that you are now aware of these things. If not, I’d have just been asleep. Or maybe those blood sugars would have fixed themselves, maybe they would’ve rebounded, and I’ve been woken up with a severe low. You just don’t know. But now I have access to that information and can see what’s going on.

[Damien Blenkinsopp]: Yeah, and you can decide not to eat nuts before you go to bed as well.

[Tim Omer]: Well yeah, that’s been a challenge, that one.

[Damien Blenkinsopp]: Oh yeah? It’s just a thing you like to do. Cool.

[56:30] Are there other types of proteins or other things you’ve discovered which you’ve actually changed or you’ve had to think about managing more that you’ve learned from the CGM?

[Tim Omer]: Definitely cutting out breakfast. Cereals for breakfast, that’s definitely quite an easy one. Noticing the spike with coffee; I do like to drink a coffee a day.

[Damien Blenkinsopp]: That’s interesting. Could that just be black coffee, or is it…

[Tim Omer]: I generally have mine quite milky, because I’m quite a wuss. So obviously it’s kind of carb based as well as caffeine. The best way I can describe it is like wearing glasses for the first time. So you’re partially sighted, you know the world’s around you, you know things are going on around you, but you can’t see. You put glasses on and suddenly it’s all clear. Now the negative side of that is you are suddenly overwhelmed by everything.

So there’s a lot more stuff that CGM can help me with that I can’t possibly process. And that kind of comes on to the artificial pancreas stuff that I’ve been working on, which actually uses this day to day to help manage my medication.

So, earlier we spoke about Nightscout, and that’s one project in the community. There’s another one called OpenAPS, an open artificial pancreas system. Again, a bit of story behind that. A couple met, Diana and — oh dear, my mind’s gone blank. I apologize, I should know this. I was only talking to them last night.

[Damien Blenkinsopp]: Don’t worry, we’ll look this up afterward and everything will go into the show notes. So for everyone at home, the post Tim mentioned on his website and all the links to that kind of stuff and everything else will be at thequantifiedbody.net/CGM and you’ll have the links to everything we mentioned. We’ll look them up afterward if we need to.

[Tim Omer]: Thank you. I can definitely say now I’m not doing the community justice or I’ll be talking here for a lot more than an hour. So anyway, this couple built a system. They captured CGM data and used it to give themselves a louder alarm, because their alarms weren’t loud enough. So at times Diana would sleep through the night and not hear the alarm. And then they captured more data and they suddenly realized, actually with all of this data we can do a simple algorithm.

In extremely simple terms, it basically says I can see my blood sugars are starting to go up [from] CGM data. I know how much insulin I’ve given myself by capturing treatments as you do as a diabetic. Therefore, I clearly don’t have enough insulin in my system. Therefore, let’s increase the background insulin on the pump.

So that’s system basically, it’s called a closed-loop system. So it takes the readings in real time, it processes the information that it already knows about the patient — the stuff I have to log as a diabetic — and it does slight adjustments to my insulin pump. The algorithm is very simple and that’s an extremely simple description I’ve just given you.

But when I started working with the xDrip stuff and getting the CGM on my phone, I suddenly realized how now I own this data, what do I want to do with it? Well, I want to integrate this OpenAPS code and import it onto a mobile phone. And right now it just runs on [59:10 unclear]. So there’s a bit of a cable system, where it’s all cabled together.

So what I have done is basically got a mobile app that now takes my carbohydrate consumption I have to log anyway, it takes my boluses, insulin I take, that’s being logged. It has a wizard in there that helps me calculate how much insulin I need based on my sensitivity and what I’ve calibrated for it. The app still requires a lot of calibration. The app knows how my insulin pump is configured.

So what it can do, it can see the real time readings of blood sugars, and go hang on. I know what Tim’s consumed, I know how much insulin his pump is delivering, I can see his blood sugars are going high, for example. Let’s give himself a little more insulin to prevent that. And that’s a closed-loop system.

So now I’m not just sitting here producing data that I struggle to analyze, I’m now putting that data to work. My insulin pump itself is Bluetooth. So technically there’s no reason why my mobile phone and my insulin pump cannot talk to each other. It’s just the manufactures and regulation bodies that don’t want it to happen.

Technically it can. So, right now I have a system called an open-loop. So what happens every 15 minutes it takes all this information. If it thinks I should adjust my insulin pump, on my Android wear watch it pops up with a message and says, “Tim make this adjustment to your pump, based on the prediction I’ve given.”

[Damien Blenkinsopp]: Giving you information for you to decide.

[Tim Omer]: So open-loop is it notify me to action. So I’ve been notified on my phone, I acknowledge it, and I manually adjust my pump. That’s open-loop.

[Damien Blenkinsopp]: That still looks great, because it takes a lot of your decision making out of it.

[Tim Omer]: It’s surprisingly, actually, quite powerful. And again, like we said, it’s that mental stress. Now I’m not constantly looking at my CGM and panicking on what to do to prevent something.

And again, I’m human; I’m going to overreact. I constantly do things wrong. I don’t know how well educated I am. Now, the system suggests — so I just wait for the system to give me a suggestion and I act on that. I’m now working with someone to help me hack the Bluetooth interface on the pump. Once that’s done, I’ll have a thing called a closed-loop system.

So not only will it do these calculations every five minutes, because that’s how frequent the data can be, it will action at every five minutes. And always doing these very slight adjustments every five minutes. It’s not going to give me a load of medication at once, or removing medication. With the insulin pump, I could turn it off potentially, so naturally let my blood sugars come high. I’m just doing very tiny adjustments every five minutes.

[Damien Blenkinsopp]: Right. And that way you reduce a lot of the risk as well. Because you’re making such minor adjustments even if it’s wrong, it’s not going to be really out of line.

[Tim Omer]: Absolutely correct.

[Damien Blenkinsopp]: Yeah. It’s better than your judgment. Will you feel more confident about this, or as confident as your own judgment?

[Tim Omer]: Well I’ve already discovered that I have less rebounds. If I don’t fight with the system and I let it [be], one it kind of triggers itself before I realize a problem, because it’s obviously checking my data constantly. So I get an early opportunity now to give myself more insulin or less insulin, depending where I’m going. Also the system will say, hang on, I’ve delivered quite a lot of insulin for you now, I’m actually going to stop. And if I acknowledge that and accept it, I am less likely to overdose myself.

So I find that I still go high and low, this will never go away. That’s a fact of life with Diabetes. But I find that the system can better manage and make decisions rather than me being emotional and overreact. And even though, as I said, the system’s not completely automated, even now if my sensor dies on me and I have a gap without, I’m a bit lost. I’ve gotten used to this system taking this worry away from me.

Now the interesting thing is there are 16 people, I believe, to date who are actually using this system fully closed. They’re using slightly different equipment than me. So they have a slightly more technical set-up, shall we say. They’re using Raspberry Pi, it’s using some older hardware. My device is more of a plug-and-play kind of install and it works. With a lot of calibration, that is.

[Damien Blenkinsopp]: So they’re doing closed already.

[Tim Omer]: They’re doing closed, yeah.

[Damien Blenkinsopp]: So it’s hands-off completely. They can monitor it, they can check it, but it’s just actually pumping itself. It’s taking care of it.

[Tim Omer]: Right. So they walk around with a little bum bag on, basically, with all the Raspberry Pi with bits in there. So it’s not an elegant solution, shall we say, but it’s very useable. And even parents are using this on their children. So this is kind of, you can see the power behind such a thing. People are very enthusiastic.

[1:03:23] The interesting risks my device brings, is mine is an Android app. So once you install the app and set all the settings — again, most of the settings as a diabetic you should know because it’s all typical stuff you have to understand. And if you have the right equipment, insulin pump and the CGM data, it’s a very easy system to set up.

And that introduces a lot of potential dangers as well. Because now you’re not forcing the system to be only, you have to be highly technical to implement it. I’m kind of bringing that barrier down. What does that mean? It can potentially be a high risk situation. So I’ve got to be very aware of what code I release, and who accesses it, and how we manage that barrier.

You know, the typical situation, you get a parent whose child is diagnosed: “Oh no, this is terrible. Oh look, there’s an app out there that will fix it.” And with pure ignorance just install it thinking it will cure the Diabetes. Again, my app makes my life easier, but it does make it that much more complicated still. Because I have to make sure the app is correctly configured.

[Damien Blenkinsopp]: Yeah, because you’re going to rely on the technology. So if the technology has a bug in it, if the app has a bug in it and maybe just turns up in a specific situation, like once every seven days or it doesn’t get spotted, then there’s that kind of risk there for someone who’s, like you say, not technically savvy to not see it. Or it just kind of goes unseen.

[1:04:36] Does this tie in with, I know you have the #wearenotwaiting?

[Tim Omer]: Yeah, and that is the community. So the community I utilize in that #wearenotwaiting, and well the name explains itself. It’s basically the frustration of diabetics in the lack of access to their data, lack of capability between devices, and the lack of progress.

And one real frustrating things as a diabetic is that you constantly have so called experts who are not diabetics making decisions for you on what equipment you get, and how you should look after yourself. And unless you live with the condition, whether you’re a good or bad expert, you’re still the expert. So, the community has kind of taken it upon themselves to kind of produce these better solutions to improve the quality of life for people.

Again, there’s loads more information on that on my blog and where the hashtag came from and the rally cry between people saying we’ve had enough. The technology is already here, and we’re already producing the data. If I can sit on my sofa and control my life from my phone, why the hell can it not talk to my insulin pump. This is not a technology problem.

[Damien Blenkinsopp]: Yes, it seems like it’s more of a regulation and things that are medical to market and managing that risk. That’s kind of the thing, it seems, that’s really holding things back.

[01:05:46] So, just for people at home, this has also been called a bionic pancreas as well as an artificial pancreas. The goal is really to just replace that body part which isn’t working that well in diabetics, right? The insulin pump, and just completely replacing it.

[Tim Omer]: That is correct, in simple terms, yes. As with all of these things to configure and manage it is a bit more complicated, but all it’s doing is monitoring that data and helping me make decisions. And that’s helped me in real time.

There are still a lot of benefits of data mining that data I capture and giving adjustments to my profile and how I treat myself. So that whole world is there to be discovered still. And there’s an open source company called Tidepool who are doing great researching in that area and publishing a platform where [you] can number crunch.

But the artificial pancreas stuff is all about giving me some kind of benefits right now. So for example, I can look at my artificial pancreas app, I can see even though I’m having a late lunch today that my blood sugars haven’t started dropping. And if it did start dropping it would tell me, and therefore allow me the opportunity to adjust my pump. So my blood sugars don’t go too low.

[Damien Blenkinsopp]: So this is pretty cool stuff, because it’s one of the first projects where it’s actually replacing a body part with this closed-loop system, as you call it. So it can just start operating. Kind of like if you took something out of the Terminator and put in your body, if you use a science fiction analogy.

I think it’s also interesting. A lot of people have probably see the press around Theranos, the big blood testing company in the US recently. That company was actually based on a patent for something similar to what you’re talking about, but for drugs. In terms of it would automatically pump drugs into patients of all different types based on readings taken from something like a continuous monitor of their blood.

And so you can see many, many applications with you guys leading the charge, because Diabetes is common and it’s a very specific blood monitoring and insulin pumping situation. But you can see how this could eventually apply to many different areas, whether it be oxidative stress and pumping glutathione into your body. Or other adjustments to optimize your biology. So I think it’s really interesting.

[01:07:47] Just wanted to make sure we do cover the legal regulatory system a bit better.

So currently the FDA and all of this is saying you’re not allowed to do this. So of course you’re not allowed to sell these devices. Is it fine for you to do this at home? Obviously there’s the risks everyone should be aware of, because if you’re not technically savvy this is DIY project at the moment. It’s not like it’s 100% signed off and stuff and it hasn’t gone through compliance testing and trials to make sure it’s 100% safe.

So how would you put it? The kind of situation for people at home if they’re interested in learning more about this, and what they should be aware of in terms of the risks and legal situation.

[Tim Omer]: So one thing to really highlight regarding that is with all the devices you can get right now, every risk here is delivering medication. That’s the real risk. If I misconfigure my insulin pump, I could still kill myself. So the risk always exists; there’s no solution on the market that removes complete risk. So you’ve always got to be aware that whatever you’re utilizing has to be utilized correctly, or there’s the potential for serious harm.

And there’s already commercial products out there that have bugs, and have had issues with them come up. So it comes down to, while the open source stuff is obviously not therefore going through the same regulations doesn’t mean the stuff that has gone through regulations is therefore perfect. You always have to be aware.

Now clearly with a community producing this open source, the main reason for that is to try and get it out there sooner. If I tried to commercialize a product I would basically be looking at X number of years in research and development. And rightly so; I’m not saying that’s wrong, but I want a better quality of life, and I kind of want it now, and I have the data and systems in front of me.

So it’s up to me if I wish to take code that’s available out there, that’s been published, and I wish to utilize it myself in something that gives me a better quality of life, that’s my decision. And that’s what I want to do, and it works for me.

Now, that’s the question everyone else needs to ask. There is a lot of code out there and a lot of information. Whether it works for you, whether you feel comfortable and understand it is a decision and a path you need to follow yourselves.

It’s not that we all hate the regulatory bodies or the actual manufactures themselves; they have a difficult job. But the reality is, the cost of managing long-term conditions has not gone down. The NHS already acknowledges that. There’s a wealth of individuals out there with a lot of knowledge and are now utilizing that in a technical way. How do we embrace that community and somehow introduce it into our kind of care pathways? No one knows.

We’re at the point now where the regulatory processes, they’re designed for a world 100 years ago. They weren’t designed for a world where in two months I can develop an artificial pancreas out of my app on my mobile. That never was possible; it now is.

So what do we do? Do we just ignore it and try to brush it to one side, or do we have to learn and try and discover how we cope with that? So I don’t have answers for that; no one does. And that’s one of the things that makes this so exciting and interesting. How do we utilize this?

And a lot of talks I give are kind of like, this is happening, it’s going to continue to happen. No one knows the answer, but let’s all start talking now and how do we control the risks. And there always will be risks.

So if people out there are interested, there’s a lot of information out there. If you’ve got the enthusiasm you’ll find it. My blog has a lot of details on where to go to get more data. Be aware of what you’re trying to do. It’s very easy to make a mistake, and anything you do if you’re messing around with your health the risks can be quite severe.

[Damien Blenkinsopp]: Great, great. Thank you, that’s great.

I think also just the fact that the movement exists is going to force companies to step up and move along, otherwise they will get left behind. So whatever happens in that situation you’re providing this positive pressure on innovation.

[Tim Omer]: Yeah, definitely. There’s already a believe that has taken effect. Especially Dexcom, they released some equipment recently and it’s believed it was fast-tracked through the FDA process more because of the community advancing the head of Dexcom, so therefore there’s no commercial product. So apparently it has already taken effect out there.

[01:11:51] And also, one other thing I do want to say, is a lot of the closed-loop trials right now, so a lot of the artificial pancreas stuff, is happening behind closed doors. They’re all trying to work on systems that are more 100%. Systems that kind of do a better job, more automated, manage more, and not only deliver insulin but also the glucagon, which can push my blood sugars up if need be. They are very complicated systems. And as a diabetic, if I can have something that can give me just a 10% improvement on my life, I’ll take it now.

[Damien Blenkinsopp]: Right. So you’re kind of saying that they’ve tried to push for the perfect solution. Whereas something that’s half as good is still going to improve everyone’s lives by a measure.

I guess it could be the model because when you’re trying to get FDA stuff, when you’re trying to run trials it’s a bit expense. So I guess they’ve got to think, okay we want to make a big stab at this. We want to make sure it’s a really good product if we’re going to invest all this money and getting it signed off with the FDA. So it could be, basically, the regulatory process that drives that.

[Tim Omer]: It most definitely can be. And it’s interesting, because I speak to some professionals in that area regarding the work, and you can see they kind of fight internally between the medically trained side of them, and then their inquisitive interest side. And one bit is kind of offended that you’re even considering doing stuff, and the other side is respectful of the fact that you’re trying to help yourself as patients. You know, reduce your burden on yourself and the health.

The NHS we have to rely on, and one of the questions I remember getting asked before was, “How do you know this is helping your diabetes if you don’t have the statistics?” And my reply was, “I feel more empowered as a patient.” And that in itself, if that’s what we’re getting from this, feeling more empowered, that’s quite a big achievement.

[Damien Blenkinsopp]: I think it also goes, as you were saying, technology is moving so fast now, and it’s moving faster and faster it’s going to be increasingly difficult for organizations. They’ll have to innovate in their models and decision making models –and governments as well, in terms of their funding and everything — in order to keep with the times as technology is going to be enabling people, enabling these kind of things, which is really cool.

But I think it’s going to challenge these organizations to change the way they work, because I think decisions are made really at a lag; it takes years to make decisions and move things into the market. And I guess that’s where frustration is coming for you guys, wanting to just go with the technology and what’s possible versus waiting for those processes to take place.

[Tim Omer]: Definitely.

According to the NHS I’m statistically a good diabetic, and for the NHS paperwork perspective that’s great. From a quality of life and how long I’m going to live, I’m not as good as I possibly can be. So, to say I’m a good diabetic is fine, but don’t prevent me from making my quality of life better. I want to go beyond this disability and I want to do the best I can. Because at the end of the day, it’s going to be my life that’s going to suffer from this.

So the ability to be empowered so I can help that is a significant mental win.

[Damien Blenkinsopp]: Excellent. I think these are exciting times. With all the health tech that’s coming up, this is going to more the case where we have these options to kind of push forward ourselves if we want to solve things and make our lives better. So there’s going to be a lot of things like this coming up in the future.

[01:14:52] Okay, last question for you. We ask this question of everyone. What would be your number one recommendation, based on your personal experience using these kind of things in terms of using data to make better decisions about your health, and to others if they just want to use data. What would you suggest is the number on recommendation for this?

[Tim Omer]: So it’s all and good my phone telling me something, and then me just reacting on it. If I don’t understand why it’s telling me that, then I’m just going down a dangerous path. Now I need to have an understanding why things are being recommended. Why trends have come up that were not there before.

Having systems like this doesn’t mean your diabetes goes away, it means you get a better understanding of it. So if you don’t try and understand that information, that’s not good.

[Damien Blenkinsopp]: Excellent point. Thank you very much for that.

Thank you so much for your time, I appreciate it. We went over a little bit longer and everything. I think this is relevant to a lot of different areas, and what you guys is doing is kind of at the forefront, just because of your specific situation. So it’s interesting to everyone.

[Tim Omer]: It’s also interesting [01:15:48 unclear] actually. It’s also going into other areas. So I have a guy who’s trying to build a deaf community based on hearing aids, basically: a hearing aid community. And they’re trying to raise the same hashtag now, we’re not waiting, and develop their own open source hearing aid because the costs are so high. So it’s contagious.

[Damien Blenkinsopp]: Yeah. It’s going to be exciting times, I think. The next five, ten years. The technologies are getting simpler, right? In terms of trying to use them. Because as I understand, you’re not even a developer. I think I read that somewhere.

[Tim Omer]: No. I’m an IT professional, but programming is a hobby. And I kind of get the gist of it, but no I’m not a developer. And now I’m producing an app that gives medical suggestions. That’s pretty nuts. The barrier of entry is so low. And the tech, my insulin pump is like seven years old, the technology.

[Damien Blenkinsopp]: Yeah, it’s pretty amazing.

[Tim Omer]: That’s insane. Would you walk around with a seven year old laptop? So the technology isn’t new, it’s not expensive to produce. It’s just the markups.

[Damien Blenkinsopp]: Really appreciate having you on the podcast, it’s been a great episode. You’ve got this hands-on experience and you’re pushing things forward so it’s a really interesting perspective on a DIY approach to making things better for yourself and using the tech out there. So thanks a lot for coming in today.

[Tim Omer]: It’s been a pleasure. To everyone out there, there’s a big community out there and they’re really doing a lot of work. I only touched on very tiny amount of it. So if you’re interested, get out there and have a look around; there’s a lot of really helpful people.

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Part 3 in our series of Fasting Self-Experiments. In this longer 10 day water fast I tracked results with a broad set of biomarkers (ketones, glucose, weight, hormones and cognitive performance panels).

This is a long post – if that scares you, jump directly to what you’re looking for:

  1. Why Do a 10 Day Water Fast? (The health benefits that we’re optimizing for)
  2. 10 Day Water Fast Results (Weight, metabolism, cognitive performance, hormones)
  3. 10 Day Water Fast Experience (Anecdotal thoughts, symptoms, and my post-fast rookie mistake)
  4. The Tracking (Details on all the biomarkers tracked and lab tests used)
  5. Tools & Tactics (Details on the exact fasting protocol I used, and some supplements taken)

Video Recorded on Day 10 of Fast Just Before Refeed

Note: I was yet to realize the post-fast rookie mistake I was making!

I’ve been fasting once per month for 5 days since my first water fast experiment in June 2015. If you are new to fasting, you can get all the why and how basic details in that post.

The results from my 5 day fast cycles have been so positive that I couldn’t help but wonder if More is Better when it comes to fasting.

This led me to ask:

“Will I benefit from a 10 day fast programmed into my life once per quarter or twice per year?”

To get an answer to that I broke that down into the following questions I was going to try to answer with this first 10 day fast:

  1. Can I remain productive during a 10 day fast?
    (10 days is a big chunk of time to strike off from work and life – far too big for my taste! Let’s be sure I’m not throwing away the equivalent of 40 productive days a year with this habit)

    • Would my mental performance suffer? Perhaps leading subtly to worse decisions, or perhaps just slower thinking?
    • Would my energy levels remain the same or decrease? Would there be a change in how many hours I could comfortably work per day?
    • How about concentration, focus and drive?
  2. Is “10 day fasting” every quarter sustainable? Specifically, where I’m doing monthly cycles of 5 day fasts in between?
    • Would I double the weight loss of a 5 day fast? And thus make it difficult to recover the weight within the following month? (The question here: Does weight loss follow a linear path based on number of days fasted?)
    • Would a 10 day water fast be as easy, psychologically and physiologically, as the 5 day water fasts? Or would I hate it? (Nothing we hate is going to get done repeatedly)
    • Is there any downside impact on “adrenal health” or cortisol regulation from fasting? (this is a question I’ve been attempting to answer since I started long duration fasting)

itunes quantified body

To try to answer these questions I tracked cognitive performance, hormones, metabolism and weight throughout the fast.

I also committed to following a normal rhythm of life and work during the fast this time. I would run life as usual, and let the chips fall where they may – I would see if the fast got in the way.

(Note: Please do not take this as advice to do this at home yourself – I’m not a doctor, and would be extremely upset if you hurt yourself – please be cautious with fasting.)

The outcome we’ll get to in the results in a second, but but first “the Why”…

Why Do a 10 Day Fast?

We’ve covered the benefits and whys of fasting well in previous episodes, however, as a quick reminder here’s the list:

  • Anti-Cancer: Leveraging the metabolic theory of cancer and Dr. Thomas Seyfried’s work, fasting may be an effective tactic to reduce our future risk of cancer.
  • Immune System Effectiveness: Cyclic fasting has been shown to regenerate immune system cells which deteriorate ‘naturally’ as we age or via environmental or other insults. Thus, it may reduce or stave off some of this natural deterioration and keep us healthier.
  • A Stronger Body: Lean body mass gains including bone density increase and muscle mass increase have also been tracked in studies and myself.
  • Body Fat Removal: Fasting or cycles of fasting can be a useful tactic for removing unwanted excess body fat.

The 10 Day Water Fast Results

Metabolism on 10 Day Fast Looks Similar to 5 Day Fast

In 5 day fasts I consistently see glucose drop to between 50 and 60 mg/dL and ketones rise to between 5 and 7 mmol/L. In the additional 5 days it seems you shouldn’t expect any big change. My numbers came back largely the same.

My ‘switch time’ from glucose to ketone metabolism continues to edge forward to happen slightly earlier with each fast I do. This time just past the 48 hour mark the switch took place – my blood ketones jumped up and glucose dropped down to their fasting equilibrium levels. My metabolism had switched to ketone burning.

10 day waterfast ketones glucose
A few interesting points:

  • There was a slight glucose upwards blip on days 6 and 7 where it rose back up to between 60 and 70 mg/dL. This was most likely caused by the sleep disruption I experienced from day 5 (see sleep details). Low quality sleep tends to impair glucose regulation – thus higher (but still low) glucose.
  • On day 7 and 9 I got several “HI” errors for my ketone readings, meaning that my ketones were over 8 mmol/L, the upper limit of the ketone meter’s range.
  • For the first 3 days post fast, days 10 to 13, my ketones were still spiking high in the evenings and quite erratic – this was most likely an anomaly this time around due to my Post-Fast Rookie Mistake.

Despite the glucose uptick on day 5, I stayed well within the therapeutic range to provide anti-cancer benefits outlined by Dr Thomas Seyfried (see explanation via my interview with him in Episode 16).

So long as you remain under a Glucose Ketone Index of 1, you are assumed to be within the therapeutic range as per chart below where I’m shown to have had a complete 8 days of therapeutic anti-cancer action.
10 day water fast glucose ketone index

Weight Loss: How Much & How Long to Gain it Back?

Over the 10 days I lost a total of 5kg (ll lbs) of weight. The weight loss was at a consistent daily rate as usual, except for Days 8 and 9 where it stalled at a weight loss plateau, before a further drop on the morning of the last day.

I regained all the lost weight by the 18th day after the end of the fast – and this was despite some digestion re-startup issues for the first 3 days post fast (see the post-fast rookie mistake for the details). So the weight was really recovered via 15 days of normal eating.

Weight Loss 10 Day Water Fast

Testosterone on a Fast: Big Drop & Libido Changes

It makes sense that you shouldn’t expect to be on top of your ‘libido’ game while fasting. When food is scarce we should have evolutionarily had more important things on our mind – like finding food to survive.

This was certainly part of my experience. The longer the fast, the less interest I had in women or sex. By day 5 my testosterone levels (DUTCH Test – see in labs) had dropped below the 20 to 40 year old male reference range.

A couple of studies I found corroborated this with testosterone dropping significantly during fasts (and then rebounding strongly with refeeding)1,2.

The Takeaway: NOT a good idea to fast on honeymoons or dates. The day after ending the fast – great idea.

Testosterone: 10 day fast

Is it OK to Fast with Adrenal Fatigue?

In previous fasting episodes I’ve noted that I’m working on “low free cortisol” levels that I’ve been tracking for a couple of years. A situation that I expect, based on symptoms I now understand dates back to as much as 10 years ago.

One of my concerns with repeated fasting (considered a stressor) was that it may not necessarily help with this situation – when you look at it through the lens of “Adrenal Fatigue”.

Specifically, I was referring to the idea that Low Free Cortisol = “Adrenal Fatigue”. Thus adding more stress could exacerbate the issue, reasoning that the adrenal glands are already overstretched in a normal everyday scenario without that added stressor.

In this fast I learned that there’s less reason for concern than I’d initially considered. You need a bit of background to understand why.

Historically, people from the functional medicine realm have referred to “adrenal fatigue” as a state of fatigue of the adrenal glands, whereby you typically have low energy in the afternoons. This can happen to me at times. It is documented and diagnosed via 4-point free cortisol salivary tests like the one from Biohealth that I’ve done previously (See the results from previous adrenal labs in this episode).

However that name doesn’t have a very accurate definition or explanation. The term is used quite vaguely for the most part. We can’t scan an adrenal gland and see it in a withered state for example. We don’t have a specific test that can show the state of ‘adrenal gland fatigue’ that ties it back to the adrenal gland itself.

So a new term that is surfacing for the situation of low free cortisol is “cortisol dysregulation” as a result. It provides at least a ‘less wrong’ definition. Cortisol isn’t normal, it’s lower than it should be – and thus is driving some fatigue symptoms. It’s dysregulated. Another term you may have heard is HPA Axis dysregulation.

The DUTCH test I used to track my hormones is useful where it comes to investigating and better understanding cortisol metabolism as it looks at both free and metabolized cortisol. Metabolized cortisol is a proxy for total cortisol output. The traditional salivary tests used look only at free cortisol levels. Thus, DUTCH enables you to assess whether your total levels of cortisol are low (the adrenal output is lower, or if it’s just free cortisol that is low, and total cortisol is normal).

As you can see below my total cortisol (metabolized cortisol) is right in the middle of the normal reference range.

Metabolized Cortisol Levels (Baseline and Fasted)

10 Day Fast Total Cortisol (Metabolized Cortisol)

So in my case, it turns out that I have above average metabolized cortisol levels – so in fact total cortisol output is well within the normal range. It’s just my free cortisol levels that continue to come back below the reference range (now cross-checked with two labs, DUTCH test + Biohealth #201).

I don’t have reduced adrenal output, I have normal adrenal output – which would fit the old definition “adrenal fatigue”.

That’s good news.

Nonetheless, the low free cortisol has to be troubleshot. The most likely explanation behind this is that I’ve been subjected to a long term stressor and my body has compensated to lower free cortisol levels. That maps to other information – that underlying stress, is most likely high ongoing inflammation levels that I have documented over several years now.

24 Hour Free Cortisol Levels (Baseline and Fasted)

10 day fast 24hr free cortisol

The Takeaway: Rather than just relying on propping up my adrenals with adaptogens, it’s pretty clear that the end game is to continue to explore and resolve all causes of stress. Inflammation is my obvious first target, although it’s another reminder to keep up my lifestyle stress management practices (adaptogens, meditation, circadian rhythm and sleep).

Note: For those who like to dig into the data – here’s an explanation of the cortisol results from the DUTCH test.

Did Mental Performance Keep Up During the Fast?

Although I’ve always “felt productive” when fasting, I wasn’t as sure that my mental performance was the same. This time round I planned to try to capture this information properly. Unfortunately the results weren’t very clear.

I used Quantified Mind, the tool we covered in Episode 33 to track my cognitive performance in terms of Working Memory and Attention Control.

The main issue I was advised to eliminate by Yoni Donner, founder of Quantified Mind was the practice effect. As we perform any mental test repeatedly we get better – to understand if a fast was impacting me cognitively, I needed to try to eliminate that. To do this I used the same test repeatedly during the few months before the fast, due to travel this wasn’t as consistent as I would have liked. The idea is that eventually you peak out, and any practice based improvements will have dried up or be minimal.

10 Day Fast Mental Performance

As you can see in the data above it looks like there were some pretty strong practice effects taking place throughout and after the fast. The fasting period is shaded out in blue.

As a result, I’ll be continuing to use the same test panel in future fasts, and in between, to see if I can separate these out. With continued repetition I should be able to isolate any fasting effects.

The 10-Day Fast Experience

With repeated cycles of fasting I have become a lot more comfortable with “how it feels” – both body and mind do feel different on the water fast – the first experience I was cautious due to this – not knowing if I had new limitations that I shouldn’t cross.

Now that I have got used to fasting, I basically run life as usual. I don’t restrict my activity level or my schedule, or need to plan for it. In this fast of course I committed to making this a goal in itself to understand if fasting limits me.

As a result, during the 10 day fast, I was out meeting friends, business contacts – and even went on a date to an art exhibition.

Nonetheless there are things to note…

Physical Weakness

I experienced less of the feeling of physical weakness than in previous fasts – a heaviness or lack of refined motor control of the arms and legs.

I tested this a bit further on day 2 with one set of 55 push ups (my current 1 set max). This didn’t feel much different to doing it in a non-fasted state.

During this fast as I was going about my days I had times when I actually felt ‘physically strong’ and was naturally walking around at a rapid pace. This was more so on the last 5 days of the fast, so that difference may simply be related to the fast being longer. In many ways the last 10 days were more physically comfortable than the first 5 days.

Sleep – My Next Challenge

On most of my fasts the biggest downside is sleep disruption. After a few days on the fast I tend to start to have interrupted sleep.

This fast was no exception. From day 5 I began to get night wakings as early as a couple of hours after going to sleep. After some of these I wouldn’t be able to get back to sleep for hours. The exception was the last night – on day 10 – I had perfect sleep, longer duration, and deeper than usual judging by the drowsy feeling combined with how refreshed I felt in the morning.

Sleep disruption and night wakings are shown to impair glucose metabolism. So it’s the likely cause of the slight rise in glucose I experienced on day 5 and 6 also.

For future fasts I’ll be making sleep a priority to investigate, track and optimize.

The Mind Retreat

The mental experience of fasting for 10 days allowed me to appreciate more clearly aspects that I’d noticed in shorter fasts. Fasting promotes a less rushed, more practical and more bigger picture thinking state of mind for me.

The contrast of this with the typical more frenetic ‘getting things done’ focus of life is very attractive. In my mind it presents a great counter balance to keep your decisions in check once a month. It enables you to look at life, work from this other perspective once per month (if you’re doing the cyclic fasting) and that strikes me as a good thing for decision making.

This was far more noticeable on the 10 day fast. Some of this may be related to the drop in testosterone (and libido!) I tracked.

The Post-Fast Rookie Mistake

If you’re thinking of undertaking a 10 day water fast yourself. This is possibly the most important section – pay attention – I made the mistake and paid for it.

For 3 days after the fast I suffered from gut and toilet problems. Severe pain the first night to discomfort and the inability to keep anything actually inside me for the 3 following days.

It was a simple mistake. I assumed that what works post-fast for 5 days, should be okay for 10 days despite having spoken with people having done 10 or more day fasts that advised caution.

The biggest difference between the 5 and 10 day fast is how you start to refeed. I prepare and eat a couple of bowls of bone broth after my 5 day fasts without issue. I’ve found it to be a great high micronutrient way to ease back into eating.

However, with the 10 day fast, this turned out to be a disaster. My body simply was not able to deal with high levels of fat found in bone broth. My appetite didn’t return as a result either, so I was having to push myself to squeeze in small meals. After 3 days of failing to get my digestion back to normality with a variety of food combinations I thought would work (vegetable soup, scrambled eggs, etc) I had to rethink my strategy.

I resorted to drinking exclusively blended green vegetable smoothies.

The turnaround was amazing. All my digestion issues disappeared literally with the first couple of glasses, and my digestion issues were completely resolved within the next 24 hours. I kept that program up for a few more days nonetheless, to make sure I was past the issues.

So my strong recommendation to anyone trying this – and myself for future long duration fasts – will be to start with exclusively vegetable smoothies for the first 24 hours as a minimum (better 48 hours). That should lay the digestive foundation to be able to move back to your usual eating patterns.

Symptoms – The Back Rash

I’ve experienced some slight rashes during fasts before. With this longer fast it was a lot more extreme.

By day 10 my whole back was covered with a rash of spots – just the back. It was quite stunning – it made me think back to the time I caught chicken pox.

This rash disappeared just as quick within a couple of few days of refeeding it was completely gone again.

The Takeaways

So coming back to the questions we want to answer:

  1. Can I remain productive during a 10 day fast?
    • Would my mental performance suffer? Perhaps leading subtly to worse decisions, or perhaps just slower thinking?
      Answer: It’s not clear as yet. It doesn’t look like there was any drastic mental performance impact on working memory or attention control. Future testing will need to be done with future fasts to further validate
    • Would my energy levels remain the same or decrease? Would there be a change in how many hours I could comfortably work per day?
      Answer: There was no noticeable big change in energy levels or hours worked during the fast. If anything I felt a little more wired, and thus had to reduce my intake of caffeine.
    • How about concentration, focus and drive?
      Answer: Testosterone is often associated with these attributes in men. Low testosterone tends to reduce these attributes, however while my testosterone dropped during the fast, that’s not something I experienced. In a future 10 day fast I’ll track testosterone on the last day (day 10) to see if the hormonal impact is greater than the mid fast impact (day 5).
  2. Is “10 day fasting” every quarter sustainable? Specifically, where I’m doing monthly cycles of 5 day fasts in between?
    • Would I double the weight loss of a 5 day fast? And thus make it difficult to recover the weight within the following month?
      Answer: Weight loss wasn’t exactly linear – there was a leveling off at one point so weight loss per day was slightly less than with that I’ve experienced with the 5 day fast. The weight was easily regained within 15 days – so there doesn’t look to be an issue with not being able to maintain my equilibrium weight when I introduce 10 day fasts every quarter in between the monthly cyclic 5 day fasts.
    • Would a 10 day water fast be as easy, psychologically and physiologically, as the 5 day water fasts? Or would I hate it?
      Answer: If anything the 10 day fast was easier and got easier as I got into it. This could be due to my growing experience with fasting – “practice effects”, or that fasts do get easier the longer you’re on them. I think it’s probably a bit of both of these.
    • Is there any downside impact on “adrenal health” or cortisol regulation from fasting? (this is a question I’ve been attempting to answer since I started long duration fasting)
      Answer: My total cortisol and 24hr free cortisol were slightly lower on day 5 of the fast compared with baseline. Despite having done many fasts my 24hr free cortisol levels have not dropped from the original values I tracked a year previously – they’re stable. My total cortisol is also well within normal output ranges. So my inclination is to say no. I’d like to check in a future 10 day fast the cortisol metabolism on day 10 to see if there is a ‘declining slide’ in cortisol output over longer duration fasts.

Episode Question: Are you convinced about the rewards of water fasting to try it yourself yet? If not, what else would you need to know to get you there? Let me know in the comments.

Tracking

Biomarkers

  • Blood Ketones (Beta-Hydroxybutyrate / β-hydroxybutyrate): Blood ketones are the gold standard for measuring your state of ketosis. During the fast, ketones are expected to peak in the range of between 6 and 8 mmol/L. Dominic D’Agostino mentions that metabolic acidosis with values over 5 mmol/L place an additional burden of processing on your body, so in non fasting states keeping values between 1 and 5 mmol/L may be optimum.
  • Blood Glucose (mg/dl): A measure of the level of glucose in the blood at one point in time. Values of between 50mg/dL and 60mg/dL are standard for fasts. Non-fasting values should be below 80mg/dL ideally, and at least 92mg/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 consistent index values of 50 or more.
  • Weight (lbs): Standard scales measurement of weight in morning without clothes (to avoid biases).

Lab Tests, Devices and Apps

  • Blood Ketone/ Glucose Monitors: The Precision Xtra in the U.S. or Freestyle Optium Neo in the UK are the current recommended monitors. You’ll need lancets, ketone strips and glucose strips also.
  • DUTCH (Dried Urine Test for Comprehensive Hormones): This advanced hormone test panel from Precision Analytical is currently the most comprehensive and convenient test looking at cortisol metabolism and sex hormones. I used it to track baseline and fasting hormones. You can download my complete lab test results here: Baseline test results / Day 5 of fast test results.
  • Quantified Mind: The free online tool used to track cognitive performance during the fast – you can learn more about using the tool in this episode with its creator Yoni Donner. I used two short tests Yoni recommended to use for a mental performance check-in requiring a minimum of time (~5 minutes):
    • Color Word Inhibition: A test that measures attention control via the stroop effect.
    • Self-Paced 2-Back: A version of the N-Back game used to assess working memory.
  • Muse Calm: Mentioned as one of the better return on effort items discovered through the Quantified Body’s exploration so far. Interview with the founder, Ariel Garten, in previous episode here.

Tools & Tactics

Fasting Protocols

  • Water Fast: “Water fasts” are the standard fast protocol used in most of the research studies, including those looking at cancer inhibition or therapy for cancer patients. People are more or less extreme with the definition of what a water fast consists of. I personally am looking for the ‘biological effects’ or results. I’m not concerned with sticking to purely water unless that’s what is required to gain those results. So my version in this fast includes some supplement support which should not interfere with the beneficial fasting mechanisms – see below in Supplements for details.
    • 5 Day Water Fast: A minimum of 3 days is required to flip most people’s metabolic switch between glucose and ketone metabolism, and attain the benefits of the fast. For this reason a good place to start with water fasting is 5 days, which incorporates 2 days of therapy time (i.e. after the 3 day lead time to switch the metabolism). You can see this effect taking place in my first 5-day water fast self-experiment. The 5 day fast is also manageable on a cyclic monthly basis: 25 days of normal life, and 5 days of fasting per month.
    • 10 Day Water Fast: To provide a deeper dose of therapy (i.e. 7 days) people are extending their fasting times to 10 days, or beyond. As per my interview with Dr. Thomas Seyfried this may be more effective with respect to the anti-cancer effects. Depending on your risk profile, this may be something you consider doing from time to time.
  • Fast Mimicking Diet (FMD): A diet designed by researcher Valter Longo to maximize activation of the beneficial fasting mechanisms while still allowing you to eat to an extent. The details of this type of fast were covered in my FMD self-experiment in episode 31.

Supplements

My goal with this fast was to support my body without interfering with the beneficial fasting mechanisms, and to stay productive throughout (work wise and socially). So this is actually what I did:

  1. Mineral supports: This was the main supplementation I took covering a broad spectrum of minerals.
    • Real Salt: I sprinkled real salt into the filtered water I was drinking throughout the fast.
    • Quinton Hypertonic: A seawater electrolytes solution with a broad spectrum of minerals.
    • Pure Encapsulations Minerals 650: Capsules containing a broad spectrum of minerals.
    • (Both of the above recommended to me by Chris Shade from this episode)

    • Ancient Minerals Magnesium Spray: Typically I apply this to my skin daily after showers for absorption via that route. However, I’ve also started to spray it into my drinking water along with the Real Salt, and continued this during the fast (Note: Spraying the oil in drinking water was a tip from Andrew Scarborough in an upcoming interview – Episode 44).
  2. Drinks: Besides water I also consumed some other drinks during the fast, primarily for productivity purposes. My usual routine is to have a coffee in the morning, with the obvious caffeine jolt – so I kept to that usual routine, just keeping it to simple no calorie versions.
    • Black Coffee: For the first 5 days I took a black coffee in the morning, however I typically found that I naturally didn’t finish it. As the first continued I increasingly felt the caffeine from this single coffee was too much of a stimulant, the effect seemed to be magnified. So half way through I switched to…
    • Teas: Mostly Green Tea, also some Rooibos and Camomile tea. I found the green tea didn’t over-stimulate as much although I was still maxed out on 1 or 2 cups. More than that and I got the jitters.

Personal Note: Background on Using Minerals in Fast

There was another, more personal, reason I included a good amount of mineral supplementation during the fast. Since the episode with Chris Shade I’ve been following his mercury and heavy metals removal protocol.

Part of that protocol requires that you take a break from time to time to halt the process and remineralize the body since a side effect of the protocol is removing needed minerals along with the heavy metals.

I wasn’t going to be following the Shade protocol during the 10 day water fast (I stop all other experiments and protocols while fasting), so it made sense for efficiency to use that time for remineralization.

Other People, Books & Resources

People

  • Dr. Thomas Seyfried: See episode 16 for a discussion of his theories and work.
  • Dominic D’Agostino: Dominic has led some of the research into the benefits of ketone bodies and metabolic therapies, he is now turning much of his research effort towards cancer similarly to Thomas Seyfried.
  • Chris Kresser: Damien first learned about the benefits of the DUTCH test at Chris’ recent seminar in London.

References:

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What defines human microbiome health? The co-founder of American Gut Project discusses the differences we’ve found in the gut microbiome and how it influences our health. We look at tools and lifestyle choices that have been shown to change the microbiome (for good, and for bad).

Our microbiome plays an important role in our ability to overcome health issues. A healthy biome can make you resilient to these challenges, while a poorly-balanced one can create or worsen health problems. We first talked about the microbiome in Episode 9 with Jessica Richman, and today we are going to dig deeper into what affects it.

In this episode, we look at how the microbiome and our life choices impact each other. This can relate to how we live, our health, and even how many mosquito bites we get. Research shows that many chronic and gut diseases are related to our microbiome. We also talk about how medical interventions like antibiotics, Cesarean sections, and fecal transplants change our biome.

Anything that’s in the literature has got to be based on population averages. And one thing we know about people is that there are tremendous amounts of variability. So what works on average in the clinical trial is not necessarily going to be what works for you individually.
– Rob Knight

Advances in DNA sequencing have made it possible to look at the microbiomes of huge groups of people. Several large-scale projects, which we’ll discuss today, aim to look at microbiomes of groups or whole countries. It is also easier for individuals to learn about their own microbiome. This lets you see how your lifestyle, diet, or medical treatments alter your biome.

Today’s guest is Dr. Rob Knight, professor of Pediatrics and Computer Science & Engineering at the University of California San Diego. Dr. Knight was chosen as one of 50 HHMI Early Career Scientists in 2009. He is also a member of the Steering Committee of the Earth Microbiome Project, and a co-founder of the American Gut Project.

Dr. Knight and the Knight Lab at UC San Diego use state of the art computation and bioinformatics to understand the microbiome and what affects it. Dr. Knight is on the forefront of this exciting research and will walk us through the topic.

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

  • What DNA and RNA are (6:52).
  • Initially researchers thought that the human microbiome would be uninteresting (8:20).
  • Advances in DNA sequencing made projects like Human Microbiome Project and American Gut possible (9:53).
  • Novel information on how lifestyle affects the microbiome (13:50).
  • The different biomes of your body, what is known about them, and how the affect the body (16:50).
  • Long-term diet has the largest impact on your gut microbiome (19:40).
  • Individuals show variation in their microbiome from day to day, and this variation could make single samples less useful (20:05).
  • Research shows that only a few activities and dietary changes significantly affect the microbiome (22:50).
  • There are still questions about how variation within an individual’s microbiome relates to health (26:08).
  • Resources like American Gut can be used to assess your own response to medical interventions like antibiotics (27:20).
  • Fecal transplants to replenish your microbiome after medical intervention is an area of promise for those battling C. difficile (28:15).
  • The effect of antibiotics on the microbiome vary among treatments and individuals (31:06).
  • The microbiome is incredibly complex, but research into a few microbes could yield tremendous health benefits (33:16).
  • Although there is anecdotal evidence that probiotics are effective at positively impacting your microbiome post-antibiotics, there are currently no clinical trials on their effectiveness (37:44).
  • The Ancestral Microbiome Project is comparing the microbiomes of people with traditional lifestyles to see if the Western lifestyle or diet has led to a loss of certain microbes (41:05).
  • Living with a group of people or a new partner can change your microbiome (42:54).
  • IBS has been linked to the microbiome, and probiotics have shown promise for treating the condition (44:20).
  • Damien and Dr. Knight discuss places to find additional information on the microbiome (45:22).
  • Dr. Knight suggests tracking travel, medications, and diet if you are interested in how your lifestyle affects your microbiome (47:11).
  • Those interested in learning more could also track their fitness, do an EEG of brain activity, or an MRI of areas of interest (49:44).

Thank Dr. Rob Knight on Twitter for this interview.
Click Here to let him know you enjoyed the show!

Dr. Rob Knight

Tools & Tactics

Interventions

  • Fecal transplant: The purpose of this treatment is to re-balance the microbiome of the transplant recipient by placing fecal matter from the donor is placed in the colon of the recipient. The most common reason for this treatment is a serious illness caused by Clostridium difficile after the healthy gut microbiome is destroyed by antibiotics.

Supplementation

  • Probiotics: Probiotics are live bacteria and yeasts that assist in gut health; this includes antibiotic-related diarrhea, IBS, and IBD. They can be found in a variety of food products (like yogurt with “live cultures”) and in capsule form. Strains of Lactobacillus and Bifidobacterium are the most commonly available.

Diet & Nutrition

  • Plant-based diet: Dietary changes can quickly alter the gut microbiome, and Dr. Knight specifically discussed the choice of animal vs plant-based diets on the rates of Prevotella and Bacteroides. Here is the paper by Gary Wu and others discussed Rob Knight. For more information, here is a paper discussing how people on animal-based diets had higher levels of microorganisms related to inflammatory bowel disease in their microbiome.

Tracking

Biomarkers

  • Microbiome community composition: To determine what is in your microbiome, labs report the percent of each type of bacteria present in your sample. We are still learning about how microbiomes affect health, so there is currently no information on what an “ideal” microbiome looks like.
  • Gut microbiome: This is the microbiome in your colon and is the most commonly assessed of the biomes. Some “good” bacteria like Akkermansia, Lactobacillus, and Faecalibacterium are associated with reduced obesity rates and gut health.
  • Fine grade fitness information: This biomarker includes daily information on caloric intake, steps taken, calories burned, sleep quantity, and sleep quality.
  • Blood and Urine Metabolites: These small molecules include amino acids, sugars, and fats. They provide insights into health, disease risks, and optimal diet. No specific biomarkers were discussed – the biomarker would be a specific metabolite. A common test is the blood metabolite panel (BMP), which looks at calcium, glucose, electrolyte, blood urea nitrogen, and creatinine levels. For urine, proteins, leukocyte esterase, and hemoglobin are all commonly assessed biomarkers.

Lab Tests, Devices and Apps

  • American Gut Project: A not for profit, research-based initiative to understand the American microbiome. Participants are asked to provide details about their diet and lifestyle.
  • Michael_Pollan_Bug_Data

  • uBiome: This test can be ordered and used by anyone in their home. The test allows collection of microbes from your gut, mouth, ears, nose, or genitals.
  • Electroencephalogram (EEG): EEGs record electrical activity in the brain. The frequency of waves can indicate whether brain function is normal or disturbed. Alpha (8-13 waves per second) and beta (more than 13 waves per second) waves are the most common in healthy, awake adults.
  • Magnetic Resonance Imaging (MRI): MRI scans are 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.

Dr. Knight’s Recommended Resources to Learn More About Microbiome

  • Follow Your Gut: The Enormous Impact of Tiny Microbes: Our guest’s book on how the microbiome affects our health. The Appendix includes information on how to interpret the results from American Gut.
  • Missing Microbes: Our guest recommended Martin Blaser’s book as a resource for those interested in learning more about microbiomes and antibiotics.
  • Not Exactly Rocket Science: A science blog written by Ed Yong, our guest suggested the posts on microbiomes as fun reading for those interested in the topic.
  • Some of My Best Friends are Germs: Written by Michael Pollen for NY Times in 2012, the article is a quick read on the relationship between microbiomes and health.
  • Jonathan Eisen’s TED talk: Dr. Eisen’s talk “Meet Your Microbes” focuses on microbes and their co-evolution with their hosts.
  • Jessica Green’s TED talks: Dr. Green is the founder of Biology and the Built Environment (BioBE) Center, and has given two TED talks on microbes.
  • NY Times Matter Column: A weekly science column written by Carl Zimmer.

Other People, Books & Resources

People

  • Jeff Leach: Co-founder of the American Gut Project, and microbiome researcher.
  • Dr Catherine Lozupone: Professor of Biomedical Informatics andPersonalized Medicine at the University of Colorado, Denver. Dr. Lozupone researchers the impact of the gut microbiome on human health.
  • Dr. Jeffery I. Gordon: A research scientist studying the link between gut microbiota and obesity. Our guest collaborated with Dr. Gordon on this topic.
  • Dr. Pieter Dorrestein: A professor working at UC San Diego, Dr. Dorrenstein and our guest have collaborated on research. A recent paper of Dr. Dorrestein’s in PNAS looks at the chemical makeup of skin surface and relates it to the microbes that live in the skin.
  • Dr. Dan Littman: Professor of Molecular Immunology at NYU School of Medicine, Dr. Littman studies the human immune system.
  • Hans Herfarth, MD, PhD: Dr. Herfarth is a member of the UNC Multidisciplinary Center for IBD Research and Treatment and the author for the UNC Patient Guide to Inflammatory Bowel Disease (IBD).
  • Balfour Sartor, MD: Dr. Sartor is the co-chair of the UNC Multidisciplinary Center for IBD Research and Treatment.
  • Dr. Peter Turnbaugh: A professor in the UCSF department of Microbiology and Immunology.
  • Dr. Dave Relman: Dr. Relman’s research focuses on the human microbiome.
  • Dr. Cecil Lewis: Dr. Lewis studies anthropological genetics, including the evolution and ecology of the human microbiome.

Organizations

Other

Full Interview Transcript

Click Here to Read Transcript

[05:22][Damien Blenkinsopp]: Hi Rob, thank you so much for joining us on the show.

[Rob Knight]: Sure, thanks Damien, and thanks to your interest on this topic.

[Damien Blenkinsopp]: It’s great. So we’ve already looked at the microbiome, but I wanted to know, why is it that you got interested in this specific area? What is it that first caught your interest, or you first got involved in this area?

[Rob Knight]: Yeah, well it was a very indirect pathway from my graduate work at Predison’s Lab in studying the evolution of the genetic codes and a large part of that was looking at RNA molecules down to particular molecules that are useful in metabolism. So from there I went to the University of Colorado working on RNA sequence states and trying to figure out how many random RNA sequences you need to look at before you find one that does something interesting.

So there were a lot of one particular kind of sequence, the ribosomal RNA molecules in the database. I really wondered why were there so many of that particular sequence that had been studied. And so I started talking to Norm Pace, who was one of the other faculty members at Boulder. And I realized they were using the ribosome’s RNA not as an object of study in and of itself, but as a tool to understand the relationships between different organisms, and to read the mass in the communities that they were looking at. Everything from rocks to shower curtains to caves.

And so it really is just going from basic studies of RNA to understanding that you could use a particular kind of RNA as a tool to find out something about microbes, and then from there realizing that the microbial communities themselves could be used as a tool to find out about different environmental conditions, including the conditions within our own bodies.

[Damien Blenkinsopp]: Great, great, thank you.

[06:52] For some of the people at home, they might not understand what RNA is in reference to DNA, and how that works. Could you give a quick overview of what the mechanism for RNA is, and what role it plays in our bodies and the other things that you’ve been talking about.

[Rob Knight]: Sure, absolutely. So I think everyone’s familiar with the idea that DNA is the genetic material we use that passes down from one generation to the next. So, the proteins are most of the catalysts that do reactions in our bodies, most of the structural elements. So what happens is the DNA gets transcribed into RNA, ribonucleic acid, which is chemically relatively similar to DNA. And then the RNA gets translated into proteins.

But there are some kinds of RNA that don’t get translated, and have a function that is of themselves. One really important kind of RNA is ribosomal RNA that actually makes up the factory in the cell, the ribosome, that makes the proteins. And so because it plays such an important role in life, you can detect similarities in those even between very distantly related organisms.

So similarities even between us and bacteria. And so you can use that molecule to reconstruct the evolutionary tree that relates all of those organisms together, based on the similarities and differences in the sequence.

[08:04][Damien Blenkinsopp]: Great. So then you, from those studies, you started working to look at the bacteria, because you saw that they had a pretty important role, and that there was a lot of similarities between the things you were studying. On a human level and in the animal level, could you tell us a little bit about what it was that kind of pushed you to look more at the microbiome?

[Rob Knight]: Yeah, sure.

Originally the tools that I was developing together with Cathy Lozupone, then a very talented graduate student from my lab but now a faculty member of the University of Colorado Health Science in Denver. Initially we were just looking at tools to compare microbial communities out there in the environment.

So looking at the effects of things like salinity and pH as the chemical factors, of drivers, for how microbes are different in different places, like different samples of soil, sea water, or other communities like that. And so at the time we thought that maybe the microbes associated with the body wouldn’t be that interesting, because at the time there was fairly heavy bias towards the idea that most people probably have the same microbes, because if you grow them on a Petri dish, you get more or less the same thing from everybody.

But it turns out there’s a huge number of microbes in there, even in our own bodies, that we don’t yet know how to culture. And as a result, when you look at them with these culture independent, they are directly sequencing the DNA that codes these ribosomal RNA genes. And figuring out what’s in the communities directly you see all this diversity in the human microbiome that no one ever suspected was there.

So, we started doing this in mice, actually, in collaboration with Dr. Jeffery I. Gordon, he’s a physician at Washington University, a gastroenterologist. He was really interested in looking at links between microbes in obesity. So we started with mice, then moved up to humans. And then increasingly we’ve been interested in looking at the microbiome not as a static system, but as a dynamic system. So looking at how it changes over time, both in health and in disease.

[09:53][Damien Blenkinsopp]: Great, great. Thank you very much. And of course you are a co-founder of a project, which is being designed to explore the microbiome in America, of the population in America. What kind of latest update of American Gut, and what you’ve been doing there?

[Rob Knight]: Let me give you just a little back-story to that project. So, before American Gut, we were involved in the Human Microbiome Project, which was a very large scale NIH funded initiative, 173 million dollars to characterize what the microbes look like in healthy people. And with their whole microbiome, is there a lot of variation person to person, and how does it vary in different parts of the body.

So during that process, and in part because of technology that was developed, during the Human Microbiome Project DNA sequencing and tools to analyze the DNA sequences made the whole process dramatically cheaper. So essentially we wondered can we bring this technology to members of the general public, using the tools that we were able to develop during the Human Microbiome Project, to essentially allow anyone who was interested in finding out about their own microbiomes to be able to do that at a reasonable cost.

Jeff Leach and I launched as a collaboration between the Earth Microbiome Project and the Human Food Project. The crowd funded initiative where basically it’s donation supporters. And people can find out directly about swabs from their gut, and how it compares to the gut microbes of other people around America, or around the world, especially including the people who were analyzed in the Human Microbiome Project.

And also including people in Africa and South America, and soon people in Asia, to try to compare what the microbes look like, and how do they relate to health and disease.

So, unlike the Human Microbiome Project, where there were very rigorous exclusion criteria, so you could only participate if you were certified by a physician as being extremely healthy, in American Gut, we are interested in anyone, essentially to see what kinds of microbiome configurations are out there in the wild when you give everybody the opportunity to participate.

[Damien Blenkinsopp]: Great, great. That’s a great back-story.

[11:54] What’s the number of samples that you’ve collected to date? You said it’s called American Gut, but it sounds like it’s not just focused on America now, that it’s spread out and it’s available to more widely internationally. Is that correct?

[Rob Knight]: Yeah, that’s correct. So it’s relatively expensive to pass inspection internationally because the shipping regulations are fairly burdensome. So what we’ve been doing is we’ve been launching spin-offs in other countries. And so we started with Australian Gut, and with British Gut essentially because it’s a lot easier to translate all the instructions from English into English, rather than to tackle those translation issues.

But we’re hoping to expand to a lot of other countries. And at the moment with the transition from the University of Colorado to the University of California, we’re essentially in a holding path, and at the moment waiting for AMX approval. But we’re hoping to scale up the project dramatically, and greatly facilitate the ability for people all over the world to participate.

[Damien Blenkinsopp]: Which approval did you say you were waiting for? Was it an academic program approval?

[Rob Knight]: Institutional Review Board Approval. So in order to ensure that the project was conducted ethically and that the results that we get are going to be meaningful, everything we do in American Gut has been approved by Institutional Review Boards from the beginning.

I moved from the University of Colorado to the University of California right at the beginning of this year. What’s happening right at the moment is we’re waiting for the ethics approvals to be transferred from one institution to another, which can take a lot of time.

[Damien Blenkinsopp]: Right, right. Got it.

[13:19] How many samples have you collected to date for the project?

[Rob Knight]: We’ve released data from about 4500 samples. We’ve sent out about 9,000 kits. We have about another 1500 samples in hand that we’re just waiting for that ethics approval to be able to move forward on sequencing.

So, for anyone who’s listening, if you’re wondering where your results are, we’ll be able to get them out pretty soon. We just need to make sure that everything is completely compliant with all the regulations that apply to the Human Subject Research in the United States. Just to make sure that everything is completely above board.

[Damien Blenkinsopp]: Excellent. So, has any analysis come out of it, or insights yet that you’ve been able to do?

[Rob Knight]: Yeah, absolutely. So one thing that was exciting about it, or already, in the Human Microbiome Project, this paper, which came out in Nature in 2012, we looked at about 250 healthy subjects. So I think we reported data for 242 where there was information from all body sites.

So you have about 250 people involved in that project. Versus American Gut, where you have thousands of people involved. As a result, with a much larger population size we have much more statistical power to look at subtle effects.

And we also put on the questionnaire all sorts of things that were considered too crazy to ask in the HMP. But in the intervening time we’ve discovered so much more about what the microbiome does, especially in a range of different animal models. And it seemed a lot less crazy to ask those questions in 2012 than it did in 2008.

As a result, we’ve been able to see associations between the microbiome, and all kinds of things you might not have expected. So you might have expected that how old you are affects the microbiome, which it does, but you might not have expected that, for example, how much sleep you say you get a night is also linked to the microbiome. And we see a statistically significant effect of that.

Similarly, you might have expected that how much alcohol you drink affects the microbiome, but you might not have expected that we can also pick up a difference based on how much you exercise. Or I should say how much you say you exercise, because all of this is reported data. But how much you say you exercise, even whether you say you do it indoors or outdoors, has an effect.

So we’re really picking up a lot of interesting associations. And what we’re hoping to do in the next stage of the project is to take a bunch of these associations and turn them into something where we can start to get causality. So what we’d love to know, if we see in association with alcohol and an association with exercise, or with sleep or with any of these other things, is to actually encourage people to change what they’re doing in those respects, or you know more obvious things like diet, or antibiotics.

Where the idea is that if you take a sample before you have a change in any of those things, and then you have the change and then you take another sample again after. Can we start figuring out which of those changes are actually caused by those different lifestyle things that you could be doing. This is watching simply effect.

[Damien Blenkinsopp]: Right, because a lot of when we’re thinking about the microbiome, and –just to make sure I’m correct here — you’re just looking at the gut, right? The microbiome of the gut?

[Rob Knight]: Well, actually with American Gut you can look at the microbiome. So most people are looking at their gut biome, but it’s also interesting to look at other body sites. We have been sending out a number of batches of kits that allow you to sample multiple sites simultaneously.

So another project we’re doing, we’ve been looking at skin. So for example, we had a very interesting paper that came out in PNE of last week with Pieter Dorrestein doing very high resolution maps of the skin in relation to the microbes, to the metabolites. And then there’s also a lot of interest in the oral microbiome, the vaginal microbiome, and so on.

So, although the gut microbiome is where most attention has been focused, there is a lot of interest potentially in looking at other body sites. And linking them not just to health effects of that site, but also to all over the body. So for example the gut microbiome has been linked to asthma and to rheumatoid arthritis, and to cardiovascular disease, all of which takes place in sites outside the gut, but are nonetheless affected by the microbiome.

And it’s entirely possible that, for example, the oral microbiome, or the skin microbiome might also be having systemic effects we’re only just beginning to understand. Whether it’s through interactions with the immune system or through release of particular metabolites, or other mechanisms.

[17:32][Damien Blenkinsopp]: Maybe it’s too early to say this, but have you seen anything that would indicate that the microbiomes are related to each other, in terms of if you have a different gut microbiome it may influence or be influenced somehow by the fact that your nose or your skin biome is different also?

[Rob Knight]: Well that’s a very interesting and controversial question. So actually, the fifth Human Microbiome Project main papers, which said that there are statistically significant but relatively weak associations between the different body sites, and then later that’s been confirmed by other researchers using different statistical methods.

At the moment there’s a lot of debate about how strong the associations are, and what effects they have on health when you’re looking at the overall configurations. But certainly some individual organisms that are very interesting. So, for example, Dan Littman at NYU has shown some very nice work linking Prevotella in the guts to rheumatoid arthritis. And so we’ll probably see a number of other associations like that with specific organisms at one site having unlikely effects on what happens, what helps with other sites in the body.

[Damien Blenkinsopp]: Very, very interesting.

I think the surprising thing for a lot of people of what you just said is that there are a lot of lifestyle factors not related to diet. Because we normally think of the biome, and especially the gut biome, being immediately related to our diet, and what do we eat, but [not] a lot of things you mentioned, sleep, age, exercise. And you said exercise indoors or outdoors can be different as well, is that correct?

[Rob Knight]: Correct, yeah.

[Damien Blenkinsopp]: So you know, it’s very interesting. These small changes in your lifestyle, nothing to do with diet, can have significant impact on the gut also, which we haven’t looked at.

[Rob Knight]: Sure, although I should clarify that long term diet has the largest effect that we’ve seen. The work with Gary Wu and others at Penn came out in 2011 in Science. What we saw there is this long-term dietary pattern had a profound effect on the gut microbiome, especially changing the ratio of Prevotella to Bacteroides, two of the major taxa in the gut. And only changing the overall configuration, more than essentially anything else.

So the only thing we’ve seen that gives you comparable changes is either antibiotics or acute infection with some kinds of pathogens. Like C. diff, for example, has a very large effect on your gut microbial community. So long term diet is really very important.

Short term diets, unless it’s something really extreme, is a lot less important than what we see in long term diet. This was maybe consistent with people’s experiences with going on a diet for a short period, losing some weight, but then going off the diet and bouncing back again. In general your microbiome is very resilient.

[20:05]Damien Blenkinsopp]: This comes to the topic of variability of the microbiome over time.

I did see one presentation of yours where you were showing the biome of a newborn baby, actually, as it was growing up. And you’re showing the changes at that stage of its life, which were quite significant at that stage. But for adults who are fully developed, in our day to day, week to week lives, are our microbiomes changing significantly? Or are they very, very stable?

[Rob Knight]: Both of those are true. So, our microbiomes change statistically significantly one day to the next. And especially when we do things like travel or take antibiotics, or if we have a chronic, immunologically associated disease. Like, for example, inflammatory bowel disease, or rheumatoid arthritis, or other conditions where there’s a lot of variability in whether you’re in remission or whether you’re having a relapse.

There can be fairly large changes there, but typically small compared to the differences between different people. So we tend to be stable in terms of, especially if we’re healthy and there’s nothing particular going on, we tend to be stable in the sense that we’re more similar to ourselves day to day than we are to other people.

But that doesn’t mean that you can’t detect the differences one day to the next. And so a very interesting question at the moment is what is the significant of those day to day fluctuations? Might it actually be more important how much you vary than what your current state is right now. And that’s one of the things that we’re just starting to investigate at the moment.

[21:29][Damien Blenkinsopp]: Yes, and in terms of how meaningful data would be for someone who’s collecting it for themselves, if they take one sample and they get one reading is that meaningful to them? Or would you suggest they take one this week, and one next week. How would you go about making sure you have something representative?

[Rob Knight]: Right. Well having one sample is certainly a lot better than having no samples, in terms of getting some information about what’s in your gut. Because even having one sample is going to do a tremendous amount to place yourself on the microbial map, relative to other people.

The question about how frequently you should sample and how many samples you should take to get a baseline, that’s something that’s actually a very active research topic at the moment. And we have collaborations with a number of different investigators exploring that in different contexts.

So, for example, one thing we’ve been doing is work supported by the Crohn’s & Colitis Foundation of America with Hans Herfarth and Balfour Sartor of the University of North Carolina, where we’re trying to address exactly that clinical question. If you have patients with IBD should you sample daily, should you sample weekly. So how does that compare to what you should do in healthy controls.

Unfortunately, the only way we can assess that baseline data is to take very frequent samples. And it’s difficult to get people to do that. So for example, I’ve been collecting my own samples daily for over six years now. It’s relatively difficult to get people to come up to that kind of level of commitment.

[22:50][Damien Blenkinsopp]: So, I’m interested. What kind of insights have you learned about yourself from that n=1?

[Rob Knight]: As you know it’s always relatively difficult to draw conclusions from a sample size of one, but it does look like things like travel have a fairly large effect. We’ve seen that for a number of different locations.

So I should clarify that only about the first two years of that have been sequenced so far. Most of the rest are in a queue for processing, but it keeps getting bumped due to things like making sure we get the American Gut results and so on. The rest of the time series is currently pending.

We’ve done the DNA extraction so that’s currently pending sequencing. And some of the things that we’re going to be really interested to follow up on, having a time series that goes that long is, for example, the seasonality effects that we seen in American Gut. And we see those even within one individual. Because if you can repeat that for many years, then you can start to see systematic patterns.

I’ll tell you about some results from another study, which is one by Lawrence David and Eric Alm at MIT, where they sampled themselves daily for a year and collected a very large number of auxiliary variables. I think they collected over 100 variables every day, including everything they ate. All kinds of things like how much exercise they did, how much they slept, and so on.

And they found very few systematic associations. So, for example, about the only thing they saw in diet was citrus, which had a significant effect, whereas many other things that they recorded did not. And they also saw associations with travel, and associations with getting GI illnesses. And that was about it.

So, I think the issue is that a lot of the effects, although they might be important, they’re probably subtle and cumulative. And so although you’re going to get very interesting information from some of these n=1 studies, like this study. And by Larry Snar here at UCSD has been doing looking at his own gut in the context of IBD, in the context of my studies myself.

Although there’s going to be some interesting stories that come out of them, those are going to be most interesting in terms of the technology development, of asking how frequently should you sample to establish a baseline, and over what interval to you need to sample to get a decent view of dynamics.

But we did a study with Noah Fierer and Rob Dunn, Greg Caporaso that came out in Genome Biology towards the end of last year looking in healthy students at the variation of the gut microbiome over the course of the semester. One thing that was very interesting about that, looking at weekly samples, was the variability itself seemed to be very important for relating to the variables that we had about each subject, and each sample.

And so it’s entirely possible that the variability itself was going to wind up being really important. But of course, it’s also a lot more difficult and a lot more expensive to look at than just looking at a single snapshot. And so the single snapshots are still very valuable, I meant to say, even though you could potentially get more information by looking at the dynamics than you would from a single snapshot.

It’s like having a video of an event can often be very informative, but that doesn’t mean that photography has vanished as a discipline despite the fact that we all carry around little video cameras on our cellphones.

[26:08] [Damien Blenkinsopp]: Great.

So in terms of the variability, is it looking that that’s a positive or a negative association? Maybe you can’t really call it yet, but have you got an idea on which way it would be going? Like, for instance, is it potentially that the microbiomes when it’s healthy it’s able to adapt a lot more to the day to day situation, travel and all those things, so it would vary more. Or have you got any insight on that yet, or ideas on which way it might go?

[Rob Knight]: Yes.

So we don’t really have enough information at this point, and as you say it could go either way. Either you might want to see a fair amount of flexibility in your microbiome to be able to adapt to different circumstances, or you might want to see more resilience, and if it’s wandering all over the place it’s more likely to fall off a cliff, and to input the community configuration.

Right now we don’t have the basis to discriminate between those two. Most of the variability studies have been done at baseline in healthy people, and that doesn’t necessarily let you conclude anything about disease.

Most of the disease studies have looked at a relatively small number of samples. Often just a single sample where you’re looking at a case controlled paradigm where you round up some healthy people, round up some sick people, and you look at the differences at that state. So, really we’re waiting for the right kinds of studies to be done for variability in these diseased populations.

[Damien Blenkinsopp]: Great, thank you very much. I mean, we could get a couple of guidelines, just for people who are already using American Gut or one of the other services.

[27:26] I’m actually just about to take some antibiotics, for instance, so I’ve got a kit I intend to use, and then once the course is finished I intend to use it again. And actually based on your presentation, I intend to do one 30 days later to see if it will recover. Is that something reasonable as a baseline experiment? Just to see what’s going on.

[Rob Knight]: Yeah, that’s certainly very reasonable.

You might want to look at Dave Relman’s paper, it came out in Pathobiology a few years ago. And what he had there was three subjects who were taking ciprofloxacin from a healthy baseline, and they measured how long it took them to come back.

What was interesting about that is three people, they all responded totally differently. But then it’s kind of difficult to figure out what you should say about that, because the sample size is only three, and they all responded very differently from one another. But it’s certainly reasonable.

One thing that’s very interesting at the moment is the concept that maybe you should freeze your stool before you take the antibiotics, so that you could potentially replenish the members of your community. And again I should point out that that’s still in its very early stages as a therapy. This is not medical advice or anything.

But the concept that you might want to have that material available in case we figure out how to replenish your microbes from it later, kind of the way people are saving their cold blood for the stem cells. It’s certainly very interesting, and has a lot of potential.

And of course, right, you’ll be hoping for is that in the relatively near future – and there’s a lot of companies and a lot of academic research groups interested in this now – the idea that you might not actually have to take the stool itself, but rather isolate just a few of the beneficial microbes from it, encapsulate those into a pill and swallow those, for example. That’s shaping up to some very interesting research direction, although at this point it is very much in the lab and not in the clinic.

[Damien Blenkinsopp]: It does sound safer, also compared to the current fecal transplants. I think one of the concerns of fecal transplants is we don’t really know what’s in them.

[Rob Knight]: Yeah, that’s exactly it.

[Damien Blenkinsopp]: You know, because just the state of technologically today.

While you might make someone better in some extreme cases, like C. difficile, obviously that’s helpful. But for someone else who has maybe taken a lot of antibiotics and they had gut issues, to take a fecal transplant could be seen as a little bit extreme, as currently we’re not exactly sure what’s in it, and we could be putting something in there that we’ll discover later is not such a good thing.

[Rob Knight]: Yes, that’s certainly a concern. I’m on the science advisory board for the American Gastroenterological Association’s Microbiome Center, and one thing we’re actively trying to set up is a long term registry for fecal microbiome transplant, essentially so that we can track people who’ve had them over time, and make sure that it remains effective.

So for Clostridium difficile associated disease, it’s remarkable effective. Like 90 to 95 percent effective in many different studies. And the last large scale study comparing it to antibiotics for C. diff actually had to be stopped early because the people who got the FMT were responding so well that it was unethical to continue withholding FMT from the people who were on the antibiotics.

So, how widely that’s going to work for other conditions, we don’t really know. One thing you can do for antibiotic associated diarrhea that’s very effective is probiotics. There’s a number of different ones that are now pretty well supported by clinical trials at reducing both the severity and duration of antibiotic diarrhea.

And so in general, it’s not because the organisms themselves are establishing in your gut, but they’re creative a favorable environment where they can crowd out the weeds, like the proteobacteria and things that often come back after antibiotics. And essentially they’re creating more favorable conditions for your own microbes to come back.

[Damien Blenkinsopp]: Great.

[31:06] So, to kind of backtrack a bit. So in the presentation I saw, you saw after the antibiotic treatment, which was a baby with earache I believe it was, the microbiome pretty much came back to where it was before.

[Rob Knight]: Yup. But remember that’s an n=1 study, because we just had one kid in there. Yup.

[Damien Blenkinsopp]: So is that a possibility for some? We always talk about antibiotics like it could be potentially permanent. Because everyone’s pretty concerned. I’m pretty concerned when I’m going on a course of antibiotics now what kind of impact down the line is it going to have.

But it seems like it can depend on the severity, because antibiotics are used in many different cases. They can be used for a couple of days in some cases, sometimes, and there’s lots of different forms of antibiotics, which have different impacts as well, and potentially more severe or less severe.

It seems that in some cases the microbiome may be able to recover, and in other cases it’s not able to fully recover, and it’s quite variable for the moment, I’m guessing. Or do you have any insights as to the insights of antibiotics and how it varies?

[Rob Knight]: Basically what we know at this point is that different antibiotics have very different specificities, so they’ll target different bugs when they’re growing in the lab in isolation. We know a lot less about what effects the antibiotics have in more complex settings. And so the same microbe might only be targeted by antibiotics in some stages in it’s growth cycle.

And so Pete Turnbaugh, he’s now at UCSF but did this work while he was at Harvard, did some very interesting research looking at the effects of the same antibiotics microbes in different communities, that had come from different individual people. And so what he found is even if you have the same microbe, whether the same antibiotics would target that microbe depends a lot on who it came from.

And that’s very interesting. It just suggests that there’s a lot of complexity that we don’t understand at this point about how microbes are going to be targeted by a particular antibiotic, or will escape that depending on what other microbes are around. Depending on whether it’s expanding its population or contracting it, and all kinds of other factors.

So I think we’re just right at the beginning of understanding what’s going on in the complex situation of the human body itself.

[Damien Blenkinsopp]: Yes, absolutely.

[33:16] I think a bit of context to that is if you look at the size of DNA in our genetics versus the microbiome, right the microbiome is a lot bigger, and we don’t fully understand DNA yet. So, basically is it a much bigger task to understand the microbiome?

[Rob Knight]: Yes, it’s a tremendously more complex task. So each of us has about 20,000 human genes, but the size of the microbial gene catalog is somewhere between 2 and 20 million. So, by that measure you could say that we’re only about one percent human, and about 99 percent microbial in terms of the gene counts that we’re carrying around with us.

And so, on the one hand understanding it is tremendously complicated. On the other hand, if you look at other fields where there’s tremendous complexity, like say nutrition for example, but if you ran a potato through the mass spec you’d see all these compounds that you’ve never seen before, and that you don’t understand, and that don’t appear in any catalog from any chemical company. On the other hand, that doesn’t mean that we don’t know a fair amount about what happens if you rely on potatoes as your main food source.

And additionally, if you look at, for example, a lot of chronic diseases from a century ago, so things like rickets, goiters, and so on. A lot of those kind of diseases have just been completely eliminated by knowing that there’s some nutrient that if you give it to the whole population, like for example iodine in salts or fortifying milk with vitamin D, fortifying flour with thiamin, and so on, you can just eradicate these diseases from the whole population.

And so, in the same way it’s going to take us a long time to understand the microbiome, but it might not take that long before we understand how replenishing some of these microbes might potentially be really important for addressing some of the chronic diseases that affect us now, including many of the chronic diseases still linked to the immune system.

[35:11][Damien Blenkinsopp]: Great, great. And there are also macro levels. It’s a pretty good example, I think, you just gave nutrition, because we look at the macros and there’s lots of discussions about proteins, fat, and carbohydrate breakdown in diets. And in the same way there’s macro levels of our microbiome, right? There’s groups of Firmicutes and Bacteroidetes and others on a macro level, which I guess you could see patterns with those as well, and don’t necessarily have to dig down to the fine levels.

[Rob Knight]: Yes. That’s exactly right. Although in the same way that micronutrients are really important, some of the rare organisms might be really important.

And a useful analogy is something like Yellowstone National Park, where the reintroduction of wolves caused a profound change to the ecosystem. But if you go to the park – and not without, but you’d never get permission to do this right – but if you went to the park, and you round up say a cubic kilometer of material and then run that through DNA sequencing, you wouldn’t find a lot of wolf DNA.

And the reason why we know their important is you know people shot them all and the ecosystem changed, and they reintroduced them and the ecosystem changed again. So on the one hand, what technology is that we have right now, we’re probably missing the equivalent of the microbial wolf that could be playing really important roles.

On the other hand, if you were trying to understand that ecosystem, you’d be crazy to ignore the pine trees and the bison and the other really abundant taxa as well. So you can tell a lot looking at what’s common as well as needing to know what’s rare to fully understand the system. But I think we’ll be able to do a lot with the understand that we have now.

And it’s important to remember that that understanding has increased dramatically just in the last decade. So in 2005 it was a major achievement to sequence the gut microbial communities out of three people. And that was expanded by a fifth to hundreds of people, and then to thousands of people. And we’re just getting a much broader picture of what kind of microbes are in there, and what their roles are in responding to different things.

And so, the idea that you might be able to look at the microbes in somebody every single day for a year, would have been an impossible dream in 2005 but the technology has gotten so much better that it’s been done for a number of people now. And the prospects for developing further technology to open that up to the whole population I think will totally transform what we can know about microbial sides of yourself.

So, being able to push that additional technology development forward I think is one of the most critical things we can do at this point.

[Damien Blenkinsopp]: Excellent, thank you very much.

[37:44] One of the things we kind of skipped over but I thought might be interesting for the audience is you spoke about probiotics being useful in connection with the antibiotics treatment, and specific types of probiotics.

Do you know specifically what those are? Or could you point us to any papers which highlighted those? And in terms of the timing, do you take them while on the antibiotics, or is it a post treatment?

[Rob Knight]: The different studies that have been done at the moment haven’t really had a lot of consistency in methodology, so it’s difficult to make specific recommendations. It’s a fairly complex topic. I cover this in a reasonable amount of detail in my book, Follow Your Guts, which is just coming out tomorrow. But essentially I give a few examples of pointers to studies that have been focused on individual probiotics that have shown to be effective for particular conditions.

So one thing to remember with this is although there’s a tremendous amount of enthusiasm to probiotics and they’re very widely available, most of the specific products don’t have any particular evidence backing them. And so it can be a bit daunting to wade through the literature and try to find the ones that are actually supported by clinical trial data.

At the moment, at least to my knowledge, there’s no really good resource that summarizes the clinical trial information to tell you what species, what strains, and what products containing those strains have actually been shown to be effective. Although that’s something that’s a clear opportunity, where if someone sets it up that will be tremendously valuable for the public, especially given the level of enthusiasm.

One problem at the moment is, in the US at least, that the FDA’s official stance is that a dietary supplement can’t modify a disease endpoint. So as a result, if you find that your product actually does modify a disease endpoint, then it gets re-regulated as a drug, and so the manufacturing standards are certainly much more stringent.

And so if you want your yogurt with live and active cultures to continue to be a buck or two a cup, rather than being a thousand bucks a cap, which is about what it would cost if you had to manufacture it as biologic, there’s that issue to consider as well. So, that’s also a substantial problem for research in this area.

[Damien Blenkinsopp]: Right, so again, in that case we’re kind of hoping that no one tries to do clinica