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

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

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

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

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

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

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

itunes quantified body

What You’ll Learn

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

Richard Sprague

Recommended Self-Experiment

Use Kefir to Change Your Microbiome

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

Kimchi for Sinusitis Treatment

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

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

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

Tools & Tactics

Diet & Nutrition

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

Sleep

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

Tech & Devices

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

Tracking

Biomarkers

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

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

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

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

Lab Tests

Microbiome Labs Overview

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

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

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

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

Microbiome Lab Tests

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

Analysis of the Different Labs

Granularity of Output from the Labs

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

Source: Damien’s lab samples

Analysis and Graphs from Richard Sprague

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

microbiome labs


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

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

microbime labs

Daily variations in the gut microbiome (Richard Sprague)

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

Microbiome labs

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

 

Other People, Books & Resources

People

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

Books

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

Other

Full Interview Transcript

Click Here to Read Transcript

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

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

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

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

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

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

[Richard Sprague]: It could be.

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

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

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

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

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

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

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

[Richard Sprague]: Yeah.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Right

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

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

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

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

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

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

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

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

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

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

[Richard Sprague]: That’s right.

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: A poodle, yeah.

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Yeah.

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

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

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

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

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

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

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

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

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

[Richard Sprague]: Yeah.

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

[Richard Sprague]: Metabolomics, yeah.

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

[Richard Sprague]: Yeah

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

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

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

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

[Damien Blenkinsopp]:With the transcriptome?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Excellent.

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

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

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

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

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

[Richard Sprague]: Yeah

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

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

[Richard Sprague]: That’s right.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Richard Sprague]: So a couple of tablespoons?

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

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

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

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

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

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

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

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

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

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

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

[Richard Sprague]: Yeah, interesting.

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

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

[Damien Blenkinsopp]: Yeah.

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Absolutely.

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

[Damien Blenkinsopp]: Absolutely.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Yeah.

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

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

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

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

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

[Damien Blenkinsopp]: Nothing? Okay, interesting.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Richard Sprague]: Yes.

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

[Richard Sprague]: Yes, okay.

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

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

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

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

[Richard Sprague]: That’s real interesting.

 

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

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

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

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

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

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

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

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

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

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

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

[Richard Sprague]: Yup.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Absolutely.

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

[Damien Blenkinsopp]: Yeah, exactly. Yeah.

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

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

So going back to this personalized…

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

[Damien Blenkinsopp]: No, I didn’t.

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

[Damien Blenkinsopp]: Okay, great.

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

[Damien Blenkinsopp]: Oh, awesome.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Richard Sprague]: Indiegogo, yeah.

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

[Richard Sprague]: Back in 2013.

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

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

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

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

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

[Richard Sprague]: That’s right, yup.

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

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

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

[Richard Sprague]: Yeah.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Richard Sprague]: Yeah.

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

[Richard Sprague]: Yeah.

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

[Richard Sprague]: Yeah, exactly.

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

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

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

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

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

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

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

[Richard Sprague]: Hmm.

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

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

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

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

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

[Richard Sprague]: Oh, I see.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Yeah.

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

[Damien Blenkinsopp]: Yeah.

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Probiotic.

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

[Damien Blenkinsopp]: Absolutely.

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

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

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

[Richard Sprague]:Yeah, that’s right.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Richard Sprague]:Yeah, that’s right.

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

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

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

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

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

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

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

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

[Richard Sprague]: Yes, right.

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

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

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

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

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

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

[Damien Blenkinsopp]: Right. N=1.

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

[Damien Blenkinsopp]: It gets stored. Yeah.

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

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

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

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

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

[Damien Blenkinsopp]: Yeah, hard to change.

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

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

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

Richard, what are your overall thoughts?

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

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

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

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

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

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

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

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

[Richard Sprague]: Yeah.

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

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

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

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

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

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

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

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

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

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

 

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

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

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

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

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

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

[Richard Sprague]: Ooo, okay.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Right.

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

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

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

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

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

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

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

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

[Richard Sprague]: Yeah.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Yeah.

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

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

[Richard Sprague]: It probably will.

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Wow.

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

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

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

[Richard Sprague]: No, Viome.

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

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

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

[Richard Sprague]: Yeah.

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Standardization. Somehow.

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: That’s ridiculous.

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

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

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

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

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

[Damien Blenkinsopp]: Exactly.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Yeah. Are you offering…

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

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

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

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

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

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

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

[Damien Blenkinsopp]: And you have it.

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Yeah, exactly.

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Yeah. Okay.

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

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

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

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

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

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

And I’ve selected the 10 that I think

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

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

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

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

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

[Richard Sprague]: Yeah.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Richard Sprague]: Yeah, interesting.

[Damien Blenkinsopp]: So I really

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]:Everyone misses them.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Study References

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What is carbohydrate intolerance? Do each of us have a personal tolerance or intolerance of carbohydrates? Does this also vary by source of carbohydrate? Learn how evolutionary tools may explain appetite regulation and carbohydrate metabolism and offer ways to regain carb tolerance through diet and lifestyle modifications.

In this episode, we explore how carbohydrate intolerance works. We look at the evolutionary template (basically the Paleo template), neuroregulation of appetite, carbohydrate tolerance, insulin resistance and sensitivity, and the factors that drive all of these.

Once the person is insulin resistant, particularly when they are heading down this road towards prediabetes and potentially diabetes, there is without a doubt one intervention that seems to work remarkably well. That’s reducing carbohydrate level to a point where it’s no longer toxic to the individual.”
– Robb Wolf

Robb Wolf (@RobbWolf) is basically the man responsible for bringing Paleo to the mainstream, in part via his New York Times Bestseller, The Paleo Solution. He also has a new book out, Wired to Eat, which covers many of the topics discussed in this episode.

Robb is a former researcher biochemist and review editor for the Journal of Nutrition and Metabolism, and the Journal of Evolutionary Health. He is a consultant for the Naval Special Warfare Resilience Program and has provided seminars in Nutrition and Strength to organizations such as NASA, the Canadian Light Infantry, and the United States Marine Corps.

One of the takeaways from Robb’s new book, Wired to Eat, is using a 7-Day Carb Test. That’s testing a different type of carb seven days in one week to see what these do to you, and what your personal tolerance is to different carbs, because not every one of them affects you the same way, or like it would any other person.

I ran that test myself and the results are further down this page. This gives you a concrete example of what Robb is talking about when he talks about the 7 Day Test, how to measure blood glucose and how to understand how these carbs are affecting you differently.

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

itunes quantified body

What You’ll Learn

  • Damien extends his gratitude to Robb for getting him back to eating meat in the year 2010, which greatly improved Damien’s health (03:45).
  • Robb’s book Wired to Eat approaches health from an evolutionary neuroregulation of appetite as starting point and progresses with dieting self-experiments (04:01).
  • The insulin resistance theory and how the 7 Day Carb Test is useful in coming up with personalized diet plans aimed at improving health (10:46).
  • The potential for low-carb / paleo diet and intermittent fasting to improve carbohydrate tolerance (18:50).
  • Robb’s plans for experimenting with donating blood to reduce potential iron overload inflammation (19:58).
  • The value of lipoprotein insulin resistance (LPIR) panel in determining ‘hidden’ insulin resistance, otherwise not detected by fasting glucose levels alone (21:05).
  • Anthropometric measures, such as the waist to hip ratio, are only somewhat reliable markers of insulin resistance (24:28).
  • Making use of the 7 Day Carb Test to track the process of recovering carb tolerance over time (24:53).
  • Why sleep is the most important health parameter and how HRV is useful for tracking sleep quality and overall health (29:39).
  • Integrating physical exercise into a busy life and optimizing exercise intensity (36:41).
  • The ketogenic diet offers numerous therapeutic and health maintaining benefits (41:35).
  • The role of the circadian rhythm in tuning meal consumption with the body’ demands throughout the day (45:35).
  • People to follow & material for learning more about this episode’s topics (51:39).
  • The best ways to connect with Robb Wolf and learn more about his work (53:14).
  • The biomarkers Robb Wolf tracks on a routine basis to monitor and improve his health, longevity, and performance (53:45).
  • The labs using NMR spectra technology to detect LPIR components with high precision (57:58).
  • Robb’s one biggest recommendation on using body data to improve your health, longevity, and performance (58:28).

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

Robb Wolf

  • Main Website: Short life & career summaries of Robb Wolf and his team.
  • Paleo Diet: An introduction on the Paleo Diet written by Robb.
  • Robb’s Instagram: Where he spends most of his social media time and answers almost all posed questions.
  • The Paleo Solution Podcast: Robb’s long running podcast exploring every area of evolutionary and paleo based lifestyles as well as many of today’s chronic health challenges.

Recommended Self-Experiments

7-Day Carb Test

  1. Tool/ Tactic: This test is described in detail in Robb’s Wired to Eat book and on his blog here. It consists of consuming 50g of carbohydrate from different carbohydrate sources (e.g. rice, lentils etc.) each day for one week.The goal is to identify which carbohydrate sources have the biggest impact on blood glucose levels, and thereby identifying which ones you are least carbohydrate tolerant for.In creating this test, Robb was inspired by the Weizmann Institute of Science’s Personalized Nutrition Project. We discussed personalized nutrition and interviewed the lead researcher, Eran Segal, from this project in Episode 48.The test entails preparing 50g of effective carbs, or another carb source, and eating only one type of this meal first thing in the morning (with the exception of coffee and water).
  2. Tracking: Track the food types, your blood glucose level before you consume the food and the time at which you eat. Exactly two hours later, test and record your blood glucose reading again.Is your blood glucose at the 2 hour mark over 115mg/dl? This can indicate carbohydrate intolerance with respect to that specific food.By understanding the carbohydrates you are personally intolerant of you can reduce your blood glucose variability significantly by just removing these from your diet (while still enjoying other carbs that your body is tolerant of).

    Robb recommends that the 7-Day Carb Test is repeated approximately every 3 months, such that the time intervals are close enough to track improvements in particular carb foods insulin sensitivity, as well as tracking the body’s overall insulin sensitivity.

Damien’s 7-Day Carb Test Results

Before recording the interview with Robb I followed his carbohydrate testing protocol for some of the carbohydrates that appeal to me more.

I made a couple of modifications of the protocol to fit my profile better.

  • First, as I’m on a ketogenic diet, I also tracked blood ketones to understand the impact of each carbohydrate source on my levels of ketosis.Did a particular carb drop me below the performance ketosis threshold (1.5 mmol/L)1? Or did it drop be below the nutritional ketosis threshold (0.5 mmmol/L)?
  • Second, from my using a Continuous Glucose Monitor for the last 3 months I know that my blood glucose readings in the mornings are not stable. They rise and fall after waking very predictably, but to greater or lesser amounts depending on sleep, stress and possibly other factors.On the other hand, since I only eat once a day typically, at my evening meal, I know that my blood glucose in the afternoons is always flatline. So I ran my experiments in the afternoon knowing that the variables were better controlled. This is not the situation for most people as Robb describes in his book, so you are most likely better off running the test in the morning as he advises.

In my case the takeaways from this self-experiment were:

  • Lentils had the least impact on my blood glucose levels and ketone levels. My blood glucose had dropped back to near baseline, below 90 mg/dl, within 90 minutes.
  • White rice had the largest relative impact on my glucose levels, but didn’t necessarily have the largest impact on my blood ketone levels. It was the only carb for which I found myself ‘carbohydrate intolerant’, as it failed to return below the 115 mg/dl cut off mark. It also had potentially not even peaked at the 2-hour mark. It was still rising as of last reading, and was just over 130 mg/dl.
Blood Glucose Response to 50g of Effective Carbohydrate

carbohydrate-tolerance-glucose2

Blood Ketone Response to 50g of Effective Carbohydrate

carbohydrate-tolerance-ketones-2

Notes for Context & Additional Observations
  • Average readings of two or three blood glucose readings were taken for each blood glucose data point. From discussions with blood meter manufacturers I’ve learned that blood glucose meters have a high variance in their readings, so when you want accurate results you need to take several readings depending on the variance of the readings (two readings if the first two readings are < 0.5 mmol apart, or three readings if they are over 0.5 mmol apart). Researchers I’ve spoken to also follow this protocol to normalize readings.
  • Unfortunately I ran out of ketone strips for the last experiment which was the black beans. This was particularly annoying since the ketone response looked pretty unique for these – so I will likely rerun this particular test in future (especially as I dabble in black beans at Chipotle every once in a while).
  • I experienced some gut intolerance/ some negative symptoms from the lentils. This was the only carb that I experienced this with and seems to go against some assumptions that autoimmune/ auto-inflammatory responses are behind the largest glycemic responses to foods. The glycemic response in my case, was the lowest for lentils while it was the only one I experienced gut intolerance with.

Sleep

  1. Tool/ Tactic: Sleep is the most important physiological parameter, and poor sleep or inadequate sleep is excessively damaging to the body. Robb argues that if one feels good when going to sleep and waking up, then this is a reasonable indication that the body is performing in healthy shape. Tactics for improving sleep quality from Robb’s blog include: reducing light saturation, reducing noise in the environment, doing intense exercise earlier in the day (due to potential shift in circadian rhythm with late evening exercise), stopping all work a few hours before sleep and making a list of your thoughts before going to sleep – then agreeing with yourself that you are best able to take care of this list after a good night sleep.
  2. Tracking: In Robb’s opinion, it is key to subjectively track physiological concepts in our bodies and to make use of understanding these perceptions. For example, this entails paying attention to feeling tired before or rested after sleeping, or feeling background symptoms of inflammation (eg. in the joints). Robb discusses the use of Heart Rate Variability (HRV) for tracking sleep quality in his blog.

Tracking

Biomarkers

  • Waist to Hip RatioAnthropomorphic body markers, such as waist to hip ratio, body weight, or Body Mass Index (BMI) are useful for understanding carbohydrate tolerance, ex. as a complement to evaluating 7 Day Carb Test after a diet intervention. However, anthropomorphic markers are not very specific measures of insulin resistance. For example, people who are lean still face carb toxicity. Alternatively, people also sometimes face inflammation caused by the immune responses to other specific food types, ex. eggs or soy.
  • Fasting Blood Glucose: Elevated fasting glucose levels indicate a progression toward diabetes. Fasting glucose is usually taken first thing in the morning after an 8 hour fasting period and optimum levels range between 70 and 90 mg/dL.
  • Hemoglobin A1C: Used to identify the average plasma glucose concentration over prolonged periods. Higher levels of hemoglobin (A1C) indicate poorer control of blood glucose levels. Normal levels are less than 5.7%, pre-diabetes levels range between 5.7 to 6.4%, while higher than 6.4% is indicative of diabetes. Both fasting glucose levels and hemoglobin A1C are useful in identifying a level of blood sugar dysregulation, but cannot be used to quantify insulin resistance at an individual level.
  • HDL & LDL CholesterolHigh – Density Lipoprotein (HDL) is the traditional measure of ‘good cholesterol’ used by doctors and healthcare. Levels above 60 mg/dL are considered protective of cardiovascular disease. Low – Density Lipoprotein (LDL)) is the traditional measure of ‘bad cholesterol’ – the type which causes cardiovascular disease. Less than 100 mg/dL is considered an optimal level, while levels between 160-189 mg/dL increase the risk for cardiovascular disease. While both measures are important biomarkers, these are not indicative of insulin resistance status.
  • LPIR (Lipoprotein Insulin Resistance) Score: The LPIR Score is constructed as a weighted combination of 6 lipoprotein subclass measures and reflects the concentrations of each into one score. The final result ranges from 0 (most insulin sensitive) to 100 (most insulin resistant). Recent studies have been using the LPIR as a more accurate approach to assessing insulin resistance improvements via interventions.2
  • GlycA: A novel biomarker useful for predicting predisposition to insulin resistance and Type 2 diabetes3, cardiovascular diseses4 and inflammation-driven diseases including cancer5. Normal GlycA levels are below 400 μmol/L. Concentrations tested above this cut-off value are considered high and indicate the need to take steps towards preventing health issues.
  • FerritinSerum ferritin acts as a buffer against iron deficiency and iron overload. Levels are measured in medical laboratories as part of the workup for detecting iron-deficiency anemia. The ferritin levels measured usually have a direct correlation with the total amount of iron stored in the body. Female normal reference range is 12-150 ng/mL and for males it is 12-300 ng/mL.
  • HematocritThe hematocrit (Ht) is the volume percentage (vol%) of red blood cells in the blood. It is normally 45% for men and 40% for women. Robb checks ferriting and hematocrit as markers for tracking iron saturation which he plans to tackle by experimenting with donating blood and because these are useful in determining iron saturation which he suspects is the potential cause of some inflammation.

Lab Tests, Devices and Apps

  • NMR Lipoprofile: The LPIR score is part of the NMR Lipoprofile run by Labcorp (example report output here). It is an additional biomarker that was added to the panel more recently. The NMR Lipoprofile was originally run by the company LipoScience, which was acquired by Labcorp. As a result, Labcorp is now the company that runs the most advanced labs using NMR Lipoprotein analysis.
  • GlycA Test: The GlycA test is also offered by the company LabCorp.
  • BioForce HRV Set: BioForce HRV is a for tracking HRV which allows users to include their choice of sensors. There is a standard Bluetooth heart rate strap or a newly developed and finger sensor. Both sensors are compatible with all iOS and most Android devices and are constructed to deliver the precision necessary for accurate HRV measurements.

Tools & Tactics

Diet & Nutrition

  • 30 Day Diet Reset: A diet scheme based largely on a Paleo diet type template, aimed at healing the gut and re-normalizing the neuroregulation of appetite. Following Robb’s guidance in Wired to Eat, the 30 Day Diet Reset should be done before the 7 Day Carb Test such that the results of the test can be objective.
  • Fasting: Damien has seen improvements in his carb tolerance with the use of fasting as a tool in various formats. Having tracked his glucose and ketone levels, he concludes that the switching point of burning ketones, instead of glucose, occurs at approximately the 72-hour mark. Over several fasts, it becomes easier on the body to switch to ketogenic (therapeutic) ranges with the switch occurring quicker (e.g. 48-hour mark). The glucose/ketone ratio charts look flatter indicating a more controlled physiological response to fasting.6
  • Ketogenic Diet: A diet which restricts carbohydrate intake, over time causing the body to switch from using glucose to burning ketones as the main fuel. There are many potential benefits from ketogenic dieting. For most people who are overweight and insulin resistant, a lower carb intervention wins out as an approach to solving these health issues. A therapeutic state of ketosis is determined by reading fasting blood glucose levels (which should be below 80 mg/dL in the morning after 8h of no food intake), while β-hydroxybutyrate (blood ketones) should be higher than 0.8 mmol/L. See Episode 7 with Jimmy Moore on optimizing ketogenic diets.

Interventions

  • Donating Blood: Robb plans to experiment with donating blood, with the aim to reduce some potential low-grade inflammation caused by iron overload. He plans to track iron saturation before and after 3 months of donating blood on a consistent basis and reach conclusions based on the data. Robb compares his case to Chris Masterjohn who personally controls an iron toxicity predisposition by optimizing his blood donation schedule. Chris discusses this topic in Episode 46 of this show, an episode focused on micronutrient status optimization.

Tech & Devices

  • Blue Light Blocking Glasses: FDA registered blue light blocking glasses used for digital light eye strain prevention. These glasses are a useful way to reduce light saturation for a few hours a night before going to sleep.

Other People, Books & Resources

People

  • Christopher Kelly: An athlete and founder of Nourish Balance Thrive which is a service offering a science-based, personalized support program to help people regain optimal performance.
  • Marty KendallAn engineer with an interest in nutrition who seeks things numerically who founded Optimizing Nutrition. Marty aims to consolidate a range of paleo and ketogenic ideas into an algorithm that will enable an individual to tailor their diet and bring about health goals.
  • Tim Ferriss: An all-round successful man, who runs a podcast focused on deconstructing world-class performers – other successful people in various niches or businesses. His podcast is often ranked #1 across all of iTunes and is also selected for “Best of iTunes” for three years and running. Robb interviewed Tim in an episode of his podcast.
  • Joel JamiesonJoel Jamieson is considered among authority figures on strength and conditioning for combat sports and has trained many athletes since 2004. Joel stands behind the BioForceHRV project, aimed at tracking HRV and implementing it in optimizing exercise to the condition of your body. Joel introduced Robb to the BioForce tracking platform which he has used ever since.
  • Alessandro Ferretti: An optimum nutrition researcher who formed Equilibria Health Ltd, which is now recognized as one of the leading providers of nutrition education in the UK. Alessandro actively does Judo and Karate and has discovered that he performs efficiently with a ketogenic diet – meaning feeling energetic, being able to undertake fasts, and remain lean.
  • Bill Lagakos: A biochemistry professor focused on circadian rhythms and nutrition. Following on Bill’s work, Robb has adjusted his diet to time-restricted eating, meaning that shortened feeding windows are assumed to be beneficial for a variety of physiological reasons. Moreover, based on his research in biological (circadian) rhythms, Bill Lagos advocates the idea that more carbohydrates should be eaten earlier in the day, such that carbohydrate backloading can be avoided. Because of these reasons, Robb has adjusted his fasts to approximately 14-16h, whereas before he would 18h fasts. Following a fast Robb eats a robust full meal, but he usually times this with jiu-jitsu exercise 2-3 hours later. This is an example of optimizing both how diet volume and the intensity of exercise.
  • Chris Masterjohn: Robb appreciates Chris’s ability to dive into the biochemistry and pathophysiology of when things are right and wrong in the body, as well as to develop whole food and supplement solutions based on his research. Chris was a guest on our show in Episode 46.
  • William Cromwell: A physical chemist who studied NMR spectra technology lipoproteins, serving as Director of Cardiovascular Disease at LabCorp.

Books

  • The Paleo Solution: A book by Robb Wolf following his perspective as both scientist and coach on the benefits of Paleo dieting, and this along with exercise and lifestyle changes can change one’s appearance and health for the better.
  • Wired to Eat: A book written by Robb which starts with the 30-Day Reset to help people restore normalized blood sugar levels, repair appetite regulation, and reverse insulin resistance. This book also features standard Paleo – based recipes and meal plans for people who suffer from autoimmune diseases, as well as advice on eating a ketogenic diet.
  • Myth of Stress: A book explaining how much of what we perceive as stressful in day-to-day life is actually generated by our brain’s anxiety response, but is not actually a legitimate stressor in terms of evolutionary times scenarios, when our brains evolved the stress response. Robb interviewed author Andrew Bernstein in an episode of his podcast.

Other

  • I, Caveman Show: Robb took part in this Discovery Channel reality show where they had to live mimicking the stone – age hunters and gatherers. It took place at 8,500 feet in the Colorado Mountains.

Full Interview Transcript

Click Here to Read Transcript
(0:03:45) [Damien Blenkinsopp]: Robb, thank you so much for joining the show.

[Robb Wolf]: Hey, huge honor to be here, thanks.

[Damien Blenkinsopp]: Yeah, it’s a huge honor on my side, because you got me back into eating meat back in 2010, just as we discussed a few minutes ago. That was great and that vastly improved my health, so thank you for that.

[Robb Wolf]: Awesome, awesome.

(0:04:01) [Damien Blenkinsopp]: Yeah.  So you just released this book, Wired to Eat, which I went through, and it’s building on what you’ve done in the past, and also looking at some of the things you’ve learned over time with all the practical experience you’ve had implementing this.

What would you say is basically the crux behind this book? Is it the neuroregulation of appetite, or how would you think about it?

[Robb Wolf]: Yeah, it’s kind of two pieces. So the front of the book is really starting this conversation from the perspective of the neuroregulation of appetite.

So I’m kind of known as being one of the Paleo guys, and I definitely use that evolutionary biology, evolutionary medicine framework to inform the question and answer process that I bring to strength and conditioning and nutrition, and what have you, but it’s a starting place. It’s not the endpoint.

And I think that’s where, in some ways, the efficacy of that whole methodology has been lost. People assume that that’s where you start and stop. Whereas for me it’s always been this is the starting place.

We’re not yet able to take a Star Trek type scanner and run it from toenails to earlobes and then say okay you need to eat this and train this way. Stuff like that may happen eventually, but we’re still very much in this empirical process.

So then if we’re in this empirical experimentation process, where the heck do you start? And I throw out this really insane, over-the-top, greasy used-car salesman notion that maybe evolutionary biology can inform some of where we start this health and performance story from.

There’s this model in evolutionary biology called the Discordance Theory. That’s basically you have an organism that is pretty well matched for it’s environment. The environment can be the weather, the food, it can be a ton of different factors, it could be bacterial or parasitical. But if things change, it could be beneficial, negative, or it could be neutral.

But if we start seeing disease processes prop up that we don’t see in the natural free-living environment, or in the pre-environmental change story, then maybe there’s something to be learned from that. That’s my crazy suggestion is that possibly our genetics are wired up for a life way and a time that no longer exists, and that as great as so many of the elements of modern civilization are, there might be downsides to it.

For example, antibiotics are amazing for preventing septic illness and death, but there might be some downsides related to mitochondrial function in our own bodies, and then changes in our gut microbiome, which we’re now understanding may have huge implications for our overall health.

Again, I use this as an orientation tool. And at the beginning of Wired to Eat I’m laying that foundation with the neuoregulation of appetite. Really trying to understand if we looked at high carb diets or low carb diets, what are the things that allow people to eat in a way that they support their activity level, support a healthy body composition but tend not to overeat.

And there are some commonalities there. The efficacy of some of these nutritional approaches becomes really obvious why they work when we better understand the neuroregulation of appetite.

And the goal on the front end of this – and it’s kind of funny because it’s fairly touchy feeling stuff – but my real goal is to help people understand that it’s not your fault if you find it difficult living in the modern world and navigating the snack aisle of the supermarket. It’s totally reasonable and understandable.

Now I’m not one of the fat accepting guys either. I do recognize that overweight and metabolic issues are damaging to our health. They are a huge cost to society.

So I’m not recommending that we just roll over and die and let life have it’s way with us, but I’m suggesting that if we can unpack all that emotional baggage and understand that this process might be hard but it’s doable, then we’re starting off at a good footing.

And then the implementation part of the book is where we get really granular in a more progressive fashion. We start things off with a triage process where we do some subjective elements, such as asking how do you feel between meals, what’s your cognitive function like, how long can you go between meals and still maintain good physical and cognitive performance.

And then we get more specific. We look at things like the waist to hip ratio, we look at fasting blood glucose. We really lean heavily on this thing called the LPIR score, the lipoprotein insulin resistance score, because for me it’s kind of the most powerful direct means for understanding where we are on this insulin sensitivity insulin resistance spectrum.

And if we are more insulin resistance then we tend to do better on a lower carb intake. And there’s a lot of variability with that. But we also have people that are overweight or experiencing some other health related issues but they are actually insulin sensitive, and these are the people that tend to do better on that moderate to high protein, high carb, low fat diet. So there are examples of both ends of this spectrum working pretty well.

But we use this triage process to get a handle on where we are in that insulin sensitivity insulin resistance spectrum. We use a 30 day reset, based largely around a Paleo diet type template, to heal the gut, re-normalize the neuroregulation of appetite. And then from there we use the 7 Day Carb Test.

There we pick a battery of different carb foods and we eat an allotted amount, which is 50 grams of effective carbohydrate. We check our blood glucose at a two hour mark. If your blood glucose is at or below a certain level, that’s usually an indicator that’s a good amount and type of carb for you.

If it’s above that, then we start asking some questions about should we reduce the portion size or is this really a good food for you. Because sometimes our elevated blood glucose level is not just from the carbohydrate content of the food but it’s from the immunogentic properties of the food.

If someone is reactive to wheat or eggs or soy, they may actually get a significantly elevated blood glucose response. And it’s not from carbohydrate, it’s from the stress response that occurs when we eat a food that we have an immunogenic response.

[Damien Blenkinsopp]: Thanks Robb. A real big download there.

[Robb Wolf]: Yeah, that was… (laughter)

(0:10:46) [Damien Blenkinsopp]: Let’s talk about a couple of the things you mentioned that stood out.

First of all you were talking about insulin resistance.

Do you see this as one of the cruxes of the issues? Is this one of the main factors? I know you’ve had a lot of practical experience in clinics and studies, and so on. So what have you seen in the populations out there in terms of how important the insulin resistant piece is?

[Robb Wolf]: Yeah. And this is a really contentious topis because people are still in pissing and squabbling matches about what brings about insulin resistance. Is it just in response to elevated insulin levels?

I think it was an interesting theory but over the course of time that has not borne out to be the best theory. It still seems to relate to an overabundance of energy causing systemic inflammatory responses within the cells that then tends to up-regulate this insulin resistant response.

But once the person is insulin resistant, particularly when they are heading down this road towards prediabetes and potentially diabetes, there is without a doubt one intervention that seems to work remarkably well. That’s reducing carbohydrate level to a point where it’s no longer toxic to the individual.

My analogy to this is basically photo exposure in getting a sunburn. Depending on what type of skin pigmentation you have you will be able to handle greater or lesser amounts of UV radiation before you get a sunburn. And if you do have a sunburn, there’s really only one intervention that makes sense, and that’s to reduce your exposure to the toxic levels of UV radiation.

And so that insulin resistance and the resulting metabolic derangement, which includes but definitely isn’t limited to elevated blood glucose levels, you can tackle that in a variety of ways. You can starve people down on a high carb low fat diet, and it can work. But in that insulin resistant state we tend to have a really serious dysregulation of the appetite and the tendency to want to eat a lot of carbohydrate.

And so this is where for most people who are overweight and insulin resistant that lower carb approach seems to work pretty magically. Even in these free-living populations where people can make a variety of choices, the lower carb intervention tends to win out.

[Damien Blenkinsopp]: I guess that refers to the saying carb-cravings, that we often hear.

I don’t know if you’ve seen this, but some people have a lot of difficulty with fasting. They’ll have dreams about food if they fast for 24 hours. I know friends who have fasted with me [for whom] it was a bit difficult. Or they get ‘hangry’ – I know that’s a term you coined in your book as well.

Have you found that that correlates with some of the lab tests? Is that kind of a symptom of potential insulin resistance?

[Robb Wolf]: Yeah. So here’s a good example of this.

My wife and I did this 7 Day Carb Test, and we’ve known empirically that I just don’t do as well with carbs.

I remain 100 percent gluten free because if I get a gluten dose, the first bathroom I hit will require a priest, an exorcism, and probably needs to be bricked over and never used again. So there’s no upside to consuming gluten such that I willingly do it. I get some cross-contamination stuff occasionally.

But I’ll have a little rice, or some corn, here and there. We’ll go to Mexican food or Thai food and I’ll kick my heels up once in a while. And I usually feel pretty rough. And I may feel rough for a day or two afterward.

Whereas my wife, I’ll ask her, “Hey are you feeling kind of carb headed from that?” And she says, “Yeah, it lasted for 20 minutes.” I wonder what’s going on with that.

And so we dug into that deeper, using this 7 Day Carb Test. And we ate the same amount of carbs – 50 grams of effective carbohydrate — and we picked the same foods. It was, white rice, white potatoes, sweet potatoes, applesauce, gluten-free bread, and a couple other items. And it was really interesting.

So with the white rice, at two hours post-meal my blood glucose was still in the 180s, damn near diabetic levels. Terrible. And I felt terrible. And Nicki at two hours was a 121, 122 or something like that. Just across the board, she had remarkably better blood glucose levels than I did.

So that was interesting, and it was kind of validative of what we had seen previously. So then kind of out of nowhere she said, “Hey, I’m going to do a dinner to dinner fast.” I was like, okay, that sounds good. We’ll check that out. And it was interesting.

So she did her dinner, and didn’t eat again the following morning. She worked out. We have a 10 month old Rhodesian ridgeback puppy that requires a ton of training, and she’s really diligent in training the dog, but it’s active. So she did her workout and then she’s running the dog around.

And we have two daughters under the age of five. So it’s a really active life that we both live, and particularly my wife being at home in that scene most of the time. By 23 hours she was getting hungry, but she was still totally cognitively on point. She felt good.

Right at that 24 hour mark we checked her blood glucose level, which was 71. That’s low, but a good low, particularly for a fasting scenario. And her ketones were at a 0.8. So she was already in a therapeutic ketosis range. And she was effectively just right at that 24 hour mark.

This is something that we just don’t see all that often in Westernized populations. This exact type of study hasn’t really been done specifically in hunter-gatherers and pre-Westernized societies, but what we see in those situations is these folks may go a day or two without eating.

They are hungry, they are definitely wanting to eat, but they don’t have a decrease in physical performance or cognitive function. You aren’t a very effective hunter-gatherer or horticulturalist if you are leaning against a tree drooling on yourself because you are in metabolic shutdown because you have to eat every two hours to keep yourself going.

So your question was — and I know that this is the longest answer to the shortest question in history. I seem to be good for that. But the question, was do we see specific lab values that tie into this?

What I’ve noticed is a tendency towards, if you are more insulin sensitive – and that will be determined by your total choleric load, your stress load, your sleep, your gut microbiome. There are lots of factors that go into that.

But if you tend to be more insulin sensitive, we tend to see more metabolic flexibility. If you have a higher carb meal, it doesn’t really knock you out and you don’t get super high blood glucose levels. You don’t have hypoglycemic crashes. And on the flip-side of that, if you need to go 6, 10, 12, 24 hours without eating, you may be hungry but you are still functional.

Whereas that insulin resistant individual, they do a piss poor job of dealing with large carbohydrate boluses. They get a super high blood glucose level, they get a rebound hypoglycemic response. And then when they have carbohydrates restricted significantly, the first couple of days – usually 72 hours – they’re in hell, because they have neither adequate glucose to fuel what’s going on and they’ve not yet kicked over to converting fats into ketone bodies in an effective way.

There are hormonally driven elements to this, and then there are also possibly mitochondrial considerations, where the mitochondria themselves may be damaged to a degree. It’s like taking a lawnmower that’s been out in the garage for two years, and it’s got some water in the carburetor and you just have to really rip the cord on that thing to get it to turn over and start using the fuel that you want it to use.

So let me know if I answered that. I know it was a long, rambly story.

(0:18:50) [Damien Blenkinsopp]: Yeah, I think you really did. Out of interest, because you noted that your blood sugar spiked to 180, how long have you been low carb for?

In a sense it seems like it’s not therapeutic, even if you’ve been low carb and Paleo for a long time, it doesn’t necessarily mean it’s going to mend these type of things, this dysregulation when you eat some rice.

[Robb Wolf]: Yeah, it’s interesting. Over the course of time, I’ve been able to push that carb tolerance up.

So now on my heavier Brazilian jiu-jitsu days I’ll be somewhere between 120-150 grams of carbs, and I do fine with that. But I also keep an eye on the types, and then I tend to put more of the carbs in the post-workout period, and similar to that. Whereas before 120 grams of carbs would have just crushed me.

So I’ve definitely recovered a lot, relative to where I was previously. And I’m still tinkering. I’m not sure if there’s still some gut health considerations. I’m actually just getting ready to start donating blood on a consistent fashion, because of some thoughts around some potential low-grade inflammation from iron overload.

So I’m going to play with that, and what I’ll do with that is I’ll probably go through three months of consistently donating blood, check the before and after numbers with regards to ferritin and iron saturation, hematocrit. And if we get to whatever delta we get from the start and the finish with that, then I’m going to revisit this 7 Day Carb Test and see if we get some improvements on that.

So that might be one final stone that I need to turn over and explore. I know Chris Masterjohn had talked about really reversing some significant insulin resistance. He had no idea what was going on, and he felt it was largely driven by that iron overload status.

(0:21:05) [Damien Blenkinsopp]: Wow, that’s interesting.

I have iron overload as well, and many other things like infections. So for me it’s a bit difficult to pinpoint what it is. But my carb tolerance has got a lot better with fasts.

So I’ve tracked with fasts, and I’ve seen that switching point you were just talking about, the 72 hours. It gets a lot easier and would happen a lot quicker as well. My ketones would go up faster, and glucose would go down quicker. And it’s been flatter over time. So it’s really, really interesting.

So you mentioned another panel just a bit earlier, a lipoprotein insulin resistance panel. What’s that?

[Robb Wolf]: So people are usually familiar with HDL cholesterol and LDL cholesterol. The cholesterol is a fat soluble, not water soluble, substance. So it would be like trying to mix oil and water together; it just doesn’t work that well.

But we need to move these substances around the body, so there are these things called lipoproteins, which actually are the vehicle that carries the cholesterol passenger around the body. And triglycerides are also, to some degree, carried around [by these], although they have their own carrier molecule as well. But these lipoproteins usually correlate pretty directly with the amount of cholesterol that we have, both HDL and LDL cholesterol, but not always.

There are certain folks that exhibit this phenomena called discordance, where you may have lots and lots of small dense lipoprotein particles and then a relatively low cholesterol level. And these are the folks that often, like a 35 year old triathlete and they work out all the time but they’re also a shift working firefighter or something and they suffer a heart attack at age 35 or 40.

And it’s like, wow, we never saw that coming. Their triglyceride to HDL ratio looks pretty good, which is a decent correlate or indicator of insulin sensitivity. And then their total cholesterol levels didn’t look that high, but under the hood looking deeper the lipoprotein numbers were super high.

And so there’s also a way that we can look at the lipoprotein numbers and their relative ratios. And there have been some really phenomenal correlation studies to tie this link together so that we can tie that lipoprotein insulin resistant score to the real world.

And there are some other methods for tracking that. There’s looking at fasting blood glucose, but there are limitations to that. There are ways that that can be misinterpreted both on the up and the downside. Fasting insulin is similar, it’s helpful but there are ways that can be circumvented. A1C [is another].

So we do like looking at several of these numbers, in the beginning in particular, and then checking back on them periodically, because it provides a lens. In particular a lens to help us better understand that 7 Day Carb Test. Because those carbohydrate numbers just in isolation can also be a little bit confusing.

But with that lipoprotein insulin resistant score, what we found in the police and fire populations that we work with – I’m on the Board of Directors of the Medical Clinic here in Reno, Nevada – we found that with the other methods for tracking insulin resistance we were missing people, particularly folks that were sleep-deprived and/or hyper-vigilante.

So they had consistent adrenal cortical response, some HPT axis dysregulation. Those people were insulin resistant, and often times significantly so, but we didn’t see it in fasting insulin levels. Specifically blood glucose levels may not have been that bad at that point, but we were seeing some really consistent long term insulin resistance when we looked at that LPIR score.

(0:24:28) [Damien Blenkinsopp]: So it sounds like it could be uncovering people that we normally miss.

How about the waist to hip ratio? That’s a nice easy thing that anyone can do at home. Did you also find the same thing, that it doesn’t necessarily capture people? Like you can be pretty thin and slim and have these same issues.

(0:24:53) [Robb Wolf]: Absolutely, and that’s where again we use it to build a case, but you can’t hang your hat 100 percent on anthropometric measures like that.

[Damien Blenkinsopp]: Great. Have you looked at how people can basically recover carb tolerance? Or have you seen that kind of period, the timeline?

Any indication of, say they did a 7 Day Carb Test now, when would it be useful to retest? Maybe 6 months after following a clear Paleo diet and all of your proscriptions. You talk about all of them.

[Robb Wolf]: That’s a really good question. Part of the inspiration for even doing the 7 Day Carb Test came out of research from the Weizmann Institute in Israel, and it was looking at personalized nutrition by tracking the individual glycemic response.

And what they did in these folks is they had them wear a CGM, a continuous blood glucose monitor – just a little disk that gets slapped on the back of your arm – and it measures your blood glucose levels once a minute, every minute for the duration of the test. I forget, but it was two or three weeks and they had 800 people signed up on the study.

So it was a massive amount of data; they had over a million blood glucose samples. They then did a gut microbiome sequencing on these folks, they did a full genetic analysis, and the standard kind of lipidology based blood work. And then they started feeding these people different meals. And the blood glucose responses were all over the map.

It was similar to myself and my wife, where one person would eat white rice and [their] blood glucose would go to the moon, [whereas] another person would eat white rice and they had a barely perceptible increase in their blood glucose response.

And then there were wacky things like hummus. Even though I’m the Paleo guy and legumes are theoretically problematic, hummus is protein and fat and fiber. There’s hardly any carbohydrate to it, but hummus was about a coin toss as to whether or not you had a good or a bad blood glucose response.

And the one thing that they did figure out with this was that if you determine the amounts and types of food that kept your blood glucose within lower bound levels, then your gut microbiome tended to improve and your inflammation and insulin sensitivity tended to improve over time.

So I don’t know that I have an exact timeline on this that I could relate, but what appears to happen is if you eat in a way where you’re not consistently deranging your blood glucose, which seems to have knock-on effects with the gut microbiome. There are some interesting theories around how acellular or processed carbohydrate can shift the way that our gut microbiome is existing. It’s a pretty interesting and elegant model.

But if you keep things within good bounds, then things tend to improve in kind of a virtuous cycle, and then conversely if you are consistently driving blood glucose out of what we would consider to be healthy bound, the gut microbiome tends to shift towards a more pro-inflammatory state. We see elevated inflammatory cytokines on circulation, we tend to see elevations in insulin resistance.

And in the book I make a recommendation that maybe quarterly. We don’t necessarily need to do a full reset as far as a 7 Day Carb Test, but I really recommend sitting down and just paying attention.

“Hey, how long can I go between meals and still feel good? If I do a little bit of fasting training, how do I feel with that? How’s my sleep? What’s my creakiness in my joints, what’s my subjective measures of inflammation?”

I am fairly geeked-out on the quantified self stuff, and I find a lot of it valuable, but I still like to get people back in their own skin so they can get a sense of where things are going right or potentially going wrong.

And a quarterly recheck, at least on the subjective level, seems to be frequent enough that if things are sliding sideways we haven’t slid so far that it’s terribly hard to get things back on a good track. But it’s also not so frequent that you just throw your hands up in disgust and you’re just done with the whole process and don’t pay attention to anything anymore.

(0:29:39) [Damien Blenkinsopp]: Yeah, absolutely. On my own journey I’ve quantified so much stuff, but at the end of the day it’s how you feel that matters. And you can even improve a whole bunch of biomarkers, but if you don’t feel better or feel less inflammation it’s not that helpful. It can be insightful and give you clues, but we’re still at quite a rudimentary level yet.

I actually interviewed Eran Segal in just the last episode of this podcast, actually. He inspired me to get into CGM, amongst some other people. So ever since I’ve been playing around that and have found it very instructive.

And not just for the food intake, but also sleep, which you talk about a lot in your book, and stress.

How important do you think those are in your experience, compared to the food? Because we always talk about the carbs and the food.

[Robb Wolf]: Even though I’m the food guy and we used to run a gym, so you would think that I would say that exercise is most important, or exercise and nutrition, but sleep is it. I mean, sleep is it. And here’s my argument for that.

You could eat the most wretched diet imaginable, and it’s going to be hard for you to kill yourself in anything short of a couple of decades. Some people can do it, but it takes a pretty Herculean effort to do yourself in with even the worst dietary practices you can imagine.

But sleep-deprivation is so injurious to our physiology that the Guinness Book of World Records, they will let you jump a rocket motorcycle across the Grand Canyon, they’ll let you juggle chainsaws that are lit on fire, but they will no longer entertain people trying to do unbroken longer periods of sleep-deprivation. The last two people that have tried it, they got right around that 9 to 11 day mark and they just died. And they don’t know why, but they are dead rather quickly.

So the sleep piece is just so incredibly important. The stress piece is important too, but there was a great book that I read and I interviewed the author, it’s called the Myth of Stress. It was really a fascinating reframing of this whole stress story. And so much of what we experience in day-to-day life that we perceive to be stress is completely generated between our own ears.

It’s anxiety about finances, it’s anxiety about how this meeting is going to go with our boss. It’s all these different things that really at the end of the day, we have an opportunity to either let this stuff eat us alive, or we can reframe it and just say that’s not actually a real threat, and so I don’t have anything to be worried about. So there’s actually comparatively little in the modern world that is in fact a legit stressor.

Now the caveat with that, we do a lot of work with police, military and fire, and those folks legitimately live in hyper-vigilant states a lot, because they have life-or-death scenarios that they’re dealing with every day all the time. So there are caveats to that.

But a shlep like me, where I live out on a small farm, we have some animals, I have two kids, I do the business stuff that I do, I can let myself get spun up and feel stressed out. Like, oh my god, one of the goats got bit by the neighbor’s dog.

This did happen this time last year, and the poor goat it’s eat got peeled off. But it was fine, we had a vet come out and gave it some antibiotics. We had to catch the little bugger and wrap it’s ear up for about a week, and then he was totally fine.

But when it first went down, I was like, why did we ever move out here, what are we doing, this is a waste of my time. And all this just internal dialogue and stress. Then I stopped and I was like, well I love living here. The kids love the animals.

There’s sometimes pain in the ass elements to this, but I’ve turned this from an acute event into what is now for me a long-term stressor, but I did it to myself. So I would throw out there that a lot of what we perceive to be stress is mainly self-generated.

And again, circling back to the sleep part, I just can’t think of a greater return on investment than trying to go to bed a little earlier, sleep a little longer, within the boundaries of what’s normal for you. Just blackout your room, have a really solid sleep hygiene process where you go to the bed at the same time each night.

It may not do wonders for your social life, but then again maybe it will because you may not be a cranky cantankerous prick because you’re actually well rested. So it’s hard to tell. And it’s liable to pull 5 years of aging off of you in just a matter of a week.

[Damien Blenkinsopp]: Yeah. Sleep is the hardest part.

Just curious, do you use anything to track your sleep? To try and keep a bit more responsible, or have you seen anything that works for people?

[Robb Wolf]: Really HRV is kind of the best thing that I’ve seen. Some of these actigraphy things are interesting. It is interesting, again, even though I’m a biochemist, I don’t know if I’ve weighed and measured so many things that I’m just like, oh my god I don’t want to do it anymore.

But I’ve just gotten into a point now, and it’s interesting. Folks like Tim Ferriss and some other folks I’ve interviewed with, they were like, “What’s your morning ritual?” And because I have kids, the morning ritual is super variable. I don’t know if somebody pooped their pants, and they’ve got poop from their earlobes to their toenails. That’s a way different morning than if that doesn’t happen.

But what I have found is I tend to have really good control over my go-to-bed ritual. So when the sun goes down – and this varies with the seasons, our days get longer so we stay up later – but when the sun goes down then, we installed dimmer switches in our house when we did our remodel last year and we drop the lights down to a super low level. We put on some blue blocker Swannie sunglasses.

Usually not too long after that I do a little bit of reading and I just fall asleep. And it’s like a ninja blow dart hits me. And when I’m consistent with that, and if I also happen to be tracking my HRV pretty consistently, I just see that HRV score improve. And then if I do have an off-night of sleep, we see some pretty immediate impact on that.

But the actigraphy, I haven’t found to be super helpful. If we had someone that was waking up in the middle of the night or something like that and we had some HRV score feedback. The thing about HRV is it tells you something is up, but it doesn’t tell you what that thing is.

It could be that we’re having a low blood sugar response in the middle of the night, so we get some cortisol release, and that suppresses melatonin production, so it pops us up out of sleep. So maybe we need more calories overall, maybe we need more carbs near dinner. Maybe we need fewer carbs near dinner, because some people are experiencing that rebound hypoglycemic event.

There’s not a one size fits all answer with it, but in general I just kind of gauge [when] I wake up in the morning, I stand up [and see] do I feel clear headed, do my joints ache because of jiu-jitsu and being 45, or do I feel good? And if all of that stuff feels good, then I’m pretty good to go. And particularly if that HRV score just stays nice and consistent.

(0:36:41) [Damien Blenkinsopp]: Yeah. I’ve been a fan of HRV also for a long time. I’ve been tracking it.

I also find it difficult, the same way you do. It captures everything, and if you’re someone who’s got some kind of chronic health or some issue like that on top of potentially not sleeping correctly, over-training. You’re doing Brazilian jiu-jitsu, so I’m sure that’s happened a few times.

And there are these different factors and you have to kind of piece the story together. But it can give you that overall number.

I’m just curious, what do you use, do you use a sort of an app or is there something specific you like because of convenience or something?

[Robb Wolf]: Yeah, I’m just kind of old school. Joel Jamieson hooked me up with the BioForce platform and I’ve pretty much just like hung out on that.

I know there are a lot of cool stuff out there and I do have a few others but I’m again, a little busy and kind of lazy with that stuff. I’ll check in on it occasionally, but it’s generally a deal where once I get a baseline established, and it’s a thing again that I know if I’m getting into bed, falling asleep, and waking up feeling good, everything else is fine.

And then on my training side I do a little strength and conditioning, a little bit of weight work, gymnastics, and also some low level cardio to support the Brazilian jiu-jitsu. I just keep my volume and intensity really modest on that. 80 percent of my rolling is more in a drilling and aerobic fashion, and about 20 percent is that white buffalo in the sky.

Like the 20 year old three stripe white belt is trying to take my head off my shoulders, and so it’s a battle for survival. But I don’t do too many of those. Maybe one day a week that there’s some pretty hard training that goes on.

And so long as I do that, everything is good. Everything is really, really good. I just try to make very small, incremental progress, in mainly the jiu-jitsu side, and so all of my strength work, all my conditioning work, all of that is of a remarkably low volume and intensity for the most part. Just to support jiu-jitsu.

If I feel the least bit knackered after a cardio session or something, I went too hard. Because I need to save that energy for rolling, and not for getting better at the Airdyne or something like that.

[Damien Blenkinsopp]: Yeah.

So when you’re talking about volume, how many hours are you doing of exercise, jiu-jitsu, and all kind of mixed together?

[Robb Wolf]: So jiu-jitsu is between three to five days a week, and usually an hour to two. Shorter classes if I’m time pressured, then I get the one hour class which is a mix of drilling and then a little bit of live rolling.

A couple days a week I usually will stay for a half hour to an hour of just continuous live rolling. I try to grab partners where we don’t set a timer and we just try to roll. We just try to keep moving, and it forces a pace that you could maintain for about an hour straight. And I really, really like that. You get lots of repetitions in in that regard.

And then as far as the weights and gymnastics stuff, I just drop in a little bit of gymnastics bodies, mobility and strength work during the course of my work day. Usually once a week I either squat or deadlift. Once a week I might do some heavier weighted press and pull weight room style stuff for the upper body.

But those weight room workouts, I warm up and I’m done in less than 20 minutes. Occasionally a little longer than that if I’m doing a lot of mobility work in between, but even then it’s not like I’m doing a CrossFit work out.

I have two minutes of rest between sets. I’ll do a set of weighted chins, a set of weighted dips, and then some weighted shoulder dislocates to work on my thoracic mobility in between those sets. So it’s not a frenetic pace.

And then the recovery cardio, I will go longer on that if I can. It may be 40 or 60 minutes occasionally, but a lot of those – my oldest daughter now is five years old and has gotten pretty good on her little dirt bike. So I will drive her and and myself over to a park right next to our house that has some dirt trails and she’ll ride her bike and I’ll run at a nice easy pace. So I’m outside and I’m spending time with my kids.

So there’s like somewhere between three and maybe eight hours a week of jiu-jitsu, there’s maybe two more hours total a week of weights and cardio. But I do try to do a ton of stuff. I’ll stick the younger kid in a backpack and go for a hike for as long as she will put up with it. We have a three acre farm where we have animals to deal with, and we just run around playing hide and seek, and stuff like that.

So I do a lot of physical activity running around with the kids, but in the gym stuff between jiu-jitsu and strength and conditioning and all that is less than 10 hours a week, for sure.

[Damien Blenkinsopp]: Yeah, so you keep the intensity monitored.

I just looked up the Myth of Stress. Was that Andrew Bernstein?

[Robb Wolf]: Yeah, Andrew Bernstein.

[Damien Blenkinsopp]: Okay. Bernstein. Cool. That sounds really, really interesting.

Does that tie in with the gratitude stuff? We hear a lot about gratitude and I’ve been practicing it for a little while. I think a lot of people have. Did he mention that at all?

[Robb Wolf]: Yeah. He would be a great interview. He’s a solid guy, a really, really good guy.

(00:41:35) [Damien Blenkinsopp]: Yeah. Excellent.

Okay. So I thought we’d also jump into a little bit of ketones, ketosis, and fasting, because I know you’ve played around with this yourself and your levels of carb. And it’s such a big topic at the moment.

You’ve spoken a bit about you can’t really do the really low carb and the Brazilian jiu-jitsu and that you can’t get away with it. What’s you overall feeling on the whole ketones and ketodiet?

[Robb Wolf]: Yeah, the last chapter of the book is called Hammers, Drills, and Ketosis: the one tool your doctor will never use. Fortunately, that story is changing. Therapeutic fasting and ketogenic diets are incredibly powerful as potential adjuvants or adjuncts to things like epileptic treatments, potentially working in synergy with conventional cancer therapeutics.

Just huge potential there, but it’s crazy because you don’t see people get into huge pissing matches about whether or not you should use a hammer, a screwdriver, or a handsaw to get something done. If you’ve got a 2×4 and you want to cut it cleanly into two pieces, a hammer and a screwdriver are terrible options, the handsaw is a great option. There’s just not a lot of drama around that.

But then whether or not you should be higher carb or lower carb becomes this religious doctrine thing. And there is a little more nuance to it, there is a little more depth. But just empirically we’ve seen people do pretty well at the power athlete end of the spectrum, the real short time indexing end of the spectrum, and quite low carb.

And we’ve also seen some people doing this ultra-endurance work at a pretty good level going very low carb. And interestingly that looks like catering to the ATP creatine phosphate pathway and also mainly the aerobic pathway.

Where we have a kind of deadzone, a no-man’s land, appears to be these really glycalitically demanding sports like soccer and MMA and CrossFit and jiu-jitsu. And there’s just, man you don’t see a lot of just empirical success there. You see people like me that try, and try, and try.

There are a few examples, there are a few people out there that are figuring out how to do it. Probably the highest level, most sophisticated person I’ve seen looking at this problem is Alessandro Ferretti. He’s in the UK. Man, that guy is smart.

And he is just doing some shockingly interesting work looking at [it]. And he does Judo and Karate, so not exactly the same as Brazilian jiu-jitsu but he’s found he runs great on a ketogenic diet, he has great energy, he can fast, and he’s lean. All the stuff is great, but then he will get kind of adrenalized and burned out in the process of doing too much high-intensity activity.

And what he’s done is just try to map out the volume and the intensity of the training he will be doing, and then match that with a maltodextrin solution or maybe a maltodextrin plus fructose, because there are some arguments for repleting some of the hepatic glycogen preferentially. And he does some really amazing work.

Now, for me, because I’m kind of lazy, it also looks a little bit like a calculus problem. Alessandro is like six times smarter than I am, and he runs a really well done clinical intervention, where they’re just collecting tons of data on people.

I’m kind of a knuckle-dragger. So where I’ve arrived out with all the stuff is I just tend to eat between 75 to 120 grams of carbs a day. Higher end on training days, lower end on non-training days.

But the overall story I think is ketosis and fasting hold enormous therapeutic potential. Potentially some great performance enhancement under certain circumstances, but it’s also a powerful tool. And like any other powerful tool it can be misused, or inappropriately used.

[Damien Blenkinsopp]: Yeah, Absolutely. I know Alessandro, I talk to him quite often too. He’s a great guy. I have to get him on this show soon.

[Robb Wolf]: Yeah.

(0:45:35) [Damien Blenkinsopp]: So thanks for all of this. Last thing on this carb thing is it doesn’t sound like you time your carbs at all before or after training, or anything like that. It sounds like you’re very much focused on the practical, which is probably 80 percent of society who aren’t super self-disciplined and robotic about this.

[Robb Wolf]: Yeah, I do time it a fair amount, in following a guy Bill Lagakos. He’s a professor of Biochemistry, I believe, in the East Coast, and really super sharp on circadian rhythms. And he kind of alerted me to this idea that time restricted feeding, the shortened feeding windows, seem to be quite beneficial for a variety of reasons.

But he made a really strong case for this idea that we would do better to eat more of the calories and more of the carbs earlier in the day. And I know there’s carb backloading. This becomes, again, if you want to get a contentious pissing match on the internet, just throw one of these concepts out there.

But Bill made a really interesting case that there’s an argument based off of circadian biology that we should eat more carbs, more calories earlier. And that is one thing that I’ve focused on.

So I will do, whereas before I might do an 18 hour fast, I’ll just do 14 and 16 hours now. And I will do a really robust meal, and then maybe 2 to 3 hours after that I have a Jiu-jitsu session. And then that meal ends up being much higher in carbohydrate. And I again kind of base it off the volume and intensity.

But then usually my dinner… I do two to three meals a day. Probably 80 percent of the days it’s three meals, 20 percent of the days it’s two meals, and that tends to be more the weekends when I’m just hanging out with family and I just want to be lazy and I don’t want to cook yet another meal for myself and all that.

I do partition closer to the pre-workout period but I’m not like taking a maltodextrine drink right before and one right after, and all that type of stuff. There might be some upside to that, but I have noticed for my digestion that the digestive process, for me, does much better with less frequent feedings, and less refined foods and all that type of stuff.

So I’ve had a pretty darn good degree of success with that so far. And I mean it is dead simple. I would be hard-pressed to think of a more simplistic way of eating and fueling. It is really, really simple.

But at 45 years old, I just got my purple belt last Saturday and I’m doing great on that. And body composition is good. My wife is still willing to sleep with me with the lights on most nights. So life’s pretty good in that regard.

[Damien Blenkinsopp]: Congrats, I saw that purple belt. It’s quite an achievement.

[Robb Wolf]: Thank you.

[Damien Blenkinsopp]: So is there anything we’ve missed that’s important about your most recent thinking on this subject?

[Robb Wolf]: No, I don’t think so. You did a great and thorough job asking this stuff.

Again, I would just encourage people to think about, if they feel off-put by this idea of Paleo diet type stuff, just give some thought to this. Is there any merit looking at biology and thinking about the evolutionary underpinnings, particularly when we see things go south?

If we don’t see health or other parameters that we would ideally like to have, if something significant is changed in that organism’s environment, do we have any insight from looking at what the environment preceding that event? So that’s kind of the totality of my greasy used-car salesman pitch on this stuff. Is there anything we can learn from that?

And it’s not just around food. It’s around sleep, and photoperiod, community, gut microbiome. All of these things really, when we see problems popping up, it’s this discordance model again. And modern medicine is shockingly well-suited for dealing with acute injuries and infections, and it has been an appalling failure with regards to chronic, degenerative disease.

And people may get their back up about that and say we work very hard. I don’t doubt that people do, but if you simply look at disease rates and incidence – Type II diabetes, Parkinson’s, Alzheimer’s – they’re increasing at exponential rates, yet we know more about the disease process than we’ve ever known in history.

Our iPhones, iPads and computers get cheaper and better every single year, and it’s because we properly apply the technology and knowledge that we have around that topic to improving the product and the outcome. We do not do that in health and medicine, and it’s because we do not start the story from this evolutionary biology perspective, and start having the conversation from there. Because if you do that, chasing symptoms no longer works, and filing people into these arbitrary buckets of disease or not-disease doesn’t really work anymore.

In the 1900s, the previous century, was the century of eradicating infectious disease, for the most part. This century is going to be about dealing with chronic, degenerative disease due to affluence. And it is not going to be solved by a pill or a potion. It’s not going to be solved by telling people to eat less and move more, everything in moderation. Because all of that completely ignores every element of our fundamental evolutionary biology.

[Damien Blenkinsopp]: Thanks, so much for that roundup.

To learn more about this, they can go and get your book. That’s available at Amazon. There were some bonuses or stuff. Is there anything like that still available?

[Robb Wolf]: The bonuses might pop back up again, but most of that was for saying thank you for people who were early adopters on it. But we’ll see. Maybe a couple of months down the road we might pop the bonuses back up.

(0:51:39) [Damien Blenkinsopp]: Okay, cool. Are there any other good books or presentations on this subject that you’d recommend?

[Robb Wolf]: Oh, man, if people are not following Chris Masterjohn, they’re really missing out. That guy is brilliant.

And he’s been doing a deep dive on kind of a series of different nutrients that you need to pay attention to. And he kicked the whole thing off, actually, with iron. Both the iron deficiency, anemia, stories and also the iron overload stories.

So he gets into the biochemistry and the pathophysiology of when things are right and wrong. And then he also starts off at whole food solutions and also makes supplement solutions, and man he is just doing brilliant work.

Who else is doing great work? The folks at Nourish Balance Thrive are doing phenomenal work. Marty Kendall over at Optimizing Nutrition. They’re just some brilliant people.

It’s funny a lot of them had an engineering background and either they got sick or spouse got sick, and then they got in and started looking at this stuff. And it’s interesting. They come in with no medical training biases, and after they start retro-engineering, literally, the disease process, they arrive at something that looks like kind of an appropriate carb, Paleoesque looking nutritional intervention with a focus on sleep and gut microbiome and all that.

I don’t know if that’s just confirmation bias, or really smart people applying their training to figuring out a process. But it certainly caters to my confirmation bias, so I tend to like that stuff.

(0:53:14) [Damien Blenkinsopp]: Cool.

What are the best ways for people to connect with you, and learn more about you and what you’re up to? Twitter or Facebook?

[Robb Wolf]: The blog and podcast live over at Robbwolf.com. The bulk of my social media time I spend on Instagram these days. My handle there is @dasrobbwolf, and I answer just about every single question that is shot across the bow there. So I do the best job I can to stay on top of that.

(0:53:45) [Damien Blenkinsopp]: Excellent.

Just a few more details maybe on our personal approach through using any tracking. I know we’ve already spoke about them, so just really to see if there’s anything else.

I was wondering if there’s anything you track yearly, or every six months, or anything like that that we haven’t already spoken about.

[Robb Wolf]: So, I do check-in on my lipoproteins, that LPIR score, or LDLP, LPPLA2. There’s kind of a suite of somewhat obscure lipoproteins which I keep an eye on about once a year.

And part of that is because at the end of my last book, I was pretty beat up from that. Then I went on a Discovery Channel reality show, called I, Caveman. And we had to live like Stone Age hunter-gatherers. We had stone tools, we lived at 8,500 feet in the Colorado Mountains while there was still snow on the ground.

We basically starved for 10 days until I killed an elk with a hand-thrown spear, and that was the first food we ate. But the long and short of that is I lost 18 pounds in 10 days, and was super beat up. And I ended up with some HPTA axis dysregulation. My thyroid was super low, I had adrenal issues, testosterone was kind of tanked out.

And so an interesting sideline with that was that my lipoprotein numbers were sky-high. My LDLP was 2,800 or something like that. Really, really high. And the clinic that I’m on the Board of Directors of here, we do tons of lipidology work. And the doctors were freaking out, you need a statin. And I said no I don’t, I’ve got other stuff going on.

So we did some poking around, and I actually went on some Nature Throid, which is kind of like armor but a T3/T4 thyroid deal. And I did kind of a classic adrenal restoration story, high dose Vitamin C, some licorice, some adaptin. And I quit traveling, and I started really paying attention to my sleep.

And within three months I was off the thyroid medication, testosterone had more than doubled, both free and total. And I felt remarkably better after that, shockingly. And my lipoprotein number, my LDLP, had gone from 2,800 to, I want to say, 1,100. And eventually it settled out at 800 or 900.

I do check back in on that every once in a while though, because that combination of super low testosterone and disordered thyroid. The low circulating T3 that really down-regulates your LDL receptors in the liver. So you just don’t clear LDL particles, so they accumulate in circulation. And once they start accumulating, then the potential for them to oxidize is much greater.

And then I also potentially have a little bit of iron overload going on. So I had a really kind of nasty situation brewing there. So I do check in on that, just to make sure everything is bumping along good. So I do a really thorough thyroid assessment, which is TSH, T3, T4, reverse T3, thyroid uptake, and then some of the just kind of background iodine status. And that gives me a pretty good benchmark about where that is.

And then I’ll check testosterone, estrogen, estrodiol, DHT, to kind of see where that part of the hormonal axis is. Because again, based off inflammation, fatty acid ratios and what not, you can start pushing more testosterone towards the DHT pathway, which can be problematic for the prostate under certain circumstances.

So I pay attention to those things, but it’s usually about once a year. But again, I’m a lazy cuss when it comes to that stuff. I know some people test it like once a month. I’m more of a once a year, maybe once every six months on some things. But more of a once a year deal.

(0:57:58) [Damien Blenkinsopp]: Thanks for that, very, very interesting. And the fact that you recovered, and you obviously see that as an actionable metric that you can keep up with.

I’m just wondering, which labs were there? If there’s any specific place, or are these just standard Quests, or something like that?

[Robb Wolf]: We tend to go through LabCore because LabCore ended up purchasing LipoScience, which is the [unclear 58:09] that developed the NMR technology around looking at lipoproteins. There’s other ways of looking at it, and they have pluses and minuses to them, but in my opinion that NMR spectra that looks at the LPIR score and lipoprotein count is head and shoulders above everything else out there.

The guy that largely developed it, William Cromwell, he was a physical chemist, a believe a PhD, which is basically a physicist who studies chemistry. And then he went to medical school, and he got into this NMR spectra jockeying type stuff, and developed this whole technology around looking at these lipoproteins. They have some really interesting correlation studies that they’re doing.

There’s a biomolecule called glycA, and by looking at glycA in relationship to some other lipoprotein fractions, they’re claiming that they can see things like Parkinson’s, Alzheimer’s, and insulin resistance decades ahead. And they’re still awaiting FDA approval on that. But it’s really interesting. So I tend to really put some pretty heavy weight on that lipidology side with regards to that LPIR score and that whole NMA spectra technology.

(0:58:28) [Damien Blenkinsopp]: Thanks very much, that’s very, very interesting stuff.

I think I know what you’re going to say here. If you were to recommend one experiment someone should try to improve their body health, performance, longevity, chronic health issues, whatever, with the biggest payoff, what would it be?

[Robb Wolf]: Sleep.

[Damien Blenkinsopp]: Okay.

[Robb Wolf]: Sleep. I mean, maybe a blood sugar deal I can make an argument for, but if we improve your sleep, there is nothing else that you could do that’s going to improve everything else more.

And the one caveat with that, if we have say a shift work population – police, military, firefighter, new parents, medical caregivers – who can’t control their sleep, then they really need to get a handle on the glycemic load of their diet and get it to a level that’s non-toxic for them.

But even then, the shift-workers, they need to pay even double attention to the sleep. When they do sleep, they need to sleep well. When there is sunlight, they need to get out into the sunlight at appropriate times. It becomes doubley important for them.

But the greatest return on investment anybody’s going to get on any of this health and wellness stuff is putting more emphasis on their sleep.

[Damien Blenkinsopp]: And should they just track hours slept, something simple like that?

[Robb Wolf]: Hours slept is good, but it’s more the ritualized process. When the sun goes down, then you dim the lights. And if you’re still on the computer, you flip on the f.lux, and you put on some Blue Blockers, and you set up a ritual.

To the degree that we set our lives up that we have to live and die by self-control, we’re mainly going to die. We’re going to fail. And so we have to set up a kind of a habituated process so it really takes the thinking out of it; it’s just what we do. So I would tend to focus more on that.

And then certainly if you want to keep an eye on approximate duration in bed, but that’s a whole other interesting feature too, is when you start paying an over the amount of attention to those things, then you start getting anxious about it. And I just see this damnable downward spiral in the quantified self space, where I just want to put a black bag over these people’s heads, drag them out into the woods and stick them in a tent.

And it’s like, there’s a creek full of fish. We’ve got them trapped behind a fish weir, you need to get them out by hand and gut them and cook them. Here’s the kit to make a fire. We don’t make it ridiculously hard, but you’re going to have to work to get your dinner, work to stay warm. And when the sun goes down you’re going to make a decision, do I want to sit up in the dark, feeding this fire on the limited firewood I have, or am I going to go crawl into my sleeping bag and go to bed.

They’re not quantifying a goddamn thing under those circumstances. And all of a sudden, all of the digestive issues disappear, and the sleep disturbances disappear, and they’re three body fat percentage point is lower after a week and it’s not because they’re hypocaloric, it’s just because they’re not inflamed and insulin resistant.

And so again, I try to get people to just live. I’ve really been harping on this thing of track what matters. And the longer that time goes along, I’m just finding fewer and fewer things that matter, relative to the experiential process. Be in your body, experience what is going on. Be in contact with what your emotions are, and develop a little bit of a zen and stoic process, where you can see these things occurring, and then you can choose to how you respond to it.

Whereas if we’re so tied to external devices for every little bit of feedback, then we’re essentially dependent on that. And I hate dependency of any variety.

[Damien Blenkinsopp]: Thanks so much for that, this is really, really interesting. It’s been a fantastic episode. And thanks for being so open, just giving all these details of your own experiences and your life. It’s a great, great show. Thank you.

[Robb Wolf]: My pleasure. It’s a huge honor being on. Thank you.

References:

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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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Is the Fast Mimicking Diet (FMD) an easier way to get the benefits from fasting? In this self experiment I tracked lean muscle mass gains, improved metabolism (ketones, glucose), strong regeneration signaling (IGF-1) and a couple of downsides.

Last month I undertook my first 5 day water fast. It is turned out to be a really helpful tool for my health and productivity, so I committed to make it a monthly ritual for 12 months.

With each month the plan was to push the edge a bit to learn more from the experience – refining the approach to the fast with the different options available and tracking the results to see what could give me the biggest payoff for least effort.

Enter the “Fast Mimicking Diet” – an easier and safer way to get the same benefits as pure water fasting. It created a spark of media coverage around it following the publication of a new research paper on it in June 2015. Two of the articles actually had two journalists become fast mimicking diet guinea pigs for 5 days (Peter Bowes at the BBC, and Victoria Lambert at The Telegraph).

It’s clear to me that most people will never do a water fast because it looks like a psychological feat fit only for diet equivalent of extreme sports fanatics. So the Fast Mimicking Diet was an obvious choice for fasting experiment #2.

If it does make the fast much easier – I just might be able to persuade some more of you to take the jump and grab some of those upside benefits for yourself.

What is the Fast Mimicking Diet?

Prolon l-nutra
Photo: L-Nutra

The exact details of what the Fast Mimicking Diet is in terms of food breakdown aren’t available publicly. Which in part, can be explained by the fact that the main researcher behind the fast mimicking diet, Valter Longo, owns a patent on the FMD (published January 2015) and a company which has designed a comprehensive packaged FMD dietary product ProLon.

For our purposes though there is enough information available to put together our own version of it. The Fast Mimicking Diet I used and the other versions below, are based on some very specific FMD design points found in Longo’s January 2015 patent and the June 2015 study (the macro and micronutrient do’s and don’ts).

The nutrition rules established for the Fast Mimicking Diet are:

  • Each month (3 / 4 cycles in studies): 25 days eat normally, 5 days FMD
  • High micronutrient content (i.e. greater than 50 percent by weight) from natural sources
  • Ketogenic: Restricted protein and a high percentage of calories from fat

In practice this translates to:

  • Day 1: 54% norm caloric intake 1,090 kcal (10% protein, 56% fat, 34% carb)
  • Days 2–5: 34% norm caloric intake 725 kcal (9% protein, 44% fat, 47% carb)

For the nutrition geeks out there I’m sure you’re already thinking up some Fast mimicking diet recipes to play with. For most of us though, this sounds pretty much like techno-babble… Don’t worry though, there’s a much easier way to look at the FMD.

Fast Mimicking Diet Recipes

avocadosIt turns out that days 2 to 5 are pretty much equal in calorie intake and macronutrient ratios to just 2 normal sized avocados (based on NutritionData numbers here).

That’s one avocado for breakfast. One avocado for dinner. Done.

For simplicity sake, you can just run all 5 days that way.

(Note: Sizes of Avocados vary depending on origin. Florida origin avocados are larger, and California origin smaller for example. If you’re using the smaller variety, it will be 3 avocados per day).

Then you need to take care of the micronutrients. For that you take 4 tablespoons of broad spectrum greens powder (a supplement made from dehydrated vegetables).

So your day ends up looking like this.

  • Morning: 1 Avocado + 2 tablespoons of greens powder
  • Evening: 1 Avocado + 2 tablespoons of greens powder

That takes all of the thought out of it.

Note: For those who are more ambitious, Josh Mitteldorf has posted some FMD recipes that you can put together.

itunes quantified body

The Fast Mimicking Diet Experiment

The Specific Fast Mimicking Diet Variation Tested

My personal goal for this experiment was to emphasize regeneration of the immune system – and I’m impatient about it. So I used a reduced FMD this time to ensure that I was giving my body as strong as possible starvation signal, while supporting its processes. For this reasons I cut out the macronutrient intake (the avocados) and only went with the 4 tablespoons per day of greens powder (micronutrient intake).

So the experiment results you’ll see below are from a modified FMD – just the micronutrient intake.

Specifically this is what I consumed during each of the five fast days:

  • 4 tablespoons of greens powder
  • Filtered water with real salt added
  • 2 cups of black coffee
  • Activated charcoal from time to time as a gut toxin binder

Biomarkers Tracked to Understand Benefits/ Risks

For the biomarkers I used Fast Mimicking Diet study as the basis, basically copying their timing and tracking with just one – albeit quite large – difference

In the study they tracked their post intervention results after 3 cycles of FMD. I would only be doing it after 1 cycle. For this reason the results could be expected in my case to be less significant – that would be the assumption, however it’s not what happened.

Biomarkers Tracked by Area

the-tracking-fmd

5 Day Fast Mimicking Diet Results

Metabolic Switch to Ketones a Day Earlier than Fast #1

My metabolism switched from glucose to ketones one day earlier than in my first 5 day fast. Like last time the fast “felt easier” once I’d switched from glucose to ketone metabolism. So by the afternoon of day 2 of the fast the hunger pangs or discomfort had pretty much gone.

At their peak, my ketones were just a little higher than last time at 7.3 mmol/L. This was 29 times my baseline, which is a lot higher than the average 9 times above baseline noted in Longo’s Fast Mimicking Diet study. We have an interview with another guest coming up in the next weeks discussing the importance of this variation in ketones (higher variation = better).

My blood glucose dipped a little lower this time also settling in at a consistent 57.5mg/dL in the fasted state. This is 64% below my baseline vs. an average 40% below baseline from the study.

Metabolism: Blood Glucose and Ketones

Ketones and Glucose Fast Mimicking Diet

I continued to track ketones and glucose after the fast ended at the 120 hour mark (end of 5 days). So it’s interesting to note that it took my body 2 days to really switch back out of ketone to my normal metabolism once the fast was ended.

Looking at Seyfried’s Glucose-Ketone Index (GKI) (from episode 16) the fast was shown to be more effective this time round. In the chart below you see #1 Water Fast compared to #2 Fast Mimicking Diet. In this 2nd fast my body spent 18 hours longer in Seyfried’s therapeutic zone for cancer (lower than an index of 1) than in the first. That extended the therapeutic window to 71 hours – an impressive total of nearly 3 days.

Metabolism: Seyfried’s Glucose Ketone Index

Glucose Ketone Index Fast Mii

My assumption here is that it’s the fact that this is my 2nd fast that my body switched to ketone metabolism quicker this second time. It’s a pretty significant change compared to my first fast, so unlikely to be just variance. It’s possible that my version of the FMD somehow supported this also – but my bet would be that its my body having learned to adapt to the fasted state quicker. Future fasts will provide more insight around this.

Does the Fast Mimicking Diet = Lean Gains?

In my last fast I ended up being concerned that I’d lose weight every fasting cycle and if repeated monthly eventually ending up a skinny strawstick version of myself. More concerning, I was wondering if it was lean muscle mass that I was losing.

This time round I had the BodPod to control whether it was lean mass or body fat I was gaining or losing. In addition, the FMD study shows a slight lean mass gain on average for people doing cycles of FMD. Although mine was a minor version I was hoping to avoid a decline in weight as with last time.

Using my Omron scales there was a 1.7kg (3.7lb) from baseline to day 7 after the end of the fast (day 12).

Weight (Kg) via Omron Home Scales

Weight-gain-fast-mimicking-diet

The BodPod results were even more promising. It turned out that I had gained nearly 3lbs (1.3kg) of lean mass over the 12 days. The body fat change was negligible.

Body Composition (Kg) via BodPod

fast-mimicking-diet-lean-gains

Note: You’ll notice that the Omron scales and weighing scales used with the BodPod did not agree. A reminder of the importance of using the same device to track whenever possible due to inter-device variances. The BodPod is the more accurate.

Regeneration & the Immune System Reset

And we come to the last but in my opinion most important item. Did the biomarkers show an indication that my body and immune system had regenerated as has been shown in Longo’s study?

The IGF-1 results are promising. There was a nice drop of IGF-1 44% below baseline. This compares with an average of 22% reported in the study. The BBC journalist Peter Jones, one of the study’s participants, had a drop of 60%. The hope was to see a significant drop and recovery of IGF-1 like this as it correlates with the gene signaling required for regeneration. Also of note my baseline IGF-1 levels hover between 115 and 120 ng/mL – these are below the typical reference range for my age (132-​333 ng/mL) likely due to my long term ketogenic dieting (~7 years with different variations at this point).

IGF-1 (Insulin-like Growth Factor 1)

igf-1-fast-mimicking-diet

The bigger interest for me was the immune system of course. The results here were a little disappointing – very hard to judge if anything happened. In the study they noted bigger changes in one class of white blood cells: Lymphocytes. This held true in my results with a larger % drop from baseline compared to all white blood cells.

White Blood Cell and Lymphocyte Counts

white-blood-cells-fast-mimicking-diet

Anecdotally, the situation is personally clearer for me. As with my first fast I had a period of a week after the fast where flu-like symptoms and fatigue taxed me. With this 2nd fast it lasted a little longer, extending to between one and a half and two weeks.

Since that time I’ve noticed once again a bump up in my perceived wellness. Less fatigue. More energy. Less symptoms in general from the lyme and babesiosis infections I’ve documented (see the complete story behind these in the last experiment intro).

So, again, the fast has been worth it for me.

But it’s not a black and white story. As we’ll see in the next section…

The Opposition: Adrenal Fatigue

Fasting is known to stress the adrenals, and for me personally this is a particular concern, since I already have documented low adrenal function. To continue my monthly fasting cycles I decided I would have to see improvement in my adrenal function compared to a baseline I established last November 2014.

Having been on treatment since March 2015 to support recovery of the adrenals I would have expected some progress. However, I felt that the fast may counteract that progress potentially. Or exacerbate it.

This may or may not have been the case. However, the results of my adrenal functional profile show continued deficiency compared to the low normal reference range.

Adrenal Functional 4-Point Cortisol Panel (Morning & Total)

adrenal-function-panel-fasting

While the fast has in my opinion lived up to the studies in terms of reseting and regenerating my immune system to some extent – it’s probably also true that it has not helped my adrenal recovery.

It wouldn’t be wise (or responsible) to continue this cyclic fast given this downside.

Potential Confounders for these Results

I’ve discussed what in my opinion are the most likely takeaways from the results so far. However, there are other possible explanations. These are the potential biases that I’ll keep an eye out for or/ and try to eliminate in future fasts.

    Metabolic Switch

  • Positive bias: Long time ketogenic/ high fat diet (5 years) which may mean I’m an outlier compared to the population with respect to switching to ketone metabolism.
  • Negative bias: Documented high inflammation biomarkers last 3 years (this tends to disrupt glucose regulation, and indeed my HbA1c numbers and fasting glucose are not as good as before this inflammation – tropical infection driven)
  • Lean Mass Gain

  • Positive bias: Creatine Monohydrate supplementation ongoing for most of the last 3 years with some breaks here and there. Last 3 months consistently. Could the 5 day break from creatine for the fast, then retaking in post 7 days have an impact? Doubtful that it would be this significant.
  • Positive bias: Currently I have a low lean muscle mass compared to historic norm due to a large amount of muscle mass I lost the last 3 years (again infection driven). This could account for a greater increase for my personal situation as my health normalizes and may not be repeatable in future cycles.
  • [?] bias: Diet change. I’ve increased the amount of resistant starch type 3 in my diet since just after Fast 1 and a few weeks before Fast 2. This means I am eating more carbs in my baseline diet. This did not change between beginning and end of the fast 2 testing period, but it is a longer term change.
  • Adrenals

  • Positive bias: Adrenal Supports. I Have been taking adaptogenic herbs and adrenal complex since March 2015, theoretically this should have led to some improvement.
  • Negative bias: There was a 3 day coffee roadtrip binge between Fast #1 and Fast #2 where I consumed 3 X coffees plus per day. A lot of fun but pretty irresponsible given my adrenal situation. This could be a greater factor in the negative results than the fasts.
  • White Blood Cells

  • [?] bias: Documented suppressed immune system for last 3 years? (consistently bottom 10-15% of normal reference range)

The 5-Day Fast Mimicking Experience

About the experience of the FMD itself – there’s not a lot to say beyond the fact that it felt much easier.

None of the symptoms I experienced last time occurred. There were no headaches like last time. There was less dizzyness when getting up quickly. Also no skins rashes. I’m tempted to attribute this to the micronutrient support provided by the green’s powder the idea being that it provides the nutrients required for detoxification and liver processes amongst others, thus better dealing with a potential increase in toxic load from lipolysis (breaking down body fats which tend to store fat soluble toxins).

Also I did more physically. On day 5, the last day of the fast, I went on a trip to London to a couple of labs to get blood labs and BodPod tests done. This wasn’t a big deal and I didn’t feel weak in doing so. This compared with the first time where on the 5th day the physical weakness was a lot more noticeable.

Potentially on day 4 and day 5 I noticed my stomach a little more than with the water fast. In my first water fast I had pretty much dropped the issue of eating or being hungry. But with this time round, possibly because I was taking the green powder- I was more aware of my stomach, and a little grumble here and there. But it was marginal and not really uncomfortable. Just slightly different.

Personally, I’m not 100% sure that all of these differences I’ve noted are absolutely physiological. Some of it could be put down to feeling a lot more comfortable in the fasted state due to having already done it before. I’d say some of it could be just me expanding my comfort zone and getting along with things while paying less attention to the fasted state.

Next Steps – A Change of Plan

While I would love to continue the fasting cycles, and I would even feel comfortable doing it as a “life routine” given the upside benefits, for now I’m going to give it a break.

The next few months I’m going to focus on adrenal recovery – with additional supports – to try to get that parameter moving in the right direction.

Once they have stabilized or shown progress I’ll come back to the fasting cycles for more…

What I’d Like to Explore Next

I’d like to explore a few of the ideas that have come up this time in future fasts:

  • Metabolic adaptation: Will my time to switch to ketone metabolism get shorter the more fasting cycles I do?
  • Lean Gains: Is it possible to continue to gain lean body mass with repeated FMD cycles?
  • Full FMD: I imagine for my next FMD I’ll take the avocados too. This will help to make the fast safer as a reintroduction after working on my adrenals. Otherwise I’d like to know how the full FMD compares to my micronutrient only FMD.

Have you done some kind of fasting before? What was your experience like? And what other types of fasting are you interested in learning about? 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 7 mmol/L based on Seyfried’s work and experience. In episode 7 Jimmy Moore notes that values over 1.0 on your blood ketone monitor give you the benefits of ketosis, and there is no need to go over 2.0. Tim Ferriss also prefers this range, noting that his best mental performance is typically with values between 1.1 and 1.7 mmol/L.
  • Blood Glucose (mg/dl): A measure of the level of glucose in the blood at one point in time. Dr. Seyfried’s therapies target reduction of blood glucose levels to limit cancer cell growth, and according to his theories high blood glucose is a biomarker of increased cancer risk. For the fast he notes values between 50mg/dL to 60mg/dL are standard. 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, Kgs): Standard weighing scales measurement of weight in morning without clothes (to avoid biases).
  • Lean Body Mass (lbs, Kg): Sum of weight of all non-body fat weight in the body. Calculated by combining your weight with a lean body mass % estimate.
  • Body Fat (lbs, Kg): Total bodyfat weight for your body based on a calculation using your weight with a bodyfat % estimate.
  • IGF-1 (Insulin-like Growth Factor 1): In caloric restriction and fasting IGF-1 drops, while consumption of high glycemic carbohydrates and protein spike IGF-1. Measured in ng/ml (or nmol/l in the UK). Normal ranges vary by age and gender (see reference here). More info on IGF-1 and its uses here. (Note: Damien’s baseline levels are 119 ng/ml, just below the “standard reference range” for his age group).
  • WBC (White Blood Count): A count of white blood cells found in the blood, low levels can indicate immunosuppression, while high levels can indicate an existing infection with active immune response.
  • Lymphocyte Count (White Blood Count): A count of white blood cells found in the blood, low levels can indicate immunosuppression, while high levels can indicate an existing infection with active immune response.
  • hs-CRP (hs C-Reactive Protein): A common marker of inflammation. As a general rule, the closer your marker comes back to 0, the better. Consistent values of 1mg/L or over are indicative of cardiovascular risk. Measured in mg/L. We discussed this marker in detail in episode 26

Lab Tests, Devices and Apps

Lab Tests

  • Functional Adrenal Stress Profile (BioHealth 201): Damien uses this adrenal functional panel based on recommendations from practitioners and his physician on its higher sensitivity and accuracy to diagnose status of adrenal function compared to others on the market.
  • Hematological Profile: Also known as Complete Blood Count (CBC). A standard test providing information on your blood cell breakdown including red blood cells, and white blood cells. Can be run with virtually any lab test company and is used routinely as a first screen by physicians and in hospitals for diagnosis.

Devices

  • 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.
  • Ketonix: Damien used the “Ketonix Sport” during this experiment to compare the results with those of the blood ketone results. The results from the Ketonix did not correlate very well with the blood ketones measured – so we’ll be sticking to tracking blood ketones directly in future self-experiments.
  • BodPod: An accurate approach to measuring your body composition and separating out your % lean body mass (muscle, organs, bone) vs. your body fat. You find BodPods in some high end gyms, but more often in fitness labs.
  • Omron Body Composition Monitor: Used by Damien for his home weighing scales although he no longer uses the body composition functionality as he finds the bio-impedance technology used too variable. As noted in this experiment the weight metrics turned out to be a fair bit different to the BodPod more accurate standard also.

Tools & Tactics

Diet & Nutrition

  • Fast Mimicking Diet (FMD): Also known as the periodic fast mimicking diet, since studies to date have focused on using 3 to 4 cycles of 5 days on the diet each month. The main summary paper, “A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan” was published in the Journal of Cell Metabolism in June 2015.

Supplements

  • HealthForce Greens Powder: The greens powder Damien used in the experiment. There are many greens powders on the market of varying quality. Another one he’s used in the past is Amazing Grass Greens Powder.
  • Activated Charcoal: A broad spectrum binder used to bind to toxins in the gut and carry them out. There are high cost versions such as Activated Coconut Charcoal (potentially less contaminants) and lower cost versions such as this. If you buy others check the ingredients – they often have added sugar and other undesirables.

Other People, Books & Resources

People

Additional Charts and Data

Click Here for Additional Charts

Inflammation (hs-CRP)

There was no significant change in hs-CRP which was in line with what was expected from the fast mimicking diet study. In the study out of range (over 1 mg/l) values will normalize to under 1mg/l, however in range values like mine see little change.

hs-CRP (C-Reactive Protein)

hs-crp-fast-mimicking-diet

References:

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A walk-through of the 5-day water fast with the tracked results (ketones, glucose, weight) and the practical do’s and don’ts to make the most of the experience.

I’m not a fan of cancer. The only people I’ve lost in memory – my grandfather and other close family – it was cancer that took them. NOT putting an end to the fun of life because of cancer has been a part of my plan since my early 20s.

So after my discussion with Dr. Thomas Seyfried in episode 16 I was looking forward to put his 5 day water fast “cancer insurance policy” to work.

As I read into the details to start planning my prolonged fast what I found convinced me even more this was something I had to do soon.

Maybe what I discovered would inspire you to try a 5 day fast soon too?

Fasting for Reasons Beyond Cancer

Since getting bitten by a tick in Phuket, Thailand a few years ago I’ve been fighting some chronic health issues.

I discovered that it’s probable that these are at least in some part due to lyme disease and babesiosis infections I only got documented earlier this year (and thus had never been treated for). It bears mentioning, since there’s a fair amount of non-rigorous and dubious material on the internet on the subject of lyme disease in particular, that this was documented via the IgM/ IgG labs, and met CDC criteria.

What does this have to do with fasting?

It comes down to this: Having a stronger immune system gives you a better chance of eliminating lyme. Since in cases like mine where it was not treated in the early stages it seems to be relatively tricky and long-winded to get rid of. I’ve made it a rule to collect and put into practice anything that improves the odds of a quicker recovery.

And… fasting is a potential new tool to speed up recovery.

Valter Longo, Director of the USC Longevity Institute, has published a large number of studies on fasting and caloric restriction and their application to treat disease and enhance aging and longevity. Some of his recent work showed that prolonged fasts (e.g. 3 to 5 days, of a similar format recommended by Seyfried) can regenerate up to 30% of the immune system.

Or in other words, a fast can eliminate old tired (and most probably damaged and dysfunctional) white blood cells and replace them with more effective shining new ones.

I’ll admit this got me excited. It was definitely something I wanted to add into the “war plan” my integrative doctor and I had put in place against lyme and babesiosis.

(Note: Before planning this fast I ran it and Longo’s research papers by my doctor to get it signed off by him. If you have any chronic health issue and are undergoing any treatments you should do the same.)

As you’ll see below, the 5 day water fast (and other prolonged fasting configurations) has many potential upsides.

After having gone through the experience and seeing the quantified results, I can say it’s something I will use as a tool frequently going forward. Most likely once per month, or once per quarter.

The Upside: Reasons to Do a 5 Day Water Fast

Beyond the potential health and longevity upsides there were also a couple of others I was particularly interested in.

    First, the health benefits:

  1. Reduce future cancer risk or as a tool for those with cancer to combat it (details in this episode with Dr. Seyfried)
  2. Promote longevity and slow aging (via similar mechanisms to caloric restriction)
  3. Multi-system regeneration providing potential improvements in the immune system and mental performance (Valter Longo’s work – this 2015 paper has some highlights)
  4. Reduce diabetes risk and cardiovascular disease risk and improve blood sugar regulation
  5. The non-health benefits are perhaps more personal to me:

  6. Building greater mental resilience through the process of overcoming the challenge of a fast? The stoics used hard life experiences to learn to deal with the mental ups and downs of life more easily.

    As an entrepreneur, where ups and downs are pretty much routine, I’ve grown to value this ability immensely. Exposing yourself to more extreme hard challenges numbs you to the emotional pain and you find you become more indifferent to life’s ups and downs (read less reactive). You can read up on this in the book The Obstacle is the Way by Ryan Holiday (which I must have listened to 8+ times), or articles on the philosophy of stoicism on Tim Ferriss’ blog.

    A 5 day fast struck me as exactly the type of “safe but challenging experience” that builds mental resilience more generally. Once the fast is done, you realize it’s absolutely not a big deal. And other life challenges also seem to dim in their intensity and importance.

  7. A new life experience: What would it feel like to fast for 5 days? How would it effect my body? physically? mentally? We should all experience the extremes of the human experience provided they are within the limits of safety and healthy. It’s an important tool to learn about ourselves, our limitations, strengths and weakneesses – self awareness is a skill that can be learned. Going to the extremes to get a real feel for the breadth of life is part of living a life well lived.

itunes quantified body

The 5 Day Water Fast Results

Big Metabolic Changes Kick Start on Day 3

My metabolism switched from glucose to ketones (and fatty acids) by the end of the 3rd day, which fits with what is generally expected based on the standard biochemistry literature.

On typical non-fasting days I’ll hit between 1 and 2 mmol/L ketones (see my baseline data in appendix here) because I eat a reasonably high fat diet. It wasn’t till day 3 till I broke the 2 mmol/L threshold and went beyond, eventually peaking at nearly 7 mmol/L blood ketones. At the same time my blood glucose hit a stable low of just under 60mg/dL.

Overall, I felt less mentally sharp and found the fast hardest between the end of day 1 till around beginning of day 3. Is this ‘harder part’ of the fast a rough period of adaptation to using ketone and fatty acids as the main fuel source? Perhaps. In my case the switch in the blood results follows closely the ease of the experience for me – once blood ketones and glucose inverted the experience was easier.

fast-glucose-ketones

Seyfried recommends the use of a Glucose-Ketone Index for monitoring the therapeutic value of the fast against cancer. The goal is to have your value of this index below 1 which is considered the ‘therapeutic zone’.

67 hours into the fast my index dove below 1, and it bottomed out around 90 hours, from then on hovering between 0.5 to 0.6. So I was in the therapeutic zone for all of days 4 and 5.

fast-gki

Exactly on plan: My blood glucose, ketone and GKIC markers settled into the expected ranges Seyfried outlines in his book for the fast. That’s between 50 to 60mg/dL for blood glucose, and between 6 and 7 mmol/L for ketones.

Lagging Metabolism Adjustment at End of Fast

When I hit the 120 hour (end of 5 day) mark I dug into a couple of big bowls of bone broth. Quickly full and satisfied seemingly as if the fast had never taken place.

The next day I had a higher carb than usual breakfast. We’re not talking crazy, just some blueberries and yacon syrup (for the gut, will talk about this soon in another episode) with bulletproof coffee (ghee, MCT oil and coffee). Despite this my ketones stayed high and actually hit their peak of the whole experiment (6.8 mmol/L) nearly 24 hours after the fast had ended.

This makes sense. It’s normal to see a lag of response of the blood readings the first 3 days of the fast while you adapt to ketones/ fatty acid metabolism. So it follows that there would be a lag in the switch back to primarily glucose metabolism.

Was Weight Loss Permanent? or Just Momentary?

Interested in the fast to lose weight also?

Cycling into 5 day fasts say once per month, could be quite effect based on my data (~loss of 1 lb per day in terms of permanent weight loss, not just momentary during the fast).

If weight loss isn’t desirable, which is my case, you’ll need to compensate to regain lost muscle weight post fast.

Within a few days I had recovered one third (3 lbs) of the 9 lbs I’d lost during the fast. I consciously made an effort to eat as per usual to see if it the weight would naturally come back on. Two weeks later after the end of the fast (day 19) it’s still stabilized at 6 lbs down. Actively compensating for this in between future fasts will require consciously eating to gain weight.

fast-weight

HRV, Muse Calm and Mental Performance

I also tracked my HRV with the ithlete app, my daily meditation sessions with the Muse Calm and my mental performance via reaction tests at Quantifed Mind.

These weren’t my main focus for this fast, so the data isn’t extensive enough to make any big conclusions. However, looking at what I collected, I plan to take a closer look at mental performance and HRV in future fasts.

First thing in the morning HRV dipped at the start of the fast (day 1 and 2) and go back to my normal range from then on. This is a pretty good fit with how I felt during the fast. The first two days were a little rough as I had a headache, but from then on I felt more ‘euphoric’ and productive than usual.

This time round I haven’t seen any noticeable increase in HRV post-fast (potentially a bit more of the opposite) whereas intermittent fasting typically raises HRV. Something to keep an eye on for future fasts especially as I have to deal with my own personal variable – adrenal fatigue.

Adrenal Fatigue Confounder? I have documented adrenal fatigue currently (low cortisol output as a knock on effect of the chronic stress from lyme disease and babesiosis infections). I suspect the adrenal fatigue would be the cause of any negative HRV impact, and would be personal to me (if you’ve tracked HRV during a fast let me know your experience in the comments).

This may have been behind or contributed to my less consistent sleep and shorter duration sleep as noted before.

It is very common (even fashionable) to fast on meditation retreats. The idea the retreats promote is that fasting helps to calm the mind.

Although I got my best Muse Calm score to date on one morning (80% calm), I didn’t notice any real difference between fasting and my normal scores.

The 5-Day Fast Experience

Two of my fellow entrepreneur buddies (Patrick Stiles and Patrick Kelly (@pjkmedia)) recently also did the 5 day water fast so we caught up to share notes on our experiences. Our experiences turned out to be pretty different in some areas. You can listen to our full note swapping discussion in this episode.

Here’s the brief highlights of my experience from the discussion:

  • Day 1 and day 2 were a little challenging in terms of hunger but not that noticeably (I put this down to my previous experience with intermittent fasting and ketogenic diets)
  • A headache from the end of day 1 to the beginning of day 3 (potentially linked to the switch in brain from glucose to ketone use)
  • On day 4 and 5 the physical weakness was a lot more noticeable and there was some slight dizzyness when standing up at times.
  • Undercover bad breath: I wasn’t actually aware of this during the fast. My sister mentioned afterwards that she feared for her 1 year old son’s wellbeing when I was playing up close with him towards the end of the fast. Given the high ketone levels, this would mostly be due to high acetone levels in the breath.
  • Rash of spots on chest: I believe this is very much personal to me and my current situation. Fasting tends to lead to detoxification, and potentially stress your detoxification system, as you break down body fat including accumulated fat-soluble toxins and process them. While dealing with lyme these have occurred from time to time (added lyme biotoxin burden causing overload), so it’s unsurprising that adding broken down fat-soluble toxins would lead to this currently. I took activated charcoal daily to help bind and clear any toxins from my system.
  • After a couple of nights of good sleep at beginning of the fast it got progressively less deep as the fast went on whereby I was sleeping between 4 and 6 hours compared to a normal 6.5 to 7.5.

What’s Next? Fasting as a Routine Tool.

The experience during and after the fast has been so positive that I’m planning to do this on a once per month or once per quarter basis. Which one I go with will depend on how my body responds.

As more research comes out on the specifics of Fast Mimicking Diets (FMDs) I’ll also want to test that out, to see if the same benefits can be achieved (or better) with less discomfort.

Immune System Reboot – Any Evidence?

It’s only 2 weeks since the end of the fast so it’s early to tell just through tracking symptoms of my chronic infections (lyme, babesiosis). Nonetheless it’s looking positive from that anecdotal basis. After a first rough work post-fast, it’s been up and up. Meaning more exercise, more activity and generally feeling better with less symptoms.

I’m cautiously positive because lyme and babesiosis are both cyclical in symptoms presentation. I’ll update this section at a later date. The real solution to understand the immune reboot potential or impact of course is more data…

What I’ll Track Next Time

I’ve already begun contacting labs and working out how to dig deeper into the fast on a few levels:

  • Further validating the immune system reboot side by tracking IGF-1 which is one of the main markers used in Longo’s paper.
  • Is this sustainable for me? Is it beneficial as a monthly routine or would that have some negative blowback? I’m looking into tracking Cortisol vis-a-vis monitoring my adrenal fatigue status, and will track weight with future fasts.
  • What’s the downside in terms of productivity for the 5 days fasted? While I didn’t feel like there was much negative impact this time (it felt more positive) it’s something that I’d like to confirm with some short mental performance tests done during next fasting round.

In Practice: How to Do this at Home

For my tracking I took readings 4 times per day for my blood glucose and ketones.

However, I recommend to reduce cost (ketone strips are expensive) and to make it more convenient, you can simply track your blood ketones and glucose once per day in the morning. This will give you meaningful results, and tell you if you’re hitting the same milestones based on Seyfried’s work like I did.

Tracking this way, for a ten day tracking (5 days as control, 5 days of fast) you’ll be looking at a budget of around $80 to $100 all in (versus the ~$500 I spent).

Step 1: Get Your Tracking Gear

  • Combined glucose/ ketone monitor: Abbott is behind the best value for money units, the Precision Xtra Blood Glucose and Ketone Monitoring System in the U.S. and the Freestyle Optium Neo Glucose & Ketone meter in the UK (the one I used).
  • Glucose strips: the latest format that work with Precision Xtra and Freestyle Optium devices.
  • Ketone strips: Purple colored strips for measuring blood ketones (Beta-hydroxybutyrate). These work with both Precision Xtra and Freestyle Optium (Ketone Strips – Note: These are ~$4.50/ unit, I managed to get these at a lower cost per unit in the UK of $1.97. If you know where to source these cheaper let us know in the comments)
  • Lancets: It’s good practice to use a new lancet each day to prick your finger with. These Lancets are the latest format and work with Precision Xtra and Freestyle Optium devices, but are cheaper.

Note: Make sure to buy adequate strip and lancet supplies. I ran out of ketone strips the day after my fast otherwise I would’ve tracked more post-fast data. You lose some strips unavoidably in my experience through a bad reading on the device where for instance you didn’t provide insufficient blood. Make sure to have a buffer of 10% or so to account for this.

Step 2: Track Some Control Data & Learn to Take Readings

This is one of those situations where a video walkthrough is better than 1000s of words. This walkthrough is with the Freestyle Optium Neo, which is identical in use to the Precision Xtra).

I used my control data week (charts in appendix here) to work through any slip ups in taking readings.

You’ll want to get some control days where you take some baseline data eating your standard diet so that you can compare it to your fast. Blood sugar and ketosis metabolism are very personal aspects of our biology as we learned from Jimmy Moore in episode 7.

So the relative change in your measurements (normal diet, fasted states) could be as insightful as the absolute numbers.

Step 3: Schedule in Your Fast

The experience of a fast is highly variable depending on your personal situation as you’ll have noticed from the discussion in this episode with the two Patricks.

There is a risk that you’ll feel pretty rough and weak, and may be a danger to yourself and others (e.g. no driving or other similar ‘responsible’ activities please).

So I recommend you plan ahead and schedule it in for a time when you can quietly do some mental type work, study or rest at home. If you’re able to do more, so much the better, but plan for not being able to do anything.

Step 4: The Fast

Pretty straightforward. Stop eating at your scheduled time (after an evening meal is when most people do it) and start taking readings as set time intervals.

I used a standard iPhone timer alarm to notify me to take readings every 4 hours while awake. If you’re just taking one reading per day, it’s simple enough to make it part of your first thing in the morning routine.

It’s also useful to keep a diary of anything interesting or unusual you notice during the fast. Items I found useful to note down were hours sleep and sleep quality, physical weakness, any fatigue, mood, and other symptoms like headaches or dizzyness. This way you can relate them back to the data afterwards for more insights.

Step 5: Finishing the Fast Points

Boom, you’re done! You’ll be feeling great if it was anything like my fast. There are a few things you may want to keep in mind at this point.

I was advised by friends, and some long term ‘fasting experimenters’ to reintroduce food slowly. The idea behind this is that your body needs a little time to restart enzyme and stomach acid production. Some people experience gut symptoms or/ and bouts of ‘disaster pants’ if they jump straight back into their usual diet (or a ravenous version of this).

In my case, I prepared a bone broth ahead of time so that my first meal was mostly liquid and ate as normal from the next meal onwards. No discomfort or adverse gut symptoms. Straight back to business as usual as if the fast had never happened.

In future I’ll be tracking data for a few days post-fast since this experiment showed that my metabolism took a while to return to normal despite refeeding with a vengence!

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 7 mmol/L based on Seyfried’s work and experience. In episode 7 Jimmy Moore notes that values over 1.0 on your blood ketone monitor give you the benefits of ketosis, and there is no need to go over 2.0. Tim Ferriss also prefers this range, noting that his best mental performance is typically with values between 1.1 and 1.7 mmol/L.
  • Blood Glucose (mg/dl): A measure of the level of glucose in the blood at one point in time. Dr. Seyfried’s therapies target reduction of blood glucose levels to limit cancer cell growth, and according to his theories high blood glucose is a biomarker of increased cancer risk. For the fast he notes values between 50mg/dL to 60mg/dL are standard. 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.
  • Damien’s Routine Tracking Devices : Some of Damien’s daily use apps featured in this experiment including the Muse Calm for meditation, the iThlete Pro app for HRV, and Quantified Mind for mental performance.
  • Healbe GoBe: Damien mentioned that he’s been testing this device, and that the tracking of hours slept works quite well – but that other functions of the device make it hard to use consistently.
  • uBiome: Damien mentioned as a side note on another experiment he’s working on to shift his whole biome to a more positive balance of bacteria.
  • Functional Adrenal Stress Profile (BioHealth): Mentioned by Damien in relation to testing for adrenal fatigue.

Tools & Tactics

Interventions

  • 3 to 5 day Water Fast: The fast featured in this episode. Recommended by Dr. Seyfried as a potential tactic against cancer (reduce risk, or fight cancer disease). More details in Seyfried’s interview. Also used to promote stem cell regeneration of the immune system as per Valter Longo’s work. These fasts are often referred to as Prolonged Fasts in the literature.
  • Ketogenic Diet: The term given to low carb-high fat diets that put your metabolism into a state of ketosis (using ketones for fuel). Damien’s day to day diet shown in the baseline results is at times ketogenic.
  • Fast Mimicking Diet (FMD): FMDs have been covered increasingly in the research and there are two papers covering human clinical trials expected to be published on them in 2015 by Valter Longo’s group. With the FMD you fast 5 days each month by restricting certain proteins and keeping calories below a specific range each day. The goal is to reduce fasting discomfort and downsides while accessing the same upsides as the fast.
  • Intermittent Fasting: A form of fasting where you fast for part of or full days. The most popular formats are using eating windows of 4 to 8 hours each day. Bob Troia discussed his results from intermittent fasting in episode 22.
  • Slow Carb Diet: Patrick 1 mentioned that he’s primarily on this diet from Ferriss’ The 4-Hour Body.

Supplements

  • Activated Charcoal: The only thing I did beyond restricting myself to filtered water and black coffee (total of 3 cups in whole fast), was to take activated charcoal once a day to aid in clearing toxins from my system. I took a handful, around 8 to 10 capsules per day.
  • Brain Octane: Damien takes brain octane every morning in coffee to help raise his ketones.

Other People, Books & Resources

People

Books

  • The 4-Hour Body: Contains a once per week intermittent fasting format that got Damien started with fasting in 2010.

Additional Charts and Data

Click Here for Additional Charts

Pre-Fast Control Data Eating My Standard Diet

Blood Glucose & Ketone Levels at Different Times of Day

control-glucose-ketones

Glucose-Ketone Index at Different Times of Day

Control-GKI

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Is some aspect of mitochondrial damage behind cancer? If so, can this theory help us take control of cancer via tactics such as yearly or more frequent “7 day water fasts”.

When we think about death, cancer is often what we think of first. If you’re like me, most, if not all, of the deaths affecting you personally in your life may have been due to cancer.

Part of what makes a cancer diagnosis so devastating is that it’s mechanisms – how it works, where it comes from, how we can treat it effectively, how we can track it’s development, assess our risk and avoid it – continue to allude us. That makes us feel powerless against it.

Today’s episode is about the theory that mitochondrial damage is behind cancer, and how this theory may let us take control of cancer. We also hear our guest discuss the power of “water fasts” as a potential tactic to beat cancer.

If that’s true then tools that we have today such as ketogenic diets, fasting, lipid replacement therapy and other approaches to mitochondrial repair may help reduce or eliminate the risk of cancer, and even treat it when we have it.

We’ve already seen how important our mitochondria, and keeping them healthy, is in previous episodes, looking at longevity and aging with Aubrey de Grey, and autoimmune diseases with Terry Wahls. Today we add to that list the role they may be playing in the cancer diseases process.

“All cancers can be linked to impaired mitochondrial function and energy metabolism. It’s not a nuclear genetic disease. It’s a mitochondrial metabolic disease… therapeutic ketosis can enhance mitochondrial function for some conditions, and can kill tumor cells.”
– Dr. Thomas Seyfried

Today’s guest, Dr. Thomas Seyfried, is Professor of Biology at Boston College, where he leads a research program focused on the mechanisms by which metabolic therapies such as ketogenic diets and fasting can manage chronic disease and cancer. He sits on the editorial boards of four research journals, and has over 60 published papers on cancer and metabolism.

He is the author of the review paper Cancer as a Metabolic Disease, appearing in the Journal of Nutrition and Metabolism in 2010, and of the textbook in 2012 entitled Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer.

He’s a frequent lecturer and speaker at conferences on the topic of cancer, impaired mitochondrial function, and using ketogenic diets and fasting tactics as therapy to treat and avoid cancer.

This was personally an important episode for me. I hope you feel more in control of your cancer risk after listening to it, as I do having followed Dr. Seyfried’s work.

The show notes, 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

Show Notes

  • How the idea that a change in mitochondrial function is behind cancer started in the 1920s (4:10).
  • The ancient energy mechanism through which cancer cells can bypass the mitochondria through fermentation instead of normal mitochondrial respiration (7:20).
  • The part of mitochondrial function that seems to be compromised in cancer – oxidative phosphorylation (8:15).
  • Different types of cancer cells and tumors have varying damage to their mitochondria. The worst and most aggressive cancers have the least mitochondrial function (9:00).
  • The oncogenic paradox (9:00).
  • Lipids such as Cardiolipins in the inner membrane of mitochondria are the part responsible for respiration (15:10).
  • How Dr. Seyfried pooled research from over 50 years together to develop his conclusions on cancer and the mitochondria (18:00).
  • Therapeutic ketosis and fasting can enhance mitochondria (23:00).
  • Ketone bodies produce cleaner energy, with less oxidative stress (ROS) than glucose molecules, when used for fuel in the mitochondria (27:00).
  • Nuclear genetic mutations prevent cancer cells from adapting to use ketone bodies as their energy source (29:30).
  • Which biomarkers could be indicative of cancer risk? (33:10).
  • Using therapeutic fasting of several days to improve your metabolism (36:00).
  • Using combined blood glucose – ketone meters to take readings and using Dr. Seyfried’s calculator to calculate Glucose – Ketone Indices (38:00).
  • It requires 3 to 4 days of fasting to get into the therapeutic glucose – ketone index zone (42:00).
  • “Autolytic cannibalism” to improve overall mitochondrial function – the mitochondria can either be rescued, enhanced or consumed (47:30).
  • The difficulties with directly measuring mitochondrial respiration vs. anaerobic fermentation and lactic acid to assess cancer status (49:50).
  • Weight loss can come in two types, pathological and therapeutic. The weight loss via fasting is therapeutic and healthy (52:00).
  • Cancer patients do better with chemotherapy, with less symptoms, when they are in a fasted state (52:00).
  • Cancer centers currently do not offer mitochondrial based therapies, only chemo or immuno therapies (57:40).
  • The biomarkers Dr. Thomas Seyfried tracks on a routine basis and his use of the ‘fasting’ tool (101:40).
  • What Dr. Seyfried would do if he had cancer (102:30)
  • Should you remove organs if you discover you have a high genetic risk for cancer? (E.g. BRCA1 as with Angelina Jolie) (103:30)

Dr. Thomas Seyfried

The Tracking

Biomarkers

  • Blood Glucose: A measure of the level of glucose in the blood at one point in time. Dr. Seyfried’s therapies target reduction of blood glucose levels to limit cancer cell growth, and according to his theories high blood glucose is a biomarker of increased cancer risk.
  • 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. Thomas’ paper on the use of GKI for cancer patients has just been accepted for publishing: The Glucose Ketone Index Calculator: A Simple Tool to Monitor Therapeutic Efficacy for Metabolic Management of Brain Cancer. It is on Nutrition & Metabolism journal here and you can download an excel sheet to calculate the Glucose Ketone index here.
    Glucose Ketone Index - Thomas Seyfried

    Glucose Ketone Index Tracking of a Water Fast as Therapy for Brain Tumors Trial – Thomas Seyfried

Lab Tests, Devices and Apps

The Tactics

Treatments

  • 3 – 5 Day Water Only 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. He recommends doing this twice yearly. For cancer patients he recommends much more intensive use of the water fast.
  • Ketogenic Diets: The ketogenic diet is a low carb diet which also raises the level of ketone bodies in the blood. We discussed this in depth, as well as the Ketone biomarkers and devices in episode 7 with Jimmy Moore on Ketosis.
  • Intermittent Fasting: An approach to fasting where you fast for part of the day or certain days per week. There are many approaches to this, however in Dr. Seyfried’s research he has found this doesn’t have a significant enough impact on raising ketone bodies to be therapeutic. He has only seen this via the water-fast.
  • Hyperbaric Oxygen Therapy (HBOT): Another therapy Dr. Seyfried believes may be beneficial to fight cancer but is relatively non-toxic in comparison to current treatment modalities (chemo and immunotherapies), and would like to trial in conjunction with fasting protocols.

Supplements

  • Oxaloacetate: A support for the mitochondria, also dubbed as an anti-aging supplement as it has caloric restriction mimicking effects. It is sold by Dave Asprey in his “Upgraded Aging” formula.
  • 3-Bromopyruvate (3BP): Dr. Seyfried would like to incorporate this non-toxic molecule in combination with fasting therapies to treat cancer patients.
  • PQQ (Pyrroloquinoline Quinone): Mentioned by Damien as a potential tool for mitochondrial biogenesis.

Other People, Resources and Books

People

  • Otto Warburg: A well known scientist who worked on cancer in the 1920s and 30s and discovered that cancer cells have different metabolism to normal cells.
  • Albert Szent-Györgyi: The oncogenic paradox was first coined by this nobel prize winner for his work with vitamin C and energy metabolism.
  • Valter Longo PhD.: Dr. Seyfried referred to Valter Longo’s work at the University of Southern California on the impacts of fasting on patients undergoing chemotherapy.
  • Angelina Jolie: The actress recently had her breast’s removed when she discovered she has the BRCA1 genetic mutation, that predisposes women to breast cancer.

Organizations

Books

Full Interview Transcript

Transcript - Click Here to Read

[Damien Blenkinsopp]: Thomas, thank you so much for joining us today.

[Dr. Thomas Seyfried]: Thank you.

[Damien Blenkinsopp]: I’d like to start off with basically kind of an overview, because you are putting for a different theory of cancer compared to that that’s been the reigning theory for a very, very long time now. Could you describe the differences between the two theories, and what is the basis for your new theory?

[Dr. Thomas Seyfried]: Well, it’s not that my theory is new. The theory was initiated in the early part of the last century, in the 1920’s through the 30s and 40s, by Otto Warburg, the distinguished German scientists and biochemist. It was Warburg who found that all tumor cells continue to ferment glucose in the presence of oxygen. Put it this way, lactic acid fermentation.

This is a very unusual condition that usually happens only when oxygen is not present. But to ferment in the presence of oxygen is a very, very unusual biochemical condition. Warburg said, with his extensive amounts of data, that the reason why tumor cells do this is because their respiration is defective. So, in our normal bodies, most of our cells generate energy through respiration, which is oxidative phosphorylation. And we generate ATP this way.

But cancer cells, of all types of tumors and all cells within tumors, generally have a much higher level of fermentation than the normal cells. And this then became the signature biochemical defect in tumor cells. And Warburg wrote extensively on this phenomenon, and presented massive amounts of data – he and a number of other investigators.

But what happened after Watson and Crick’s discovery of the structure of DNA, and the findings that genetic mutations and DNA damage were in tumor cells, and the enormous implications of understanding DNA as the genetic material, this just sent the whole field off into a quest to understand the genetic damage in tumor cells. And it gradually became clear to many people that cancer was a genetic disease, rather than a mitochondrial metabolic disease as Warburg had originally showed.

[Damien Blenkinsopp]: Right, so when you were talking about the energy and respiration of the cells, just a minute ago, that was actually in fact the mitochondrial respiration, and energy generation from mitochondria within cells.

[Dr. Thomas Seyfried]: That’s correct. That’s correct, it’s mitochondrial. It’s an organelle within all of our cells, the majority of our cells – erythrocytes have no mitochondria, so they ferment. But the mitochondria are the organelle that dictates cellular homeostasis and functionality, and provides health and vitality to cells in our organisms, and ultimately our entire body.

And when these organelles become damaged, defective, or insufficient in some way, cells will normally die. But if the damage or insufficiency is a gradual chronic problem, the cells will resort to a primitive form of energy metabolism, which is fermentation. Which is the type of energy that all cells had, all organisms had before oxygen came onto the planet, which was like a billion years ago.

So what these cells are doing then is essentially going back to a very primitive state of energy metabolism, which was linked to rapid proliferation. Cells would divide rapidly and grow widely before oxygen came onto the planet. So what these cancer cells are doing is just falling back on the type of energy metabolism that existed for all organisms before oxygen came on the planet.

[Damien Blenkinsopp]: Does that type of fermentation type of respiration, metabolic activity, is that originating from the mitochondria, or from the cell itself?

[Dr. Thomas Seyfried]: No, there was no mitochondria before oxygen came on the planet. So this was purely a reductive activity within cells. It doesn’t require mitochondria, it’s a purely cytoplasmic form of energy. Glucose is taken in, and rapidly metabolized to pyruvate through cytoplasmic in the cytoplasm, and then the pyruvate is reduced to lactic acid or lactide, which is called lactic acid fermentation.

And this then could drive energy metabolism, and the processes that can emerge from this type of energy metabolism. But it’s a very inefficient form of energy generation, and it’s often associated with rapid proliferation.

[Damien Blenkinsopp]: Right, thank you very much. So, in very simple terms it seems like, basically what you’re saying is, as the mitochondria get damaged they stop functioning, and then the cell goes back to the original form of energy generation, and it’s as if the mitochondria weren’t there any more.

[Dr. Thomas Seyfried]: Well it’s not that they’re not there. They are there, and they can also participate in certain kinds of amino acid fermentations. They still play a role in generating energy and nutrients for the cell, but it’s not through the sophisticated aspect of energy generation through oxidative phosphoryation. That part of their function seems to be compromised, but other parts of their function can take place. But they’re not generating energy through what most cells would generate energy through, which is respiration or oxidative phosphorylation.

And I also want to point out, it’s not a complete shut down of oxidative phosphorylation. Tumor cells, depending on the grade, and how fast they grow, and how aggressive the tumor is. It is true that some very, very aggressive tumors have very few, if any, mitochondria. So these cells are primarily massive fermenters.

But some tumor cells still have some residual function of their respiration, and they grow much more slowly than those tumor cells that have no function, or very little function, of their respiration. So it’s a graded effect, but the bottom line is the cells continue to grow, but they’re dysregulated. Because the mitochondria do more than just provide efficient energy. They are the regulators of the differentiated state of the cell. They control the entire fiber network in the cell. They control the homeostatic state of that cell.

So these organelles play such an important role in maintaining energy efficiency. And when they become defective, the nuclear genome turns on these oncogenes, that are basically transcription factors that drive fermentation pathways. So the cells are able to survive, but they’re dysregulated.

[Damien Blenkinsopp]: Right, which becomes cancer.

So, in what ways are the mitochondria getting damaged. What is the context for this kind of damage that takes place today? Is this a modern phenomenon, because, obviously cancer has become a bigger and bigger target of medicine over the years, and, potentially, it’s been growing. I’d like to hear your view on that.

Is cancer something that’s always been around, or is it something that affects us more today, and how is it that the mitochondria are getting damaged?

[Dr. Thomas Seyfried]: Yeah, what you said there is referred to as the Oncogenic Paradox, which has been discussed by Albert Szent-Gyorgyi, who received a Novel Prize for his work on Vitamin C and energy metabolism and these things, and John Cohn from England. These people had referred to this phenomenon as the called the Onogenic Paradox. How is it possible that so many disparate events in the environment could cause cancer through a common mechanism?

And when we think of what causes cancer, we think of carcinogens. And these are chemical compounds in the environment that are known to be linked to the formation of cancer. So there’s a whole array of these kinds of chemicals that we call carcinogens. Then there’s radiation can cause cancer. Hypoxia, the blocking of oxygen into cells, can be linked to the formation of cancer.

A common phenomenon and finding is inflammation. Chronic inflammation that leads to wounds that don’t heal. This is another provocative agent for the initiation of cancer. Rare germline mutations, such as the mutations in the BRCA1 gene that a lot of people hear about because of Angelina Jolie bringing attention to that area. Viruses, Hepatitis virus, papillomaviruses. And there’s a variety of viruses that can be linked to cancer. Age. The older people get, the greater the risk of cancer.

All these provocative agents all damage respiration. Their common link to the origin of cancer is damage to the mitochondria, and damage to the respiratory capacity of the cell. So the paradox is solved once people realize that these disparate, provocative agents work all through a common mechanism, which is basically damage to the cellular respiration.

Now, but people say, “Well what about all the genome mutations? What about all these mutations?” Which is a major focus in the field right now, is that cancer is a nuclear genetic disease. Now what happens is the integrity of the nucleus and the genetic stability of the nucleus becomes unstable once energy from respiration becomes defective.

Now it’s very interesting. All of the so-called provocative agents that are known to cause cancer through damage to respiration release these toxic reactive oxygen species, which then cause nuclear genetic mutations. And this is what most people are focusing on. The nuclear genetic mutations in the tumor cells are the targets and focal point of the majority of the cancer industry. Now, when you look at the disease as a mitochondrial metabolic disease, the nuclear genetic mutations arise as secondary downstream epiphenomena of damage to the respiration. So what most people are focusing on is the downstream effect, rather than the cause of the disease.

[Damien Blenkinsopp]: You’re saying that because mitochondria are damaged and energy output is damaged, that causes the cell to lose it’s integrity?

[Dr. Thomas Seyfried]: Lose the genomic integrity.

[Damien Blenkinsopp]: Ah, genomic integrity.

[Dr. Thomas Seyfried]: Yeah. Most people you talk to about this, they say “Oh, cancer’s a genetic disease. We’re trying to talk all these genetic mutations. Every kind of tumor has all kinds of mutations. We need personalized therapies because the mutations are different in all the different cells, and the different types of cancer.” And that’s true, but all of that is a downstream effect of the damage to the respiration.

So, people are focusing on red-herrings. They’re not focusing on the core issue of the problem, which is stabilized energy metabolism. And this underlies the reason for why we’re making so little progress in managing the disease.

[Damien Blenkinsopp]: So, I don’t know if you can break it down into a bit more detail. The mitochondria are made up of several parts: the outer membrane, the inner membrane, and so on. Is it certain parts, or is it any part of the mitochondria that’s getting damaged?

[Dr. Thomas Seyfried]: Yeah, it’s very interesting. It seems to be we’ve defined the lipid abnormalities, the lipid components of the inner membrane of the mitochondria. So there’s certain types of lipids that are enriched primarily in the inner membrane of the mitochondria. This lipid called cardiolipin. It’s an ancient lipid that’s present in bacteria and in mitochondria, but it plays a very important role in maintaining the integrity of the inner membrane, which is ultimately the origin of our respiratory energy, which is that inner membrane.

And many of the proteins that participate in the electron transport chain depend, or are dependent under interaction in the lipid environment in which they sit. So, lipids can be changed dramatically from the environment, which then alter the function of the proteins of the electron transport chain, effecting the ability of that organelle now to generate energy.

This is a real issue, and that inner membrane can be effected by all these carcinogens, radiation, hypoxia, viruses. The viruses themselves, or the products of the virus, will enter into the mitochondria and take up residence, thereby altering the energy efficiency of the infected cell.

And most of the cells die. When you interfere with respiration, most cells die. But in some cells of our body that have the capacity to up-regulate fermentation, these primitive energy pathways, they survive, and they go on to become the cells of the tumor.

[Damien Blenkinsopp]: Great, thank you for that. So, this is a very different theory to that which most people have come across, which, of course, you just outlined with the DNA mutations. Which bits of research have you pulled together in your book, and in your presentations, that you feel like present this view of the world the most strongly. Are there key research elements, researchers that have gone on, and maybe it comes down to four pieces that you feel strongly support this versus the other argument?

[Dr. Thomas Seyfried]: I think that’s an extremely important point. What is the strongest evidence to support what I’ve just said? And what I did in my book in evaluating the therapeutic benefits that we’ve seen in managing cancer by targeting fermentation energy. How is it possible that we overlooked this information? It’s very interesting.

Over the last 50 years, various sporadic reports had been published in the literature showing that if the nucleus of the tumor cell is placed in a new cytoplasm, a cytoplasm that has normal mitochondria – and this is cytoplasm either from a newly fertilized egg, or an embryonic stem cell. Because now we have this technology where we can do these kinds of nuclear transplantations. And this ultimately was what lead to the cloning of Dolly the sheep, and these kinds of experiments. These had been done many, many years earlier in frogs, and in mice, before we moved on to the larger mammals and things like this.

But it became clear that when the nucleus of the tumor cell was placed into the normal cytoplasm, sometimes normal cells would form, and sometimes you could clone a frog, or a mouse, from the nucleus of the tumor cell. Now this was quite astonishing. Because people were thinking you would get cancer cells, because the mutations in the nucleus, if the hypothesis is correct that this is a nuclear genetic disease and the gene drivers are in the nucleus, then how is it possible that you could generate normal tissues without abnormal proliferation. In other words, normal, differentiated tissues from the nucleus of a tumor cell.

I was able to pull together a variety of these reports that had been sporadic in the literature over 50 years. And when these reports came out, it was considered kind of an oddball report that didn’t support the gene theory, but most people discounted it, because it was one singular report. But every four or five years, another report. Eight years would go by, another kind of report. And some of these studies were done by the leaders of the field, the key developmental biologists, the best there were. These people were heavy-weights in the field.

And they were coming to the same conclusions. That we were not getting tumors from transplanting the cancer nucleus into a normal cytoplasm. We were cloning mice, we were cloning frogs. We were seeing normal regulated cell grow. Now how can this happen, if the nucleus is supposed to be driving the disease?

So what I did was, I put all these reports together in a singular group. And I distilled it down to what the ultimate results showed. And then when you look at the whole group of papers, together for the first time, and the conclusions are consistent from one study to the other, using totally different organisms, totally different experimental systems, the results are all the same. The nuclear mutations are not driving the cancer disease.

And then if you take the normal nucleus and put it into a tumor cytoplasm, you either get tumor cells or dead cells. You never get normal cells. So this was clear. It became very clear to me, and when people look at these kinds of observations in their group and their totality, it’s a devastating statement on the nature of the disease. It’s not a nuclear genetic disease, it’s a mitochondrial metabolic disease. And the field has not yet come to grips with this new reality.

[Damien Blenkinsopp]: Just on that point, quickly, if you were to predict the future, do you think that this view of cancer metabolism is going to get traction in the near future? Say the next five years, next ten years, and what will it take to make that happen?

[Dr. Thomas Seyfried]: Well, it’s already gaining a lot of traction. People are now coming to realize that metabolism is a major aspect of cancer. But, unfortunately, what the field has done, there’s still links to the gene theory. So, the top papers come out and they say, “Oh, the abnormal metabolism in cancer cells is due to the nuclear gene mutations. Therefore, we still must be on the quest to find out what these mutations do.”

They have not evaluated in the depth of the information that I’ve presented. It becomes clear that this is not a nuclear genetic disease. So the mutations are not driving the disease, they’re the effects of the abnormal metabolism.

Now, there’s a groundswell of new interests in this. Now this opens up a totally different way to approach cancer. Once you realize it’s not a nuclear genetic disease, but it’s a mitochondrial metabolic disease, you have to then target those fuels that the tumor cell is using to stay alive. These amino acids and glucose, which can be fermented. Those molecules that can be fermented through these primitive pathways now become the focal point of stopping the disease.

So it becomes a much, much more manageable and approachable disease once you realize that if you take the fuel away from these tumor cells, they don’t survive. They become very indolent, they stop growing, they die. And now this gives you an opportunity to come in and target and destroy these cells, using more natural, non-toxic approaches.

[Damien Blenkinsopp]: Right. If you could reinforce that a little bit, because as I understand it, the current approach, which is pushed the most, is to target all of the different nuclear genetic mutations – and there’s many, many thousands of them, you can’t really count how many there are, because it’s constantly developing – versus, with mitochondria, as I understand it, mitochondria are all the same. So it’s a completely different problem when you look at it from that respective. Am I summarizing it correctly?

[Dr. Thomas Seyfried]: Yes, I think you’re absolutely right. I mean, it’s a completely different problem. It now becomes a problem of energy metabolism. And the nucleus becomes a secondary peripheral issue.

[Damien Blenkinsopp]: Right. And the fact becomes much simpler, because you’re targeting the same problem versus thousands of different problems.

[Dr. Thomas Seyfried]: Absolutely.

[Damien Blenkinsopp]: And then therapy is… Today we’re developing thousands of hundreds of different drugs to target different types of cancer.

[Dr. Thomas Seyfried]: Yeah, it makes no sense. And the issue is every single cell in the tumor suffers from the same metabolic problem. But every single cell in the tumor has a totally different genetic entity. And we’re focusing on the very different aspects of every cell, rather than the common aspects of every cell.

The problem becomes a much more solvable problem once you target the commonality. The common defect expressed in all cells, rather than the defects that are expressed in only a few of the cells. You would not do that until you came to the realization, and saw the data, that this is a disease of energy metabolism, not nuclear genetic defects. It’s a totally different way of viewing the disease.

[Damien Blenkinsopp]: Right. Thank you.

This may be kind of off subject for you, let me know if it is. But, I understand it, there’s also, more and more people are starting to link other types of diseases – say multiple sclerosis, Parkinson’s, and some of the other chronic diseases that we have and are not very solvable today – to mitochondrial disease. So I’m wondering if in any way you link that to the same origin of cancer, here. That we’re discussing.

[Dr. Thomas Seyfried]: Well, those diseases, that’s true. There are mitochondrial abnormalities in Parkinson’s disease, Alzheimer’s disease, epilepsy, and Type 2 diabetes. I mean, you can go right down the list and find a mitochondrial connection to a lot of these different diseases. But the mitochondria can be damaged, and insufficient, and influenced in many different kinds of ways. So, only cells that can up-regulate, significantly up-regulate fermentation, can go on to form tumor cells.

But many of our cells are not killed outright, and they struggle. For example, the brain. We rarely get tumors of the neurons in the brain, because if you damage the respiration of the neuron, the neuron will die.

Many of the tumors in the brain come from the glial cells. These are supportive cells of the brain, they play an extremely important role in the homeostasis of brain function. But those cells have a greater capacity to ferment than do the neurons. So when mitochondria are damaged in neurons, the neurons usually die. You can never get a tumor cell from a dead cell.

Now Parkinson’s disease and Alzheimer’s disease, these are situations where populations of neurons die from reactive oxygen species. So these reactive oxygen species, which are produced by inefficient mitochondria, kill the cell. And the cells never form tumors, they just die. So you have populations of cells in the Substantia nigra in Parkinson’s disease, or in the hippocampus in Alzheimer’s disease, where the neurons are dying. And they’re dying from mitochondrial energy inefficiencies.

And the idea then, is can we enhance neuronal function by using therapies that will strengthen mitochondrial function. And the answer is, yes. And this is why these ketogenic diets are showing therapeutic benefit for a variety of different ailments, a very broad range of ailments. But the diets and these approaches – what we can therapeutic ketosis – can enhance mitochondrial function for some conditions, and can kill tumor cells in other conditions.

So one now has to appreciate a new approach to managing a variety of diseases that may have a linkage through inefficient mitochondrial metabolism.

[Damien Blenkinsopp]: Could you talk about – we’re coming into treatment here a little bit now, based on your theory. There’s the difference between ketone, or like, fat versus glucose metabolism in the mitochondria. And you were just talking about efficiencies. Could you go over that? What is the difference there? Why is it that glucose metabolism is different that of fats and the production of ketones?

[Dr. Thomas Seyfried]: Yeah, well the body is very flexible. It can burn energy from carbohydrates, which is glucose, or it can burn energy from fatty acids. Or it can burn energy from ketones. And we evolved as a species to survive for considerable periods of time without food. It’s amazing how people don’t understand this. They think if they don’t eat food in a week or less, they’re going to drop dead. This is nonsense.

We evolved as a species to function for long periods of time. As long as we have adequate fluids, water, the human body can sustain functionality for extended periods of time without eating. Now, you say to yourself, well where are we getting our energy. We evolved to store energy in the form of triglycerides, which are fat. And many of our organs store fats to various degree, and we have fat cells that store fat.

Now, when we stop eating, the fats are mobilized out of these storage vacuoles in the cells. And the fats go to the liver, and our liver breaks these fats down, like a wood chipper, to these small little ketone bodies, which now circulate through the bloodstream, and they can serve as an alternative fuel to glucose. So we can sustain, because the brain has a huge demand for glucose, but the human brain can transition to these fat breakdown products called ketone bodies.

So this all comes from storage fat, and our brains can get tremendous energy from these ketones. The energy in food comes from hydrogen carbon bonds that were produced during the production of the food. Ultimately from planets and the sunlight. But the energy in the bonds is ultimately derived from the energy of the sun. Now, our bodies break down these bonds, and recapture that energy. What we’re doing then is just recapturing this energy.

Now ketone bodies, when they’re burned in cells, they have a higher number of carbon oxygen bonds. They produce more intrinsic energy than does a glucose molecule, which is broken down to pyruvate, which is a glucose breakdown product. And when ketones are metabolized, they produce fewer of these reactive oxygen species. They work on the coenzyme Q couple within the mitochondria to produce clean energy, energy without breakdown products. It’s a very efficient form of energy.

[Damien Blenkinsopp]: I like that analogy there, because people could relate to how we had lead gas before, and we cleaned it up a bit, and now we’ve got less waste products in the environment.

[Dr. Thomas Seyfried]: Yeah!

[Damien Blenkinsopp]: It’s a little bit similar.

[Dr. Thomas Seyfried]: It’s the same thing. I mean, our bodies are so super energy efficient when we begin to force them into a situation. In the past, this was done all the time, because in the past the humans almost were extinct a number of geological epochs, for the ice ages, lacks of food and all. And I mean, we have a very energy efficient machine in our bodies that can generate this energy from within. Clean, powerful, efficient energy that allows us to sustain our mental and physiological functions for extended periods of time.

And this comes from the genome. Our genome has a remembrance and a knowledge to do this. It evolved over millions of years to do this. The problem today is that this capability is suppressed by the large amounts of high energy foods that are in our environment. And what happens, this then creates inflammation and the kinds of conditions that allow inefficiencies, and eventually inflammation and the onset of cancer.

So, returning to the more primitive states allows our bodies to reheal themselves. And, as I said, here’s the issue. The nuclear genetic mutations that collect in these cancer cells prevent those cells from making the adaptations to these food restrictive conditions. So, because the mutations are there, the cells are no longer flexible. They can’t move from one energy state to the other, like the normal cells can, which have integrated genomes.

So, the mutations can be used to kill these tumor cells, but by forcing the body into these different energy states in a non-toxic way. It’s not necessary to have to poison people, nuke people, surgically mutilate people to make them healthy. There’s natural ways we can do this, if we understand the differences in metabolism between normal cells and cancer cells.

[Damien Blenkinsopp]: So, from your perspective, anything that would help to repair mitochondria, would that be helpful against cancer?

[Dr. Thomas Seyfried]: Oh, absolutely. Absolutely. You’re not going to get cancer in cells that have very healthy mitochondria. If mitochondrial damage is the origin of cancer, and the cells have very high efficient mitochondria, it’s very unlikely. The risk of developing cancer in those situations is remarkably low.

There are groups of people that we have in the United States, the Calorie Restriction Society of America. It exists in other areas throughout the world. These people have a very low incidence of cancer. They’re in a constant state of ketosis, and the incidence of cancer in these people is very, very low.

Now, I have to admit. This is not an easy lifestyle. People don’t want to be restricting themselves all the time, and doing this stuff. This is the issue. We live in an industrialized society that has come a long way to create an environment that is free of the massive kinds of starvations, and these things that existed in the past. So it’s hard to take your body and go back into these primitive states to do this kind of thing.

[Damien Blenkinsopp]: Right. So, there’s [unclear 31:58] a really big focus on what you’ve been saying on reactive oxygen species, which is kind of like the mini explosion that takes place inside a car when it’s running. And I think people can relate to the fact that all engines are causing damage while they’re running, because they’re producing heat, and so on.

So, with the mitochondria, it’s basically the same. And you’re saying that when we’re on a ketogenic diet, or where we’re fasting and we’re producing this more efficient type of fuel, it reduces our assets [unclear 32:23] causing less damage. And it’s an important type of the damage that is caused to mitochondria.

And this is why eventually it helps with the status of the mitochondria, to heal them and repair them, or to limit the additional damage that goes on which would help to promote the cancer. Is that a good summary, or have I got some things wrong?

[Dr. Thomas Seyfried]: It’s a very close analogy. I would say this is exactly what it is. We damage our body by the kinds of foods we eat, the kinds of environments we’re exposed to. And the mitochondria in certain cells just get damaged, and these cells then revert back to a more primitive form of energy, which is fermentation, which then leads to a total dysregulation of the growth of the cell. Collects these mutations that come as a secondary downstream epiphenomena of this.

And the thing of it is is, how do you target and eliminate those kinds of cells. And cancer, people must realize, this is systemic disease, rather than a focal disease. People say, “Oh, what does he study? He’s a liver cancer, breast cancer.”

These cancers are all the same. They’re metabolically all the same. You need to treat cancer in a singular global systemic way, and this then will marginalize and reduce the growth of these cells. And you have to be able to do it non-toxically.

And these ketogenic diets, or therapeutic ketosis, is just one way to enhance the overall health and well-being of the body while targeting and eliminating these inefficient cells. And this can be done if people do it the right away.

[Damien Blenkinsopp]: Great, great. Thank you very much.

So, based on this theory, what kind of biomarkers would give us insights into someone’s potential to develop cancer? Because today we look at 23andMe data, for example, genetics to kind of asses our risks of future cancer. For instance, on mine it says my highest potential cancer is lung cancer. And that’s pretty much the only markers that we’re given. Are there markers related to mitochondrial function, or damage, that you would feel that would be relevant to estimating a future potential risk of cancer?

[Dr. Thomas Seyfried]: Yeah, well I think one of the risks of cancer is high blood sugar, blood glucose levels. I mean this creates systemic inflammation, which underlies a lot of the so-called chronic diseases that we have, including heart disease, and Type 2 diabetes, and Alzheimer’s disease, and cancer. These are just the predominant number of chronic diseases that we’re confronted with.

So, if we know that high blood sugar is a provocative agent that increases the risk for cancer, then making sure your blood sugar levels are low. And the other thing too is elevation of ketones. So we developed what they call a glucose-keton index that can be used for people to prevent cancer, as well as managing the disease.

So if the glucose-ketone index, which we have defined as the ratio between the concentration of glucose in the blood to the concentration of ketone bodies in the blood. If this index can be maintained as close to 1.0 or below, the body is in a very high state of therapeutic energy efficiency. Which is then going to reduce the risk for all of these different kinds of chronic diseases. So, and if you look at most people with chronic disease, their index is about 50 or 100, rather than 1 or below 1.

We’ve just developed this, and we’re working on a paper. It’s called the Glucose-Ketone Index. It was designed basically for managing cancer, because patients who have cancer, if they want to know what these therapies are doing, how they’re working, you look at your index.

Now, people who don’t have cancer, who would like to do something to reduce their risk, they would do the same thing. And people would say, “What’s your index today?” “My index is 1.2.” You’re in a very good state of health.

And if most people – I can guarantee – people who eat regular foods, their indexes are about 60 or 70, not 1.2 below. Because what you do is when you have a lot of carbohydrate in your bloodstream, the ketones are very, very low. They’re like 0.2, 0.1. And you’re blood sugar is like 4 or 5 millimolar, and your blood ketones are 0.1 millimolar. Well what do you think your index is going to be? It’s going to be huge.

But then if you increase your ketones, if you can bring the ketones bodies up to the same level as glucose, then I have a 1.0.

[Damien Blenkinsopp]: Is this sensitive enough to manage potential? You made a very clear scenario of 60, where that’s a very dangerous situation to be in.

[Dr. Thomas Seyfried]: Oh no, no. I don’t want to say it’s dangerous. I want to say it’s the norm.

[Damien Blenkinsopp]: Oh, okay. Great.

[Dr. Thomas Seyfried]: It’s not dangerous. When you take somebody who has Type 2 diabetes, and his blood sugar is like 300 milligrams per deciliter – and you have to divide that by the number 18 to bring it down to millimolar – and his ketones, you can’t even measure them. I mean, these guys are inflamed. Their bodies are in an inflamed state. And inflammation will cause all kinds of effects.

So, you want to bring people down. How do you get these low numbers? Well, you can either go on these calorie restrictive ketogenic diets, or you can do therapeutic fasting, which is water only fasting, for several days. You’ll bring those numbers right down. You’ll get into an extremely healthy state. Because the ketones go up naturally when you don’t eat, and blood sugar goes down naturally when you don’t eat.

So then you enter into these states, it’s called therapeutic ketosis. The problem is it’s very, very difficult for most people in our society to do this, because our brains are addicted to glucose. If you take somebody who stopped eating for 24, 36 hours, this guy thinks he’s going to go crazy. It’s almost like trying to break the addictions to cigarettes, alcohol, drugs. It’s not easy. It’s very, very difficult to break the glucose addiction.

[Damien Blenkinsopp]: Absolutely. It takes a little bit of time to change your metabolism.

[Dr. Thomas Seyfried]: Yeah.

[Damien Blenkinsopp]: So we spoke to Jimmy Moore before. I don’t know if you connected with him before, and his book…

[Dr. Thomas Seyfried]: Yeah, I know Jimmy.

[Damien Blenkinsopp]: Right, right. So we spoke about some of the different ways to measure ketones. We had the blood test, the blood-prick test with the precision, which is a little bit expensive today. And you have the breath test, the Ketonics, which has just come out. With that index, are you using the blood-prick test, or are you using maybe blood labs, or something a bit more complicated?

[Dr. Thomas Seyfried]: There’s a couple of companies that use the blood test, the most accurate. It’s more accurate than the breath, blowing into a ketosis meter. Or you do urine sticks. So the most important measure, of course, is blood. So you have to take a blood stick. There’s only a few meters that can do both ketones and glucose, using the same meter.

You have to use different sticks. There’s a ketone stick, and a glucose stick. So from the same drop of blood, you can get your blood sugar, and then you can put a new stick into the machine, which is a ketone stick, and then you can take the same drop of blood and get your ketones.

Now what we did was we developed a calculator so that all the person would have to do is to push the button on the meter, and it would calculate already your glucose-ketone index. This would give you a singular number from a drop of blood.

[Damien Blenkinsopp]: So you’ve developed your own device, you’re saying, which does that calculation?

[Dr. Thomas Seyfried]: We developed the calculation. It’s called the Ketone Index Calculator. And because you have to convert everything back to millimolar. Because many of the ketone meters give you blood sugar in milligrams per deciliter, and ketones in millimolar. So we have to convert. You can do all this by hand, you just have to do the divisions and all of this stuff.

[Damien Blenkinsopp]: So you’ve got an online calculator where people can put their values in and it will give them the index?

[Dr. Thomas Seyfried]: Well, we don’t have that yet. What we did was develop the calculator that could be incorporated into these meters.

[Damien Blenkinsopp]: I see.

[Dr. Thomas Seyfried]: This is the thing. So people, regardless of whether you’re a cancer patient and you want to manage your disease, or you’re a person who wants to prevent cancer, or you’re an athlete who wants to know what his physiological status is, or you’re someone who wants to lose weight. All of these issues, you can get a sense, a good solid biomarker sense, by looking at your glucose-ketone index.

And everybody can do that from these meters that are capable. But the meters right now are not designed to give you glucose-ketone indexes. And this is what we’re saying; it’s the index that will tell you your overall status, your health status.

[Damien Blenkinsopp]: Right. So I imagine, right now, you’re approaching the providers of these tools to see if they can incorporate this calculation into their devices?

[Dr. Thomas Seyfried]: Yes. Exactly. They don’t have it yet. They’re not even aware yet of the potential market, or interests, among the general population. Not only for people that are afflicted with various diseases, but people who are healthy and don’t want to get those diseases.

So this is a very simple tool. The only drawback from it is you have to stick your finger with a little prick to get a little bit of a drop of blood. The people with Type 1 diabetes do this regularly. This is not an issue. But for those people who are into this, and they want to do it the right way, and they want to get accurate biomarker measurements, then they would do this. For those people who are interested in this.

This is invasive in the sense that you have to prick your finger to get a drop of blood, but it’s not invasive in the sense that you have to take tissue samples, or any of this kind of thing.

[Damien Blenkinsopp]: And so this is something that people could do on an on-going basis? So I’m guessing for someone with cancer – I don’t know if this would be something you would say – they’d probably want to look at daily, or every few days, or something like that. And someone else, maybe it’s just something they need to do a lot less intensive routine, in terms to just monitor the levels of their general ketogenesis.

[Dr. Thomas Seyfried]: Yes. You’re absolutely right about this. People who are trying to manage their diseases thoroughly might want to do this maybe once or twice a day. Just like someone who might have Type 1 diabetes. They measure their blood sugar several times a day.

The issue right now is the glucose strips are relatively cheap – they’re like 50 cents a piece – but the ketone strips are much more expensive. They can range from anywhere from $2 to $5 a stick.

[Damien Blenkinsopp]: Do you know if that’s due to economies of scale? Or if it’s simply because not enough people are using them yet?

[Dr. Thomas Seyfried]: Yes, it’s an economy of scale, absolutely. Because very few people measure their ketone levels. But now, linking those ketones to your overall general health, a lot of people would be interested in this.

And people in general like numbers. They want to know, and especially a singular number that would dictate your state of health. If you can say to somebody, “Listen. My index is between 1.1 and 0.9,” people would automatically know this guy is in a tremendous state of health.

People like to know that. You say, “Where is your number?” And people like to keep log books. They like to record these numbers. And they also link this to a greater sense of well-being. People who have their numbers down in these ranges, they tell me – and I’ve done it. Some people get into a state of euphoria. It’s like unbelievable.

When your body starts burning these ketones, it’s like you enter a new physiological state. And athletes are doing this sometimes. So it’s a whole new realm of how to monitor your own health with accurate biomarkers that give you an indication of your health status.

[Damien Blenkinsopp]: So do you follow a similar prescription to Jimmy Moore? I believe you understand his approach, where he’s eating a high fat diet, or sometimes he’s fasting. Kind of like intermittent fasting, which has become pretty popular these days.

[Dr. Thomas Seyfried]: Well intermittent fasting is, from what we’ve seen in our work, you don’t get the health benefits, the power of the health benefit, until you’ve gone three to four days without any food. Just drinking water. And then those who can go a week, like a seven day period, this is really when you start to see your blood sugars going down and your ketones going up.

But once you can get into this zone – we call it the zone of therapeutic management – where now you know your in the zone, this is where the health really comes in. And when you say periodic fasting, now there’s a lot of people that I know – numbers of people – who have a rather restrictive diet for the week, and then one day a week they’ll not eat anything. So, it’s one day off on food, like a 24 hour period where they’ll just have maybe a green tea, no calories, or just pure water.

[Damien Blenkinsopp]: Some of the intermittent fasting regimes propose that approach, a 24 hour fast every two days.

[Dr. Thomas Seyfried]: Yeah, but then you’ve got to know, okay what did that do to my index? How effective was the 24 hour fast on my index? And you look down, you say, “Well, I didn’t get my ketones up very far. They went from 0.1 to say, 0.5.” Okay, but if I go four or five days, it goes from 0.1 to 3.0. Oh wow, this is the magnitude difference.

[Damien Blenkinsopp]: Yeah. So have you looked at different people, because when we were talking to Jimmy, he was saying that different people have different responses. It’s based on their current state of metabolism. They’ll have to be more extreme in their approach to get the same level of ketones, and the same impact on an index, depending on, potentially, how damaged their mitochondria are. I don’t know how you look at it.

[Dr. Thomas Seyfried]: Yeah, no, that’s a really important point. It’s certain people. It’s also certain sexes. Women can get into these ketone states much easier than men. And young people can get into these zones much, much easier than can older people.

So it’s an age issue, it’s a gender issue. We’ve seen some of our students get down their blood sugars down into the low 30s, which people would say would be a crisis situation, you’d have to go to the hospital. But their ketones are elevated, and when the ketones are elevated, you have no crisis situation. It’s only when you lower blood sugar and don’t elevate ketones that you have this situation.

Males have a lot more muscle, they tend to burn protein, which can be converted to glucose. So their blood glucose doesn’t go down as sharply as women, the blood glucose of females goes down. Females can get their blood sugars down and their ketones elevated – from all the data that we’ve seen for several years on different gender – and this is what we see.

And older people are simply locked into a much longer lifestyle of high glucose. And for them to get their blood sugar down, it’s a real struggle. And also their muscle mass over the age. They have a lot of other issues that play into this whole thing.

And you’re absolutely right, it’s an individual thing. Some people can’t tolerate this. They get really sick, they get light-headed. Where other people make the adaptations much more quickly. So again, people have to know their own physiology.

But they have to have the biomarkers that let them know. They need to see these numbers, and once they see these numbers they’ll know that they’re on the right path, and they probably can do this if they persist a little bit longer. Rather than throwing their hands up, not knowing what’s going on, being very frustrated. And as I said, once you have this information and knowledge, that these kinds of things become much easier.

[Damien Blenkinsopp]: Yeah. It definitely helps with your confidence in something if you can see that, maybe you don’t feel better, or you don’t feel a difference yet, but if you see the numbers starting to move then it gives you that sense of accountability, and motivation also. I think that’s one of the very helpful aspects of these kind of indexes that you’re talking about.

[Dr. Thomas Seyfried]: Absolutely. This is a very important point, you’re absolutely right about this. Because when you see that you’re killing yourself, and nothing’s happening, or you don’t feel anything, but when you see numbers starting to change in the direction you know your hard work is starting to pay off. And then you get motivated, and you want to see then how far you can push these numbers.

Now this is not going to hurt anybody. You’re just lowering blood sugar and elevating ketones, and your body gets into a new state of health. And people feel it, believe me. You can feel this stuff happening. But there’s a rocky road going from the high glucose state to the high ketone state. And that rocky road can be more rocky for some than others.

[Damien Blenkinsopp]: Absolutely. So there are other aspects to mitochondrial health that certain people are looking at at the moment. I don’t know if you’ve come across any of these, but I thought I’d just throw them out in case you had some comments on them.

Some people are talking about mitochondrial repair, in terms of repairing the membranes with specific lipids, by providing those lipids to help reinforce the mitochondria. Other people talk about things like PQQ to help stimulate biogenesis of new mitochondria. I don’t know if you’ve heard about these things, or have any ideas or opinions on them.

[Dr. Thomas Seyfried]: Well, in my book I called it autolytic cannibalism. And this is basically, the mitochondria can either be rescued, enhanced, or consumed through an autophagy mechanism. And when you stop eating, now every cell in the body must operate at its maximal energy efficiency. That means that the mitochondria in those cells must be operational at their highest level of energetic efficiency. Otherwise the cell will die, and the molecules of that cell will be consumed, and redistributed to the rest of the body.

Now, in cells that have some mitochondria effective, or more efficient than other mitochondria within the same cell, the inefficient mitochondria can be incorporated into the lysosome. The parts of that mitochondria can then be redistributed to the healthy mitochondria within the cell. And this way you eliminate internal energy inefficiencies, but without having to kill the cell, because the cell is able to repair itself.

Whereas those cells that can’t repair themselves die, and their molecules are then consumed by macrophages, excreted back into the blood stream, and the nutrients now are used to support the health and vitality of those cells in the body that have this higher energy efficiency. It’s a remarkable state of efficiency. So it works both with individual cells, and throughout the whole entire physiological system.

[Damien Blenkinsopp]: Great, great. Thank you. I’m just thinking, you’ve spoken about fermentation versus respiration. Is there any way to measure that, that you know of? Is that being done in studies? So are the studies coming out are comparing the state of fermentation versus respiration taking place in people’s bodies, and correlating that to cancers, or anything like that?

[Dr. Thomas Seyfried]: Yeah, that’s kind of hard to do, because we all have lactate in our bloodstream, and the lactate comes from erythrocytes, our blood cells. The blood cells have a shorter half-life than many of the other cells in our body, and those cells have no mitochondria. They have no nucleus. So they’re little cytoplasms that primarily ferment.

But they don’t use a lot of energy, because the role of that cell is simply to exchange gases. So it floats around in our tissues, it deposits it’s oxygen and picks up CO2, as more or less a little mailman running around, picking up this and dropping that off. And they have a shorter half-life. But they have lactate.

Now if you have a tumor, or if you’re under hypoxic stress, lactic acid will go up in your bloodstream. But it’s hard to know if a tumor will do that. Sometimes what tumors will do, they have a phenomena called cachexia. This is where the tumor cells will send out molecules that will digest proteins, or dissolve proteins in our muscles and other proteins. And these proteins then go to the liver, and are broken down into amino acids, and the amino acids are conjugated into glucose.

So the glucose goes now into the tumor cell, and some of the proteins and the amino acids go to the tumor cell after being broken down. So the tumor is essentially causing our body to starve to death. We might be eating, but it looks like we’re not gaining any weight, and we’re becoming moribund and looking like we’re starving to death. This is an effect of the tumor,.

Sometimes you don’t see that. Sometimes lactic acid will go up, and sometimes it won’t. So there’s a lot of ambiguity of looking at a good biomarker to assess the state of what level of tumor growth you might have, other than the fact that you’re losing weight even though you’re eating. Which is the cachexic state; you’re kind of wasting from within. This is the whole thing.

And this is one of the fears that the medical profession has with cancer patients, because they say these poor people are losing weight through this cachexic mechanism, and then you come along with a metabolic therapy, and they say, “Oh, this can’t work.” But the issue, of course, is that there’s two types of weight loss. One is a pathological weight loss, and the other is therapeutic weight loss.

Pathological weight loss is cachexia, and of course if you treat it with toxic chemicals and radiation, you get so sick with fatigue, nausea, diarrhea, vomiting. I mean, this is pathological weight loss. Therapeutic weight loss is you’re losing weight, but your body is getting extremely healthy, and killing cancer cells at the same time.

So weight loss can come in two different varieties: pathological and therapeutic. And people have a tremendous difficulty in understanding the differences between these kinds of weight loss.

[Damien Blenkinsopp]: I think we’ve mentioned on a podcast before that when people are fasting in this state, they actually feel better, even if they have, for instance, chemotherapy. They tend to do better in chemotherapy when they have been fasting.

[Dr. Thomas Seyfried]: Yes, because it reduces inflammation. We published a number of papers showing how therapeutic fasting reduces systemic inflammation. Systemic inflammation contributes to a pathological state, and facilitates tumor growth.

So therapeutic fasting, while at the same time you’re taking a toxic drug, it’s like what are you doing here. But it does take the sting out of that toxic drug. People feel better when they’re therapeutically fasting. I think Longo’s group down at University of Southern California has clearly shown that some of these cancer patients can do a lot better, and feel better, when they’re fasting while they’re taking chemotherapy.

But you’re absolutely right about that.

[Damien Blenkinsopp]: Thank you so much for this interview[unclear 53:08] Thomas. I want to ask you just a few more questions to round off now.

What do you think will happen in the next five or 10 years, or hope? What are your visions for this area, in terms of biomarkers, like testing devices, or change in the way we approach this? Do you think there’s specific opportunities ahead, are there specific questions you’re looking at at the moment to resolve, in research, or so on?

[Dr. Thomas Seyfried]: Yeah, well I think the people themselves are demanding a change. The issue is that they haven’t been shown other alternatives, other than the standards of care, which are conducted by the major medical schools: Dana Farber Cancer Center, MD Anderson, John Hopkins, Yale Cancer Centers, Sloan Kettering, UCSF. The major industries of cancer and academics are closely aligned in how to do this.

And it’s not working. We’re having about 1,600 people a day are dying from cancer in this country. And the statistics in other countries in Europe, and China, and Japan, are not far off of this. And if we had Ebola outbreak in this country, where 1,600 people were dying a day, this would be of the greatest catastrophe that people can imagine.

But for cancer, it seems to be okay. This is the norm. Well it doesn’t have to be this way. It doesn’t have to be this way. And the issue here is that the people see that we have more, and more survivors, and people doing pretty well on these metabolic therapies. Why are we not doing this as more of a general treatment as opposed to these toxic approaches to manage the disease?

So I think the change will come from the grassroots. I don’t see it coming from the top medical schools, because these people are not trained. They’re medical education doesn’t give them the training to identify these approaches to therapy. It’s not part of the medical training.

There are a number of physicians that are recognizing this now, and they want to become part of this new approach to cancer management. Now, you have to realize that we’re just beginning. This is just a new field, it’s a beginning field. Even though the science is well, well established, the implementation of this science for patient health is just at the beginning. It can be refined, it can be modified.

A lot of this now we’re talking about, the potential for managing cancer in a non-toxic way with greater therapeutic efficacy, is just beginning. So, I think that we need more trained people. We have to have people that understand this. Eventually, these kinds of approaches will be more and more recognized, and more and more implemented in the overall society.

The problem is people have not yet found a way to make a large profit on this kind of an approach as you can with certain drugs, and immunotherapies, and these kinds of things. But that will probably come in time, once people understand what the best approaches and techniques are.

[Damien Blenkinsopp]: Another aspect I wanted is there’s more research being undertaken on mitochondria over time. Do you think that will help, in any way?

[Dr. Thomas Seyfried]: Yeah, I think it will help a lot, like you said, with the lipids. And we’re looking into this ourselves. I think there’s ways that we can enhance mitochondrial energy efficiency through various diets and supplements, and things like this.

And there will be a real quantitative measures that can assess this, for people to recognize what works and what doesn’t. So I think it’s just that it’s an area that has been not well appreciated, and not well recognized.

And as long as people think that cancer is a nuclear genetic disease, the focus on the mitochondria hasn’t been there. People have known the importance of mitochondria, and it’s been a very major area of scientific research. But it’s not recognized as the solution to the problem. It’s kind of a side effect.

What we’re looking at is understanding mitochondrial functions, and it’s interaction with the nucleus and other parts of the cell to maintain a healthy cell – a healthy society of cells – and a healthy overall physiology. All linked to the mitochondrial energy metabolism. This is going to be a very exciting new development.

[Damien Blenkinsopp]: Yeah, I agree. There’s not a day that goes past that I don’t think about mitochondria these days. And hear someone talk about it. It happens a lot on this show, also.

If someone wants to learn more about your work, and this theory of cancer, and the index you were talking about, where should they go?

[Dr. Thomas Seyfried]: Well, I wrote the book On Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of the Disease. That’s published by John Wiley Press. Unfortunately, it’s a science book and it’s not cheap, like you’d find most of the Amazon books, but it gives you the literature, it gives you the science. It gives you the hard evidence to support everything that I’ve said.

Another book that’s just appeared is Tripping Over the Truth: The Metabolic Theory of Cancer, by Travis Christofferson, who’s written a book for the layperson, where he actually read my book and went back to test all the things that I was saying, and actually talking and visiting and interviewing those scientists who work in the gene theory, and work in the metabolic theory, and get the word directly from them. It reads like a novel, and it’s much less scientifically intimidating than what I wrote.

I wrote this book to convince my peers, and people in the cancer and scientific field, the evidence that supports what I’m saying. This sometimes can be intimidating to the layperson. Whereas Travis went out and actually interviewed those scientists, and asked them the specific questions. And now it becomes a very intriguing story; I mean, how did this cancer thing get so far out of whack with what we know about it. People like to see this, and read it.

So that is another book that’s generating… If you go on Amazon, you’ll see the reviews. They’re all quite outstanding for Travis’ book. And I’ve been privy to a number of other books that will be coming out over the next year, which are harping on the same general theme, that cancer is a metabolic disease, and it can be beaten by metabolic solutions. Totally different than what’s been going on in the main focus.

And this is kind of shocking, because you go to the top cancer centers, and they don’t speak anything about this. They’re still talking about the standards of care as they have been done, or they’re talking about immunotherapies, which is the new buzzword for the cancer field, where you’re going to identify all the mutations, and then make anti-bodies to the defective proteins, and then treat people. And they show a few survivors on the cover of the Wall Street Journal saying how wonderful this works. But they don’t show you the other evidence showing how many people are dying from this.

All this will change, because the people in this society, the public, is going to be fed up with the lack of progress, and what we have is a new way to approach this problem based on solid scientific fact. It’s just that these facts are not well understood or recognized at this point.

[Damien Blenkinsopp]: Great. Thank you very much, and we’ll put all of this in the show notes, so people will find these links easy. Also the index you spoke about, I’m guessing there’s nothing really published about that. If people go to your website in the future, will you have something on there which will talk about that in more detail?

[Dr. Thomas Seyfried]: Yeah. We have a paper that’s under review right now, where we’ve submitted a paper for the index, and we’re in the process of making some revisions on the index. And the index was, in this paper, was mostly focused on managing brain cancer, but we also noted that this index could have a broad applicability to a whole range of different diseases.

And in the Journal of Lipid Research, which is the top journal in the field of lipid biochemistry, I edited one of the issues that was entitled Ketone Strong: Emerging Evidence for the Role of Ketones and Calorie Restriction for the Management of a Broad Range of Diseases. So, more and more scientists are getting involved in this, and more and more information will be coming out. Both in the professional scientific journals as well as in the public interests articles in journals, and magazines, and radio shows.

More and more people will be coming to know this, and I think the field is going to have to deal with it. And I think in the long run, we’ll emerge into a new way to manage these chronic diseases with a lot less toxicity, and greater efficacy.

[Damien Blenkinsopp]: Great, great. Thank you. Now, just two more questions, personal questions for you.

What data metrics do you track for your own body on a routine basis, if any?

[Dr. Thomas Seyfried]: Well, basically I try to get on a scale and see how much I weigh. Obviously, if you can keep your body weight at a stable level for a period of time, this is certainly one way to maintain homeostasis.

I’ve done the three day fast, but as I said, when you’re older like myself, it’s very uncomfortable, but it’s certainly doable. It’s like training exercise. You’d have to do it probably a couple of times a year to get into the state. I think every time you do this, you become more confident in your ability to do it again.

There is a state of uncertainty and discomfort, like, “Oh my god, I’m not eating any food. How can I go, and I feel uncomfortable, and a little light-headed.” And you try to drink water to say, “Maybe I can fill my stomach up with water and I won’t feel as hungry.” And then you start getting water intoxication. And eventually you realize that you really don’t need to drink a lot of water, and you just have to bite the bullet.

But as I said, as we begin to do this, we realize that it’s not so life-threatening as everybody would think it would be. So I think I try to do that. But as I said to a lot of people, they said, “Oh, you must do this all the time.” No, I don’t do it all the time. But if I had cancer, I’d know exactly what I would do.

[Damien Blenkinsopp]: What would you do? Just to speak it out clearly.

[Dr. Thomas Seyfried]: I would stop eating.

[Damien Blenkinsopp]: Completely?

[Dr. Thomas Seyfried]: I’d get my index down below 1, that’s for sure. And then I would transition off to these high-fat, nutritious kinds of diets, ketogenic diets, and maintain my index. And then of course, we’re investigating – it’s very hard to get funds to do this kind of stuff too, because it’s not considered sexy science – what is the best combinatorial therapy that would work with therapeutic fasting and ketogenic diets, that would put the greatest amount of pressure.

And most of it has to do with what kind of non-toxic drugs would you dovetail in with therapeutic fasting and ketogenic diets? And like hypobaric oxygen therapy, 2-deoxyglucose, 3-bromopyruvate, oxaloacetate. I mean, we can go down these lists. Most of these are non-patentable drugs, but they have tremendous power when used together with these other therapies. And most of this stuff is just trying to figure out the dosages, the timing.

These kinds of issues, it’s just like perfecting the engine. How did the car engine become so efficient today from the way it was in 1900?

[Damien Blenkinsopp]: Right. So the things you just mentioned either stress the cancer cells specifically, like hypobaric oxygen, or they support the mitochondria, oxaloacetate, right?

[Dr. Thomas Seyfried]: Yes! Exactly. What you’re doing is you’re enhancing mitochondrial function in normal cells, and you’re putting maximal metabolic stress on the tumor cells. For the first time, we’re using our normal cells to directly combat and battle the cancer cells, while enhancing their health and efficiency.

[Damien Blenkinsopp]: So for someone who has, say we do a 23andMe test – like a lot of people on this podcast do their 23andMe test – and it comes out with some DNA, and it says, maybe you have a pretty high chance of cancer in your lifetime – and it could be lung cancer or whatever. Lung cancer’s not a good one, because often it’s smoking. So, one of the other more general ones, like breast cancer.

What would you basically say that they should be fasting once per month for three days, or twice per year for seven days, and maybe looking at those therapies you just outlined.

[Dr. Thomas Seyfried]: Yeah. People who have Li-Fraumeni syndrome, which is an inherited germline mutation in the gene for P53 which encodes a protein in the electron transport train, or BRCA1. Product of the BRCA1 gene has been found in mitochondria. We look at a number of these so-called inherited genes that increase your risk for cancer. But as I told you, everything passes through the mitochondria The mitochondria are the origin of the disease.

So, the inherited mutations simply make that organelle slightly less efficient in certain cells of our body. Not all cells, but only certain cells, like the breast, the uterine, or these kinds of things. And we know that there are people, like if you inherit the BRCA1 mutation, your risk of cancer goes up significantly. But not everybody who has BRCA1 mutation develops cancer.

So clearly the environment can play a huge role in determining whether that gene will be expressed or not. You can do prophylactic removal of organs, and things like this, to reduce your risk. But it would be just as effective in my mind to transition the body to a metabolic state that would minimize the problem of that gene influencing the mitochondrial function. It seems a lot less draconian than doing these massive surgical mutilations.

Or you can do both. The idea is some of these inherited mutations, they might have a preferred organ – like a breast, or a uterus, or ovary – but you’re not going to remove all your organs. You’re not going to remove brain. You’re at a higher risk, so what can you do to lower your risk? As I said, if you keep your mitochondria healthy, the risk is going to be significantly reduced.

People need to know this so they can make choices that would be best suitable for them.

[Damien Blenkinsopp]: Thank you so much for the information today. This is really an information packed episode. It’s got this great new take on cancer, which I think is very positive, because it’s talking about something which people can have more control about. So it’s not just that this is a new approach, and the older approach has been struggling for quite a while, it’s become very expensive, and so on, with not so much success, but also that this is an approach which is within people’s own manners, sphere of management.

A lot easier to start having an impact on their own lives. So it’s very positive from that perspective also.

[Dr. Thomas Seyfried]: Yeah, I agree. Absolutely.

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