Recent investigations have shown supplements to not always contain what they say they do. Or at other times to have unwanted contaminants such as heavy metals. Learn to use 3rd party lab testing to select supplements that contain the active ingredients needed to provide the results you seek.

Sometimes on this show, we discuss using supplements as tools to get desired results. Examples in past episodes included curcumin, activated charcoal, NT factor, Greens powder, oxaloacetate and many others.

I’ve been aware for a long time that not all supplement products are equal in quality. For instance, if they actually contain as much of the active ingredients as the label says on them, or if they are contaminated with heavy metals or pesticides, for example.

Last year this issue was given more publicity when the New York State Attorney General’s office investigated supplements found at GNC, Target, Walmart and Walgreens, and sent ‘Cease and Desist’ letters to each for some of their supplements that neither contained the active ingredients, and at times contained other undesirable ingredients that weren’t listed on the labels.

The unfortunate takeaway is if you truly want the results from supplements — so if we talk about results that can be achieved through a supplement on this show – then you can’t just take it for granted and buy any supplement. You have to make sure they contain what you want and don’t contain what you don’t want.

In practice, how do we do that? I’ve been using a lab service for a few years now that tests and reports on the quality of supplement products. So I can select the products that will achieve the results while minimizing the cost. Sometimes you don’t need to buy the most expensive brand to get the best quality, which is kind of cool.

The service was ConsumerLab.com, which is a subscription service, so unfortunately, you have to pay. However, the good news is that an open alternative is now available that has been publishing extensive lab testing data on popular supplement categories.

That company is Labdoor.com. If you have the internet available it will probably be useful to check out the rankings the company is publishing while listening to this episode to see what the end result is, and what they’re actually publishing.

“I think there are categories where 70 percent of products fail, there are categories like creatine where 10 percent or fewer products fail. And then there’s kind of the in-between zones where, with fish oil, about a quarter of the products have rancidity [fat oxidation] issues. And so we’re filtering that, and that’s a part of our [supplements testing] purity score.”
– Neil Thanedar

Today’s guest is Neil Thanedar, CEO and Founder of Labdoor.com, and Founder of Avomeen Analytical Services, which is a company that specializes in product lab analytics to see what they are composed of. Labdoor is now four years in the making and sets to start growing at a faster pace and covering more supplement categories now that they’ve got some sort of funding behind them.

In this interview, Neil walks us through the types of analysis they run on supplements to understand their quality and some of the most interesting and useful results they found in the supplement markets. It features highlights, such as we shouldn’t really be trusting user reviews that you find on the internet on places such as Amazon – because there doesn’t seem to be much of a correlation. And there are other big similar takeaways, which, I’m sure, goes against what we’ve all been doing.

itunes quantified body

What You’ll Learn

  • Neil’s research interests and orientation towards quality control supplement testing (3:57).
  • Labdoor is a spin-off business, diversifying lab testing services compared to what’s offered by Avomeen (5:40).
  • Labdoor and Avomeen are split in leadership between Neil and his father (7:50).
  • A consumer-aligned model and efforts to eliminate bias in producing objective information (8:03).
  • The major quality control issues with dietary supplements (10:04).
  • Defining supplement quality and criteria used for rating supplements (11:13).
  • The technologies used for testing supplements and the science behind interpreting results (12:19).
  • Customizing supplement ranking formulas and tailoring results to individual customers, ex. vegan or child categories (18:54).
  • Establishing accuracy in nutrient analysis and maximizing trust in results (20:25).
  • How Labdoor manages an active role as part of the supplement industry (22:54).
  • Dealing with testing newer or complex composition supplement products, where research is still accumulating (25:05).
  • Consumer demands and targeting of testing results to differing audiences (27:15).
  • Labdoor’s role in supporting an informed market (29:21).
  • Overview of tested categories of supplements (33:10).
  • Discovering products and prioritizing particular supplements testing (39:15).
  • A severe lack of price correlation in the supplement industry (40:58).
  • Cooperating with companies when Labdoor testing does not confirm producer certificate of analysis testing results (42:08).
  • Labdoor’s plans for reaching out to manufacturers more proactively (47:23).
  • The potential of re-testing for capturing trends in the supplement industry and increasing confidence in obtained data (48:30).
  • Case studies and key takeaways for particular categories of supplements (52:19).
  • Little brand correlation in same category products and guidelines for choosing supplements (54:21).
  • Caveats for non-scientific approaches towards choosing supplements (57:20).
  • Future prospects of wide-spread product testing aimed at empowering consumers to make science-based health decisions (1:01:44).
  • Reasons for re-organizing the supplement market, such that the best products are making the highest sales (1:03:59).
  • Scientific or practical business assumptions which Neil has changed his mind about (1:06:06).
  • The biomarkers Neil tracks on a routine basis to monitor and improve his health, longevity, and performance (1:08:21).
  • Recommended self-experiments for improving mental performance (1:14:07).
  • The best ways to discover the field of supplement testing (1:15:55).
  • How you can best connect with Neil or find out more about Labdoor (1:18:54).
  • Neil’s request for you – The Quantified Body audience (1:20:32).

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

Neil Thanedar, LabDoor

  • Avomeen: A chemical analysis lab specialized in failure analysis work (when products go wrong). Initially, it was started by Neil but is now run by his father – a scientist continuing his work and research in his retirement years.
  • Labdoor: A company currently run by Neil focused on providing scientifically-backed analysis and ranking of dietary supplement products. The company offers objective information on supplements and aims to empower people to make informed decisions. Check out Labdoor’s supplement rankings.
  • Labdoor’s Facebook & Reddit: The two fastest ways for you to reach out to Labdoor. Hundreds of questions have already been answered on these forums and Neil hopes new ones will spark lively debates on topics across the field.
  • Neil’s Twitter: Where Neil shares his ideas about testing and his opinions on how Labdoor touches other industries.

Recommended Self-Experiment

  • Tracking Time: Keep track of how you spend time for 10 days in a row with an app such as Hours. You should discover many useful takeaways such as areas where you waste the most time or activities you should cut. Neil suggests repeating approximately every 6 months to track improvements and optimize over time.

Tools & Tactics

Supplementation

  • B Complex: It contains Vitamin B12 – a molecule which is used in the metabolism of every cell and acts in DNA synthesis and regulation. B complex also contains folate which is needed for DNA repair and proper DNA methylation – see episode 5 with Ben Lynch. This product contains the active forms of B vitamins increasing their bioavailability.
  • Curcumin BCM95: The active ingredient of turmeric, also found in limited amounts in Ginger. Curcumin is a potent anti-inflammatory and cancer preventative molecule. Previously we have discussed this supplement in the context of lowering oxidative stress or inflammation in episode 4 with Cheryl Burdette and episode 25 with Josh Fessel.
  • Activated Charcoal: This is a medical-grade purified product which is highly absorbent of toxins. It promotes a healthy digestive track and improves brain functionality. Taking activated charcoal reduces the body’s toxic burden – a subject discussed in episode 23 with Kara Fitzgerald. This is a lower cost (value for money) Activated Charcoal option.
  • NT Factor EnergyLipids: A blend derived from soy lecithin extract specifically. This product is formulated and used for supporting memory and cognitive function. There’s also an NT Factor Energy Wafers option which is a chewable product packaged in pieces.
  • Greens Powder: A mix of alkalizing green foods, antioxidant rich fruits, and support herbs. This product is used as a dose of whole food nutrition – essentially aiming to supply a healthy background of nutrients.
  • Oxaloacetate (Aging Formula): A metabolite of the Krebs Cycle which improves blood sugar regulation, improves energy levels, and increase endurance. Previously we discussed oxaloacetate as an anti-aging supplement in episode 30 with Alan Cash and in the context of blood glucose regulation in episode 22 with Bob Troia.
  • Fish Oil: This supplement is useful against inflammation. Fish oil can be used post workout sessions or if inflammation is part of a disease state. Labdoor tests EPA and DHA content (beneficial Omega 3 fatty acids) in fish oil supplements. According to their data, often there are products which contain 50% Omega 3 instead of the labeled 90%.
  • Lypo-Spheric Vitamin C: These are liposome encapsulated vitamin C tablets and this maximizes the bioavailability of the active component. Previously we have discussed Vitamin C and its potential for preventing colds in a timely manner by tracking Heart Rate Variability (HRV) in episode 41 with Marco Altini.
  • Calcium: This supplement is aimed at improving the composition of bones. Calcium also plays a key role in muscle contraction thus this mineral supports neuromuscular health. The major benefit of calcium is lowering the risk of developing osteoporosis.
  • Magnesium : This mineral in supplement form is used to support nerve, heart and muscle functionality. See episode 17 with Dr. Carolyn Dean for testing and fixing magnesium deficiency.
  • Zinc: An essential mineral which plays a role in many enzymatic functions. Zinc supports immune system function and is an important component of the body’s antioxidant systems.
  • Creatine Monohydrate: This product is targeted for using after workouts to aid in the recovery process. Approximately 5-10% of these products are faulty, according to Labdoor supplement testing results data.
  • Garcinia Cambogia: A small fruit traditionally used to enhance the culinary experience of a meal and as an aid to weight loss. Garcinia cambogia was the worst category recorded by Labdoor. Up to 70% of products in this category do not actually contain the active ingredient (defined as less than 10% of the labeled ingredient quantity).
  • Ginseng: This supplement is effective for mood, immunity, and cognition. Examining the ginsenoside content is important in these products because Ginseng quantity is different from the active ingredient. This causes consistency problems because extraction processes differ. Neil advises patience before purchasing these supplements and, of course, waiting for Labdoor’s data on particular products.

Diet & Nutrition

  • Protein Bars: In the future, Labdoor plans to take on testing food beverages. For example, increasingly protein bars are marketed as a meal replacement, thus approaching the supplement (or functional food) category. Eventually, even well-known products such as a McDonald’s Big Mac, a Chipotle burrito, or liquid beverages such as Pepsi could be tested.
  • Baby Formula: Manufactured food products targeted for feeding infants under 12 months of age. Often, these are manufactured using methods similar to those used for the production of supplements.

Tracking

Labs Tests

  • Liquid Chromatography: Chromatography is a diverse set of laboratory techniques for the separation of mixtures. Detecting the concentration of specific substances out of a whole is key for objective supplement testing results. In liquid chromatography, the mixture is turned into a liquid phase which moves through a column or plane (solid phases used for detection). Individual chemicals can be detected based on a constant property, ex. by affinity for the solid phase coating material.
  • Gas Chromatography: This method is used for analyzing compounds that can be vaporized without decomposition. In vaporized form, chemicals travel through a column at different speeds and reach the detection surface at different times – known as retention time. This is a constant for individual types of chemicals and is the principle behind detecting particular types of chemicals in gas chromatography.
  • Mass Spectrometry: Mass Spec or MS as it is known is becoming increasingly popular for analysis of all types of samples from testosterone and other body metabolites or proteins to understanding the composition of any material.In a typical MS procedure, the sample is initially ionized by bombarding it with electrons. These ions are then accelerated by subjecting them to an electric or magnetic field. Individual substances are detected according to their mass-to-charge ratio. Ions of the same mass-to-charge ratio undergo the same amount of deflection on the detection surface. This is transferred into information about concentration.

    Liquid / Gas Chromatography is often used as a pre-analytical method for preparing isolated sets of chemical subgroups, before digging deeper using mass spectrometry to obtain accurate supplement testing results.

Apps

  • Headspace: A meditation, or mindful awareness, training app. It is useful for improving mental performance, to relieve anxiety, and increase endurance.
  • Lucid: An app focused on mental training for professional athletes.
  • Hours: An app used for tracking activities throughout the day, thus mapping time expenditure. This is useful for improving mental performance. Because tracking itself can be time-consuming, Damien suggests undertaking focused projects – one lasting a few weeks before moving to the next.

Other People, Books & Resources

Organizations

  • ConsumerLab: A company offering supplement testing service. Damien used ConsumerLab Reports until Labdoor appeared on the market and started offering supplement testing free of charge.
  • Thorne Research: A company manufacturing dietary supplements, separated in programs tailored towards health categories, ex. cardiovascular or immune support. Their products are usually sold through doctors, thus Labdoor has missed these in their initial supplement testing categories.
  • Life Extension: A manufacturing company producing supplements including vitamins, minerals, herbs, or hormones.
  • Elysium: A relatively new company gaining ground in the supplement industry, partly due to their science-strict operational and marketing model. Elysium is sponsored via venture capitalism investments – a business model different from Labdoor’s.

People

  • Gary Vaynerchuk: Recognized by Neil as an important voice in the understanding the link between marketing and consumer trust.

Other

  • Yelp: Neil draws a parallel between Labdoor and Yelp – a service specialized for ranking business of different categories ex. restaurants or shopping venues. This comparison demonstrates that Labdoor requires customer and manufacturer feedback to grow its business and to accomplish more ambitious challenges.

Full Interview Transcript

Click Here to Read Transcript
[Damien Blenkinsopp]: Neil, thank you so much for joining us.

[Neil Thanedar]: Yeah, absolutely. Thanks for having me.

[Damien Blenkinsopp]: You’re in a pretty niche area. There have been a couple of companies around which have been testing supplement products for a while. And of course there’s been a fair amount of news over the last year or so talking about the high variability in supplement quality, and whether we’re getting what we want.

So I was just interested in how you got into this whole area. Where did this start for you?

[Neil Thanedar]: Yeah, absolutely. I grew up in research, I grew up in science. My dad’s a Ph.D. Chemist. When I was two years old he quit his job as a researcher and started his own lab. And it was just him for a couple of months, and he slowly grew that lab all the way up until I was in college. So he had retired by the time I was in college.

When I was trying to figure out what I wanted to do with my career, the first thing I really wanted to do is, I had really thought about biotechnology or inventing new medicines. And those had been the first things I had thought of. And throughout the process, I found out that the existing process, the existing medicines and supplements just weren’t clean; they weren’t safe. And so I jumped right back into the same industry that my dad did, which is quality control.

And so right out of college I started a lab. It was a chemical analysis lab called Avomeen. We did product development and failure analysis work. We figured out for manufactures when something went very wrong: a pill had a black dot on it, your baseboards were yellowing, there was an odd smell coming from a multivitamin. Any sort of something going wrong, the company would come to us, we would do all of the testing required to figure out what they should go and fix.

(00:05:40) [Damien Blenkinsopp]: You just mentioned baseboards. What are baseboards?

[Neil Thanedar]: Literally the baseboards like in the floor, that connect the floor to the carpet. That little white strip? That’s actually a product that we did once. The white boards were turning yellow as soon as they were installed.

[Damien Blenkinsopp]: So you actually started from analyzing a broader spectrum of products, not just dietary products.

[Neil Thanedar]: Yeah. It was anything from that to household cleaners to a sunscreen to a multivitamin to even pharmaceuticals. Generic versus brand name medication.

And so we were doing it, but we were doing it in a very reactive way and we were doing it for manufacturers. And really one day I just had the idea that really we should do the opposite business.
What if we could, instead of being reactive we could be very proactive. We could go into a Walgreens or CVS and buy every product off the shelf and pretest it. So you would already know if it was good or bad. And if something failed, you would know ahead of time.

At this point, I had — as kind of a back-story — my dad had come in and started working with me to come out of retirement. He was starting to work at Avomeen. And so what I decided was I really felt like LabDoor needed its own focus. And so we kind of split up, and he went and he’s taking care of Avomeen now, and I fully run LabDoor.

So this was, for me it was a new way to work in the business. I kind of just jumped into the industry expecting it to be like it always was, and then just one day being the new person. I was just like, hey this is weird, why don’t we just start by testing everything?

(00:07:15) [Damien Blenkinsopp]: Cool. So how long has Avomeen been around?

[Neil Thanedar]: So that company has been around for about seven years now. And LabDoor has been around for just over four. It’s been all LabDoor for me for the last four years.

[Damien Blenkinsopp]: Okay. Cool. It’s very interesting. So it’s always good to see a family business. Your father’s kind of proud of you for carrying it on, the whole research lab area.

[Neil Thanedar]: Yeah, it’s so interesting. We always talked about it, but it was never something he asked me to do. It was just always interesting to me. And I think the science is so fascinating, when you figure out exactly what’s inside something. You get to break things down and you get to reverse engineer, it’s just fun.

The problem in the industry is really just, how do you get paid. Consumers need to see the data but they’re not going to pay ahead of time. It’s really just paying for this testing that’s the hard part.

(00:08:03) [Damien Blenkinsopp]: Right, yeah. So I guess you’ve got a slight advantage because Avomeen is associated with you, but how does LabDoor get paid so that you can do this for everyone else? Because the information is available for free, right?

[Neil Thanedar]: Yes. And so, what we want to do is do all the testing ahead of time and help you have all the data to make the research decision. And then what we’re finding out is that people, the next thing you’re doing is buying. And so if we just affiliate links down, we’ve got 10 percent of the conversion. And that really is most of the business.

And I think it’s what we, we love that kind of alignment with the consumer. So you’ve got the sense of I don’t get paid unless you actually find something you like. If you return it, we lose the commission. It’s this whole process where we can really be performance based.

And it’s also something where it’s sustainable. Every single day, there’s going to be tens of thousands of people who shop this site. They’re going to buy stuff, and that’s going to support the next round of testing.

[Damien Blenkinsopp]: Right. And I’m guessing it doesn’t matter what they buy. Are you putting Amazon links on most of the stuff?

[Neil Thanedar]: Yeah. So it’s really easy to put it on every single product. And we get some debate about this. The D and F products have affiliate links on them too.

[Damien Blenkinsopp]: The DN…

[Neil Thanedar]: The D and F. So it’s A through F. Every single product has the link.

[Damien Blenkinsopp]: Right. Well, I think that’s the way to go because you’re unbiased.

You’re not there to promote one product versus another. It’s just that you provide your objective information, and if someone buys something from using the information on your site to make that decision, you get a commission. But like you say, you’ve put a few links on the worst products and the best products, so there’s no official bias there.

I bring that up because there are some sites out there on the web which have been out there for quite a long time, and I’m sure people are aware or these – which are basically just affiliate review sites. And they have their number one product where they are getting paid, and all the others they are not getting paid. And obviously, they are just trying to cash in there.

But yours is a professional company without the bias.

(00:10:04) [Damien Blenkinsopp] Okay, so let’s talk about supplement quality to actually understand what the issues are. What is the context for us first? Why should people be interested or worried about dietary supplement quality?

[Neil Thanedar]: I think there are two parts of it.

I think the first part is actually that there are some products that legitimately have problems. They’re either massively under-dosing — and that’s maybe a third of the products that we see. So the active ingredient isn’t there, there are some sort of heavy metals or purity issues. And that might be the D or F grade products on the site.

And then there’s really this other group of products that you should worry about quality-wise — I would say the B and C products — where they’re just not highly concentrated. Maybe there’s some famous brand that you’ve always heard of, but like the fish oil is 50 percent Omega 3 instead of 90 percent Omega 3. Or the protein powder is 40 percent protein instead of 80 percent protein. And those are kind of the B and C products.

So those are the two things that you have to worry about: are you not getting what you paid for or are you really being cheated? These are the two types of quality control issues that we really find on a regular basis.

(00:11:13) [Damien Blenkinsopp]: Right. These are the most common things. How would you describe supplement quality? Because I know you’ve got your own kind of internal rating system, where you look through a whole bunch of different criteria.

[Neil Thanedar]: Yeah, I think what we really want to do is start by, it’s really kind of rewarding active ingredient quality and quantity, and starting to penalize for the negative inactive ingredients. And so, as much as possible it’s very, the calculations we try to be as intuitive as possible with it.

The number one factor is going to be the concentration of active ingredient. So it’s going to be the Omega 3 concentration in fish oil or the protein concentration in protein powder. Next, we’ll look at the quality of the active ingredient. We’ll look at the EPA and DHA in fish oil, we’ll look at the amino acid profile in protein.

We’ll look at label accuracy. So we’ll look at how those numbers compare to the label. And we’ll look at purity. We’ll look at mercury and PCBs in fish oil. We’ll look at arsenic, lead, and heavy metals in protein powder. And that’s really it. I think we want to try to look at purity and potency and figure out, ‘Does it work?’ and ‘Is it safe?’.

(00:12:19) [Damien Blenkinsopp]: Great. Thank you for that. So, how do we go about testing these things? What kind of technologies are you using to look at the supplements?

[Neil Thanedar]: Yeah, so it’s really kind of classic analytical chemistry. So we’re looking at chromatography and spectroscopy, like an HPLC or a GC-MS, ICP-MS.

[Damien Blenkinsopp]: Okay. Could you quickly describe that? I know what you’re talking about, but I think these are terms that the majority of people don’t really understand.

I look at chromatography as basically splitting things apart so that you can look at them. And then spectroscopy as actually doing the analysis. I don’t know if you’ve got a better way to explain it.

[Neil Thanedar]: So yeah, we’re basically separating, identify ingredients, and we’re figuring out their quantities. So an HPLC could actually look at anything from caffeine content or a kind of vitamin content, or it could even look at something like sunscreen content and look at the different sunscreen ingredients.

What we’d like to do, and I think this is a big part of our process, is if we can get a couple of HPLCs in the building and really ramp up our testing in supplements, that will allow us to start experimenting with other types of products that we could test.

And so really we’re looking at, in any of those machines, is we have standards of the ingredients. What are the best quality ingredients supposed to look like? You can run that through an HPLC and you’ll get a curve. Then you can run the product through the HPCL and get a curve and you can see the difference.

[Damien Blenkinsopp]: Great. So, when you say HPLC, what does that stand for again?

[Neil Thanedar]: It’s a High-Performance Liquid Chromatography.

[Damien Blenkinsopp]: Okay. Right, for separating things out.

[Neil Thanedar]: So yeah. I think those are the things where we’re not inventing, really. That’s not our, I mean there are a lot of scientific start-ups out on the market that are truly on the frontier of science. I think a lot of the work we do, there are new methods every year and things are advancing, but for the most part, it’s an established industry.

The testing part is established. I think the part that we’re trying to work on is – how can we test thousands of products. How does it get to a point where we test thousands of products?

[Damien Blenkinsopp]: I guess that’s primarily about cost?

[Neil Thanedar]: Yeah, it’s a chicken and egg problem, right? Because we’ve got to do the testing before you show up. So we need to, there’s kind of a constant process of kind of testing a little bit, add one more category, bring money back into the business.

And that cycle is really important to us. And the cycles are going faster at this point. We want to be at a point where we can test, instead of 25 products a month, 50 or 100 or 150 products a month.

[Damien Blenkinsopp]: So, with the approach to testing that you use, do you have to say what you’re looking for? Or does it actually show up, everything that is in the substance? So do you have to pre-decide that I’m looking for mercury, for example, or will you pick up other things in that process?

[Neil Thanedar]: You’re looking for specific ingredients.

[Damien Blenkinsopp]: Okay.

[Neil Thanedar]: So that’s the HPLC where you would look at caffeine versus a caffeine standard.

[Damien Blenkinsopp]: Yeah.

[Neil Thanedar]: And I think that’s the part that we haven’t quite, these ideas, these magical devices where you scan your food and it tells you every ingredient simultaneously. That’s truly on the frontier; that’s not science that exists today.

So we’d love to have more information on it. Until then there is, at some level, brute force work being done here. And at some level, we’ve got established panels of ingredients we can look for.

So you can look at all of the heavy metals at once, or you can look for a whole set of carcinogens at once. There’s a whole set of banned substances that you can all do in one scan. There are certain things that we’ve set up, and with everything else, there is a bit of brute force work. Especially with the active ingredients.

[Damien Blenkinsopp]: So when you say brute force, what does that mean?

[Neil Thanedar]: So you would have to, for example, for a multivitamin you would have to separate every individual vitamin out of there and test them each individually. And it might even be as far as vitamin A is going to be in the product in three or four different forms. So you would have to test each of the four forms of vitamin A individually.

That’s when I start thinking about, that’s truly where we start getting into reverse engineering for active ingredients. Where you need to get down to that individual level because we want our calculations to take that into account. We want to have, if different vitamins A forms have different bio-availabilities, we want to use that as part of the calculation.

[Damien Blenkinsopp]: So I guess in your process of trying to understand each new area, you plan a new category. For example, fish oil you’ve done, but then you come across something else so you’re like okay, maybe this is a growing supplement or something that people are getting more interested in so we’ll attack this category now.

I guess, first of all, you’re looking at some research to kind of see what the issues are, what kind of things you want to look at. And then you have these standard things, like carcinogens and metals that I’m guessing you’re looking for in most things, just because… I guess if something is made in China, the odds that it could have some metals in it, that’s one of the big concerns.

[Neil Thanedar]: It’s even beyond that. I think, well also almost every supply chain is global at this point. So we just test everything for heavy metals off the top. So those are certain things where it’s just automatic. An ICP-MS is expensive, but it gets a lot of use.

Whereas something like each individual ingredient, I think we have to make a decision on [what to test]. For example, with protein powders, we started with a very simple analysis. We started with just a [unclear 0:17:35], nitrogen analysis. So we were just looking at the total nitrogen content. And then we started looking at total amino acid content, and then we started looking a pre-amino acid content, subtracting pre-amino acid content out.

So there’s a whole range of how we get to the final data. I think the work’s never done because the next thing we’d want to do in protein is get into are there specific amino acid ratio [that are] more bio-available. So could we build into the calculations a system that scores the amino acids? That’s something that we would be interested in doing.

So at some level, there’s this constant improvement that has to happen. Many of the products on our site we’ve tested only once, because we test on a yearly basis and it’s the first year. That’s another thing that’s going to improve the data. So year two or year three, we’re going to get more data, we’re going to see is there any batch to batch, year to year variation.

So all of that stuff is part of our expansion process. It’s part of our growing process where it’s why we purposefully limited it to 25 products per month. That was our case, and we can hold to that. And we can consistently deliver that kind of quality, but we’re not going to go in and say, hey look we have 100,000 products on our site. It’s just not possible to do.

(00:18:54) [Damien Blenkinsopp]: Right, it’s not feasible. It sounds like you’re going to be on a learning curve. Say you did protein like two years ago, you do it another year and you’re like, you know what, last time we learned this, so we can integrate that and we can look for that this time, and that’s going to be important for the new formula.

Is that the process you’re going for with some of the main supplements?

[Neil Thanedar]: Yes. And it’s also, you get a lot of consumer feedback after that, because we might build our quality rankings based on usually very quantitative, what we talked about. Very quantitative factors like concentration.

But then what we need to figure out, and what we’d love to add, is more types of rankings. So there are other reasons or other ways for people to make a decision. And so we used to just have one set of rankings, and we found out that some people weren’t buying the number one.

And we said, hey, why do people not buy the number one? Oh, there are some people who are vegan so that’s not their number one. So we added a vegan filter. Some people were buying products for kids, and so we added a children filter. People were buying by value, so we added a value ranking that’s completely separate value ranking.

And I think in a perfect world, there would be, you could take a test where we would just know who you were, and your perfect LabDoor rankings would show up. And they would be perfectly customized to you. We’re on that lifelong path of getting to the point where we can perfectly customize it to you.

And quality and value and kind of vegan and sugar-free; we’re hitting the major ones right now. And then it just keeps getting better and better.

(00:20:25) [Damien Blenkinsopp]: Excellent. And so how accurate is the volume aspect? So you can identify and say that fish oil has DHA in it, or it’s non-oxidized. But how do you understand the actual amounts of this, and how accurate is that?

[Neil Thanedar]: So we’re looking at percentages.

So if you look at a fish oil capsule, it’s anywhere from 10 percent of that capsule is Omega 3, to 90 percent is Omega 3. If you tested the same product again that was at 90, you might see it at 92 or 88.

There might be a little bit of a variation there between tests, but you’ve got a good sense. The product that tested at 90 versus the product that tested at 80, there is a clear separation there.

[Damien Blenkinsopp]: Sure. So what is the swing, and is that, I mean that could be just due to each capsule, right?

[Neil Thanedar]: We’re taking an average of at least 10 plus capsules. So we’re getting a little bit of a range there.

It’s that kind of a range, so maybe in the 2-5 percent range. Sometimes in certain categories with many ingredients sometimes you see a 10 percent variance. But these things are pretty consistent. Once you put that first test out, you have good data.

And I think that 10 percent variance off of the label; the labels are often very inaccurate as well. So the labels tend to be more than 10 percent inaccurate. So I think what we want to do is as soon as we put that first data point there, you’ve already got better data than you had before.

And now our job is to go in and solidify that. And so there’s a constant tradeoff between ‘do we go to a new product’ or ‘do we test the old product again?’

[Damien Blenkinsopp]: Right. So when you’re taking the average, are you taking, say from one bottle you’re taking like 10 capsules or are you trying several bottles? How do you approach that?

[Neil Thanedar]: No, so we’ll want to take it all of it from the same lot. So we’ll try to buy three or four bottles and have it be the same lot.

And so then we might need 50 to 100 total samples because you might be 10 per test or similar. So you will end up using about 100 of those capsules in a round, and save the other 300 just in case a company comes back and questions the data, we need to retest. All of these kinds of things, so it’s important for us to do.

So we’ve got a decent range there. And I think what we found out is these companies are generally doing between two to four major batches of product a year. If you grab any one of those products off the shelf, you get really close on that first test. And then everything after that, we just have to test every year.

(00:22:54) [Damien Blenkinsopp]: Right. So you’ve mentioned lots and batch. Are they the same thing?

[Neil Thanedar]: So I think a lot of people would think, I mean there might be multiple lots in a batch. So it’s a little bit of manufacturing lingo.

I think we are starting out, so that’s part of our learning curve as well. We’re trying to get more into how manufacturers work, and how that side of the industry works because I think we jumped in just totally as consumers. And we were just like how can we figure out how to make this data out.

And then what we found out was there’s different, I mean from the industry there are companies complaining about, hey you’re sharing our proprietary blend. Don’t do that. Or, that data is wrong, or our data shows something else. Our internal lab says something else. And there’s a lot of that.

And in the early days I think we almost didn’t have the time to handle all of the information at once, and if we had to focus on one thing it would be consumers. We’d want to focus on the people who are taking the products. But now I think, as we step back and get a little more organized, we’re starting to figure those things out.

How do you talk to companies, how do you manage the system, how do you figure out and return that data back to the manufacturer? If we find something, can we alert them? I think we want to do a better job with that, we want to do a better job of being a part of the entire industry, instead of being this kind of renegade on the side.

[Damien Blenkinsopp]: Right. Do you get a lot of manufacturers reaching out proactively to you then? Has that happened a lot?

[Neil Thanedar]: It’s a slow, steady pace. There might be a manufacturer a month or something who will come out.

And I think there’s a whole range of them. I think the majority of the complains are honestly like A- companies who…

[Damien Blenkinsopp]: Right. The one’s who really care.

[Neil Thanedar]: Yeah, they really care. “I’m number 8 and I want to be number 1, and here’s why.” And there’s literally 20 reasons why, and five studies attached. And we love that; that’s wonderful. If you do that, our scientists will read all of those studies and we’ll talk about it over a meeting and it’ll be interesting to us.

And if you can convince us, [great]. That’s one of the big things that the protein manufacturers are trying to argue, add an amino acid scoring system. And maybe the ranking will shift a little bit. I don’t think it’ll do very much, but there might be a few products that fall out.

(00:25:05) [Damien Blenkinsopp]: Yeah. So I guess there’s the other subject that some of these products have been around for a long time. So protein is pretty well standardized as a market, and fish oil as well. But of course, then you have some of the newer supplements.

Those must be a bit more challenging because the research can still be evolving, in what the active ingredients are. “We’re not 100 percent sure, but we think it’s this one” kind of stuff.

[Neil Thanedar]: That’s a tough one. I think that is a lot more in our calculations. So the testing is much more straightforward.

So the nice thing is, even if we’re testing a nootropic or something, there would be specific ingredients where even if the clinical research hadn’t completely proven that that ingredient works or not, we could 100 percent know whether it’s there or not. We could at least know that.

[Damien Blenkinsopp]: Right. Because the first thing you’re doing is you’re just comparing the label. The label says it has this, and actually, it has something a little bit different in it. So it’s an easy comparison to start with.

[Neil Thanedar]: That’s easier. The part that we need to figure out, and sometimes we’re staggering that. We might really focus first on the ingredients that have really clear claims.

And now we’re kind of, we are getting more and more into specialty products now. So we are now ramping into testing B complex in glutamine and all of the joint support.

So now we’re going into things that have more complexity or variety. We’re starting to unpack our old categories. So now protein is going to have protein bars, and protein shakes. There’s going to be new categories.

[Damien Blenkinsopp]: I mean, a protein bar tends to be pretty complex in its makeup, right? It has all sort of ingredients.

[Neil Thanedar]: We want to figure out the protein quality in the protein bars because that’s such an important thing. We’ll start testing vegan Omega 3s in the next couple of months.

So it is that kind of constant process of expanding the existing categories, getting into new categories, and then doing the research on the fly. And we’re finding that in some places there’s not good research.

When you test an ingredient, and you have all the data and then, it’s garcinia cambogia and there’s no great evidence that says that it works. And in many cases, we still try to plug that data into our rankings, and you get like in our garcinia rankings, there’s not a single A grade product on the ranking. Because there’s just not enough efficacy in the calculation to get the score up.

(00:27:15) [Damien Blenkinsopp]: Right. So you have five criteria. [First is] label accuracy, which is very straightforward for you guys, you basically just compare. Then you have product purity. What is that exactly?

[Neil Thanedar]: We’re just looking at the heavy metals and contaminants versus upper limits.

[Damien Blenkinsopp]: Okay, great. And then the nutritional value, would that fit more into what we were just discussing about garcinia cambogia? How would you say that?

[Neil Thanedar]: Garcinia cambogia. No, nutritional I would think like the RDAs or daily values of the macronutrients.

So that’s what we’re looking at. We’re working on all of these names, and we’ll have to figure out exactly what they are.

[Damien Blenkinsopp]: Yeah.

[Neil Thanedar]: But I think nutritional value, I pour it over the daily value type stuff.

[Damien Blenkinsopp]:Okay, so you compare there. And then you’ve got ingredient safety.

[Neil Thanedar]: So I’m looking at the quality of the inactive ingredients. So what’s the safety risk of the inactive ingredients?

[Damien Blenkinsopp]: Okay. So if people don’t like aspartame or something in their pills, there you go. And then projected efficacy, would that be going back to our other discussion right now, as in is this really an active molecule?

[Neil Thanedar]: Yeah. So that’s concentration of active ingredient and the quality of the active ingredient.

[Damien Blenkinsopp]: Okay, cool.

Just so people know when they go to your site what they’re looking at and how to navigate it properly. So it makes a lot more sense and they understand where things are at, and how these things are based over time. And obviously, the label accuracy is the thing that they can trust the most from the get-go.

[Neil Thanedar]: It’s really interesting, and I think we look at it that we want to have different people weigh it different ways. That’s another part of our learning curve.

Some people want to be entirely efficacy focused. So it’s just like, give me my active ingredient. And I think that’s really important to people. “I want a 95% pure Omega 3.” And some people are very focused on purity, and purity is the only thing that matters to them. And they’d almost rather take a placebo that’s pure.

And then there’s a group of people who are all about honesty and label accuracy. And I think what we want to do is we have our own weighing system, and I think we’d love that as part of the personalization process.

We’d love to have a process where you put in your own weights for what you think is most important, and the rankings change based on that.

(00:29:21) [Damien Blenkinsopp]: Great. A lot of people in the supplement industry have certificates of analysis from the manufacturers. Is this something you get from the companies?

I guess you’re not reaching out to all of these guys, you’re just kind of buying up the products.

[Neil Thanedar]: No, it’s really a retail process for us. It’s an independent purchase.

The A- people will send us their certificate of analysis. And that’s fine. Anytime we’re working with manufacturers and there’s science going back and forth, we’re in a good place.

[Damien Blenkinsopp]: Yeah, cool. So their certificate of analysis is basically the same kind of analysis or something similar, to say what’s in it, that they’ve had done either by their manufacturer or themselves or a third party lab normally. And then they can compare it to yours and say hey, I want to be A+.

[Neil Thanedar]: Yeah, and sometimes it’s the other way. Actually, more often it is a request for a certificate of analysis from us because they want to go to their supplier and complain.

[Damien Blenkinsopp]: Ah, interesting. So do you think they’ve got false certificates of analysis? Or they just didn’t…

[Neil Thanedar]: Well there’s just so many moving parts in any of these supply chains. So if you’re making a multivitamin you might be sourcing 30, 40, 50 ingredients. And so if you see the LabDoor report and two are off, you know which supplier that is and you can go find out.

And that’s something that’s really interesting data that could help the supply chain and manufacturers. And honestly, we just haven’t found a way to package that data back up. It’s just that we’ve always purely focused on how to get the data first to consumers.

And as we build up more and more data, as we start seeing trends and see more years of data, that will be another type of business that I think would be interesting for us. Because that’s important to us; I think we’d want to be more and more integrated over time.

I could see a place where maybe LabDoor does all of those types of certifications. Instead of an Organic certification and a Gluten certification and the Tested for Sports certification all being different companies. LabDoor is going to have to do all that testing anyway. So if we could somehow say look we’ve already done the testing, here’s the certification, that could be a really interesting thing for us.

We’ll look at every part of the industry in every way that we can help. That’s part of the expansion process, it’s part of how we learn, how we grow, how we provide more value.

[Damien Blenkinsopp]: And now just to consumers but, like you say, to the manufacturers and the suppliers to improve the supply chain in general. Because it’s not necessarily the brand owners.

He could design a great product and he could ask a manufacturer depending on his due diligence, and [unclear 0:31:59] just to pick up on these things. And the testing given to him might not be his fault, but it’s not exactly what he wanted in the first place.

[Neil Thanedar]: Yeah, I think it’s between that and there are so many things that they’re focusing on. And I think that we want to be the place where if you’re a manufacturer, just focus on making the best product. We’ll help show it to consumers; don’t spend money on marketing, spend money on quality ingredients.

And we’ll give you the data you need. It’s really transparent; we’re really transparent with the A- people about what it takes to get to an A. And we’ll do that with everyone else.

Every company knows, obviously, the reason I’m losing to the number one guy is they have twice as much Omega 3 per gram as I do. Now I know that it’s going to be three times more expensive for me to increase my Omega 3 concentration. But that’s a tradeoff, and they’re going to have to make that equation.

And we would love it if LabDoor was driving so much sales to the high concentration folks that the math eventually worked out, that you should just make higher quality products.

[Damien Blenkinsopp]: Right, because you’ve provided more information into the market, and more people are making informed decisions, and thus it becomes more in their interest to raise the quality because their sales volume increases based on it.

(00:33:10) [Damien Blenkinsopp]: So what types of supplements have you looked at so far, and as an overview how have you found the general quality of supplements to be? Was it what you expected? Especially based on the articles that all came out last year about testing Walmart, CVS Pharmacy and places like that. There were a lot of issues that were brought up then.

[Neil Thanedar]: I think, well there are a couple of things. So one, we’re about to release glutamine, which will be our 20th category. So if you go to LabDoor.com/rankings, you will see the 19 rankings we have done so far.

So it is more than just protein and fish oil, there’s multivitamins, prenatals. We’ve also looked at vitamin C and D, calcium, magnesium, and zinc. We’re trying to go through category by category of the most popular.

And so under that list of the top 20 are the next 50 that we’re looking at. And those, really, consumers go in and vote on what they want to see next.

[Damien Blenkinsopp]: Oh. So you’ll do that, if people are like, “Yeah, I want this reviewed.”

[Neil Thanedar]: Yeah. LabDoor.com/rankings.

[Damien Blenkinsopp]: Okay, and they can vote for something new that they want ranked.

[Neil Thanedar]: Yup. And so there’s a whole bunch of categories in there. We’re just trying to grab them as quickly as possible.

So some of the most popular ones on there like glutamine and B complex and glucosamine are already in the lab. We’re already working on them. And just keep voting. Basically, you’ll get an email when that category is available.

What I’m going to try to do is over the next year or so finish those 50 categories. Really go through and say hey, in the supplement industry you can really come up with any major product and LabDoor will have it. Have at least one set of data on it. Just enough to get you in.

And I think once we do that and really get the lab fully up and running and instead of 25 products a month we really should be doing 100 plus product per month. That’s when I would say maybe we’ll look at other categories.

Maybe we’ll look at food and beverage, maybe we’ll look at meal replacement. I mean, we’re already kind of there. Protein bars are already starting to touch meal replacement and functional foods. Even baby products, like baby food and baby formula, are really on the edge of being a supplement; they’re manufactured in very much the same way.

And so any of those types of things we’d love to be in places where you feel like there’s some uncertainty. If you feel like, I don’t know what I’m buying, that’s enough for LabDoor to jump in.

It doesn’t necessarily need to be the supplement industry where you get data every week saying something goes wrong. I think it’s even a case where you are buying baby formula and you have no idea what’s in it. At any point where there’s any of that kind of insecurity, you should look to places like LabDoor to get some science and data, and make that decision with more backing.

I actually don’t think that the, I want to try to make sure that the supplement industry doesn’t get all negative stories. Really that’s where it’s starting to go, it’s really kind of pushing it to a lot of negative stories. And that’s not really our market. You’ll see that LabDoor is not the person driving a lot of those stories.

[Damien Blenkinsopp]: Sure. I mean, what do you think of the market? You’ve got the data on nearly 20 categories now. Where would you say it’s at? If you had to explain in objective terms, where is supplement quality currently at?

[Neil Thanedar]: I think there are about three even groups of companies.

There are a third that are doing a really great job. And those are basically the A products in the market.
There is a third that are like the B and C products that are just not worth it for the money. And those are usually the guys using brand or marketing to sell products. And then you’ve got the D and F…

[Damien Blenkinsopp]: When you say brand or marketing, could you give an example of that, maybe naming a specific company? But what does that mean to you? Brand or marketing?

[Neil Thanedar]: These are companies that I’ve literally looked at some of these companies that have, first the head of R&D works for the head of marketing in a lot of these companies.

You’ll see these companies haven’t made significant investments in R and D but are spending 20, 30, 40 percent of their budget or more on marketing. And these are companies that are truly spending more on marketing as a percentage of revenue than they are on the products themselves.

And you see that in the data. And those become the B and C products that are actually usually, more expensive than the A products. We’re finding that there’s really no correlation between price and quality. There’s just none in this market.

There are people who are in the middle group who are just medium quality for high price.

[Damien Blenkinsopp]: Right. So you’ve got some products which are brand driven. They’re a premium brand and have put a lot of good marketing behind it, but actually, the product doesn’t back it up.

[Neil Thanedar]: Yeah, that’s the second third.

And I think the third is honestly the D and F grade products, where people are honestly cheating. There are, and it’s different by different categories.

Something as simple as a creatine product you usually don’t have to worry about as much. It’s just creatine in a bottle. There are fewer things that could go wrong. Those products, maybe 5 or 10 percent of products, have problems. But there are things like garcinia, 70 percent of products have problems.

[Damien Blenkinsopp]: Wow. So it really does vary a lot by [category].

So creatine has been around for a long time, and it’s extremely standardized. So I imagine there’s a bit of market development. There must be so many manufacturing facilities now that the technology is well standardized at creating creatine and everything, so it’s a little bit easier.

And it’s also something very straight forward. It’s not like it gets damaged easily, like fish oils and so on. So yeah, I guess each category can be quite different.

[Neil Thanedar]: Yeah, so each category is quite different. Overall, it’s about what we need to do is try to get people to the top third as much as possible. If we can do that, if we can really help you focus when you’re in the store.

Because that’s what’s happening in the store. There are 100 fish oils. And how are you picking with 100 fish oils? And I think that’s why the branded marketing thing works so well.

When there’re 100 fish oils, you see the brand you recognize and that just makes that purchase easier. And what we want to do is say, what if those 100 fish oils were instead ordered from one to 100 in some sort of other system based on science?

(00:39:15) [Damien Blenkinsopp]: Yeah, excellent. A couple of questions. I realize you probably don’t want to name companies, but I’m interested in the Trusted Science brands, the ones that look like they’re doing research and backing it up with content like Thorne Research, Life Extension. People tend to trust these kinds of brands.

I don’t know if you’ve looked at those types of brands. Not necessarily those guys, but similar ones which are putting out a fair amount of content on their sites, and they talk about their research. Do those tend to have reasonable quality?

[Neil Thanedar]: We haven’t tested as many of those yet, and I think the reason why is because our initial way of picking the most popular products by category was to use online best-seller lists. And the Thorne and the Life Extension are usually sold through doctors so we missed that in the first round.

[Damien Blenkinsopp]: Probably a bit more expensive for most people as well. That might be a smaller market.

[Neil Thanedar]: It’s more expensive and just in different channels.

We’d like to prove that. We’d love to test those products and see is there really a price and quality correlation there. Because otherwise, industry wide there is zero price correlation. And there are honestly categories on our site where literally the cheapest product in the category is the number one in quality.

[Damien Blenkinsopp]: Wow.

[Neil Thanedar]: It’s amazing. It doesn’t work [unclear 0:40:29] maybe in handbags or cosmetics. So these are the types of industry where that works, right?

[Damien Blenkinsopp]: Could you give us an example? Is that something like creatine? Where it’s very simple?

[Neil Thanedar]: It might have been creatine. It might have been something like creatine where the people who were really trying to jazz it up with the fancy box, and five artificial sweeteners and not enough creatine, those are the people who are expensive and at the bottom.

And vice versa; the people who just throw 100 percent creatine monohydrate in a bag do pretty well.

(00:40:58) [Damien Blenkinsopp]: Cool. Okay, so we talked about the price correlation, and that there isn’t much, which is interesting. You looked at online reviews from consumers on Amazon as well, I noticed just recently. What were your results there?

[Neil Thanedar]: Same thing. Zero correlation. And what we might need to figure out is they might be answering totally different questions. The user reviews might be totally answering the qualitative question, and we’re answering the quantitative question.

And first of all, there are certain categories of supplements, like a multivitamin for example, where other than pill size there isn’t that much qualitative that you need to worry about. You’re not taking a multivitamin like, oh I feel better today.

There’s not that much qualitative to do. These decisions should be more quantitative. They should be more scientific. And so the thing we try to talk about as much as possible is for most of these categories we should be letting user reviews go and really be focusing most of our energy on scientific reviews.

[Damien Blenkinsopp]: Yeah, well unfortunately, they’re not around everywhere. You’re working on it, but it can be hard to come by.

I used to use Consumer Lab Reports, which is the other company that was doing it. And then you guys came along, and it’s a free service versus a paid service, so it helps me out that way.

(00:42:08) [Damien Blenkinsopp]: What I want to bring up, I don’t know if you’ve seen this new company, which is kind of trying to position itself right at the top of the supplement industry which is Elysium?

[Neil Thanedar]: I’ve seen that, yes.

[Damien Blenkinsopp]: With their anti-aging. And they have a scientific board of directors.

So they’ve really tried to go more the scientific approach that we should be trusted, we’re using a pharmaceutical grade production process. We have a scientific board of advisers of some of the top scientists in this area in the world.

I found that was really interesting and really encouraging in terms of really taking a step up. And it’s got VC funding. So it’s a completely different business model, really.

And I guess it’s only been possible now because of the size of the market, where they can now have a VC driven model where they can go and get top scientific advisers on board, sometimes Nobel prize winning guys to be able to raise the standard a lot.

So, it would be interesting if you help with your work to promote that kind of activity as well.

[Neil Thanedar]: Absolutely. I feel like guys like that are the new generation of the Thorne and Pure Encapsulations. And there are more people like that. I think honest companies really try to do that not just in supplements but in cosmetics and household products.

So there are a lot of places where there’s renewed interest in that kind of high quality and direct to the consumer brand. And I think that fits really well with where LabDoor is. I think we want to, we need to get to a place where that product is in a category, versus the other people.

And that would be really interesting. There’s now food test on some of those same ingredients, for example. And there are a lot of generic manufacturers who have the same ingredients as Elysium does, but there’s an issue of do you trust the generic manufacturer.

[Damien Blenkinsopp]: It’s interesting, because I looked on Amazon, of course, for the ingredients — because they’re being transparent about the ingredients, which is another thing. Not all companies will tell you exactly what it is in the product.

Some companies you can ask them for their certificate of analysis. A lot of consumers don’t know that, but you can just contact them. And sometimes they’ll give it to you. It depends on their policy. And sometimes they’ll say sorry we don’t hand out that for propriety reasons. Or whatever.

So there are a fair number of certifications out there. I don’t know if you’ve looked at any of these. Sometimes we see these stamps on products and we don’t really know what’s behind them, a lot of the time. Have you looked at any of those?

[Neil Thanedar]: We’ve looked at it a little bit.

So, I think my general issue with certifications is there are many of them and consumers don’t really understand what they all mean. I worry that in a situation where if you give too much information, it’s an overload and actually doesn’t get paid attention to.

So that’s one of my issues with certifications. What we’d like to do at LabDoor is to try and figure out if there’s some way to get beyond a certification, beyond a pass/fail system and get to is the product really good.

Because there are two different parts to this. There’s the part where hey here are the third, or two thirds of the products that are bad. That’s fine, but I think our business is really dependent on can we help you make a good decision. Can we help you get into the good third?

And so what we need to do as much as possible is find that way of saying I’m just highlighting the good products. I think for us that’s really we have to keep focusing on it that way. And so I want to, as much as possible I would like that not to be certification based.

I think if we wanted to say, look it’s not about whether it’s organic or not, it’s about what’s the quality of the product. And in many cases, just because it’s organic doesn’t mean it’s pure, in many cases, organic products can catch a lot of heavy metals.

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

[Neil Thanedar]: So all of those things we don’t want to get into, we don’t want to outsource the decision to that single certification. That you really should be having your decision on a holistic approach to the product.

[Damien Blenkinsopp]: Yeah. I guess whether it’s organic or not, that’s kind of a philosophy. But at the end of the day, it’s the pesticide resides and the heavy metals that people are really interested in, a lot of the time.

[Neil Thanedar]: It’s very much like the filters, to me. So, if you want to have a vegan filter, or a sugar-free filter, or an organic filter, a non-GMO filter in your life I think that’s fine.

I think that’s just a fundamentally different decision criteria that’s almost like the quality and value ranking. We’ll let those things be, let them cross, and that is useful as a filtering tool.

[Damien Blenkinsopp]: Also, I think we kind of covered this, but have you come across instances where the certificates of analysis have been different to what you found?

[Neil Thanedar]: Yeah. What we’ll do is there’s a kind of a standard process.

So if we have our testing and our certificate of analysis, a company comes with their own, then we will go to a third party lab and we will get testing done there.

And the idea is basically if the grade goes up, we’ll pay for it. If the grade goes down, they pay for it. And that’s it, right? It’s just I think that is, we want to figure out a system where it’s just [fair].

I mean, at any given point we’re defending 700 products, and soon we’ll be defending thousands of products. And so we want to be able to say at some level we want to be the referee and we understand that not everything is going to be 100 percent perfect. And we’ll just be open to it.

And if you think that something is wrong, challenge us on it. And challenge us with scientific data with a certificate of analysis and look we’ll test it. We can always test more. That’s possible. The thing we can’t do is kind of get into shouting matches with companies.

(00:47:23) [Damien Blenkinsopp]: Yeah, sure. So in terms of, to give people an idea, how often does that come up? Does it come up a lot or is it relatively rare?

[Neil Thanedar]: I would say it’s less than five percent of the companies who will ever kind of come and talk to us.

And I think a lot of people indirectly come and talk to us. We’ll get emails from their customers complaining, or things like that. There are all kinds of side things.

I think it’s something where there are some very passionate people on the manufacturing side of the industry, and I think we’ve tried to be really open with it. I think it’s important for us to actually be talking to more of the industry.

I actually should be going – and I’ll do more of this — is going and travel, spend time at supply side conferences, where people are actually talking to the manufacturers. I need to do that. And I think that’s something that as we get bigger I should be talking to half or more of the industry.

Because I think if LabDoor’s data gets back to the companies, it’s going to be good for the industry. It’ll have rapid feedback. You’ll have feedback from consumers and from the lab. Both of those things are incredibly valuable for manufacturers, and it’ll make the products better.

(00:48:30) [Damien Blenkinsopp]: So we’re talking about the technologies you’re using are relatively standardized now. They’ve been around quite a long time. I think they’re currently getting better in terms of cost, right? They’re expected to get cheaper over the next years. That was just a training I was at recently.

But I was just wondering if you think there’s some variability. So say if they did come with another certificate of analysis and then you went to a third party lab, how much variance does there tend to be between labs?

Because just in my own testing, I test a lot of different things, and there’s a fair amount of variability between the labs, unfortunately. We’re still in the middle of a kind of, I guess it’s mostly the processes and ironing out all of these things, and some of the technologies are getting more mature over time and more stable.

For these particular technologies, how stable would you say they are in the accuracy?

[Neil Thanedar]: You’re getting good data out of it.

I think even in a situation where there’s a 10 percent lab-to lab-variation, firstly there are different labs and I think [with] the labs we use we’re seeing some 10 percent variation. And in many cases, we were talking about 2-5 percent batch-to-batch variation.

So even different labs, different product in a different batch, we’re seeing pretty similar results. And that’s just some of these products, and it’s with the established companies. The thing that we’re finding is there are some companies where the product is vastly different, from category to category. There are certain things where I worry less about that.

I think what we need to do is build repeat testing into the model. Because any sort of calculation like this the confidence goes way up when you get the second, third and fourth test. So I think that’s where we’re at right now.

The first test is good data, and it’s important for consumers to get it. And then every other test, the second, third, or fourth, you get a lot of increase in confidence, and then you just have to be consistent. Then you have to get on your yearly or every-other-year basis, and we’ll be humming along normally.

And so I think for us, LabDoor Year 5 out of a 10-year process of really kind of stabilizing everything and having a fully operational machine. And then we’d want it to just automatically test products.

Like every month people request new products, we test it. We’re automatically getting into new categories, we’re automatically maybe thinking about new ways to rank products, we’re getting deeper and deeper into personalization. But it’s a very, it’ll be a very consistent improvement process.

[Damien Blenkinsopp]: Have you got plans to retest any categories yet? Or are you doing your first retest with any category yet this coming year, or is it going to be a little way off yet?

[Neil Thanedar]: No, I think, well yeah, we’ll be doing retesting. I think we’ll get multivitamins retested next year. There will be whole categories.

We want to be, in 2017 if we can get to the point where we are not just, we’re marking the dates on when we tested it last and predicting when we’re going to test it next. And really as much as possible, say the popular categories are every year, the less popular every two years.

And again, just like everything, we can start shrinking those things because right now we’re on basically two-year testing cycles. And we want to push everything to yearly testing cycles.

And it would be great to say that LabDoor 2016 protein data is this and 2017 protein is this, and let’s see the trend of which brands have been consistently at the top and consistently at the bottom. Those are all things that it is about, we need more lab capacity. We need more testing.

We’re going out and we’ve raised venture capital. And so that’s a big part of this process and a big part of the reason why we think we can do 100 products a month next year instead of 25 products per month. That’s a big part of that too.

That’s how we’re going to get there. We’re going to have to get there 100 products a month at a time. We’re not going to be able to download the database of 100,000 products because that doesn’t exist.

[Damien Blenkinsopp]: Yeah. It’s step by step. You’re building lab capacity basically over time and trying to make sure it’s monetized. So it’s a step by step process. Great.

(00:52:19) [Damien Blenkinsopp]: Now let’s talk about some specific case studies from some of the more interesting takeaways. What have been some of the worst lab results you’ve seen in categories?

[Neil Thanedar]: I mean, the garcinia cambogia was still the worst category we ever saw. There were fully 70 percent of the products that did not have the labeled active ingredient.

[Damien Blenkinsopp]: So they had zero, had nothing?

[Neil Thanedar]: No, they had less than their quantity, but they had…well we’re talking about 10 percent or less than the label claimed, that kind of thing. For most of those products. To the point where it’s essentially nothing.

And what that is is that was a lot of fly-by-night, they are usually selling on Amazon. This is something where you can just spin up a brand out of nowhere, white label it, throw it onto Amazon and there’s no check. There’s nothing between you.

And then theoretically, there are user reviews between you and that product, but then these companies buy user reviews too. And so that’s it, there’s literally nothing between you and this product hitting the market.

And so we’ve seen, the cool thing is you go and look at a lot of those affiliate links and they’re broken, which means that the products have come off of Amazon, so not being sold anymore. And so there’s some sort of cat and mouse game there.

I’m sure some of them have spun up and made new products, and we’re going to have to go chase those down. But at least in some of those cases, we’re seeing that they’re gone, they’re not there anymore. And I think in those cases we do our job, when we show people what’s right and wrong. I think we’ve done a good job.

I think there are categories like that where 70 percent of products fail, there are categories like creatine where 10 percent or fewer products fail. And then there’s kind of the in-between zones where with fish oil you’ve got about a quarter of the products have rancidity issues. And so we’re filtering that, and that’s part of purity; that’s a part of our purity score.

So we’re seeing in different categories there are issues, but I think in the other categories they’re more like, hey there’s this like, half of the products that you need to avoid. Or there’s 30 percent of products or 10 percent of products you need to avoid. It’s still worth checking. Right?

In any of these situations, it’s still worth checking, but that’s the range we’re at. Somewhere between 10 and 70 percent you’ve got to worry about.

(00:54:21) [Damien Blenkinsopp]: Excellent. So, as you were talking there, I kind of took some guidelines or rules away from the situations you brought up.

Do you have any guidelines in your mind from the research you’ve done so far, on like if there is no data, having been through your research process, have you seen any patterns where you’re like, okay instead I’d use this heuristic to decide which product to buy, if I don’t have access to the data right now.

[Neil Thanedar]: We’re not seeing very much brand correlation. There’s not a ton of brand correlation.

One thing we find is that companies that only make one or two things do really well. So like a company that specializes in probiotics does a really good job in probiotics, but actually has a B- multivitamin or something. Those types of things happen a lot.

And so you have a protein specialist or the creatine specialist that does really well there; fish oil is the same way. So think about that. I think that might be one thing to think about, people who are specialists.

And then really other than that, send us the link on LabDoor and we will add it to our site. I think we need to test those products. We’ve had the luxury I think a little bit of kind of growing quietly. I think a lot of people are just learning about us five years later.

And we did that on purpose. And we did that very, kind of fundamentally we said we’re going to just focus on one category. We won’t go to the press saying, hey LabDoor is this great company, we’ll say hey look at LabDoor’s fish oil data, or look at LabDoor’s Vitamin C data. Look at LabDoor’s multivitamin data.

That part of it I think we’ve been focused on just, come listen to us about what we know. We’ll be an expert in certain things. We’ll be a destination in one category at a time.

And now I think we’re at a point where we need to move faster. And I think that’s why we’ve gone and raised more money. We are kind of going in and buying HPLCs and bringing them into the building. We’re buying auto-samplers. All this kind of stuff to make things go faster.

And so at this point, if you can find things that are specialty products and you trust them, take them. Otherwise, I’m really at the point where I’m waiting. I’m actually saying, well I’m thinking about taking curcumin, but I’ll wait six months until LabDoor tests it.

I might be in that process, I think because I know curcumin is going to be one of many other categories that are going to be… You’ve got an extract that certain companies, certain products are going to really pull a lot of heavy metals out of that extract. There are different extraction processes.

[Damien Blenkinsopp]: Yeah. There are some like that which are going to be challenging, for sure. Because it comes from turmeric, and turmeric can come from all sorts of places. So you can tell that one is going to be a complex one.

[Neil Thanedar]: And that reminds me of something like Ginseng, where the ginsenoside content you can look at. Ginseng is different than the active ingredient, and so you’re not always getting the same extraction. And it’s not consistent. And so in cases like that, I would basically say wait. And that’s how I do it. I wait until LabDoor has some data.

[Damien Blenkinsopp]: And you’ve got the inside guide to that. Okay. Great.

(00:57:20) [Damien Blenkinsopp]: The other heuristic I was thinking of was you were talking — because I’ve seen this a lot in Amazon — is you have these one product wonder companies, where they basically just make one product. And I think they just pop up.

There’s a new fat loss supplement that they just kind of jump on board. And you see that this company otherwise doesn’t seem to be anywhere or doing anything, but it’s just made this one product. Even it’s website sometimes isn’t great.

But on Amazon they’ve got thousands of reviews, and sometimes they’re at the top of the category. And you’re like what’s going on here? And often they’re giving away products for reviews, and they’re using a whole bunch of marketing tactics to establish themselves there.

But if you look a bit more into the company they don’t have a strong background and they’re just going to come and go. So that’s one of the things I’ve also noticed a little bit that might be worth thinking about.

[Neil Thanedar]: Yeah, we see those a lot too. I think LabDoor is really meant to replace heuristics with kind of a scientific method as much as possible. And I think that’s just really what, bringing us all the way back to the beginning, it’s really what motivated the idea of LabDoor at the beginning.

It was just the idea of imagining standing in a Walgreens with 100 options, and how are you making that decision? You’re going to use the heuristic, you’re going to use… If you were buying wine you would buy the second cheapest. There’s all these goofy heuristics that you can use. Maybe you buy the cheapest, maybe you buy the house brand, maybe you buy the famous brand, you buy the most expensive.

Everyone’s got their system. And we are kind of just consistently finding that any one of these heuristics has no correlation to the scientific data. So you really just have to keep coming back to the data to make your decision.

[Damien Blenkinsopp]: It’ll be interesting at some point for you to publish which heuristics were the worst in correlation.

[Neil Thanedar]: Oh man, I’d love that. That’s a great one.

I think we mess with this all the time, and I think this is another thing that we’d love to do more at LabDoor is get outside of just the testing that we have to do to grow the site. If we’re able to test 100 or 150 products we might have some leeway to take 10 or 20 or 50 products and just say, hey you want us to test a Chipotle burrito or a McDonald’s BigMac, we’ll do that too. Just because it’s interesting to us.

Or we might want to get into talking about user reviews. We might want to talk about trying to figure out a system to verify user reviews, or figure out whether…

Maybe actually teach people about these correlations. Teach people that there’s really no correlation between price and quality. So you shouldn’t use price. There’s no correlation between user reviews and quality in these categories.

And you should really think about what kind of products are experienced based products, where 10 minutes after you finished your meal you know whether it was good or not. And which products are truly scientific products.

[Damien Blenkinsopp]: And which are just subjects of experience. Someone’s just like, oh yeah I kind of like the brand and I bought it and I really enjoy the brand.

[Neil Thanedar]: Yeah. And so we really want to make, we have to figure that out. And I think that is such a — I mean we did that in VC meetings.

We literally, I was walking to the elevator after one of these VC meetings of an investor who said no. And he said, “You know the entire history of the universe, marketing has won.”

[Damien Blenkinsopp]: Marketing will find a way.

[Neil Thanedar]: And I said look, maybe we will. And we’ve kind of thought about that, and we said look maybe we just need to market the science better. We need to figure out ways to make the data easier to understand. We need to go, and that’s part of our team.

And so I think we’ll do that. We’ll find easier ways to teach this. Maybe we’ll redo the Pepsi challenge. And you redo the Pepsi challenge and you talk about, hey, there were problems with the Pepsi challenge. First, Pepsi was running the Pepsi challenge, and there are some credibility issues there.

And all of these things, and you can teach people through very simple systems that they already understand. “Hey this is how you’re currently making decisions, and this is how you are currently being marketed to and here’s how you should be marketed to. You should be marketed to based on science, based on the data, based on transparency and objectivity.”

[Damien Blenkinsopp]: I think the fact that Elysium and other companies like that are now showing up is showing that there is something changing.

Of course, marketing is always going to be important but I think some of this authoritative input is starting to become a lot more important, and trust. You see it across the markets, and there’s a lot of people talking about it. And so Gary Vaynerchuk and I, some of these people — I don’t know if you’ve ever heard of him.

[Neil Thanedar]: Yeah. Yeah, yeah.

(01:01:44) [Damien Blenkinsopp]: Yeah. But I think they’ve definitely got a point about trust for authority, and so on. And it’s going to become bigger and bigger. What are you looking forward to in this space? Are there going to be changes in technology which are going to help you over the next five or even 10 years do a better job of this? What are you looking forward to in this space?

[Neil Thanedar]: I honestly think it’s, for us, it’s as simple as getting 10 times bigger. I think if we get 10 times bigger every part of the system makes sense for us. And I think that’s what we’re trying to figure out.

We just got to 15 employees. This is a pretty tight unit here. And we need to go, as we grow from 10 to 100 employees here, and these are going to be mostly science and technology folks, those are the structures right now where we’ll be able to unpack some of these jobs. People who are doing five or six or seven jobs will be just doing one.

And we’ll be able to add some redundancy, we’ll be able to add more testing, we’ll be able to go faster. And really we’ll be able to, the spool engine will be running where, well really the old categories are paying for the new categories. All of that stuff needs to happen.

And as we grow, as we do that, I think this is where I see LabDoor becoming a more and more mainstream brand over the next 5, 10 years. And I want to have, very much like more experienced products like restaurants, you don’t buy without checking Yelp.

I think you really want to say for scientific products, for medical products, for health products, you don’t buy without checking LabDoor.

[Damien Blenkinsopp]: Where you want a functional benefit, you’re looking for this functional benefit.

[Neil Thanedar]: Does it work if it’s fake? Then, the more you think about that, you make so many decisions like that.

I just did this with a household cleaner. I was thinking about buying this Method cleaner versus this Honest company cleaner versus this Clorox cleaner. Does the green cleaner work? Does that organic certification matter?

You’ve got all the same problems. Is there anything toxic in this? I’m going to breathe this in, I might eat it. You’ve got all the same problems as you do with a supplement, and you make that decision even more casually than you do with a supplement because there’s even less data.

And we have to get into more and more of these categories. And I need it to be in a place where maybe I have your whole profile, I know exactly what you’re allergic to, I know exactly what your preferences are and I’m helping you in the entire drug store to make quality decisions.

(01:03:59) [Damien Blenkinsopp]: For a little case study there, I’ve been testing a whole bunch of pesticides and heavy metals and so on.

One of the more unique and interesting things I came out with in my samples was really really high atrazine mercapturate. Which was interesting because it’s been banned in the EU where I’ve spent some time since 2004 I think.

And so mine was off the chart; it was like 96th percentile. So I was hunting around trying to figure out where this stuff was coming from.

[Neil Thanedar]: Wow.

[Damien Blenkinsopp]: And I recently, I’ve been keto since January and so I started using different oils. One of them was macadamia oil, and it just happens to come from Australia where atrazine isn’t banned.

And I’m guessing [it’s out] because I’ve stopped that now. I looked into the research and it’s very probable that that’s where it came from. So I’m guessing that will be gone from my system the next time I test.

But yeah, just to say that this isn’t a theory. It happens and if you test your own body samples you can come up with stuff, and you’re like, “Whoa, I’m eating something toxic and I had no idea, didn’t even think about it.”

And I’m one of the guys who tests a lot more and thinks more about this stuff than most people. So if I’m getting that kind of effect, I figure most people are getting more of an effect than me.

[Neil Thanedar]: Absolutely. It’s so important to check. And I think, there’s too much. I hear too many of these stories.

Whenever you see that new negative supplement story, I think what happens is people withdraw and they become less likely to buy. Or they become more attached to their existing purchases. They stick to their existing brands.

And I think both of those kinds of withdrawing motions are wrong; you actually should go out and get more data. But the problem is it becomes this thing where there’s a lot of negativity and you don’t want to go out and get more data.

And so I think what we want to do with LabDoor is say look, well focus you on the best products. We’ll focus you on the A grade products, and let’s make it a good story. Let’s focus sales in the market, let’s put 100,000 of people a month and let’s focus them on the best products in the market.

Let’s reward companies for doing a good job and making a great product. And let’s see if there’s something really positive that we can do. Can we really reorganize the market to where the best quality products are making the most sales?

(01:06:06) [Damien Blenkinsopp]: Alright, so this could be a more challenging question, I guess. Just because some people wonder about this, but it can be really interesting what comes out of it.

Is there anything you’ve changed your mind about in the last few years in the testing area, or in supplements in general? Is there an underlying assumption of how you go about things, or what you’ve been thinking, that you’ve kind of turned on its head?

[Neil Thanedar]: There’s been a couple. I think one of them was really, we’ve kind of gone in two different directions with the data. We started with very technical, these long reports.

And then we went all the way in the other direction with this A through F grade, which was very simple, and the rankings were very simple. And we definitely needed to do that because I think that’s really what helped people actually use LabDoor.

And what we’ll probably do is slowly taper it. Our idea is to do every version of it. We’ve actually thought about this idea, we used to think of that as a fight between more data or less data. And I think the answer is actually all of the above, but we need to organize it.

So first you see the A, and the A breaks down into five categories. And those five categories break down into this data. And so what we’re trying to do, as much as possible, is everything. This is the point where we used to get into these fights of more or less, and I think the right answer is everything. And that’s one of the big things we’ve learned.

I think the bigger one, in terms of my mind changing, was really — we talked about it a little bit earlier — the manufacturers. I think I used to just be 100 percent consumer focused, and just said this is all about being the consumer watchdog.

And it still is about being the consumer watchdog, but more importantly, we are a marketplace that’s organizing these decisions for consumers. And so I think when it really comes down to it, our job is connecting consumers to the best companies and the best products.

And if that connection then makes us really good, and it’s not… The thing where we show people that there’s a bad product on the market is part of our job, but it’s not the core job.

And I think that was the thing that we switched. We came out there kind of guns blazing wanting to try and find the bad stuff, and increasingly we’re realizing that our job is just to find the good stuff.

(01:08:21) [Damien Blenkinsopp]: Okay. I’d like to hear a little bit more about you.

Do you look at improving your body and use of tracking? You’ve kind of already given us a couple of takeaways, but is there anything you track in terms of metrics or biomarkers or anything like that? For yourself?

[Neil Thanedar]: So these days my biggest focus is very, really into mental performance.

So I have a tracker of my major daily tasks that I do. And then I have a time tracker, where I’m measuring how much time I’m spending in a day learning versus planning versus training versus communicating versus executing in the business.

And so I’m separating my time and I’ve been using that to figure out… And I’m using that for optimization right now. For example, I’m noticing that as our company scales, I’m just noticing more push from executing to communicating. I’m seeing that switch, and really communicating is starting to become the more dominant mode.

And so I think for me between that and between more… I really like Headspace and Lucid, which are two mental training apps. Lucid is more focused on almost professional athletes. It might be more of strength training for your mind. Whereas I think something like Headspace might be more about conditioning, and it’s more about the endurance of kind of long-term training.

And so really that’s been my focus. In terms of my physical health, it’s really simple. I have Vitamin D and Fish Oil that I take every day, and protein and creatine that I take after workouts, and that’s really my base stock. There’s not really much that I’m doing.

There are, after that I’m curious about a lot of different ingredients that I’m waiting for us to test. I used to be a wrestler for many years, so I have achy knees. And so I’ve always been looking for joint supportive curcumin products. So that’s been something that’s really curious to me.

I really have been curious about nootropics and different kind of mental [supplements]. I’d love to see more caffeine plus thiamin plus other ingredient research. Try to figure out ways where LabDoor can get better at thinking about synergies between ingredients.

Those are things where it’s almost like we need to figure it out. We need to figure out the science before we can do the ranking, but those are the types of things we’re figuring out. And I think if we did that I would love to experiment more into the nootropics side, if I could get it right.

And so that’s how I track, but I think the last two or three years have been very mental focused. I feel like maybe the 10 years before that, between sports and through college I was so focused on all my physical numbers. And every since LabDoor especially it’s been very focused on my mental output.

[Damien Blenkinsopp]: Great. So that time tracking thing that you’ve done, are you tracking every minute of your day with an app in your phone or something? How do you do it?

[Neil Thanedar]: Yeah, so it’s an app called Hours. So all you have to do is turn it on in the morning, and then you switch it between different tasks. I don’t switch it between things too often, so it might only be five or ten total transitions per day. It measures it over time.

That’s really the most zoomed out version of it, and I try to do these things in sprints. So it reminds me the same thing of calorie tracking. I got a really great recommendation from a dietician once that said, “Track every calorie for 10 days and then stop.”

And that’s basically the same thing I’m going to do with this tracking. I’ve been doing it for seven days; I’ll do it for 10 every quarter or every six months, something like that. And I would come back to it and make sure.

The Headspace or Lucid I’m actually doing that at least, Headspace at least 3 times a week, mental training at least 5 times a week. So those I’m actually getting into the gyms, so to say, and getting my work in. But the really detailed tracking I try as much as possible to limit into specific sections.

[Damien Blenkinsopp]: Yeah. Tracking can be time-consuming. That’s the way I found it, to be more beneficial as well, basically doing what I call projects.

I do a project for a couple of weeks or something, make an adjustment. Hopefully, an action or something comes out of it and then move on to the next.

Actually, a lot of my friends have also done the time tracking thing. I did it for about 3 months, many many years ago. I learned so much about where my time was going, and I made adjustments on an every day basis. I haven’t gone back to it; maybe I should go back to it at this point, because who knows what’s happened now.

Did you get any, what are your big takeaways so far in the seven days? Do you make any changes, like, “Wow, I’m spending a lot of time there”?

[Neil Thanedar]: One thing that was initially bothering me that I felt like I wasn’t spending enough of my time actually executing.

And I think it actually taught me that when I was actually tracking what I was doing with that time instead, I was realizing that it was a lot of casual, like grab someone for 10 minutes and talk to them about something specific that we’d want to improve. And that was really high-value time.

And I was scared to do it because I felt like sitting at my desk writing emails seems much more productive. So I think that was really what it is. And I think so much of the mental training and kind of this work was actually just kind of confidence that you’re doing the right thing.

This is kind of just bringing the calm down, and kind of just bringing yourself into your zone as much as possible, and just feeling like… Just getting your priorities right.

I think that was the other thing. I had my priorities right and I was worried about it. And I think that’s why the 10 days really works because it’s just a nice check in. And if you feel like you’re doing a good job, or in the time like now that’s a bit of a transition, you can make a move.

(01:14:07) [Damien Blenkinsopp]: Great. Great. If you were to recommend one experiment someone should try to improve any aspects of their body, like mental performance or whatever you would think to have the biggest payoff, or likely to have a payoff, what would it be?

[Neil Thanedar]: I’m going to make sales for this mental training.

I came up with a system where also I think part of habit forming is attaching it to something. Attaching it to something where your new habit is attached to something that you do a lot.

And I think, one thing I noticed was I always get into moments where I’ll work for an hour or two, and then I’ll get up and want to pace or something. And then I’ll come back and sit down.

And so what I did is I said the first time, I noticed that the trigger for the pacing was something like I would get agitated or I had been working for too long. That’s the trigger. It feels negative, something negative is that trigger.

And what I attached it to is that first time I felt that kind of, I need to get up off my desk and go somewhere else, the first time of the day I felt that I would take my mental training app and do a 10 minute session. In that moment where I’m frustrated and agitated, I would take that moment.

And there are a couple of magical things. First, every single day of my life I have an agitated moment, so I always train. And it reminds me that when I’m agitated, it calms me down and then I get back. So it’s like a positive rep.

And any time I can turn that, you try to take a negative rep and turn it into a positive rep it’s always a huge improvement. Because it does a [unclear 1:15:35]. And so I’m trying, as much as possible, to focus on the atomic unit of the habit, and just getting it right each time.

[Damien Blenkinsopp]: Cool. Thanks for that. This is really interesting. Basically attaching it to something that happens to you all the time. And that you want to get rid of. So you’ve got that trigger, and you just turn it around.

(01:15:55) [Damien Blenkinsopp]: Okay. Where should, I mean we probably already know, but where should someone look to learn more about this topic from you?

Are there any good books or presentations on testing? Is there any more information if they want to geek out on this?

[Neil Thanedar]: The thing you want to do, I mean obviously for anything testing related go to LabDoor.com/rankings, that’s where we’re going to do all the voting. So to vote for things, I think that really helps us. Send us emails or Twitter or Facebook messages and tell us what you want us to test and we’ll test it.

Everything after that I think what we’d really like to do, and I think I really want to focus on people knowing that there are good supplements in every category. These things are safe. This market is safe. And it really is a matter of just doing your research.

And I think as much as possible if we can push and we can get into a sense where we’re focused on the research, and we’re buying based on science, that’s really what’s going to drive this. The more and more people who buy through LabDoor, if I can go to a company and they know that 20 percent of their sales are from LabDoor, that starts becoming a thing where, hey this is one of my major sales channels.

And that’s going to happen. And I think right now we might be in the 5 or 10 percent range for some companies. And we’re growing. And in some companies, it’s in different ranges.

And we want to get that up, and we want people to pressure themselves to focus more on science. To really make these decisions the right way. And I think it will pull up. I think the whole industry will come up and we will all get better products, and we’ll all be healthier out of it.

[Damien Blenkinsopp]: So when they go to your website, are there more details on what you’re doing? If some of the guys are listening to this today and they want to understand better what you’re doing, are there any resources on your website or anything they could look at?

[Neil Thanedar]: So, that’s honestly something we’re not doing a great job of right now.

So there’s some stuff on our site. If you go to LabDoor.com, it’ll explain how we make money, a little more detail to explain what labs we use and things like that. It even, on our top bar, it will say how we grade. So if you want to click there and get deeper into what the five grades mean, that’s something that we can do as well.

But I think the thing that we want to do this year, over the next 12 or 18 months a big focus for us will be bringing people into the lab. Can we do experiments for you? If anyone had a question or just wanted to do an experiment, I’d want to be able to do that more. I want to be able to bring cameras into the lab more.

All of that stuff, I want people to ask those questions. We’re working through YouTube right now. We’re trying to, we have a new studio that I’m standing in now that we’re trying to [use] to answer questions as much as possible.

And so I think for us, as much as possible it’s just being as transparent as possible, and doing Podcasts like this. Just talking to people. I think the first four or five years we needed to be quiet and do our work as much as possible.

And this is we’re just doing that transition point where we might step out, look up, and say hey people come look at this. We’ve got something here.

(01:18:54) [Damien Blenkinsopp]: Excellent. How can people best connect with you? Either you or the company?

[Neil Thanedar]: Facebook and Reddit are the two fastest ways that people get to us.

So if you want to talk to the company it’s just Facebook.com/LabDoor, or our Reddit user is just LabDoor and we’ve answered hundreds of questions on there. And sometimes that sparks lively debate, and we love that. The idea of why should certain rankings matter? Why does label accuracy versus projected efficacy, the weightings. It gets really into the details. That’s a really interesting way to do that.

I’m on twitter if you want to find me at Neil Thanedar. On Twitter, you’ll find I’m using talking about LabDoor or different things, like my ideas about testing. I think as we grow I started to think more and more about how LabDoor touches other industries.

While at the core we’re this scientific lab, there’s a big part of us that is a technology start-up. There’s a big part of us that is an online media company. At some level we’re journalists. And so as it unpacks, as we get deeper and deeper into LabDoor, my interests of what LabDoor can have kind of expanded.

So if you have any ideas about what we should test next or what, hey you should grade it differently, or you should think about LabDoor in a different way, I love thinking about that. I love dissecting what are the moving parts in any sort of industry. Not just ours, in any industry or business, it is fascinating to me.

So unpacking those is always so interesting. So yeah, ask me questions about that, happy to chat forever about stuff like that.

(01:20:32) [Damien Blenkinsopp]: Excellent. Thanks, that’s great. Do you have anything to ask or request from my audience? Anything specific?

[Neil Thanedar]: It really is, never buy supplements without checking LabDoor. Use our affiliate links, help support LabDoor’s business. And if there’s anyone that you know that, just help spread the word at this point.

I think we are right in that phase where I mean Yelp is really only 15 or 20 years old at this point. It took them a good 5 or 10 years to establish that brand. And that’s really that zone that we’re in right now, where we’re going from this ugg start to this trusted rating agency.

And part of that, most of that, is really going to be people telling their friends about LabDoor, and saying once you try it, you trust it and you keep using it. That’s really our business, and we’re going to grow as fast as people help us grow.

And so as much as possible, if there’s any way that your folks can share the word, we’d love that.

[Damien Blenkinsopp]: Okay. Thank you.

Neil, thanks for your time. It’s been a really great interview. I really learned a lot about the whole testing situation, and where it’s at. So it’s going to be really useful for everyone.

[Neil Thanedar]: Yeah, absolutely. Thanks for having me.

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Micronutrient status is a foundation of health, performance and chronic disease minimization. This episode looks at how to optimize fat soluble micronutrients status.

In this episode we look at ensuring micronutrient status. Ensuring your body has the building blocks it needs to do what it needs to do. This is an important lever to increasing your health span and current functionality and performance.

Previously we discussed micronutrient status with a focus on magnesium in episode 17 with Dr. Carolyn Dean.

This episode is about fat-soluble micronutrients including vitamin A, D and K. I personally look at micronutrient status as a foundational piece to get covered first. It is easier to do than most things and has wide ranging impacts thus it’s a good place to start.

Something else I wish to highlight for you to pay attention to in today’s episode is looking at the body as a set of dynamic systems. Typically we think we just have to raise one value into an optimum range with blood work or labs or so on.

However, as you will learn today, even with respect to basic vitamins it is often not that simple. It can be personally nuanced (different for each person). There are interplays between different markers to consider, thus the benefits of looking at several markers at one time, which we have discussed before. For instance, making use of a panel to get a realistic picture, by looking at several markers which point out one aspect of functionality in your body.

You focus on vitamin K but you may not realize what’s ultimately missing is something upstream that’s allowing vitamin K to fulfill its function. Just throwing vitamin K at the system isn’t going to do anything. It’s really important that we continually improve our understanding about how to figure out what the weakest link in the chain is because we’re always going to get the biggest benefit from fixing what’s missing.

– Chris Masterjohn

Today’s guest is Chris Masterjohn. He has a PhD in Nutritional Sciences and he is currently Assistant Professor of Health and Nutrition Sciences at Brooklyn College, part of the city university of New York.

In the last five years Chris has been responsible for originating influential ideas and papers on the fat-soluble vitamins A, D and K. The importance of their role in the body and addressing that status, the status of these micronutrients to promote health.

If you follow the Paleo, Ancestral Health or Western A Price Foundation communities it would be difficult to not have already come across some of his work. Chris now has both a podcast as well as his own blog named The Daily Lipid, where he covers his ideas and research on optimum nutrition. His podcast is both technically detailed and has a lot of practical takeaways. I highly recommend you also check that out.

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

itunes quantified body

What You’ll Learn

  • How Chris developed interest in researching fat soluble micronutrients (4:16).
  • The health issues our guest was better enabled to resolve by studying fat soluble micronutrients (6:30).
  • Chris primarily researches vitamins A, D, and K all of which are tightly connected in a functional physiological network (7:56).
  • Vitamins are integral parts of a broad system which can be optimized, as opposed to individual separate nutrients (9:32).
  • Examples of how molecular mechanisms involving micronutrients are inter-dependent in regulating a range of functions (10:28).
  • Focusing on improving the most deficient part of an interconnected nutrient system – thus bring about the greatest benefit (15:08).
  • Different diseases often share common root causes, involving lack of micronutrients or improper distribution in the body (17:00).
  • The science of interpreting vitamin K deficiency in children and young people (19:30).
  • The differences between vitamin K1 and K2 in managing risks factors for various health issues (27:02).
  • Pharmacological doses of vitamin K2 and how these are tested and used (28:44).
  • It is preferable to take vitamin K in doses close to the range of maximal concentrations obtainable from food intake (29:29).
  • Micronutrients have independent functions including regulation of gene expression – thus leading to biological complexity (30:13).
  • How the body manages vitamin K when faced with deficient supplies (34:00).
  • Variation of micronutrient intake from various diets and caveats for analyzing outcomes of specific diets (36:00).
  • Managing a healthy micronutrient system with various types of diets (42:28).
  • Testing, supplementing, and understanding the factors influencing vitamin D in complex physiological systems (43:48).
  • Maintaining balanced vitamin intake by diversifying food types and lifestyle changes (49:49).
  • Why adding fermented foods is the optimal strategy for properly managing vitamin K2 intake (52:50).
  • Subscribing to local farms and weekly auto delivery of groceries (54:20).
  • Strategy for maintaining variability in consuming vegetables by weekly rotations (54:52).
  • Parathyroid Hormone (PTH) is a more specific marker of inadequacy in the body’s calcium-vitamin D economy, compared to 25(OH) vitamin D (56:39).
  • Deriving conclusions regarding nutrient intake based on ‘shotgun’ genetic analysis is tricky; often sufficient scientific evidence is lacking (1:02:08).
  • Vitamin A testing and how deficiency influences impaired eye vision (01:07:10).
  • Making nutrient test ranges actionable and novel biomarkers (1:08:52).
  • A Dutch company offers testing specifically for the inactive form of Matrix Gla protein (MGP), as of yet only via research-purpose contracts with clinicians (1:13:02).
  • The broader context in understanding testing for Vitamin K2 deficiency (1:14:16).
  • What projects are the main focus of Chris’s current work (1:15:27).
  • Using of high dose fish oil in resolving inflammation issues (1:18:24).
  • What Chris has changed his mind about in the last few years (1:19:26).
  • What biomarkers Chris tracks on a routine basis to improve his health and performance (1:20:38).
  • The legal aspects of drawing larger amounts of blood from consenting adults, or yourself at home (1:24:26).
  • Chris’s recommendations for routine monitoring of our health (1:25:49).
  • Discovering more about Chris and keeping up with his work (1:29:23).

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

Chris Masterjohn (Ph.D), The Daily Lipid Blog

Recommended Self-Experiment

  1. Tool/ Tactic: Improve your body composition by becoming more aware of your caloric intake. Chris believes is a high impact lever for most people, and will likely have downstream benefits for insulin sensitivity and the other systems discussed in this episode.
  2. Tracking: Build a habit of tracking your waist circumference, your body weight and keeping a food log with an app like MyFitnessPal.

Tools & Tactics

Diet & Nutrition

  • Vitamin AThe physiologically active form of vitamin A is retinol which occurs only in animal foods. However red, orange, yellow, and green colored vegetables are rich in carotenoids – precursors to retinol. To maintain your vitamin A at recommended daily allowance (RDA), one serving of liver per week covers vitamin A nutritional requirement. Liver cod oil is also a rich source.
  • Vitamin K: The general population obtains Vitamin K primarily via cheese and egg yolk consumption. Vitamin K2 is a sub-type of vit K found in animal products and fermented foods. Vitamin K1 is found in green-leafy plant foods. Vitamin K2 is more effective at activating your body’s vitamin K-dependent protective system. The richest source of vitamin K2 is natto, a fermented soy food popular in east Japan. You can use the natto bacteria to prepare homemade fermented vegetables as a good source of vitamin K2.
  • Vitamin D: Different foods contain varying amounts of particular nutrients. A fish’s liver tends to be high in vitamin D and A for instance. The same is not the case for terrestrial animals’ liver meat – because terrestrials store vitamin D primarily in blood and not the liver. You can compensate for not eating traditional sources of Vitamin D (such as fish), by increasing sunshine exposure. Eating UVB irradiated mushrooms is also a rich source of vitamin D.
  • Variety In Dieting: Adding different foods to your diet, such that steady levels of necessary vitamins can be achieved. This can be done by week-to-week rotations of food types.
  • Thrive Market: An online service for ordering groceries ex. for weekly auto-delivery. Subscribing to local farms is another useful tip for increasing productivity in diversifying your diet.
  • Vegetarian / Vegan: A vegetarian diet excludes meat by focusing on plants for food. In addition to excluding all meat products, a vegan diet usually also excludes all animal products, such as cheese and eggs. Genetic compatibility with diet types plays is important for vitamin nutrition. For example, common genetic polymorphisms, dietary and metabolic factors influence body’s ability to convert carotenoids to retinol. Note: Both Damien and Chris experienced exaggerated symptoms of tooth decay during vegan dieting – indicating insufficiency in calcium flow to bone tissue including the teeth.
  • Paleo: A diet focused on foods which paleolithic humans might likely have eaten. It is based on the idea that modern diseases result from a mismatch between our evolutionary and current-day environments (including dieting style). Whether paleo effectively supports your micronutrient system depends on defining the diet. A paleo diet based on restricting foods (often similar to an average American diet except grains, legumes and dairy) is not sufficient. Paying attention to organ meats is a solution because these are rich in fat-soluble nutrients.
  • KetogenicA high fat, moderate protein and low carbohydrate diet. Metabolism is altered so that ketones are used instead of glucose for fuel. See episode 7 with Jimmy Moore for detailed discussion on the benefits of this dietary approach. Carbon dioxide is required for the functionality of vitamin K. Given that carbohydrates produce up to 50% more carbon dioxide than fats do, you must must maintain minimal necessary carbohydrate intake – especially with ketogenic dieting.

Supplementation

  • Targeted Reason: Most-often supplementing an individual vitamin is not necessary solely based on a low result. Upstream factors often influence the functionality of a particular nutrient on a systemic level. Have a targeted reason for supplementing, start with conservative doses, and titrate to higher levels based on response.
  • Vitamin K Pharmacological Doses: Vitamin K supplementation has been shown to be more effective than osteoporosis drugs in reducing the risk of bone fracture. The adequate intake level for vitamin K is set at 90 μg/day for women and 120 μg/day for men. In trials involving very high vitamin K intake (ex. 500mcg doses), it remains unknown whether the effects seen at such pharmacological doses are already achieved with much lower doses. For example, the initial 45mg of the dose might be sufficient to cause equal effects.
  • High Dose Fish Oil: Fish oil rich in EPA has been found to be counterproductive in balancing the inflammatory effects of omega 6-fatty acids. Other interactions alter EPA influence in resolving inflammation pathways. Damien promises to include the topic of resolving inflammation by using high dose fish oil, because this is specific to him.

Tracking

Micronutrient System

  • The System: Consists of vitamin A, D, and E – collectively known as the fat-soluble vitamins. These micronutrients are absorbed in fat and stored in tissues, for example in the liver. The system demonstrates multilayered biological complexity. Understanding the interdependence of vitamin-regulated physiological mechanisms is key to taking action and optimizing micronutrient status.
  • Reference Ranges: In general for fat-soluble micronutrients, Chris prefers people to remain in the middle of a range compared to the lower range portion. Damien argues that it is worthwhile to be in the top third of most ranges, because the general population is characterized with non-optimal health.

Biomarkers

  • Matrix Gla Protein (MGP): A vitamin K-dependent protein which regulates calcium flow. MGP continually removes calcium from arteries (where calcium is a risk factor for plaque formation and cardiovascular disease) and moves it into bone tissue (where calcium is needed for proper bone metabolism and preventing osteoporosis). Quantifying MGP in its activated form is not a useful biomarker for vitamin K status.
  • desphospho-uncarboxylated Matrix Gla protein: This is the inactivated form of MGP and serves as a useful biomarker for vitamin K status. If inactive MGP levels are measured high, this indicates poor supply of vitamin K specifically in blood vessels. Currently this marker is not available in the US.
  • % of Carboxylated Osteocalcin: Osteocalcin binds and moves calcium into bone tissue. Similar to MGP, vitamin K is required to carboxylate osteocalcin – thus enabling calcium binding. Carboxylated osteocalcin levels alone are not useful in determining vitamin K status in blood. Instead the percent of carboxylated osteocalcin is a useful marker – encompassing micronutrient functionality in calcium flow. For example, if vitamin K supplementation produces a notable increase of % carboxylated osteocalcin, this indicates operating in a range of inadequate vitamin K. For a more in depth look, see this article on osteocalcin by Chris on the Weston Price blog.
  • Serum Retinol (Vitamin A): The most effective way to quantify your vitamin A status is to measure the active form of this nutrient – known as retinol. Low retinol levels indicate vitamin A deficiency. The reference range for retinol is based on the role of vitamin A in supporting night vision. The lower end of this range is approximately a concentration at which you can see during night time without symptoms of distorted vision.
  • 25-OH Vitamin D: The most common marker for measuring vitamin D is a downstream metabolite of vitamin D known as 25-OH vitamin D. The Vitamin D Council suggests an optimum level of 50 ng/mL of 25(OH) vitamin D. Chris also suggest that vitamin D optimal ranges are downward of 60 ng/mL 25(OH) vitamin D.
  • Parathyroid Hormone (PTH): A hormone produced by the parathyroid gland in response to changes in calcium blood levels. Compared to 25(OH) vitamin D, PTH is more specific for detecting inadequacy in the calcium-vitamin D system. Deficiency in vitamin D or calcium results in chronically active PTH production (high serum levels). From this perspective, remaining in the lower half of the PTH range (~30pg/mL) is optimal for a functional vitamin D-calcium system.
  • Ferritin: Serum ferritin acts as a buffer against iron deficiency and iron overload. Ferritin levels have a direct correlation with the total amount of iron stored in the body. Chris has a genetic predisposition for hemochromatosis, a condition in which too much iron builds up in the body causing toxicity. By optimizing his blood donation schedule, Chris maintains ferritin levels at around 150 ng/mL. The reference range for ferritin has an upper limit of 500 ng/mL.

Lab Tests

  • Amino Diagnostic Systems: A company working on gaining FDA approval for a test aimed at measuring the inactive form of MGP protein. Therefore, this test in still not available in the US.
  • VitaK: A company based in the Netherlands which offers testing for the dephosphorylated inactive form of MGP protein. However, they offer this test only to clinicians and for research purposes.
  • Quest Diagnostics: Testing of both serum retinol and serum vitamin A palmitate – the main form of serum retinyl ester. A formula for testing vitamin A overdose includes measuring levels of serum retinol and retinol palmitate in fasting state. If serum retinyl esters are greater than 10% of the sum of the values obtained from both tests, then this indicates liver vitamin A overload.
  • 23andMe: The largest personalized genetics company offering testing directly to customers. While health analysis data is no longer provided in 23andMe reports, the obtained data can be used with other gene analytics services. Chris discovered a predisposition for his iron overload condition via 23andme testing. Also see episode 5 with Dr. Ben Lynch featuring the use of such data in optimizing methylation.
  • SpectraCellDamien took this test in 2012 (see full report here) – the report did show a slight vitamin K2 deficiency at the time, which is one of the items he took action on by looking into Chris Masterjohn’s work at that time. Chris disagrees with the micronutrient testing SpectraCell report because it leads to conflicting conclusions. For example, there is very little scientific evidence that nutrient levels inside immune system blood cells.

Devices and Apps

  • MyFitnessPal App: A free application for tracking calorie intake and energy use, including a large database of foods and exercises. A useful tool for optimizing diet and improving fitness. Initial experiments can be tracking weight / waist circumference or keeping a food log to deduce your body composition. The app also integrates with other fitness devices and apps, such as the Fitbit and Withings which we have discussed before. See episode 24 with Troy Angrignon for the value of wearable devices or episode 32 with Paul Abramson on the potential of self-tracking in medicine.

Other People, Books & Resources

People

  • Weston Price: A researcher who documented the nutritional transition that occurred in many different cultures across the globe. He concluded physical degradation as a result of the switch from traditional diets to modern refined foods diets. Chris notes that traditional diets put strong emphasis on nutrient dense animal foods which supplied fat soluble vitamins.
  • Dr. Bruce Ames: A scientist whose major accomplishment is the Triage Theory. In summary, when the supply of nutrients is compromised, the body prioritizes vitamin K usage for acute survival needs over investing in long term health. When vitamin K is marginally inadequate, the liver gets top priority to activate blood clotting factors. Meanwhile the bones, blood vessels and other vitamin K-dependent systems perform with reduced functionality. This is a valuable tool for understanding the functioning and optimizing the vitamin K system.

Organizations

Books

  • Nutrition and Physical DegenerationA book by Weston Price on the micronutrient system, focused centrally on tooth decay. Chris found it useful for understanding the roles vitamins play in bringing about a protective effect on teeth.

Other

Full Interview Transcript

Click Here to Read Transcript
(00:04:16)[Damien Blenkinsopp]: Chris, thank you so much for joining the show.

[Chris Masterjohn]: It’s great to be here Damien. Thank you for having me.

[Damien Blenkinsopp]: I just want to get a little bit of an introduction from you, so that the audience that hasn’t come across you already, although I expect most of them already have, can get a bit of an idea where you’ve came from and how you got into what you do.

[Chris Masterjohn]: Sure, I have a Ph.D in Nutritional Sciences and I’m currently assistant professor of Health and Nutrition Sciences at Brooklyn College, in Brooklyn New York. I had always been interested in nutrition, at least since my teenage years but I sort of got set along my current path when I went vegan for awhile and didn’t have very good health outcomes on it.

I actually really improved my health a lot when I learned about Weston Price who studied, at an opportune time in the 1930’s, and documented the nutritional transition that occurred in many different cultures across the globe from traditional diet to diets of modern refined foods and documented the physical degeneration that took place there.

What struck me from that, that really provided a lot of utility to me at the time, was that in traditional diets that were associated with great health there was a really strong emphasis on nutrient dense animal foods that supplied fat soluble vitamins.

So in learning that and implementing principles that helped turn my health around I became very interested in the fat-soluble vitamins, and that’s why studying vitamins A, D, and K, which is one of my passions and current focus of research, has been something that I’ve been so interested in.

Over the course of, even leading up into graduate school, I had done a lot of work trying to understand the interactions between the fat-soluble vitamins and I published a hypothesis paper about that. When I was in graduate school I actually studied energy metabolism and glycation and antioxidant defense, but then in my postdoctorate at University of Illinois at Urbana-Champaign and now at Brooklyn College, I’m moving back into studying the fat-soluble vitamins.

(00:06:30) [Damien Blenkinsopp]: Excellent, thank you for very much for that. I’m curious, what kind of health issues did you have and you found resolved through this journey?

[Chris Masterjohn]: Most of what I experienced was an aggravation of existing predispositions. As an example, as a child I had been fairly predisposed to tooth decay, when I was vegan this became very exaggerated. So, in one single trip to the dentist I found out that I had over a dozen cavities and I needed two root canals. I had had digestive problems since I was a baby but when I was vegan they became much worse to the point where they were really interfering with my day-to-day function.

I had been predisposed toward anxiety probably at least since my early to mid-teens, but the anxiety and panic disorder really became strong and really started interfering with my day-to-day function when I was a vegan.

And Weston Price’s work actually focused centrally on tooth decay so when I was reading his magnum opus, “Nutrition and Physical Degeneration” I was most interested in, “How can I fix my tooth decay?” What really surprised me was that my mental health was completely revolutionized without me even trying to fix it once I started to incorporating nutrient dense animal foods into my diet.

(00:07:56) [Damien Blenkinsopp]: Very interesting. I had a similar experience I did vegan, for not as long as you probably, I think I did about four months but it was around that time also I started getting tooth issues. I started having all these fillings and so on, so it’s interesting. Maybe that happens to a lot of people and of course today I’m doing much better. I don’t really need to go to the dentist that much these days, so that’s cool.

I wanted to jump into this whole area of fat-soluble micronutrients, which you’ve done a hell-of-a lot of work in, and your work is very well known for this area. Would you say, first of all, just to isolate what we’re talking about, when you say, “fat-soluble micronutrients” what area you talking about? Is it the A, D, and K or a little bit broader? How would you categorize that?

[Chris Masterjohn]: The fat-soluble vitamins there are four of them, they are A, D, E and K. In my research I have also done a lot of research into the antioxidant defense system and I view vitamin E as a functional part of that system.

When I was in graduate school my work was very closely related to vitamin E, but I view vitamins A, D, and K as being involved in a functional network together where there is a whole set of specific physiological functions that those three vitamins cooperate together in, in a way that vitamin E is not as closely aligned with that system. So, most of the work when I refer to the fat-soluble vitamins, technically that includes vitamin E, but more often than not I’m referring to A, D and K.

(00:09:32) [Damien Blenkinsopp]: Right. I find it really interesting, because I noticed when I was doing preparation for this that you talk about it as a system, because a lot of people think of vitamins as separate things but it seems the way you look at it is it’s a system. You look at this whole systemic level and when you’re optimizing or improving it you have to look at it from that broad perspective. Is that correct?

[Chris Masterjohn]: Absolutely. I think that most scientists who actively think about this sort of thing would agree that during the course of the 20th century we did a really good job of breaking things down into fragments and we did not do a very good job putting them back together again.

So the task that lies before us in the 21st century is to take all of this fragmentation and all of this very granular knowledge that we’ve obtained about specific things and then figure out how they fit together in systems. I think that is the frontier of science right now.

(00:10:28) [Damien Blenkinsopp]: Yeah, it’s exciting stuff. If you were to describe this as a system, is there anything else you’d add in, beyond what you’ve already said about it, which gives people the overview of that whole system? Not to get into too much detail, but to get the highlights. Is there anything to add?

[Chris Masterjohn]: Yeah, absolutely. I think biological complexity is kind of like an onion, you peel away one layer and then as soon as you look beyond that layer you come across another layer, you come across another layer, and you come across another layer. To take an illustrative example of how some of these things would fit together into a system lets just take one specific protein.

Matrix Gla Protein or MGP is a vitamin K-dependent protein that’s responsible for putting calcium into our bones and teeth where it primarily belongs and preventing it from going into the places that it doesn’t belong, like the the soft tissues, particularly the blood vessels or the kidneys, where it would contribute to vascular disease or kidney stones.

Now you take this one protein. We call it a vitamin K-dependent protein because vitamin K is necessary to activate it and give it that ability to control calcium, but how do we get it in the first place?

Well vitamins A and D are responsible for telling the cell to make that protein but vitamins A and D can’t do that on their own, because to strip away to the next layer, when vitamins A and D tell the cell to do something they do it because they are metabolized into signaling compounds that then bind to a receptor that then binds to DNA and controls the degree to which genes are expressed.

When they bind to their receptor, the only way the receptor can bind to the DNA is because there are interlocking finger structures that fit together, kind of like if you were to clasp your own fingers together in your hand and you imagine that one set of fingers from the left hand is the receptor and the other set of fingers from the right hand is the DNA.

They fit together basically just like that, but what’s responsible for the finger shapes is the coordination by zinc. So, if you don’t have the zinc there, you can have vitamin A there, you can have vitamin D there and they can bind to the receptor but the receptor won’t bind to the DNA and the function won’t be carried out. So zinc is clearly important there.

Then you could take magnesium. I almost think that trying to get granular about all the specific things that magnesium does would cause you to underestimate its roles, because if you just take two of the roles magnesium plays and ignore all of the other specific enzymes it activates — magnesium is necessary to activate the enzymes that are involved in translating genes into proteins.

So imagine that vitamins A and D, with the help of zinc, are binding to the DNA and telling the DNA to be expressed. If magnesium isn’t there that compromises the ability to synthesize those specific proteins as well as every other protein in the body. Magnesium also plays other roles in regulating the distribution of calcium that would ultimately allow MGP to fulfill the function we were talking about before.

To take another example, carbon dioxide is necessary for the process because when vitamin K activates MGP, what it does is by taking carbon dioxide and adding that to the protein. And that addition of carbon dioxide is actually what allows that protein to start controlling the distribution of calcium.

Carbon dioxide is produced primarily during energy metabolism and that means that supplying that carbon dioxide is dependent on your metabolic rate but also the macronutrient mix in the diet plays a role as well. For example, carbohydrates produce fifty percent more carbon dioxide than fats do. So getting adequate carbohydrates is important.

So I just peeled the layer back to the third layer. I’m sure that we could keep going and ultimately if you just keep peeling it back and peeling it back what you find is that everything is interdependent with everything.

But what I have tried to do in my writing is: we can’t make any use of the information if we don’t simplify it and try to develop a working paradigm to talk about it and to understand it. I think that it’s necessary to have that top layer of the onion where we focus in on some of the key points, or otherwise it would just be information overload and we wouldn’t really be able to do anything with it.

(00:15:08)[Damien Blenkinsopp]: Absolutely. I’m hoping my processing and learning and things like that will eventually be able to get around that and actually understand all of these complex systems. It’s kind of obvious that it’s going to be beyond human level of understanding just because there are so many moving parts and it’s a dynamic system. You change one thing and something else is going to get distorted.

Is it safe to say that anything that would be deficient? Say, it could be one of the vitamins or some of those associated micronutrient minerals you mentioned, like magnesium or zinc, could distort the system and therefore get an output you’re not looking for?

[Chris Masterjohn]: Absolutely. That is one of the reasons why it’s so difficult to really answer questions about what’s going on in many cases. Because you can say, “I’m prone to tooth decay or I’m prone to… my children tend to have a narrow palate.” And you can say, “Well, vitamin K dependent proteins should be necessary to broaden the palate and to supply mineralization to the teeth.”

So, you focus on vitamin K but you may not realize what’s ultimately missing is something upstream that’s allowing vitamin K to fulfill its function. Just throwing vitamin K at the system isn’t going to do anything.

It’s really important that we continually improve our understanding about how to figure out what the weakest link in the chain is because we’re always going to get the biggest benefit from fixing what’s missing. If we take something that’s 80-90% good and we make that 95% then that’s going to be relatively little benefit, but spending the time to figure out what might be really missing at 20%, moving that up to 80% could provide huge effects.

(00:17:00) [Damien Blenkinsopp]: Yeah. Would you say of the things you’ve looked at, this system of vitamin D, K and A is basically a high impact lever for changing health scenarios because you feel like deficiency of any of these can affect a lot of systems in our body?

[Chris Masterjohn]: Yes, I do. If you look at some of the most common diseases that we would be concerned about you can see, particularly with heart disease, fat-soluble vitamins likely play a very vital role in protecting arteries from calcification. Calcification of arterial plaque is one of the driving forces of that plaque which eventually leads to a heart attack or an ischemic stroke. That’s a major concern.

We see a correlation between heart disease and kidney disease and osteoporosis. All of that can be grouped under this general malfunction of putting calcium where it’s supposed to be. If calcium is going into the kidneys and into the blood vessels and it’s not going into the bones.

The wrong way to approach that is to send the person to the bone doctor to look at the bones, send the person to the heart doctor to look at the heart, and send the person to the kidney doctor to look at the kidney.

That may be necessary to manage the disease process but what we want to be doing is figuring out, “What are the commonalities here?” and “What is the central defect in this system that’s contributing to all of these different things?”. That can very easily be explained by a malfunction of the fat-soluble vitamin dependent system of putting calcium where it does belong and keeping it out of where it doesn’t belong.

If you take that out of the area of the elderly and you put it into the area of children then you will see similar things where attaining proper growth and not just getting tall, but also having a broad dental palate that fits all of your teeth, and so on and so forth. All of those aspects of growth are also powerfully affected by fat-soluble vitamins.

Although there is some controversy over how you would interpret the data it does seem, to the degree that we’ve measured it, that there is a very high prevalence of poorly activated vitamin K dependent proteins in children when they’re in their growth phase. So I would say from the cradle to the grave it seems like there is, within the context of modern civilization, there seems to be this lifelong deficit in this system.

(00:19:30)[Damien Blenkinsopp]: Interesting. You’re basically saying it’s pretty common and there are a number of issues you think are quite common through society which are affected by this? Can you give us any example? Are there any studies? Or what kind of evidence is there to show how prevalent this kind of deficiency or these kinds of problems in this system is?

[Chris Masterjohn]: I want to take a step back and say there are two versions of this story. One is the clean version and that’s what I’ve been delivering you so far. That version is the version where you can make a strong case where this is true.

There is another version of this story that gets very dirty, and that is that when we try to assess the prevalence of these issues it becomes very sticky because we’re always learning more and more about how to interpret blood markers.

And if we are honest, that has to force us to continually revise how we’re interpreting those blood markers. We could get into the topic of testing of vitamin D status, which is wildly controversial, but let’s stay on vitamin K for a moment.

One of the ways we could look at vitamin K status in children is to look at the percentage of osteocalcin that is carboxylated. Osteocalcin is a protein that’s made by bone cells and carboxylation is the process where by vitamin K activates that protein to allow it to bind to calcium.

Now through most of the 20th century into the 1970’s no one knew about osteocalcin. Through that whole time we just saw vitamin K we though it was important to blood clotting and nothing else. Then the new era, over the ensuing decades the vitamin K research communities started developing a body of literature around osteocalcin. Then the phase after the 90’s where they started producing reviews that other people could read and this idea became popularized.

Up through the end of the 20th century and into the really recent years in the last decade, what emerged out of osteocalcin research was this idea that under-carboxylated osteocalcin is a marker of vitamin K deficiency because if vitamin K carboxylates osteocalcin then if you are adequate in vitamin K then all of your osteocalcin should be carboxylated.

That seemed totally logical and totally rational. There are multiple studies, I can’t site the exact figures off the top of my head, but what we can do is put links to the studies in the show notes if you would like, for the podcast. But there are multiple studies showing that in children the percentage of osteocalcin that is under-carboxylated could quite often reach sixty or seventy percent.

What this looks like with this simple interpretation of osteocalcin, is that children have massive vitamin K deficiency because two-thirds of their osteocalcin is not being activated by vitamin K. Now what has emerged more recently in the last decade is that we now know that vitamin K is needed to carboxylate osteocalcin so that it can bind to the extracellular mineralized matrix of bone. But during the process of bone resorption that osteocalcin, after it had already been carboxylated, will be decarboxylated and released into the serum.

Not only that, but that under-carboxylated osteocalcin that’s released into the serum is actually a beneficial hormone that acts on, in males, on the testes to increase testosterone production; and in males and females, it acts on adipose tissue and possibly multiple other tissues to increase insulin sensitivity and it acts on the pancreas to increase insulin output. But what that increased insulin output occurs in the context of being very sensitive to the insulin.

So overall it causes a very radical increase in metabolic health. And I would say that no one really knows why this system has evolved the way it does, but you could speculate that it might be a way to link to bone resorption to the anabolic affects of insulin and testosterone.

So you would want bone resorption to be tied to bone growth and if you’re in a process of greater bone remodeling then perhaps the resorption causes osteocalcin to be released into the serum and then provide an anabolic stimulus to help rebuild that bone. That’s just speculation.

What isn’t speculation is that this causes a real challenge to interpreting, “What does it mean that such a high percentage of osteocalcin is under-carboxylated in children?” Does it mean that the children are not getting enough vitamin K?

Or does it mean because those children are engaging in a rapid period of bone growth, that their bones are just producing more of this hormone in order to provide a greater anabolic stimulus, which is exactly what they should need as growing children? Or is it both?

I actually am of the opinion that it’s both, [for] several reasons. One, is that whenever you take someone who has a considerable percentage of under-carboxylated osteocalcin in their blood and you give them vitamin K supplements, you increase the carboxylation status. That seems to provide some proof of principle that they are operating in some range of inadequate vitamin K.

But also, if you look at the fracture rate of children. Growing children actually reach a point during puberty where their fracture rate is equal to elderly people who are starting to have their bones deteriorate. So I believe that probably both of these things are true.

And although under-carboxylated osteocalcin is not a clear, clean, straight-forward marker of vitamin K adequacy; I do think the data overall suggests that children’s bones are growing faster than the mineralization of those bones can keep up with.

I think the reason that the fracture risk temporarily increases is because: imagine that you’re stretching a rubber band. If you are stretching that you are putting pressure on the system and it can break. So you are expanding the bone matrix and you are not at the same rate mineralizing it.

That’s like stretching out that system too thin and in that case you temporarily undergo this position of greater fracture risk, until the bones can eventually keep up. Because eventually you stop growing and then if you just get a little bit more mineral at a time you can eventually fix the problem you created during the time period of rapid growth.

I will say that my working paradigm is that this system is inadequate but I don’t want to give the impression that it’s incontrovertible. I also don’t want to give the impression that, just to be clear, it’s equally controvertible if someone is going to take the opposite position. This is a reasonable debate.

(00:27:02)[Damien Blenkinsopp]: Right. There are two ways to look at it. If you were trying to resolve that — if you did a controlled study through the teenage years, with families where they were getting more vitamin K, getting more nutrients from the system, versus the other, some kind of study like that. Would it help resolve and potentially give us the answers?

[Chris Masterjohn]: That’s another line of evidence that we actually do have. There are multiple observational studies that suggest that higher vitamin K2 intakes. To clarify vitamin K2 is a specific form of vitamin K that is found in animal products and fermented foods, as opposed to vitamin K1 that’s found in green-leafy plant foods. Vitamin K2 is more effective at activating the systems that we’ve been talking about than vitamin K1 is.

If you look at vitamin K2 intakes, observationally people who are in the highest — depending on the study, tertile, or quartile, or whatever they looked at — intakes of vitamin K are likely to have better bone mineralization, a lower risk of heart disease and blood vessel calcification and also, we didn’t even get into this, a lower risk of multiple different types of cancer.

There are cases, to my knowledge I don’t know of a study showing that in children you can reverse that increase in the fracture risk during that period with vitamin K supplementation but there are some, multiple, successful vitamin K interventions in elderly where very high doses, possibly pharmacological doses used in Japan, caused a dramatic decrease in osteoporosis risk that was more effective than osteoporosis drugs.

(00:28:44)[Damien Blenkinsopp]: What would be a pharmacological dose?

[Chris Masterjohn]: If you look at what you’re going to get from food, the highest intakes of vitamin K2 tend to be topping out at 200mcg a day. Most people would not be getting that, but you could find that among people who are eating whole foods. In the Japanese trials they were using 45mg, a microgram is a thousandth of a gram. You’re talking about orders of magnitude higher than what you could get from food.

But no one has tested lower doses of vitamin K. So with the osteoporosis trials, it’s sort of this question, “Was it the first 500mcg that caused the decrease in risk and the rest was just chafe?” Or do you actually need 45mg to cause that effect.

(00:29:29)[Damien Blenkinsopp]: It takes a while to find the minimal effective dose. I’m guessing vitamin K2 isn’t toxic at high doses?

[Chris Masterjohn]: In those Japanese trials there were no reported adverse effects. Anecdotally I have talked to some people who seem to be hypersensitive to vitamin K and seem to anecdotally have negative experiences from supplementation.

I think there is reason to speculate that it would be preferable to keep vitamin K in doses closer to the maximum of what you can get from natural whole foods, because there are some biochemical effects that you could reasonable construe as negative, when you get into really high doses.

(00:30:13)[Damien Blenkinsopp]: Great, thanks. You just mentioned cancer. I guess we didn’t really go through the complete list of things of issues you think could be associated with this system. Are there others that we haven’t mentioned which you would see as commonly or with a high potential associated with this system and a deficiency?

[Chris Masterjohn]: When I’m looking at vitamins A, D, and K in a functional network, I think the system where that really stands out is the system of calcium distribution. When you start talking about cancer it gets a little bit less clear how they interact.

Vitamins A and D are involved in the expression of numerous genes that are not coding for vitamin K dependent proteins. They have independent affects, where vitamin A does something and vitamin D doesn’t do and vice versa, but there are also genes that are regulated cooperatively by vitamins A and D that don’t relate to vitamin K.

In addition to that, although the best characterized function of vitamin K is to activate proteins by adding carbon dioxide to them or that carboxylation process that we were talking about before.

One of the things that for a long time that we could speculate about was, “Why is it that that process occurs in one part of the cell and we actually find most of the vitamin K in the nucleus and the mitochondria?” What we’re finding out now is that vitamin K also plays a role in energy metabolism. Vitamin K also plays a role in gene expression and so on and so forth.

When you start thinking about gene expression then anything that is a failure of the cell to behave in a way that that cell should behave, suddenly becomes a candidate risk of a deficit in that system.

For example, Autoimmune conditions makes a lot of sense to look at when you’re thinking about at vitamins A and D. I don’t know of any studies that have shown when vitamins A and D are given together in humans, will do anything positive in type I diabetes.

But I do know of at least one study where they showed when you take pancreatic stem cells you can regenerate the insulin producing cells that are being lost in type I diabetes by providing the active signaling compounds that are made from vitamins A and D together in those cells. Does that translate into a human affect? I don’t know, but that’s one possible candidate risk that we can be looking at.

When you’re looking at vitamin K, probably the most compelling study was one where they looked at liver cancer in women who are at very high risk and I believe — it’s been awhile since I’ve looked at it — but I believe the risk was caused by the existence of viral cirrhosis. That showed that the incidence of cancer in a controlled trial, that vitamin K supplementation virtually obliterated the rate of cancer, like lowered it by over 80%.

There are also multiple other cancer related endpoints that could be related to vitamin K because we have cell studies where we can say, “Okay, we can drop vitamin K in this specific form on the cell, and this is what it does.” Most of that has not translated into human outcomes.

And most of it has not really — so little is known about the mechanism. When I was telling you about how A, D and K interact to regulate this calcium distribution system; we have a lot more understanding, mechanistically, of how that system operates. I suspect that there are a lot of interactions between nutrients that we could eventually uncover when looking at autoimmune conditions or cancer, but we just don’t have the mechanistic basis to understand it at that level yet.

(00:34:00)[Damien Blenkinsopp]: Thank you for that clarification. It sounds pretty broad spectrum. If you’re thinking about tackling this and are in any of those spots we were just describing it might be worth looking at this because it’s not something really hard to fix or address either. I was just wondering, because you were just talking about cancer, if you’ve looked at the work of Dr. Bruce Ames and his triage theory? And if you think that’s something that could be playing a role there?

[Chris Masterjohn]: Yes. Not exhaustively, but I think with respect to vitamin K metabolism that Ames’ triage theory is pretty well known. I actually know about it from studying vitamin K and I suspect that if you were to talk to leading vitamin K researchers probably most would consider it a very valuable tool in understanding vitamin K metabolism.

If you look at triage theory in that sense the implications of that are — So triage theory is the idea that the body is going to prioritize acute survival needs over investment in long term health when the supply of nutrients in compromised.

In the case of vitamin K what we see is that if that you are marginally inadequate in vitamin K then your liver seems to get top priority to activate blood clotting factors and the bones and blood vessels and all these other systems that are dependent on vitamin K, lose out.

That’s the rational decision of the body saying, “Look, if I get cut and bleed to death that’s much more of an imminent risk than if twenty or thirty years down the road I get arterial plaque, or a heart attack, or a stroke, or osteoporosis with this slow degeneration of the bone matrix.”

So I think there is pretty good evidence that the body does prioritize vitamin K that way and I think it’s almost become standard, in the field, to use that as a working framework to try to understand how that prioritization occurs.

(00:36:08)[Damien Blenkinsopp]: Thank you. I’m always interested how different ideas overlap and where people’s work is using similar frameworks and so on.

I think in my audience people are actually using a variety of different diets. They could be doing whole foods, vegan, paleo, keto, or maybe something a bit more standard. It might be hard to answer this question, but how relevant do you think it is to each of those groups, more or less? Are some of them going to be better positioned to not have a deficiency than others and some, like you were talking about vegan earlier, are potentially going to be more at risk?

[Chris Masterjohn]: One of the issues that comes up here is genetic polymorphisms. One of the areas in which we are starting to get a lot of research in is in the ability to derive vitamin A from plant foods.

So the physiological form of vitamin A, meaning the form that we need in our bodies to fulfill the functions we’ve been talking about, is retinol. It only occurs in animal foods, whereas red, orange, yellow and green vegetables are rich in carotenoids which can act as precursors to retinol.

Since 2012 we’ve been accumulating a small body of evidence showing that there are very common genetic polymorphisms that strongly affect the ability to convert carotenoids to retinol. In addition to the genetic effects there are also a huge number of dietary and metabolic factors that also affect that conversion.

I can list those if you want me to. But even if you were optimize the dozen factors that can affect that conversion rate you may be just be stuck with poor genetics in terms of the ability to convert carotenoids to retinol.

My suspicion is that in vegans, one of the determinants of whether someone is going to do well or not do well on that diet is: what are their genetics like for the ability to derive vitamin A from plant foods? And because this is so dependent on genetics and metabolic health and other dietary factors there’s no saying that a vegan will become deficient in vitamin A.

But I think people who are going to be vegan have to be conscious of how they’re going to respond to that because if they fall into that category of poor derivation of vitamin A from plant foods, then that would likely be a weak spot for them.

A vegan also wouldn’t be eating fish or traditional sources of vitamin D but they could compensate for that by getting sunshine. People can also take vitamin D supplements and I think it could be debatable to whether this is the best choice, but there are also UVB irradiated mushrooms that are on the market as a food source of vitamin D.

For vitamin K I would say that that also would tend to be limiting on a vegan diet, and that’s not because you can’t get it. In fact, by far and away the best source of vitamin K2 in terms of quantity is natto, which is a fermented soy food which is popular in eastern Japan.

But the fact of the matter is when you look at the general population most of the people are getting most of their vitamin K2 from egg yolks and cheese. So if you take out egg yolks and cheese and you don’t put in natto to compensate for that, you’re going to have a huge drop in your vitamin K2 intake. I think that could be very significant.

So in the case of the vegan, for vitamin D and K, it’s really a matter of properly designing the diet in order to compensate for those changes. With respect to vitamin A there is also an element of, “Is your constitution really well matched to this diet?” If it’s not, then you need to either rethink the dietary strategy or you need to supplement with vitamin A.

I think if you look at paleo and keto, it kind of depends on what foods are being incorporated. Some people define paleo based on what foods it’s restricting. Other people might define paleo more based on the theoretical framework: that much of modern disease is caused by a mismatch between our environment and our evolutionary environment.

People who are thinking of it more like that are more likely to say, “How were our ancestors eating?”, They were getting nose to tail and they were getting all the organ meats when they killed an animal.”

I think if someone is doing paleo and they’re doing that then they’re going to be in a much better position than if they’re eating what the standard average American is eating, or average person in modern society are eating, minus the grains, legumes and diary. Just taking those foods out is not at all going to guarantee you good nutritional status, but paying attention to the organ meats will.

Most people, back in the day, paleo tended to be equated with low-carb. Nowadays there is a greater diversity of approaches towards carbohydrates. Keto obviously is low carb.

It is important to recognize that carbohydrates do play a role in supporting the system. Like I was saying before, it results in greater carbon dioxide production, that would be relevant. Carbohydrates also supports greater thyroid status and thyroid hormone helps cooperate to produce vitamin K-dependent proteins just like vitamins A and D do.

Also, vitamin K, you use it one time and you have recycle it. And recycling vitamin K is dependent on NADPH. NADPH is a form of niacin that carries energy from glucose to a variety of other systems. So the glucose is ultimately supplying the energy to recycle vitamin K.

When you look at all of those things, I think there is a grey area there where you want to be careful that you’re monitoring the health outcomes on a ketogenic diet. Because, to be honest, I don’t think anyone has really studied, “How does a ketogenic diet affect the carboxylation of matrix Gla protein?” Or anything like that. You can speculate there are a lot of things you want to be careful of, but ultimately what we need is more research to look at the actual outcomes on those diets.

(00:42:28)[Damien Blenkinsopp]: Right. It sounds like no matter which situation you are in you have to be cognizant of this. As you were saying, people are doing lots of different paleo diets, and it’s the same for keto as well. Some people will be eating primarily cheeses and diary and things like that, and others will be more focused on the meat. I think there is quite a wide variety.

It sounds like you have quite a few principles which can cut across all of these areas and, no matter which diet you’re following, could potentially resolve this system if you keep to those rules? It’s kind of independent of any of these diets.

[Chris Masterjohn]: Yeah, to a degree. You could even broaden that to other diets. So what is the diet that most greatly restricts egg yolks and cheese? It’s the, “I’m trying to be healthy diet.”
You don’t have to be paleo, or keto, or vegan to restrict egg yolks and cheese. You just need to trust the system and be health conscious.

[Damien Blenkinsopp]: Right. Absolutely.

[Chris Masterjohn]: That’s the message: to be heart healthy you get rid of foods that are high in saturated fat and cholesterol. The hell with nutrients, that’s been the prevailing approach to health consciousness. I think this is an under appreciated system that cuts across all of these diets and people really need to pay attention to it.

(00:43:48)[Damien Blenkinsopp]: Excellent. Thank you.

When I was doing preparation for this I was looking at one of your presentations that was really good on YouTube, it went through all of this area. In that, you established some principles behind optimizing this area, or this system. And you already brought up some of them that are important, like genetics, that can play a role in this.

It would be good to cover a few of these to give people an idea of the system. I think there are some misunderstandings. When it comes to vitamin D for example. For many years we’ve just been thinking, “Okay, I have low vitamin D compared to other vitamin D count says. I have to take a supplement to raise it.” Where I think what you’re saying is it’s quite a bit more complex than that, and that doesn’t necessarily help you.

[Chris Masterjohn]: Well that’s true. That’s not only true because of the other interacting factors, but it’s also true because 25-OHD which has been promoted as a specific marker for vitamin D nutritional status, isn’t one.

It is very true that if someone is low in vitamin D status their 25-OHD status will be low and if you supplement them with vitamin D or restore nutritional status it will rise. That is true. And yes it’s useful as a marker of vitamin D nutritional status, but there are also numerous other things that are both good things and bad things, that can affect 25-OHD.

For example, calcium deficiency can lower it because you’re using more vitamin D at a greater rate. Vitamin A supplementation could potentially lower it because you’re increasing utilization of vitamin D to fulfill cooperative functions that they’re needed for together. There are genetic differences that just make some people metabolize it to the active form at a higher rate and that seems to be associated with better health outcomes.

One of the things that I have been advocating especially recently to better understand 25-OHD as a marker of vitamin D nutritional status is to look at parathyroid hormone, or PTH. This is a test that you could very easily ask your doctor for. It is not difficult to get.

But the reference range for PTH is based on diagnosing parathyroid disorders, so it’s sort of not useful for this. But if you look at the rationale for putting the cut-off of vitamin D adequacy at a certain 25-OHD, it’s actually because on a population level that 25-OHD is associated with maximal suppression of parathyroid hormone.

The parathyroid gland is the resident expert within the human body and your individual calcium-vitamin D economy and PTH output increases in direct response to that economy of vitamin D and calcium being inadequate.

Instead of saying on a population level, “This much 25-OHD on average is associated with maximal suppression of parathyroid hormone.” We can take the same mainstream conventional principle and apply it to the individual by looking at, “Is that individual’s PTH maximally suppressed or not?”

My tentative conclusions about this are if you look at PTH you want it to be in the lower half of the reference range. That’s basically thirty, in picagrams per milliliter, seems to be the sweet spot, thirty or below.

If someone’s at thirty-five I don’t know if that’s concerning. But when it’s forty, or it’s fifty or it’s sixty I think that is a very good corroborating sign that that persons’ body perceives itself to be inadequate in vitamin D. I think that can really help us get a more nuanced and sophisticated approach to looking at that. That’s one thing that I would mention.

Also, as we’ve been talking about, you add vitamin D to this system and it needs the other cooperating nutrients to fulfill those roles. One of the problem points here is — Let’s take, “What is the prevalence of low serum retinol in the population?”

Well it’s really low like two or three percent of people have serum retinol below the reference range. So everyone says, “Well people are a lot more likely to get too much vitamin A than not enough.” So they tell everyone to avoid vitamin A.

Then people come in and say, “Lets ten fold increase your vitamin D intake.” Now all of the sudden you are taking that person, if you’re 10x-ing their vitamin D exposure, you’re taking them out of that original population and putting them into a totally different population of “10x vitamin D” status. In that case, what is happening to your vitamin A status?

I think there are a lot of reasons to be concerned that all of the sudden vitamin A intake becomes very relevant to most people when you move them into that high dose vitamin D supplementation. I think that if you’re going to tweak this system it’s really important that you pay attention to the whole system and not just take one element and blast it out of the system hoping that the one element is going to turn things around.

The most important principle of that is even if you’re going to supplement, first of all, have a targeted reason for the supplementation. Be conservative about the dose and titrate it up to higher doses based on how you’re responding to it, if needed. Also be very careful that the background diet is supplying all of those extra nutrients.

If you’re going to supplement with vitamin D, be conservative about it. But also, get your liver once a week, get your daily egg yolks in, get your fermented foods in, get this background supply of nutrients up to par so if you do perturb the system the rest of those factors make the system robust and it can handle the changes that you’re putting into it.

(00:49:49)[Damien Blenkinsopp]: Definitely balance versus saturation of one micronutrient. You’re saying [to] get a good background of foods there. Is one of the principles behind that, that foods tend to be naturally balanced in these nutrients? If you look at liver, it’s got vitamin A and D combined. It comes from a body so you’d think it wouldn’t be completely out of whack with the needs of a body.

[Chris Masterjohn]: I actually don’t think that’s true. If you take a fish’s liver then fish liver tends to be high in vitamin A and D, but that’s not true if you take a terrestrial animal’s liver. That’s because mammals, we store vitamin D primarily in the blood and not in the liver. So our metabolism is a little bit different that a fish’s metabolism.

If you were using the blood in the animal and you were using the kidneys in the animal and you were truly eating the whole animal, that would probably balance out. But it’s not necessarily true that you can say, “My substitute for eating nose to tail is that I will eat liver once a week.” That’s not necessarily doing you any favors with respect to vitamin D.

What it is doing is it’s making you robust to any problems with your derivation of vitamin A from plant foods. Lets take the person who really is terrible at making that conversion. If they eat one serving of liver once a week, [then] they’re meeting the RDA through vitamin A.

You can debate what is the optimal level of vitamin A intake and is it higher than the RDA or not, but if you take that liver out and they aren’t good at getting vitamin A from plant foods, what other foods besides liver or cod liver oil is going to bring that person up par? Nothing.

What you’re doing by doing that is not — the liver isn’t going to magically make the whole balance of the diet. Even if you were to catalog all the potential polymorphisms you have in the enzyme that makes that conversion you’d kind of get stuck no where because every time a new study comes out we identify these new polymorphisms.

So you really have no idea what your conversion is, at all, unless you subject yourself to a randomized cross over study where you’re undergoing multiple diets and collecting data on it, and no one does that. So just including liver in the diet, you can put that question to rest. You don’t really have to care about that conversion if you make that one step.

When it comes to vitamin D you need to get regular sun exposure. That’s not the only reason to go out in the sun. Include some fatty fish, include some pastured egg yolks, get outdoors. That in most cases, in the absence of some constitutional or disease issue, for most people covering those bases covers vitamin D.

Get your egg yolks in, get your fermented foods in, get your leafy greens in. For most people who don’t have a specific vitamin K related problem, just getting the diversity of vitamin K rich foods in covers the bases.

(00:52:50)[Damien Blenkinsopp]: When you say fermented foods, you mentioned natto earlier. Are there other ones you recommend?

[Chris Masterjohn]: Honestly, for the average person cheese is going to the be most potent one if not on their list. Part of the issue is that it depends on the bacteria. If you take the natto bacteria and you make homemade fermented vegetables with it instead of fermented soybeans my understanding is that would be a pretty good source of vitamin K2.

By contrast, if you are eating, say sauerkraut, you are getting some vitamin K2 from that and that’s good but it’s incomprehensibly less than what you would get from natto. Even if you just compare sauerkraut and cheese together, cheese is way ahead of sauerkraut.

I think diversification is the best strategy here. You can micromanage it and you can look at the table and log your K2 intake everyday. But if you want to be practical about it and you don’t want to be spending exorbitant amounts of time thinking about it and managing it, then I think what you do is you say, “Okay fermented foods in general, but particularly cheese and also egg yolks are convenience sources. If I just rotate these in my diet on a regular basis and don’t think about it too much then that secures a baseline level of adequacy.”

[Damien Blenkinsopp]: So variety is a big principle here.

[Chris Masterjohn]: Yeah. The more you restrict your diet the more you need to micromanage it.

(00:54:20)[Damien Blenkinsopp]: In terms of productivity, I think you do this as well. You basically do auto-order. I have local farms I subscribe to. You fill out the stuff you want and it gets auto-delivered every week, so I don’t have to think about it.

On the other hand that means I’m probably not getting the maximum variety because I’m always getting over delivered with food if I was trying to maximize the variety. I don’t know if you, in terms of productivity, if that’s something you deal with? I think you use Thrive Market right?

[Chris Masterjohn]: I do.

(00:54:52)[Damien Blenkinsopp]: In terms of variety do you kind of switch yours up? Have a look at your list and just change it each week or do you leave it on auto?

[Chris Masterjohn]: I actually don’t auto subscribe to things like that, although the way that I deal with it is actually pretty close because I mostly have mobile apps where I just tap, tap, tap, tap, tap on the things that I’ve been ordering recently and it’s that simple.

A lot of the ways that I deal with variety is to deal with it on a week-to-week rotation basis. To take an example, I find trying to get variety in within a day or from one day to the next is extremely taxing. It’s not only taxing mentally on trying to think about what I’m trying to put together but it’s also taxing on my ability to not throw food away, because getting that variety in would mean that I would have to over order things.

I try to get a variety of green leafy vegetables in, but what that means is that on a given week kale will be my cooked vegetable that goes into a big batch of starches that I just take out of the refrigerator and reheat in two minutes each time I use them. And I will get a box of some type of leafy green that I would eat raw and I’ll just eat platefuls of that.

But the next week I will switch out the kale for a different green vegetable that I make cooked and I will switch out whatever those raw leafy greens were, for a different one. So I get my variety in more on a week-to-week basis where I’m rotating different types of similar things into my diet rather than within a day or from day-to-day.

(00:56:39)[Damien Blenkinsopp]: Excellent. Thank you for that. I like to make sure the information is practical. I will probably have to change mine up based on that.

I wanted to go back to the testing, this is a quants show at the end of the day, a lot of the time. When you were talking about the PTH earlier that was basically a downstream marker of vitamin D, kind of like an indirect measure versus a direct measure where you’re looking directly at the blood, D-3 to 25-OHD. Is that a typical strategy you’d take for this area if you were — I think it would be interesting to find if you think it’s actually worth testing in this area because I know in some areas it’s not that useful at times.

So first of all, is it useful to start looking at testing in this area if it’s a concern of yours? And second, is a downstream strategy often best versus going for the direct ones, similar to the D-3 in the other areas?

[Chris Masterjohn]: Well, no one uses the direct strategy with vitamin D. If you consume vitamin D you consume it as vitamin D and measuring vitamin D in your blood is virtually useless as a marker of nutritional status. Everyone is using the indirect strategy of measuring 25-OHD which is a downstream metabolite of vitamin D.

The issue is, in every case, when you’re looking at a biomarker for anything the questions that you’re asking are: is it sensitive? And is it specific? Quite often we may think that something is specific then when our understanding of it increasingly evolves we need to revise that.

I think that PTH is a more specific marker of inadequacy in the calcium-vitamin D economy than 25-OHD is. One of the ways to think about this on an intuitive level is: what is the parathyroid gland doing? It is continuously monitoring the vitamin D-calcium economy using sensors of receptors that sense the concentration of calcium in the blood.

If you have serum calcium dip for even a millisecond the parathyroid gland will sense it. And on a scale of less than a fraction of a second it will respond to that and carry out a downstream cascade of events that will start operating within seconds and basically finish operating within minutes to normalize serum calcium.

If you take someone who is consistently deficient in vitamin D or calcium; what you wind up with is that person will have a higher level of PTH because that PTH is being chronically activated to compensate for that deficiency.

If you’re to compare PTH and 25-OHD. I’m not going to argue that PTH is a hundred percent perfectly specific but it adds a lot interpretive power to the 25-OHD. To take an example of one of the confounding factors, if we look at people from different ancestries we will see that there seems to be differences in how they metabolize vitamin D.

People of white/European ancestry actually seem to be outliers in the amount of 25-OHD they need circulating in their blood to maximally suppress parathyroid hormone. Now remember, when we set the benchmark for, “What is an adequate 25-OHD?”, that is set on the basis of maximally suppressing PTH. That is the benchmark that is accepted.

I’m not advocating a different principle. I’m advocating individualizing the principle. If you take someone who is African-American or someone who has Inuit ancestry, probably if you take someone who has Asian ancestry and you compare that to someone who has white/European ancestry you will see that on average they will have lower 25-OHD.

But they will also have higher levels of calcitriol, which is the fully active hormonal form of vitamin D. They will also have lower levels of PTH. If you trace that further what you’ll find is that there are genetic polymorphisms that are more prevalent in those populations that trace to different ways of metabolizing vitamin D.

One of the ways to interpret that is: different populations are adapted to different levels of 25-OHD needed to maximally suppress PTH. One of the problems with that is that’s just on average. If I take the average of white girls and black girls in Oklahoma then on average all those things that I just said will be true of those groups.

But then when you take the group and you separate them into individuals, the genetics aren’t separated into those two groups perfectly. Some of the African-American girls will have the genes that are more prevalent among the white girls and vice versa. In order to actually treat the individual you can’t just define them by their group.

In that case, what better way to do that than to actually look at whether PTH is maximally suppressed in that person? I think all you’re doing is taking the conventional standard strategy and saying, “Is this actually operating the way we’re saying it should operate in this particular person?”

(01:02:08)[Damien Blenkinsopp]: It’s a great reminder that you have to look at this on a personal level for a lot of things, just as you’ve talked about these complexities.

It reminds me a bit of methylation. I’m sure you’ve looked at methylation a bit, but with all of the polymorphisms and everything, people react completely different to supplementation and when you’re trying to tackle that. It sounds exactly the same with this.

In terms of other tests that I’ve come across, one of them is SpectraCell, the micronutrient testing they have. I don’t know if you’ve looked at that and if you’ve thought it’s useful? It has vitamin K2 and K1 I believe, if I remember from memory.

[Chris Masterjohn]: I do not like SpectraCell. Unless they have radically changed how they do it in the last couple of years, I haven’t looked at a recent SpectraCell report, but I basically disagree with the entire principle behind the SpectraCell report. I also think that it generates pretty bizarre conclusions as well.

I will say that, I don’t want to sound like I’m singling out SpectraCell. I would say it’s generally true of all of the shotgun approaches to practically anything, even genetic polymorphisms. You can take your 23andMe data and run it through various software or web apps that will give you back a report that will give you ridiculously conflicting practical conclusions like, “You have this polymorphism, so take methyl-B12. You have that polymorphism, so avoid methyl-B12.”

I think that’s an inevitable consequence of trying to do too much at once. I think it is possible to do many things at once and I think we’re eventually heading towards that area, it’s just that you can’t sacrifice the integrity of the methodology in order to get more stuff.

In the case of SpectraCell, and I don’t know if they’ve changed this in recent years, but at least a couple years ago when I was looking at SpectraCell reports what they were doing was taking lymphocyte concentrations of these different nutrients. One of the problems with that is that there is practically zero research on that.

Take for example vitamin D. There are thousands of studies that span tens of thousands of people looking at 25-OHD levels. There are at least hundreds, if not thousands of useful studies that are worth looking at in terms of, “How does it correlate with disease risk? How does it correlate with metabolic factors?” and so on and so forth.

And by contrast we don’t have a lot of data on, “How do white blood cell concentrations of vitamin D correlate with these factors?” Although there are huge limitations to interpreting 25-OHD that I was just describing for you, the only reason I even know about those limitations is because there is so much research on it.

With leukocyte concentrations of vitamin D I can’t tell you what those limitations are because we don’t have a huge body of literature assessing its usefulness. But I can tell you is that there is no particular positive reason to assume that is a useful marker.

I can also tell you that I had a consulting client who was taking vitamin D supplements, who had really high 25-OHD and a really low leukocyte concentrations of vitamin D. SpectraCell told him to take more vitamin D.

By any accepted definition he should have been, if anything, cutting back on his vitamin D. What does it mean that his leukocyte vitamin D concentrations were low? To be honest, I have no idea. I don’t know what it means, but neither does SpectraCell.

[Damien Blenkinsopp]: As you were saying it could be some of the things like genetic polymorphisms, people are just different that way. All of these things that aren’t uncovered because there’s no research.

[Chris Masterjohn]: Also leukocytes are a part of the immune system and the immune system uses these things and profoundly affects their metabolism. One of the things we know is that one of the reasons that you can have low 25-OHD is because of inflammatory activation.

Even for example in the recovery for surgery the immune response that is involved in tissue repair will cause a pretty large drop in 25-OHD acutely in that sense. And probably it’s true of chronic inflammation as well.

So one of the things that you want to ask is: Why does a leukocyte decide to concentrate vitamin D and does it decide to do that some times and not others? And does that leukocyte concentration of vitamin D have a lot more to do with what that leukocyte is deciding what to do because of the context of immune signaling in that person and not nutritional status of vitamin D? That’s a question of, we need research studies.

Ideally research studies come before you start practically applying tests rather than after. The ideal time to say, we tested this, now you should go out and do this is when we have a lot of information about what that means. Not so we can ten or twenty years later hope to get some information about it.

(01:07:10)[Damien Blenkinsopp]: Absolutely. Thank you for that.

Are there any other tests that you’ve come across in this area, either bad or good? Ones you don’t think are worthwhile doing or anything good?

[Chris Masterjohn]: Specifically on vitamin D or across the board?

[Damien Blenkinsopp]: Yeah, the whole fat-soluble.

[Chris Masterjohn]: Yeah, a few others that stick out. First of all, for vitamin A status the most useful measure is serum retinol. Serum retinol does not perfectly correlate with vitamin A status but it will tend to be low if you are running low on vitamin A and in general the reference range is pretty good on that.

The reference range if you just get a Quest report for serum — I will warn you it should be called serum retinol and at least Quest Diagnostics calls it serum vitamin A, but in any case it’s the same test. The reference range for that is based on the role of vitamin A in supporting night vision. If you are within the reference range that should preclude virtually all cases of impaired night vision as a result of vitamin A deficiency.

Now, I think there are some big question marks over whether that is actually the most sensitive marker of adequacy? I will tell you from my personal experience, I had some pretty severe eye related signs that indicated to me that I was vitamin A deficient. I made a very intensive effort to improve my vitamin A status over the course of the week.

After I did that, I was still resolving my vitamin A status, but I have my serum retinol tested and it was towards the bottom of the reference range, but it wasn’t below it. You probably don’t want to be operating at the bottom of the reference range.

(01:08:52)[Damien Blenkinsopp]: I think one of the baseline rules that we’ve spoken about before on this show is like if you’re in the top third for a lot of these standard reference ranges because the normal population tends to have a fair amount of chronic illness and non-optimal health. Is that a rule you could take for this test?

[Chris Masterjohn]: I’m not quite sure about that, but I will say I would prefer to be in the middle than on the bottom. I don’t want to encourage people who are in the middle to get up to the top third, but I would say if you’re towards the bottom you should definitely try to get towards the middle.

If you’re at the top sixty or seventy percent, I’m not going to recommend you get down to the middle. The data isn’t really that clear, but you want to keep your distance from the bottom of the reference range in my opinion.

I will also say that in rats, I can’t remember if it was rats or mice, but there was a recent paper that came out that showed that obesity compromises tissue vitamin A status. I shouldn’t say tissue, tissue besides the blood. The blood is a tissue.

But it compromises vitamin A status in many tissues without decreasing serum retinol. So there are caveats that we are just starting to learn about with these tests. I would say in general serum retinol, despite potential limitations, is very useful to have.

I want to say one more thing about vitamin A. If you’re concerned you’re getting too much vitamin A there’s a good formula to use. That is to get your fasting serum retinol and your fasting serum retinyl esters tested.

I know that Quest Diagnostics actually calls these two tests serum vitamin A and serum vitamin A palmitate. That means retinol palmitate which is the predominate retinyl ester. This has to be fasting. If in the fasting state you add those two values together and your serum retinyl esters are greater than ten percent of the sum of the two values then that is an indication that your liver is overloaded with vitamin A and you either need to cut back or you need to correct some backup in your metabolism.

It could, for example, if someone has fatty liver disease that will compromise their liver’s vitamin A storage, then that could play a role in it. If you are lean and healthy with good body composition, the most reasonable interpretation of that would be that you’re overloading your liver with vitamin A.

With vitamin K, I am not happy with any test that’s currently available, at all. I do not think it’s useful to look at leukocyte vitamin K concentrations. I don’t think it’s useful to look at plasma serum or red blood cell concentrations.

What I [do think] would be useful is the carboxylation status of osteocalcin. I don’t remember which lab it is, but last I looked the only lab that was offering this gave you under-carboxylated osteocalcin without giving you, “What is the percentage of the total osteocalcin that’s carboxylated.” Just looking at total under-carboxylated osteocalcin is not useful.

On the horizon there is a company called Amino Diagnostic Systems that two or three years ago told me they were trying to develop a test for desphospho-uncarboxylated Matrix Gla protein, or DCUCMGP which put simply is the inactivated form of MGP. That’s the protein that protects soft tissues from calcification and helps direct calcium into bones and teeth.

If that’s high it’s a very good marker that you don’t have a very good supply of vitamin K to your blood vessels. They told me two or three years ago they told me they were hoping to get this test past FDA approval and I asked them this morning, in preparation for this show, if they’ve made any progress on that. They said, they’re working on it.

[Damien Blenkinsopp]: Wow, awesome.

(01:13:02)[Chris Masterjohn]: I think on the horizon we can eventually see the inactive form of MGP be a very useful marker of vitamin K status in the blood vessel. When that comes out I’m going to be super happy and tout it with fanfare all over the place. But right now nothing is available that isn’t a waste of money, in my opinion.

I will say also, that there’s a company based out of the Netherlands called VitaK. They offer testing of all of these things to people who form contracts with them. I do not know if they would form those contracts with clinicians who are testing it in patients. I do know that I was talking to a clinician who was doing clinical research and he was taking samples from patients to do a research study and he just sends them to them. They measure all this stuff and give the data back to him.

This is not going to be helpful for patients or for the average person but if there are any clinicians listening, they may be worth approaching about this to see if you can come to an arrangement with them to start collecting some clinical patient data.

(01:14:16)[Damien Blenkinsopp]: Awesome. That’s some amazing stuff there. You’ve obviously kept up to date with all of this stuff.

It’s great to hear about the SpectraCell. I did SpectraCell about three years ago and so it would have been the same test you looked at. It had some stuff like K2 deficiency. There wasn’t actually that much that come of it for me. Nothing really interesting.

[Chris Masterjohn]: Just to add one thing. I had someone who had the same result and they said because K2 was deficient they should supplement with vitamin K1 because it’s a precursor to K2. And all of the evidence indicates that humans tend to be relatively poor converters of K1 to K2. So that’s just one more example of how the data is not translated well into practical recommendations in those shotgun tests.

[Damien Blenkinsopp]: I would say with tests, a lot of the lab tests, they have these recommendations which, if you look at organic acids or a lot of different tests, are spit out through an algorithm based on a marker being low or something. I think most people say not to look at those. Just as a general rule across most tests because it’s not very useful. It’s not taken in context of what else is going on.

[Chris Masterjohn]: Right, but there is no reason that that’s not doable. I hope that we will be moving forward into an area where that aspect of that testing can be improved.

(01:15:27)[Damien Blenkinsopp]: Yeah, it would be awesome if it could eventually be automated.

So this has been great. So much great information. I’d love to know what you’re up to right now. Is there some current research, some questions you’re trying to answer? What’s sort of top-of-mind for you right now?

[Chris Masterjohn]: Right now my top priority is putting together a special report that I will be selling once it’s out, on a very practical guide about how to resolve chronic inflammation using essential fatty acids. One of the things that I think has been profoundly misunderstood since at least the 1990’s, is how the inflammatory process works and how it’s resolved.

Many of the things that have traditionally come out of the outdated 1990’s framework, like take high-dose fish oil to inhibit the inflammatory effects omega-6. Or particularly, take non-steroidal anti-inflammatory drugs to inhibit the inflammatory actions of omega-6 are possibilly down right backwards.

So what I’m trying to do is put together a really practical approach to what is the minimal effective dose for a healthy person of different fatty acids, and in different disease states what is that effective dose? What are the factors that could actually be distorting a metabolism that could be fixed? And things like that.

That’s the sort of the longer term project I’m working on. Some of the more immediate things I’m working on are I just started my own podcast, The Daily Lipid. Anyone can search for that in their favorite podcast app. I’m upping my social media game. I finally got back into tweeting. I finally got active on Instagram and most recently I’ve joined Snapchat.

I’m doing some useful content on Snapchat. A lot of the things I hope to eventually put into permanent content I’m snapping as I’m thinking about them. For example, yesterday I snapped a video tutorial about how people who have gotten their 23andMe post-FDA debacle can despite “No Alzheimer’s” report still hack the system to still get their APOE genetics and stuff like that.

Eventually that will become a YouTube video that’s part of a blogpost, but that could be a month down the road. This way, you follow me on Snapchat and you get these cool little things as I’m thinking about them. That sums up what I’m up to at the moment.

I’m also lining up some potential interesting research for the fall academic year. I’m playing with a couple ideas and I am not ready to really say for sure what I’m going to be doing but with the right amount of help I may actually start looking at how vitamin A and genetic polymorphisms and sleep disorders relate in student populations. If that pans out that will be pretty exciting.

(01:18:24)[Damien Blenkinsopp]: Thank you. I’m really interested in the inflammation stuff actually because I’ve actually taken high dose fish oil to resolve some inflammation but we’ll talk about it later because it’s very specific to me. Not necessarily everyone who’s done that. Maybe you know something about it.

[Chris Masterjohn]: There is value to the fatty acids in fish oil it’s just that if you are effectively resolving inflammation then it’s probably through a very different mechanism than what’s been traditionally touted as the mechanism.

[Damien Blenkinsopp]: You’re saying the Omega-6 vs the Omega-3 mechanism?

[Chris Masterjohn]: I mean what the Omega-3 fatty acids are actually doing there. The traditional idea has been that the EPAH should inhibit our arachidonic metabolism and what we’re finding out now is that’s counterproductive. There are other mechanisms where omega-3 fatty acids come into play. But actually understanding why also provides insight into: what kind of dose should we use? What should we take it with? What’s the best way to optimize the process?

[Damien Blenkinsopp]: It sounds very interesting. Maybe we can have you back on the show later whenever that comes out because inflammation is a big topic right now.

[Chris Masterjohn]: For sure

(01:19:26)[Damien Blenkinsopp]: You know what would be really interesting? Is there anything that you’ve changed your mind about in the last few years?

[Chris Masterjohn]: Change my mind about? There’s probably a whole bunch of things. One thing that I’ve changed my mind about that really relates to the stuff we’ve been talking about here today is 25-OHD status.

When I first started looking at vitamin A, D, K interactions I kind of focused all of my critical analysis into those interactions and took for granted what a lot of the vocal vitamin D community was saying about, “You want to have fifty to sixty nanograms per milliliter, 25-OHD” I’ve really revised that downward as I’ve started to applying the same critical analysis to that particular issue.

Moving outside of that, I was never really an advocate of low-carb diets per se. But I think that I did buy in to a lot the theoretical framework of low-carb approaches even though I figured, “I’m lean so I don’t have to worry about that, etc, etc.” I’ve sort of become a little bit more critical of the low-carbohydrate approach to a lot of issues and trying to build a bit more of an appreciation of carbohydrates recently. That’s an unrelated thing that I’ve changed my mind about.

(01:20:38)[Damien Blenkinsopp]: It’s always very interesting to see people going back on stuff. It’s very important to be able to go back on decisions and change your mind. As you’re saying, it’s all developing all the time. It’s hard to stay on one topic and be sure of it.

Is there anything that you track in terms of metrics or biomarkers, for your body on a routine basis? And why?

[Chris Masterjohn]: I try to take the information one at a time because I feel like I could track everything but then I would probably get lost in the information. Also, in the last year I’ve been recovering from “workaholic syndrome” where I was not tracking anything because I was consumed with the work that I was doing.

I’m trying to gently move into targeting the highly specific things that I know I need to track. For me, one of the things I was tracking over the last few months was my protein intake and my caloric intake and I wound up losing thirty pounds and a pretty hefty amount of body fat that I’m pretty happy with, over the course of a few months.

I’ve kind of moved on from that but still actually track my calories most days because I’m trying to strategically move into fat loss and into gentle muscle building without much fat gain, so that’s something that I continue to track. That’s kind of partly a health thing, partly a vanity thing.

One thing that’s much more straight out health related is my iron status. I am homozygous for the relatively common allele that interferes with the hemochromatosis related pathway. It’s thought that it only causes hemochromatosis when it’s paired with a more severe allele. I just have two of the minor ones, but that puts me in the top three percent of dysfunctional iron absorption in the population.

Theoretically I shouldn’t get diagnosable hemochromatosis. But what I find is that if I do not give blood regularly my serum ferritin is high-ish, but no where near even the middle of the reference range, so maybe it’s 150. A lot of people say it should be lower than that, but the reference range says that if it’s under 500 it’s fine.

What I find is that my transferrin saturation starts getting out of the upper end of the reference range and my unbound iron binding capacity starts getting out of the bottom of the reference range. That means that relative to my capacity to deal with the iron, my iron is being overloaded and that increases the risk of free iron running around, that can contribute to oxidative stress in my body. I actually think that that has a huge impact on my metabolism.

I discovered this slowly over the course of several years. Before I knew I had these genetics and before I had ever tested my iron what I noticed was when I was a guinea pig in my doctoral lab and people would take my blood, I would always feel better.

One of the best responses I ever felt was when I was a guinea pig for a pharmacokinetic study where my lab mate put a catheter in me so she could take twelve blood draws in a single day. Then a thirteenth blood draw the next morning and I felt awesome.

That was when I started thinking about it but then it was a year or two after when I got the 23andMe and that showed me I had those alleles and that motivated me go out and measure my iron status. Once I got a full iron panel that’s when I really put it all together.

With balancing work and life it’s been difficult to maintain a regular schedule of blood donation. That’s my number one health priority right now, is just trying to stay on top of donating blood every eight weeks. And next time around I think I’m going to try my first double red cell donation, so we’ll see how that goes.

(01:24:26)[Damien Blenkinsopp]: Cool. Is it legal to do that at home? Because just recently I’ve been basically forced to get my own blood samples at home because I’m traveling sometimes. And in the UK sometimes sending stuff to the US because the tests are over there.

[Chris Masterjohn]: Oh, for testing?

[Damien Blenkinsopp]: Yeah well you could take more blood out. That’s why I was wondering if there was a legal repercussions?

[Chris Masterjohn]: I honestly have no idea. I know that if you were a student in the high school the teacher would be legally bound to report that. But for a consenting adult that knows what they’re doing, I don’t know why that would be illegal, but I am not a legal expert.

[Damien Blenkinsopp]: Yeah, I guess they’ve never thought to do a rule about it. Probably, I guess they’ve never given the number of people.

[Chris Masterjohn]: When I was in grad school – the rules in Connecticut, they differ state-by-state, were anyone who gets properly trained can take blood. People would just practice on themselves just to get practice. I don’t know.

[Damien Blenkinsopp]: This iron error sounds like something you’re going to have to monitor.

[Chris Masterjohn]: For sure. Right now, I have a sense of how often I need to do it but it’s definitely something that after a few times I’m going to monitor and try to get a precise idea of how many times I need to donate to bring it down to the level that I want.

(01:25:49)[Damien Blenkinsopp]: Excellent. Very interesting.

It’s funny how the number of people I interview on this show that end up with something like this, a very specific thing that they found out about themselves that they then begin to start monitoring very routinely. It starts to make me think that everyone in the world has one specific thing, just for diversity, that a little bit out of whack. Once they look into the numbers a little bit they’ve discovered there’s this one strange thing. It just seems it comes up more than it should.

If you were to recommend one experiment someone should try to improve their body, whether it’s for health benefits, performance, or longevity with the biggest payoff, what would that be and how should they track it to understand it?

[Chris Masterjohn]: Do you mean in terms of measuring something or in terms of intervening without having any data about it?

[Damien Blenkinsopp]: Just taking some kind of action. Ideally having some kind of way of knowing that it’s actually successful. Or it could be something in your opinion where you say, “98% of people, if they do this it’s going to be beneficial in some way.”

[Chris Masterjohn]: For the very reason that you just said, I suspect that there isn’t one thing that 98% percent of people can do and have it equally payoff among them because they all have one particular weak thing to work on.

I would say, to be honest, if we’re talking about the general population, then I think that biggest payoff would be a self-experiment to find a sustainable way to modify your body composition. A few things that I would toy with would be protein intake and habit formation.

I think you have to look at your self and your individual psychological traits. I will say that for me tracking my calories with MyFitnessPal is one of the most effective things that I’ve ever tracked because I always had a problem where if I didn’t eat enough food I would have insomnia from it. Because of not tracking my calories I would constantly overshoot in order to preempt any possibility of not falling asleep because I didn’t eat enough food.

I was always eating a little bit more food than I needed. I was able to titrate my caloric intake to the sweet spot that allowed me consistent weight loss but also to optimize my sleep. Had I not been tracking calories there is no way I would have found that sweet spot.

I don’t want to make a blanket recommendation that everyone track calories, but I do think that, maybe this isn’t true for your audience because everyone so is on top of tracking everything, but if I were to go out to the general public for sure, I would say that self-experimenting, if you track waist circumference, and body weight to get some insight into your body composition and you keep a food log, and experiment with: is there a specific set of very simply habits?

Or actually tracking calories and serving sizes and those things that can come together to produce a consistent movement in a positive direction with body composition is where I think the biggest payoff would be because there are so many downstream metabolic dysfunctions from carrying the wrong mix of fat in the wrong places in your body.

Even the systems we were talking about today, normalizing your insulin sensitivity and your thyroid hormone and all that stuff that can come from managing your body composition can make the fat-soluble vitamins work much more effectively than they would otherwise. That’s what I would give.

(01:29:23)[Damien Blenkinsopp]: Thank you, that’s a great takeaway. This pretty much winds it up. You’ve mentioned your podcast, your podcast is great. You started it recently and it’s extremely detailed. If you guys listening today enjoyed this talk, there is even more detailed stuff on the podcast which is The Daily Lipid.

Is there any specific other requests? We already mentioned your Snapchat, I saw you’re on there, and some others. Is that the easiest way for people to connect with you? Facebook, Twitter?

[Chris Masterjohn]: If you want to follow consistently everything that I get, I think the best way to do that is to go to my blog, blog.cholesterol-and-health.com. If you subscribe by email or to the RSS feed there, you will get all of my long-form content that way. Anything that I write, any of my podcasts and so on and so forth.

Definitely I would say I’d love to have you following my Twitter, Snapchat and Instagram, but of course that’s kind of a different way of following me. When people follow someone on Snapchat or Twitter they don’t see everything that they put out. They stream it at a given time and if something’s there they see it, if something’s not there they don’t.

On Facebook, one thing I’m trying to do consistently now is to do Facebook Live, once a week. When I do Facebook live that shows up in 150,000 to 300,000 people’s newsfeed. If I post something on Facebook it shows up at something like 500 people’s newsfeed. You can follow me on Facebook but if you do that probably what you will actually see in your newsfeed is my Facebook Live Q&A sessions, so check those out as well.

[Damien Blenkinsopp]: Cool, thanks so much for what you do Chris. It’s been a great conversation with awesome details. Thank you so much for your time.

[Chris Masterjohn]:Yeah. It’s great to be here. Thank you so much, Damien.

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Putting the body into ketosis and controlling blood glucose levels may prove to be effective therapy against certain cancers. This real case reveals one aggressive self-experimenter who used a combination of the ketogenic diet, fasting and other tools to control his epilepsy and send his brain cancer into remission.

This episode examines the ketogenic diet as a tool to fight against cancer. It is a follow up of the episodes on ketosis and fasting that we have done with Dr. Thomas Seyfried in episode 16, and Gene Fine in episode 36. You definitely should check those out for context before or after you dive into this one to fill in any gaps.

We are talking to someone who has actually used ketosis by a combination of ketogenic dieting and fasting as a therapy to fight his brain tumor. Our guest has gone through a variety of extreme approaches to ensure he remains in a high state of ketosis. In his case, his life depended on it. This episode is not just for those with cancer or epilepsy, but also for those interested in the benefits of the ketogenic diet. You can take some of the tools he used to improve your own state of ketosis if you are having trouble maintaining it.

[W]hen I have my blood tests . . . and [test] a number of markers for potential tumor progression, internally, I am actually much healthier than before I had cancer . . .
– Andrew Scarborough

I met Andrew Scarborough at a conference where he spoke about his experience with ketosis and its effect on his brain tumor. After being diagnosed with a type of malignant tumor called an Anaplastic Astrocytoma, Andrew underwent several months of unsuccessful chemo treatment. He decided to take his cancer treatment and management of his epilepsy into his own hands and to go the ketosis route. This decision was based in a small part on researching Thomas Seyfried’s work, which we will also discuss in the episode.

Fortunately, this decision has yielded very positive results for him, and his tumor has shrunk. In fact, it has disappeared from scans (seen below) and his doctors are now giving him the all clear. Andrew is now working with London-based hospitals to develop clinical trials for treating brain cancer patients using an optimized ketogenic diet.


Andrew's brain tumor before and after being on the ketogenic diet.

Andrew’s brain tumor before and after being on the ketogenic diet.


There are a lot of details in this podcast on how Andrew went about using the ketogenic diet, including the types of foods he ate, how he optimized the diet for his situation, the extreme measures he has taken, and how he has been able to keep up physical activity. We will talk about everything on his journey, including things like eating bugs and sheep’s brain, and quitting eating plant-based foods altogether.

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

itunes quantified body

What You’ll Learn

  • The beginning of Andrew’s brain cancer story (4:46).
  • Andrew is diagnosed with a grade 3 Anaplastic Astrocytoma (12:14).
  • After unsuccessful chemo treatment, Andrew devises a treatment using the ketogenic diet (19:19).
  • Using MRIs to visualize changes in the metabolic activity of the tumor due to the ketogenic diet (20:52).
  • Scans show complete remission since using the ketogenic diet (23:40).
  • Optimizing and maintaining the ketogenic diet for brain cancer management (26:40).
  • The biomarkers Andrew tracks to monitor the effects of the ketogenic diet (28:08).
  • The glucose-ketone index (29:13).
  • Andrew’s typical diet (32:58).
  • Maintaining a healthy 1:1 ratio of Omega-6 to Omega-3 (33:35).
  • The ketogenic foods Andrew eats (36:10).
  • Variations on the traditional ketogenic diet (41:30).
  • Supplementing the diet with insects (46:30).
  • Keeping up ketone levels and controlling seizure activity during exercise (50:16).
  • Andrew’s research on an optimized ketogenic diet for brain cancer patients (54:50).
  • More on Omega-6/Omega-3 ratios (59:15).
  • Limiting protein and fasting (1:00:32).
  • Using magnesium to prevent seizures during a fast (1:02:08).
  • Mimicking chemo naturally with diet (1:06:44).
  • The resources Andrew recommends for those facing cancer or epilepsy or interested in the ketogenic diet (1:11:47).
  • Andrew’s advice on what biomarkers to look at and where to start with the ketogenic diet (1:18:34).

Thank Andrew Scarborough on Twitter for this interview.
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Andrew Scarborough

Tools & Tactics

Interventions

  • Hyperbaric Oxygen Therapy (HBOT): A therapy Dr. Seyfried believes may be beneficial to fight cancer but is relatively non-toxic in comparison to current treatment modalities (chemo and immuno-therapies). It exposes the body to higher levels of oxygen via having the person sit in a pressurized tank with higher oxygen concentrations. Andrew is adding this therapy to his current tools. Typically you visit centers that provide sessions inside hyperbaric oxygen tanks, however some new smaller and lower pressure HBOTs are now beginning to appear in the market that you can buy to use at home.

Supplementation

  • Ketosports KetoForce: KetoForce contains the endogenous ketone body beta-hydroxybutyrate (BHB) in sodium and potassium salt form. The compound BHB can be used as an energy source by the brain when blood glucose is low. Ingesting KetoForce raises the levels of blood ketones for 2.5-3.0 hours after ingestion. (Note: A similar product from the same company is Ketosports KetoCaNa). Andrew uses KetoForce to increase his ketone levels during gentle exercise.
  • Ancient Minerals Magnesium Spray: Most people with epilepsy have a magnesium deficiency. Magnesium supplementation has been used to reduce seizure activity in people with epilepsy. Andrew prepares his own magnesium chloride solution that he takes transdermally multiple times every day (about 230 mg per day) and during exercise, which can be a seizure trigger for him.
  • Curcumin BCM95: Curcumin is a derivative of turmeric which is an anti-inflammatory antioxidant and potentially has anti-cancer properties. Andrew takes Curcumin in tablet form with DHA because it increases the uptake of DHA to the brain.

Diet & Nutrition

  • Ketogenic Diets: The ketogenic diet is a low carb diet which raises the level of ketone bodies in the blood. Tumor cells are inefficient at processing ketone bodies for energy. The diet is commonly used to help control epilepsy in children.
  • Paleo Diet: A diet that mimics the nutrition of early hunter-gatherers, and consists of all lean meats and fish, fresh fruits, and non starchy vegetables.
  • Water Fasts: A water-only fast of at least 3 days and preferably 5 days is recommended by Dr. Seyfried as a tool to reduce cancer risk and to lower your glucose – ketone index to 1.0. They are the standard fast protocol used in most of the research studies looking at cancer inhibition or therapy for cancer patients. Learn more from Damien’s experience with a 5-day-water-fast.

Tracking

Biomarkers

  • Blood Glucose: A measure of the level of glucose in the blood at one point in time. Blood glucose is a biomarker for increased cancer risk. Therapies target reduction of blood glucose levels to limit cancer cell growth. Blood glucose levels vary throughout the day. Ideally levels should be kept below 100 mg/dL and below ~85mg/dL for fasting glucose. Andrew maintains his around 60-70 mg/dL.
  • Glucose – Ketone Index (GKI): The ratio between the concentration of glucose in the blood to ketone bodies in the blood. The calculation is Glucose (mmol)/ Ketone (mmol). Dr. Seyfried created the index as a better way to assess metabolic status. Therapeutic efficacy is considered best with index values approaching 1.0 or below. Patients with chronic disease like cancer have index values of 50 or more. Check out the episode with Thomas Seyfried here.
  • Cholesterol-HDL and LDL: The cholesterol biomarkers include lipoproteins and triglycerides which are found in the blood. There are standard markers that all doctors and labs will run, and some newer specialist labs that are more specific and accurate. There are two main types of lipoproteins, HDL and LDL. We covered these markers extensively in episode 7.
  • Omega-6/Omega-3 Ratio: Many Western diets are deficient in Omega-3 fatty acids, such as DHA, and have excess Omega-6 fatty acids. A high Omega-6/Omega-3 ratio promotes inflammation and the pathogenesis of many diseases, including cancer, whereas increased levels of Omega-3 (a low Omega-6/Omega-3 ratio of about 1) exert suppressive effects.
  • hs-CRP (high sensitivity C-reactive Protein): a marker for systematic inflammation that can be measured over a period of time to determine effectiveness of treatments such as the ketogenic diet. Ideally CRP levels should be <1 mg/L. High levels are associated with chronic inflammation, which is common in cancer and other chronic diseases.

Lab Tests, Devices and Apps

  • Glucometer: is a device used to measure the level of glucose in the blood. Andrew and Damien use the Freestyle Optium Neo Glucose/ Ketone meter. Andrew’s ketones and blood glucose levels hover around 65 mg/dl, which puts him somewhere around 0.6-0.8 on the Seyfried index. Check out episode 16 to learn more about the Seyfried Index.
  • Omega Blood Count: Measures the levels of Omega-6 and Omega-3 fatty acids in your blood. (Note: This test is only purchasable via offline retail stores such as pharmacies and health shops in the UK – an alternative test that Andrew recommends that you can buy online in US or UK is OmegaQuant.com)
  • Complete Lipid Panel: measures total cholesterol, triglyceride levels, HDL and LDL cholesterol, which are all found in the blood. High blood lipoprotein levels are associated with cancer.
  • Complete Blood Count: is a blood panel that measures the levels of the different cells in the blood. Numbers of the different types of cells vary depending on disease status and even between people. The test is often used to monitor cancer progression and treatment.
  • Magnetic Resonance Imaging (MRI): MRI scans use pulses of magnetic energy to visualize internal organs and structures. It can be used on almost any area of the body and provides information on tumors, bleeding, injuries, blood vessels, or infection. MRIs were used to monitor Andrew’s brain tumor.
  • Positron Emission Tomography (PET) scan: A PET scan is a functional imaging technique used to image body processes. A PET scan can be used to identify cancer presence and severity. A radioactive tracer, fluorodeoxyglucose, is used to tag cancerous cells so they can be visualized. Check out episode 36: Quantifying Cancer and Reexamining Which Cancers May be Inhibited by Fasts with Gene Fine to learn more about PET scans and cancer.

Other People, Books & Resources

People

  • Dr. Thomas N. Seyfried, PhD: University of Illinois, Urbana-Champaign. Dr. Seyfried’s research focuses on the mechanisms by which metabolic therapies manage chronic diseases like cancer, epilepsy, and neurodegenerative lipid storage dysfunctions. Check out Dr. Seyfried’s episode on “Water Fasts as Potential Tactic to Beat Cancer.”
  • Dr. Dominic D’Agostino, PhD: Assistant Professor in the Department of Molecular Pharmacology and Physiology at the University of South Florida Morsani College of Medicine, and a Senior Research Scientist at the Institute of Human and Machine Cognition. His research focuses on developing and testing nutritional and metabolic therapies for neurological disorders and cancer. His own website is Keto Nutrition
  • Dr. Colin Champ, MD: A board-certified radiation oncologist and Assistant Professor at the University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center. He is also board-certified in integrative medicine by the American Board of Integrative and Holistic Medicine. His focus is the role and effect diet and nutrition may have in cancer treatment.
  • Dr. Adrienne Scheck, PhD: An Associate Professor of Neurobiology at Barrow Neurological Institute. Her expertise is in neuro-oncology and her lab has been involved in investigating the effects of the ketogenic diet on brain cancer.

Organizations

Books

Other

  • Ketogenic Diet Resource: Andrew says this website has answers to just about all the questions you could have.
  • Clinicaltrials.gov: This site can provide you with information on clinical trials that are currently being done relating to the ketogenic diet and different cancers.

Full Interview Transcript

Click Here to Read Transcript

[Damien Blenkinsopp]: Andrew, welcome. Thank you so much for coming on the show.

[Andrew Scarborough]: Thank you for having me.

(04:39) [Damien Blenkinsopp]: Yes. You have quite an amazing story that a lot of people are very interested in hearing about. It’s always good to get the context of how this happened to you, and where it all started? Could you go into the beginning, how you made the discovery that you had this condition? How did it start?

[Andrew Scarborough]: Yes. I was studying a Master’s in Nutritional Therapy at the University of Westminster. This is before my diagnosis, and I was suffering from migraine headaches for a few months. Until suddenly I had lost my speech in February 2013, this was nearly 3 years ago now.

What I didn’t know at the time, that was my first partial seizure, and just being a man I carried on.

[Damien Blenkinsopp]: So to describe that, did you have difficulty saying words, or what exactly happened?

[Andrew Scarborough]: I went very dizzy, and then lost my speech completely for about five to six minutes, I was with a friend and we laughed about it because it was a bit strange. Because it was quite a cold day, it was February, I was just thinking when you get cold and shivering. You just stutter and loose — you struggle to speak, but it was a lot more serious than that.

I didn’t do anything about it. A couple of months later, I was experiencing very similar symptoms with pins and needles in my tongue and throat. To cut a long story short, I went on the train after a heavy gym workout. And, I felt like I actually have a lot of energy after the workout, even though I really struggled through it.

I just felt completely wiped out, even though it wasn’t the most difficult workout. I suffered more seizure activity afterwards, when I was getting on the train, very busy train actually in London to go home. And I devastatingly had a crushing headache, like my head was in a nutcracker.

The pressure was constantly building up, then I suffered a quite a traumatic brain hemorrhage, and grand mal seizure on the train, which wasn’t too pleasant, and the whole train stopped. I was rushed to hospital. There was so much blood in my brain that they didn’t know what to say, what actually was the cause.

As I was in hospital not knowing — feeling very confused not able to speak or walk at this point. I was given a CT scan and all that was shown was this massive blood in my brain. It looked like an explosion had gone off. I was still experiencing horrific grand mal seizures at this time, so I had things explained to me, and at the time, they were going in one ear and out the other, because I was so out of it.

That was quite a tough time from my family, and my first diagnosis was an AVM, which is an arteriovenous malformation. Because it looks so poor on the scans — because CT scans are quite ambiguous. All we could really see was just a tangle of blood vessels and arteries.

[Damien Blenkinsopp]: So, they thought it was an artery that had grown the wrong way, or you’d been born . . .

[Andrew Scarborough]: They saw it as being an unusual tangle of mess.

[Damien Blenkinsopp]: Okay, the arteries growing in the wrong way.

[Andrew Scarborough]: Yeah. They said, “No it’s not probably like that, it’s probably a Cavernous Hemangioma instead, which is a tangle of abnormal blood vessels, not tangled in the arteries.” Which is better because it was a bit less life-threatening, but I was given a number of misdiagnoses before. Eventually, I had an operation, because I was continually having these grand mal seizures that were starting to cause me cognitive difficulties, and my speech was getting worse, so I wasn’t able to speak at all at this stage.

(09:11) [Damien Blenkinsopp]: So, going back to the hemorrhage is that a stroke, is it the same as a stroke, or is it slightly different?

[Andrew Scarborough]: It’s very similar to a stroke, it was caused by the pressure of the tumor. Pushing against the side of my skull, and also it was between the speech movement area invading into the motor cortex, that’s why I had lost my speech completely. I had an operation not long after, in May 2013, to try and remove as much as possible, if this very vascular and invasive tumor, which was slightly larger than a size of a golf ball — but invading into the motor cortex area of my brain.

They couldn’t remove all of it because otherwise I would be completely paralyzed or dead. Because I was misdiagnosed, I should’ve had the operation awake but I was unconscious during it. The neurosurgeons said after, “Yeah we probably.”

If he has to do it again, he would have it awake so he could potentially get more out of it, but he couldn’t remove all of it because of where it was in the brain.

[Damien Blenkinsopp]: That’s interesting, what is the difference between you being unconscious and awake, are they able to get some feedback from you?

[Andrew Scarborough]: Yeah. You’re kept awake so they can monitor your responses, while they’re poking around in there to see what can be removed and what can’t, and what healthy brain tissue and what isn’t. One of the main issues with the brain surgery is it’s very difficult to distinguish what’s healthy tissue, and what’s the tumor.

[Damien Blenkinsopp]: So, this is what date now that you’ve had your surgery, and you’ve been given a clear diagnosis?

[Andrew Scarborough]: This point now? It’s two and a half years coming up to three.

[Damien Blenkinsopp]: Okay, it was a few months after your hemorrhage.

[Andrew Scarborough]: That was two months after that I’ve had the operation because they didn’t know what to do with me. There was a lot of blood in my brain, and if you think about a malignant brain tumor, it’s not a great thing if you’ve got a constant blood supply there — and it’s not a fantastic thing if you’ve had this thing that looks like an explosion in the brain, scattering around the cells, and blood everywhere. So, it just makes it more migratory, I guess if that’s the word.

More likely to spread into other areas, which is not ideal. I then had my pathology, finally, and it showed that the tumor was indeed extremely vascular. And there was still some significant scar tissue, as well as some slight enhancement there, but we didn’t know exactly what that was.

[Andrew Scarborough]: So you’re saying, is that a scan?

[Andrew Scarborough]: Yes, sorry.

[Damien Blenkinsopp]: Okay.

[Andrew Scarborough]: — This was the MRI scan after my operation.

[Damien Blenkinsopp]: Is that a straight MRI?

[Andrew Scarborough]: Yes, this was just a standard MRI, but I also had my pathology report from the amount of tumor that was able to be removed, and that came back as an Anaplastic Astrocytoma, which is a Grade 3 Astrocytoma — affecting the glial cells, the astrocytes in the brain, and quite important components of the brain. It’s not a great thing to have, particularly a high grade glioma, which is what mine was.

Brain tumors come in different gradings, so it’s like we’re staging how — with the brain it’s Grades 3 and 4 are highly malignant, and Grades 1 and 2 are slow growing. Grade 1 is typically a solid mass, that you can — if you can operate it can be curable. Even Grade 2s are known to come back, and do grow, but grow at a slower rate. But Grade 3 and 4 are the fastest growing, they grow quite fast. Mine was showing to be heterogeneous, it had quite a few Grade 3 cells in there.

[Damien Blenkinsopp]: Does that mean that it has different types of cancer cells there when you say heterogeneous?

[Andrew Scarborough]: Well, yeah. It showed numerous mutations. It’s very difficult to explain, but it showed that it wouldn’t be chemosensitive, it was negative for IDH1 which is a predictor of longest survival and chemosensitivity. It was also unmethylated for MGMT, which is a repair gene.

And that’s also — it’s not a good thing that it was unmethylated, so it was one of these gene mutations that they say is good to have for longer term survival. I also had tumor suppressor genes missing which again, with these Grade 3 tumors the timescale for survival is variable until it comes back. But in my case, I had just about the worse. It’s scenario terms with the pathology.

(14:33) [Damien Blenkinsopp]: So, did they give you a rough timeline, I guess at that point?

[Andrew Scarborough]: They said it was difficult to tell because of my age and the location of the tumor. Typically in that scenario, it’s around two years when it comes back, and that’s one of the best cases in that particular scenario. It’s a strange type of tumor because in a different scenario with different kind of pathology it can be up to five years or sometimes seven that it comes back.

It’s quite variable, but in my case it didn’t look so good, and I still had some scar tissue where there was lots of — healthy blood supply that could’ve had any enhancement that was present at the time, not great.

[Damien Blenkinsopp]: Must have been a shock, must have been a pretty big shock for you when that one came about.

[Andrew Scarborough]: Yeah, most definitely. I was told that even though my tumor was not chemosensitive that I should probably go ahead and have chemotherapy and radiotherapy, which I did for a short period because I was quite ignorant about it. I thought that it would potentially give me a bit more time.

But then once I’d looked into it I realized that it was only going to cause further mutations for me personally, and I didn’t want to see that. I started to learn my carbohydrate intake and go on a restrictive ketogenic diet after I’ve learned about it prior to my diagnosis, when I was studying a Master’s in Nutritional Therapy.

(16:17) [Damien Blenkinsopp]: Right, what was your lifestyle like before this all happened to you, and how old were you when this happened?

[Andrew Scarborough]: 27, 28. It’s difficult now thinking back, because my birthday’s at September 1, so I was 27 going on 28. It was two and half years ago and I’m 30 now.

[Damien Blenkinsopp]: So roughly 28 or 27.

[Andrew Scarborough]: Yeah. I was on a diet that I thought was healthy, so I was on a low fat, high carb with a complex carb diet, all whole foods, so I thought I was doing a good job, no processed food. I actually had quite a low body fat percentage and quite a high lean body mass. I thought I was very healthy, and I was very athletic.

I’d worked as a personal trainer for a few years. I was studying my Master’s in Nutritional Therapy and it was a shock to me that what I was learning in my undergraduate degree in Nutrition was completely useless, because I was learning all these new information that contradicted all the older information, but I was just learning about it. I thought it was interesting but it seemed to go against most of what I’ve studied for the past few years before that.

I thought I was healthy.

(17:44) [Damien Blenkinsopp]: When they gave you the diagnosis for the cancer —people at home are probably thinking, “Well is this one of those — metastasized, so it would spread to other parts of the body, or does it tend to stay concentrated?”

[Andrew Scarborough]: Yeah, well primary brain tumors typically just spread into the brain, which isn’t great because your brain is very useful. Apart from medulloblastoma, which can spread down the spinal fluid and into the central nervous system. It’s the central nervous system that can spread down the spine, and other also spread into the brain.

Mine is an astrocytoma, it would’ve just spread into the brain, and there can also be secondary tumors that come about as a response in the brain. It’s not a great type of tumor to have.

[Damien Blenkinsopp]: No, tumors are good ones to have, but it’s one of the nastier ones.

[Andrew Scarborough]: It’s the step down from glioblastoma, which is the most common type of brain cancer.

[Damien Blenkinsopp]: That always the worst, is the Type 4. . .

[Andrew Scarborough]: Yeah. I thought with my approach, with my own treatment strategy — I thought I have a little bit more time to play around with things and adjust to strict ketogenic diet. If I had a glioblastoma I would’ve pushed things a lot quicker. I did push things quite a lot, and I go to extremes with this diet and this approach.

(19:19) [Damien Blenkinsopp]: Yeah. Did you consider any other options? You said you took a little bit of chemo and radiotherapy —radiation, and pretty quickly you stopped, was that a couple of months?

[Andrew Scarborough]: I stopped after four months because I was proposed to have it for up to two years which is a long time, and I said no after a few months experiencing how horrible that was, and still having these horrible seizures. I thought, “Well, I want my quality of life to be good at least.” I stopped it, because my scans were still showing this enhancement.

I thought, “Well, we don’t know if that’s necrotic tissue or scar tissue, or if it’s the tumor activity.” But I thought that, because my tumor looked so glowing on the scan that it was potentially very responsive to carbohydrate restriction. So you do get some cancers that seem to use more glucose for energy, and you get some that actually use glutamine more for energy than glucose.

More or less they use both for energy, but because mine was so glowing up — lighting up like a Christmas tree I’d like to say, it showed that it was potentially more efficacious to just really cut down on the glucose, and see what was going to happen from that.

[Damien Blenkinsopp]: So these were all MRIs they were giving you?

[Andrew Scarborough]: Yeah, and interestingly even though it’s different from other cancers where you get a PET scan, and you can still see the enhancement there, on an MRI, that was interesting to me.

[Damien Blenkinsopp]: Do you know why that was? We spoke recently to Gene Fine who is talking about the PET scan, in the use of cancers. Do you know why you were able to see it quite clearly on the MRI in your case? Is that specific to brain cancers?

[Andrew Scarborough]: Yeah, I think from what I’ve seen in the literature it is, I don’t know exactly why that is. I guess it’s just you’re able to see the metabolic activity even with — I think it’s an iodine solution, not the good kind, the more radioactive iodine that they give you, rather than the supplemental iodine which you can get which is actually really good for hormonal control and certain cancers.

[Damien Blenkinsopp]: So, they give you an IV of that when you go to your MRI, so they can see more?

[Andrew Scarborough]: Yeah, that’s the contrast injection that they give you. Sometimes with PET scans, they do give you the — that shows up quite nicely with the contrast dye. I view my scan straight after I have them, so it’s interesting to view that.

[Damien Blenkinsopp]: Yeah. So I think its gadolinium, is that the contrast dye you’re talking about?

[Andrew Scarborough]: That’s one of them, but I don’t have that one from my scan, I have something else. I can’t remember exactly what it’s called, but I’ve had a few different kinds of scans. I’ve also had MRI spectroscopy which is a fascinating type of scan.

It works with lights, allowing you to see the microenvironment in the brain. And we’re looking at how the ketogenic diet is changing that environment within those biomarkers within the brain as I’m progressing. That’s really interesting to see.

(23:02) [Damien Blenkinsopp]: Yeah, so great. What kind of scans have you been having over time, and how frequently? And how have you seen the ketogenic diet impact that over time?

[Andrew Scarborough]: Well initially I had a standard MRI scans which were quite boring. The cancer cells, [unclear 23:19] was that wasn’t the best for brain cancer, even though it’s world-renowned for other cancers. At that time, I had the enhancement and significant scar tissue, and I had Hemosiderin, which is a blood staining, that was quite a lot of that showing on my scan.

Since then I’ve had progression in a way that I’ve been given a statement saying that I have a response, that I’ve achieved complete remission, and the enhancement is no longer present. I’ve also had significant healing of the scar tissue, and I’ve had vast improvement of my symptoms. So, I am completely off medication for epilepsy which I was told by five different neurologists — that I’d be crazy to even reduce the medication, and I should increase it because my seizure activity was so bad.

I’ve just had a linear progression of improvement in that respect, so I’m completely off medication for the epilepsy, and for that, I do a number of things which controls my seizure activity. And if I forget to do those things I instantly have seizures — it’s like being on a tightrope you have to keep up with doing all these things, I haven’t had a seizure in a long time. When I start to stop doing these things, or I slip up even a little bit I get an aura, which is a warning for me that I’m going to have a seizure.

I have emergency measures to reverse that, which I’ve devised myself largely. It’s interesting.

(25:07) [Damien Blenkinsopp]: Yeah, sounds very interesting, we’ll jump into that. So the epilepsy is a symptom, it’s driven by the hemorrhage that you had and some damage?

[Andrew Scarborough]: Yeah, and also it can provide these for an indicator of where you are with cancer with the brain. Particular with the temporal lobe epilepsy which is a typical response from a temporal lobe brain tumor. My tumor was between the temporal and frontal lobe, so I have three different types of seizures, which is fun.

Monitoring my symptoms and my seizure triggers, and my theories on what would resolve the seizures, not just the ketogenic diet but things I could do with the ketogenic diet to optimize it specifically for brain cancer management. I was able to work out what worked out most effectively for me personally and relate that to the literature as well. I was then able to go to my neurologist and say, “Well what do you think of this?”. And then when they said, “I think it’s absolutely ridiculous, there’re no science behind it.”

I was able to show the science behind it and my results. And then they could say, “Well that’s very interesting.” I’ve had success that they didn’t expect.

(26:42) [Damien Blenkinsopp]: That’s great. So when were you given the sign off, when they say, “Okay your scans are clear.” Did they say it’s in remission or do they say it’s clear?

[Andrew Scarborough]: With that kind of cancer it’s never deemed as curable and I don’t think it can be curable, but personally I think you can achieve and maintain complete remission, and maintain that status indefinitely. From close observation of the animal studies, when they come off the diet after they’ve achieved complete remission, same kind of cancers, that it comes back almost instantaneously. The unpublished human studies I know the same thing, the same occurrence.

I am very keen to stay on this very strict ketogenic diet, and I actually feel quite good on this. Internally, when I have my blood tests which I have a myriad of different blood tests just to see how I’m doing in terms of my general health. A number of markers for potential tumor progression. Internally I am actually much healthier than before I had cancer, which I find that kind of funny.

(28:08)[Damien Blenkinsopp]: So what kind of improvements have you seen, what are the biomarkers that stand out for you, the test results that have come back, and been useful?

[Andrew Scarborough]: The first thing I looked at was my vitamin D. When I was first diagnosed it was in a severely deficient range, and now it’s in the suboptimal range. People would say it’s too high now, it’s 200, and previously was 20.

I also have my triglycerides tested, I have my cholesterol done, and all those fun markers. I have a full blood count, my white blood cell count was pretty good, I can’t remember the exact figures. It’s actually better than before I had cancer, which is not typical even years after you had cancer, immunity can be compromised, so your white blood cell count is typically quite low, and I found that quite interesting.

(29:13) [Damien Blenkinsopp]: It’s great to hear about that progression. Let’s talk about the actual things that you’ve done in terms of where you started in your ketogenic diet, because I know that people said they’re ketogenic. Have you been tracking your blood ketones and blood glucose since the start? And have you seen how that’s changed as you’ve changed your diet?

[Andrew Scarborough]: Yeah. The first thing I did I went out and got a glucometer to measure my blood ketones and blood glucose, and I was comparing that to book cancerous [unclear 29:45] disease, and the glucose-ketone index that Thomas Seyfried devised and came up with, with his colleagues. I had a number of conversations with him about it, just over email, and I was amazed that he got back to me.

I found it very interesting, I started with trying to do the fast, to start with, to get me in ketosis quite quickly. But I realized with epilepsy that’s not a great idea. I had quite a few bad breakthrough seizures attempting that.

I decided not to try it that way, I decided to do it gradually and over time I managed to get into the therapeutic range within just a few weeks.

[Damien Blenkinsopp]: When you say therapeutic range what is that?

[Andrew Scarborough]: I was using the glucose-ketone index, which you use a ratio where you divide your blood ketones by the blood glucose, and you come up with a number, and you try and make sure that number is — I think it’s above one. I don’t measure it anymore in that way because I’m consistently in very deep ketosis with very low blood glucose, so I don’t have to do it anymore.

[Damien Blenkinsopp]: Yeah, we actually covered the index with Thomas Seyfried before. I think it’s a glucose divided by ketones, and there’s a couple of other little things you have to do in there, it’s not super straight forward. I put a spreadsheet up for some people who are asking, when he was talking to us he said it was under one.

So I guess that’s what you are aiming for and you seem to be saying you’ve gone…

[Andrew Scarborough]: Yeah at that time, that’s what I was aiming for, but now I’m consistently above 3.5, so I don’t have to worry about that so much.

[Damien Blenkinsopp]: Oh, in the glucose-ketone index?

[Andrew Scarborough]: Well my ketones are typically above 3.5, and the blood glucose is typically hovering around 3.5 — at the very least one to one.

[Damien Blenkinsopp]: Okay, so for the people at home, because in the US the blood glucose measurement isn’t millimolar. So you’re talking around in between 54 and 72 mg/dl, like 3-4 millimolar. I’m guessing you’re hovering around with the Seyfried Index somewhere around 0.6, 0.8.

So it’s well below one that’s what you’re saying because your ketones are so high.

[Andrew Scarborough]: Yeah. In the evenings it goes sky high, well the ketones go sky high, the glucose goes really low.

[Damien Blenkinsopp]: Do you mean from 5 o’clock onwards — it’s interesting because I saw that in some of my fast and some of my earlier experiments also.

[Andrew Scarborough]: Yeah. I guess it’s a hormonal thing that happens, and also because there’s that period of time where I only have typically two meals a day, that’s the in-between period, I guess where it goes that high. So that’s where I’ve unintentionally fasted for that period of time even though the diet’s mimicking fasting itself.

(32:58) [Damien Blenkinsopp]: What is a typical day look? What are you doing now, what is your typical day look like? I’m assuming at the moment you’ve got the most extreme version of your own program for this, is that correct?

[Andrew Scarborough]: Yeah. Typically I have 85% of fat and 15% protein in my diet, but over the last few days, I’ve experimented with 90% fat and 10% protein, and negligible carbs. Typically on my 85% and 15% protocol that I follow which is very similar to the animal studies, and quite similar to very strict ketogenic diet for children with epilepsy.

I restrict my calorie intake to 1,600 calories — calorie restriction is extremely important for brain cancer management. You probably discussed that with other people I’m guessing. What’s also important I think is the other things that I’m doing.

Personally, I think it’s very important to make sure you have correct therapeutic ratio — I like to call it of omega 3 and 6 in the blood, and I have at home testing kit for that which I send off to the lab every few months.

[Damien Blenkinsopp]: Okay, that’s interesting, is that a dry spot test?

[Andrew Scarborough]: Yeah, it is. You just have to collect quite a significant amount of blood, and it gives you a report back just saying what you’re ratios of omega 3 and 6 are in your blood.

[Damien Blenkinsopp]: Which lab are you using for that?

[Andrew Scarborough]: Well, the testing kit is by — if you go on Omegasense.com it comes up. There’s a center called the NutriCentre in London, and I just get it from there. It’s a pretty good test, very accurate.

[Damien Blenkinsopp]: Have you seen that change? This is actually the current levels ratio, it’s not like it’s your diet of the day like we were talking about — the blood glucose and the ketones which are changing all the time. It’s a more stable marker which is evolving over time, so you’re choosing for a range you want to keep it within.

[Andrew Scarborough]: I’m just trying to get us close to 1:1 ratio as possible, and I’ve experimented with a 2:1 and a 3:1 ratio in favor of omega 3 which is quite hard to do, but it’s very interesting. We know that omega 3 fatty acids exhibit neuroprotective properties and can represent a potential treatment for a variety of neurodegenerative diseases. It’s really interesting, we know that they are shown to be cytotoxic to tumor cells themselves.

Ideally, an optimal ketogenic diet for brain cancer should have, in my view a better ratio than omega 3 and 6. I think the standard ketogenic diets that are applied to humans at the moment are way to high in omega 6 which is inflammatory. I struggled when I was doing a standard ketogenic diet because of that.

[Damien Blenkinsopp]: What are you taking in order to raise your omega 3 levels? What are you doing in diet specifically?

[Andrew Scarborough]: Well, initially I was eating lots of brains because they are the best source of omega 3 that you could get, and that’s high in DHA, and one of the main fatty acids in the brain is DHA. The brain is 70% fat, and the rest is mostly water, it just makes sense to me to have in my diet mostly fat and water, that was my main reason for doing that.

We also know that the fatty acid composition of gliomas differs from that founding non-malignant brain tissue quite significantly. The reduction of glioma DHA content is really interesting to view — we know that in gliomas which is what my tumor was, and what a glioblastoma is as well. We know that they have significantly less DHA in and around them.

If we can increase that — the literature shows that it can have a very potent effect, particularly when on a ketogenic diet, in shrinking these tumors.

[Damien Blenkinsopp]: That’s great so you’re still eating brains today, is this a large part of your diet? What types of brains?

[Andrew Scarborough]: I was eating lamb’s brains, but, unfortunately, I’ve stopped eating them because of the very, very low risk of Scrapie which is like a CJD, a Mad Cow disease but the lamb form. Even though it’s a very small risk, and you probably have that same risk if you were to eat any infected tissue of that same animal, I just thought it would be a good idea to avoid it, which is a shame because it’s my favorite type of food on the ketogenic diet.

It’s a perfect ketogenic food, but my second most therapeutic ketogenic food that I found is sweetbreads which is the pancreas and the thymus gland of — in my case I get them from lambs again. I’ve done an experiment which is on YouTube, on my YouTube channel, just look at Andrew Scarborough, and look at my sweetbreads experiment, I’m testing the myoglobin of sweetbreads and it comes up very high on the glucometer for ketones.

When I test my blood after my postprandial blood glucose and my blood ketones after eating, my ketones shoot up very high, and the blood glucose stays more or less the same as before I started eating.

[Damien Blenkinsopp]: That’s interesting. Out of interest, how much do sweetbreads cost? Are they relatively cheap or expensive?

[Andrew Scarborough]: Well I mostly get them for free, sometimes I have to pay a pound for them.

[Damien Blenkinsopp]: Okay, so they are very cheap.

[Andrew Scarborough]: Yeah, because no one wants them.

[Damien Blenkinsopp]: Right that’s what I was thinking.

[Andrew Scarborough]: They’re incredibly nutrient dense, rich in trace minerals such as zinc and selenium, and they’re rich in protein, and omega 3 fatty acids. Like the brain, and like all the fish — the great source of omega 3. They also raise ketones very high.

[Damien Blenkinsopp]: Yeah, that’s very surprising. I don’t know if you’ve heard new supplement ranges which I’ve been playing around with it, exogenous ketones.

[Andrew Scarborough]: Yeah, I take those as well. I take KetoForce, mostly when I’m trying to do exercise because exercise is a huge seizure trigger for me. So yeah I play around with that.

[Damien Blenkinsopp]: It sounds like the sweetbreads are more effective than the KetoForce, KetoCaNa and the other ones.

[Andrew Scarborough]: Yeah. I actually made a supplement, a sludgy juice that the sweetbreads come in because I have them completely fresh straight after the animals are being slaughtered, well not straight after, but not long after, because they have to do a number of things just to make sure they are safe to eat. I made a supplement out of that and tested it, and it was very interesting the results, but it tasted absolutely foul.

[Damien Blenkinsopp]: Is that a downside of sweetbreads, they’re really awesome except they taste bad.

[Andrew Scarborough]: Yeah.

[Damien Blenkinsopp]: Okay.

[Andrew Scarborough]: It’s not the best tasting, you have to boil them for a long period of time, but they’re very nutrient dense and very effective.

[Damien Blenkinsopp]: How do you eat them? Have you got a quick recipe for the people at home, and they’re like, “Oh like a great thing to try out.” But if it tastes horrible is there some way to mask it.

[Andrew Scarborough]: The best thing to do is boil them for about an hour, that’s actually a short period of time typically for sweetbreads. Normally, it’s a lot longer. And then if you add tarragon to it, it actually compliments the flavor, and it actually tastes a lot nicer.

That’s one of the things I do, it goes well with tarragon. I just consume every bit of the animal, and I don’t have any carbohydrate so that’s how I get around possible nutrient deficiencies from not having any fruits and vegetables. And it allows me to not count carbohydrates, so it’s a Paleo-Ketogenic diet.

[Damien Blenkinsopp]: It’s a pure meat diet, right? Basically a pure carnivore?

[Andrew Scarborough]: Meat and fish, and fat, and that’s it.

(41:37) [Damien Blenkinsopp]: I do know there’s a little bit of story behind the reason — first you were on a ketogenic diet and you were doing more of a straight forward one with the coconut oil, and all of these kinds of things, what happened?

[Andrew Scarborough]: I noticed that with certain people with certain types of brain injury, your brain can be more sensitive to salicylates which are found in coconut oil, various vegetables and fruits, especially ones that have seeds. I wasn’t able to have avocados or any of the staple ketogenic foods that you have. I also couldn’t have dairy because I had a reaction to that, and I wouldn’t advise dairy anyway on a ketogenic diet for anyone with cancer let alone — brain cancer, because of IGF-1.

It just doesn’t make sense to me that there’re so many ketogenic diets for cancer management that have been based around dairy.

[Damien Blenkinsopp]: Right. There’s a lot of cheese, cheese is pushed quite hard…

[Andrew Scarborough]: Yeah, loads of cheese and double cream, and it’s not efficacious for me, even though I’m astounded that they get any results with these trans fat. And they do get some results, that’s encouraging for me on my — what I would call a more beneficial and effective ketogenic diet for this circumstance.

(43:06)[Damien Blenkinsopp]: Could you explain quickly the IGF-1, because there are people at home that are not quite up to speed on the IGF-1 and the dairy aspect of it. What’s the problem there?

[Andrew Scarborough]: It activates insulin-like growth factor and that can cause cancer cells to proliferate faster. One of the ways I get around that — I used to eat lots of butter, but because it’s more insulinogenic and it has milk proteins and casein. What I do is I have Ghee, which is clarified butter so the milk solids and the casein have been removed, and it’s much less insulinogenic and I actually get a much better blood ketone readings as a result as well compared to butter.

I find that interesting in itself, and we also know that compared to coconut oil, Ghee has much more omega 3 fatty acids, and coconut oil only has omega 6. If you’re basing a ketogenic diet around — just loads and loads of coconut oil which is just omega 6. Even though coconut oil is fantastic for achieving ketosis, I would advise it in moderate amounts if you can tolerate it because it’s really good.

I would say that making sure that you have enough omega 3 by having more animal fats is more beneficial in terms of the overall nutrient profile than just consuming tons of coconut oil.

(44:44) [Damien Blenkinsopp]: Right. You mentioned you eat all the parts of the animal, I’m guessing you mean all of the organs…

[Andrew Scarborough]: Yep.

[Damien Blenkinsopp]: Do you consume what you would call a variety of these? Do you try to cycle them, and the widest spectrum possible? So what other organs are you eating, are you literally eating all of the different organs on a rotation each week?

[Andrew Scarborough]: Yeah. Literally everything but mostly heart, because it’s very very cheap, it would cost me 60 pence at a time, and you get quite a substantial portion— because lamb hearts are quite fatty, there’s a huge chunk of fat on them. I can just eat them as they are, and I don’t need to add extra fat.

It’s a fantastic source of iron, zinc, selenium, B vitamins, folate, and it’s the best food source of coenzyme Q10. It’s funny how people pay an absolute fortune to get pills that have a coenzyme Q10, and I just get the best source that you could possibly get for 60 pence at a time.

[Damien Blenkinsopp]: There’s a psychological barrier about the taste, and it’s just what we’ve become used to really. I’m definitely nowhere near as far as you — I’ve been eating more organ meats and I’m trying to push it up, I just made another order today from a new company actually. I’m slowly building my way up, and it’s a taste I’m struggling with, recipes I think help with that, learning how to cook and deal with the different tastes, and just getting used to them.

[Andrew Scarborough]: Yeah. I actually did quite well to start with brains, they’re actually the most tolerable in terms of tastes because they just taste like creamy eggs.

[Damien Blenkinsopp]: Oh, I would’ve never thought that.

[Andrew Scarborough]: They taste like creamy salty eggs.

[Damien Blenkinsopp]: You just don’t look at them while you’re eating them.

[Andrew Scarborough]: No. And a number of things I do are just for entertainment, to keep the diet interesting, to make sure I have enough trace minerals. That’s why I added insects to my diet quite early on because anytime you eat the whole animal you’re getting a variety of nutrients. When you eat insects you’re consuming the whole animal — it just makes sense that it would be a beneficial thing to have.

[Damien Blenkinsopp]: How do you consume those? Because I know there are cricket bars out there in the US, how are you consuming insects?

[Andrew Scarborough]: What I do is I get the fattiest insects that are ketogenic, I get waxworms and super worms. Mostly insects that reptiles eat, I get them from a pet shop that sells them for reptiles now, I used to get them online.

[Damien Blenkinsopp]: Oh, man. Okay did you used to buy from [check 47:31 – Bug Grow], was that the specific brand — was that the only place you bought from?

[Andrew Scarborough]: Yeah, I tried a few, I tried silk worm, pupa as well — a few different insects have different medicinal properties, they’re in Chinese medicine. They’re really interesting in terms of the properties that they have. But we largely ignore that, mainly what I do now is I get them from the pet shop.

I just stick them in the freezer to kill them, and then I’ll give them a gentle wash and eat them …

[Damien Blenkinsopp]: You just eat them straight?

[Andrew Scarborough]: The problem, if you get them online is that they’ve been dehydrated and cooked so much that the nutrient profile isn’t as good as if you have them fresh after they’ve been wiggling about. I also grind them up and make my own flour after I’ve frozen them. That makes quite nice breads, I make a zero carb ketogenic bread which is very useful. People actually think it’s proper bread…

[Damien Blenkinsopp]: You don’t tell them right?

[Andrew Scarborough]: I’ve actually offered it to people without telling them, and they quite like it, and then I tell them what it is, and they want to punch me. But it’s actually surprisingly quite nice.

[Damien Blenkinsopp]: A quick story here, I was in Mexico 15 years ago and I went to Taxco. Anyway you go up into the mountains, into this old city and they were selling plastic bags full of live insects for eating. It’s something that we used to do — we don’t do in modern society. . .

[Andrew Scarborough]: If you look at anthropology, and how we evolved, it’s largely ignored especially with these Paleo diets — we evolved primarily eating a variety of insects, and in quite a large amount. It suggested that the man would go out and go hunting — would only about a 20% success rate catching these larger animals.

The woman would be mainly collecting insects for food. Seasonally they would collect nuts and berries, but it’s a fact in anthropological studies that we did consume a large amount of insects before we moved closer to the coast to eat fish, and that’s how our brains developed more. It’s an ignored fact.

(50:16)[Damien Blenkinsopp]: It’s really interesting, we’ll get there. There’ll be people writing books — maybe you, about the missing parts of the Paleo diet, Paleo upgraded. You did mention that, when you exercise you’re taking exogenous ketones, because of your epilepsy, why is that?

[Andrew Scarborough]: When I exercise my blood ketones go down, lower than my individual therapeutic reading for seizure control for me personally. I have to do that, and I also have to take another experimental treatment of mine which is proved effective, which I learned from the literature on epilepsy. It’s a magnesium chloride solution that I mix into water, and I have a specific amount that reverses auras.

An aura for me is when you have all symptoms that you’re about to have a more serious type of seizure. An aura is a partial seizure in itself.

[Damien Blenkinsopp]: Okay. Maybe you would loose your words a little bit?

[Andrew Scarborough]: I would get pins and needles in my mouth and throat, and I would feel very dizzy, and faint. I have this horrible feeling like I’m going to collapse and have a tonic-clonic seizure. When I take the magnesium solution that I take three times a day, it actually reverses that aura, it is a potent preventative measure that I found to control seizure activity extremely effectively.

People with any kind of epilepsy, their levels of magnesium drop very low, and there are certain types of the day that magnesium is at its lowest, and typically that’s when seizure threshold is also at its lowest. If we can control that, we can control seizures very effectively. Also, on a ketogenic diet, supplemental magnesium — particularly magnesium chloride are found most effective.

It acts as a natural statin, it has a beneficial effect not only on cholesterol, in a natural way not like a typical statin where it’s actually destroying that process, it’s working with your body to do it naturally. I find that it also controls blood glucose — it regulates blood glucose very effectively too. I see it as my replacement for my medication that I was on previously, and the medication interestingly actually causes magnesium deficiency as well as calcium deficiency, deficiency in vitamin B-12 and vitamin D.

[Damien Blenkinsopp]: Which medication where you on?

[Andrew Scarborough]: I was on the maximum dose of Levetiracetam, which the brand name is Keppra and Sodium Valproate the brand name for that is, Epilim. I was both on those and the highest possible amount that you could be on. You can imagine the side effects of that, and the nutrient deficiencies that caused were just quite substantial.

When you’re withdrawing from those drugs you could actually get breakthrough seizures if you don’t address those nutritional deficiencies, and those seizures can actually cause SUDEP — it’s shorthand for sudden unexpected death in epilepsy. I was told consistently that I was highly likely to have that if I was to — not only come off my medication which is what I eventually did but reduced the medication. I have to reduce that medication for a period of almost two years.

I had to do it very slowly, and adding these nutrients and trace elements so that I was not having these breakthrough seizures that were life-threatening. It was a difficult balance, but I achieved it.

(54:50) [Damien Blenkinsopp]: It makes it easier when you titrate down slowly, but still you’ve been courageous in pushing for all of these things when you’re getting this pushback which is saying it’s really dangerous. Just in terms of the exercise, how do you bump your ketones up – is it the KetoForce?

[Andrew Scarborough]: Yeah. I consume that throughout my workout but I tend to mostly just do quite a light bodyweight exercise because I don’t want to stress my body too much. Thomas Seyfried himself recommends that cancer patients don’t push themselves too much with exercise, because it just puts too much stress on the body and on the brain. Mostly I just go for long walks, in an area with lots of oxygen, and I’m actually going to start having hyperbaric oxygen therapy fairly soon.

I’m in discussions with a number of facilities about that, and I’m going to start doing case studies on patients. I’m actually working part-time at the moment with Imperial College London in Charing Cross Hospital, to start-up clinical trials hopefully next year with brain cancer patients using — what I would call an optimal ketogenic diet.

We’re looking at magnesium for these brain cancer patients, we’re looking at the omega 3 and 6 ratios in the blood, we’re looking at C-reactive protein as a marker for a systemic inflammation, and we’re able to measure that for over a period of time to see how that changes while on a ketogenic diet.

[Damien Blenkinsopp]: With cancer is that typically high the hs-CRP because of the inflammation, or is that just a. . .

[Andrew Scarborough]: Yeah. It’s typically higher than normal, but one of the main ideas of measuring that is to have a marker that you can measure over time. I’m a huge fan of testing and I know that even if these things have no effect on cancer, they have an effect on epilepsy and blood glucose management.

We know that these are prognostic factors and they’re also effective at managing epilepsy which many brain cancer patients have as a result. I’m very keen to start doing this in patients more, and I’m working very hard to do that.

[Damien Blenkinsopp]: It’s very exciting that you’re able to work in hospitals. This is starting next year you said, potentially?

[Andrew Scarborough]: Yes. It would also be featured in, New Scientist magazine early next year. My story and my approach will be featured, and that’s very exciting as well because it’s getting the message out there and we can then have the actual data on humans which is missing. It would be — as I’ve said before it will be efficacious.

We’ll be able to not just translate the diets that have been used for children with epilepsy which I don’t believe …

[Damien Blenkinsopp]: As good, as they could be?

[Andrew Scarborough]: I don’t think that they’re translatable for brain cancer patients because I think it’s just very different. For example, when I was on the standard type of ketogenic diet, they did include those ingredients. I developed symptoms that were similar to Temporal Arteritis, where my temporal arteries became so inflamed that I nearly went blind and I was prescribed steroids for it.

But instead of taking the steroids what I did is I looked at how much omega 6 I was taking in my diet, and even though my blood glucose and ketones looked fantastic, and the ketogenic diet is anti-inflammatory in itself. I was having these inflammatory responses which were only controlled and reversed when I re-addressed the balance of omega 3 and 6 ratios. That in itself is quite powerful.

(59:15)[Damien Blenkinsopp]: Interesting. Where did your omega 6 ratio start? We read studies where the standard American diet, for example, is you can get ratios of 20:1, 10:1 — quite far off.

[Andrew Scarborough]: I’ve read up to 40:1.

[Damien Blenkinsopp]: Were you not so bad because you said you had a reasonable — you were trying to have a reasonably healthy diet before. I wouldn’t expect you’d have the sad numbers.

[Andrew Scarborough]: Yes, prior to initiation of the diet, I would say I was most likely about a 10:1 ratio. But, on the ketogenic diet, it was probably quite similar actually because it was including lots of nuts, coconut oil, coconut milk, coconut cream, lots of vegetables that were high in omega 6. I just thought it could be done better — then I transferred on to what I like to call a, fishogenic diet.

I was consuming a lot more fish, and I felt instantly much better and then as I cut down on the vegetables – cut them out completely. I had an instant response where I can’t even remember the last time I had a headache, even a mild headache.

(60:32)[Damien Blenkinsopp]: Great to hear. I’m conscious of your time I know that you’re really busy currently. But there’re a couple of things — I do want to make sure we cover before you go. We didn’t speak about glutamine and I know that an important part you mentioned up front that’s something you had to restrict quite sharply. But how did you do that practically?

[Andrew Scarborough]: Well, the first thing I did was limit protein quite significantly, and I did a number of therapeutic fasts, and it wasn’t until then that I actually saw the greatest response in my MRI scans, in terms of the complete remission. One of the other things that’s quite effective is with the magnesium it has an effect on that as well. I need to find the study for that, but I can send it to you if you’re interested in reading it.

Another thing that I’m actually looking into for the long term is Metformin, because Metformin on a ketogenic diet has quite a potent effect. It has a number of mechanisms which I can’t remember all of them off the top of my head, but that’s one thing that I’m playing around at the moment. It gets an effect on MAMP and a few other things.

It’s quite hard to explain, it’s quite technical.

[Damien Blenkinsopp]: In terms of the fast, you said that’s when you really started seeing the effects, so that would mirror — we had Thomas Seyfried on here and he was talking about the importance of the fast. How many days — was that a pure water fast? Was it a seven or five day fast?

[Andrew Scarborough]: It’s interesting because I think that — when these researchers are talking about fasting for brain cancer patients particularly if they have epilepsy, what they fail to note is that there’s ionic changes that are happening in the brain when you’re doing these fasts. A patient with epilepsy can’t — especially if they have brain cancer in my opinion shouldn’t just do water-only fast.

I think that they need to do what I call, a ’magnesium fast’. When I fast I have my magnesium water solution that I make up myself, and that prevents me from having breakthrough seizures while I’m fasting because I have such low body fat percentage. My longest fast has only been nine days. I aimed for 10 but I couldn’t do more, I’ve done that a few times but I need to have my magnesium-chloride solution or I instantly have breakthrough seizures, not the good kind either.

I found out the hard way initially, but now it’s just the easiest thing that I do.

[Damien Blenkinsopp]: You’re taking specifically magnesium chloride, is that because it’s a spray kind or is it actually the magnesium chloride specifically — there’s something about the chloride which is helping?

[Andrew Scarborough]: It has something to do with hydrochloric acid and how you digest it. I’d say it’s more bioavailable and it seems to me to be just in my personal experiences that it seems to get the brain very quickly. The literature doesn’t actually say that, but personally, I found that — even though there is not much in the literature about that.

[Damien Blenkinsopp]: Are you buying a specific brand? We’ve talked about using magnesium spray transdermally, but I’m just wondering if you’re using one of those sprays? How much you’re taking of it?

[Andrew Scarborough]: It’s designed to be primarily used transdermally this particular type, and I just get it from a health food shop, it’s mainly people who do sports who take it, which is interesting and funny. I typically take about five sprays three times a day. I can’t remember exactly how much that is, for 10 sprays it’s 150 milligrams of magnesium.

It’s variable depending on how mixed up the solution is — typically around 230 milligrams in a day that I would take. If you consider our water is too high in calcium and not high enough in magnesium. It’s addressing that imbalance that we have, we know that we should have at least a 2:1 ratio of magnesium to calcium, that addresses that imbalance.

We know that in the mornings after we wake up, magnesium levels are lowest. Primarily take it in the morning, after waking up in the afternoon, and before I go to bed.

[Damien Blenkinsopp]: Have you checked your RBC magnesium levels?

[Andrew Scarborough]: I haven’t because I don’t think it’s an accurate measure. I just go by how I feel, and sometimes — I see the epilepsy as a blessing because everything to do with epilepsy with brain cancer is typically very similar to what would work for treating the cancer. If something is working for the epilepsy, you’ve got a pretty good idea that it’s beneficial for the cancer, and most of the things that I actually research about what helps in terms of my epilepsy, experimentally and otherwise.

I found incidentally that it has quite potent anti-cancer benefits as well. It’s really interesting the relationship. It’s quite empowering as well. What I would call spectacular results because I still can’t believe I’m not having these horrific seizures all the time without medication. It’s quite empowering to know that it’s potentially having the same benefit on the cancer.

(1:06:44)[Damien Blenkinsopp]: Yes, it’s pretty amazing your journey. I don’t know if you’ve come into contact with other people with similar stories to tell — I know that some other people who had cancer, you said, unfortunately, they’ve passed away — the ones you were relating to. But if you come across any other people who have been experimenting like yourself.

[Andrew Scarborough]: Yeah. I actually have a group of friends now who I came into contact with just through seeking out long-term survivors, and I have a group of long-term survivor friends who had glioblastoma many years ago, and now have no sign of disease. I have a group of friends with various other cancers who are still here now. They’ve mostly done a drug cocktail treatment on themselves, which is very interesting.

Personally, I wanted to try and copy that drug cocktail treatment but do it in a natural way just using diet.

[Damien Blenkinsopp]: When you say drug cocktail, is that chemo or is that more Metformin and things like that?

[Andrew Scarborough]: It’s more Metformin and statins, and phosphates, and various other DCA, and other very interesting drugs. Personally, the only one I’m considering is Metformin, and potentially a few others, but mainly Metformin and Curcumin which I take in tablet form with DHA because they work synergistically. Curcumin actually increases uptake of DHA to the brain.

Because we know that around these tumors, or where the tumor was – DHA is very low. We know that if you have Curcumin and DHA that’s a powerful combination. Curcumin is cytotoxic to the cells. We know that DHA is, and is essential for brain functioning.

[Damien Blenkinsopp]: You really have built a whole lot of armory against this — it sounds like you’re doing really well. On the Curcumin – there’s many forms available on the market today, you’re taking one of the bioavailable forms…

[Andrew Scarborough]: Yeah, it has piperine in it as well.

[Damien Blenkinsopp]: Okay.

[Andrew Scarborough]: It’s a component of black pepper. I have a number of strategies that I use, and I’m constantly optimizing my metabolic formula.

(1:09:14)[Damien Blenkinsopp]: Do you feel constant improvement? I don’t know if there are any symptoms because it seems like you’ve got most of it under control. Do you think you’re going to be able to repair your body, do you feel any signs of that in terms of potentially resolving the epilepsy?

Do you think this is more likely something that you’re just going to optimize and maintain so that it never bothers you, so you never get the actual symptoms?

[Andrew Scarborough]: As my brain has been visibly healing at a very fast rate on these scans while I’ve been utilizing this protocol, I’ve also found my symptoms have improved with that quite substantially as well. I had facial paresthesia constantly all throughout the day, everyday, and a number of other debilitating symptoms I couldn’t even go out and walk a few steps. The fatigue was horrendous as well.

Being able to do what I am now and this non-stop activity, and just doing so many different things, and having my seizure activity controlled in such a great way that’s much better than before — even before when I was doing all these things I was still getting more activity. I haven’t actually done that many more things if I compare to even just a few months ago. Definitely improving in quite a dramatic way, despite having to keep up with all these things.

It’s getting easier to control, to the point where I have days now that I have no symptoms at all, but if I get overconfident and I forget to have my magnesium drink or do something that’s just out of my routine, I’d definitely have more seizure activity coming. Even though it’s not to the degree that I used to have.

[Damien Blenkinsopp]: I guess really say why you’re saying epilepsy is a bit of a bonus for you because it’s early warning detection system for you…

[Andrew Scarborough]: Yeah.

[Damien Blenkinsopp]: — Whereas cancers can creep up on you and you won’t know unless you’re watching the scans and even the scans aren’t showing a small progression. So right now you can still have a small amount of cancer left, but you can’t see it. It does seem like a pretty nice little tool, even though it’s not nice to have it, in the longer term it sounds like it’s a beneficial thing for you.

[Andrew Scarborough]: Yeah, I can see it as beneficial now, I couldn’t before but it definitely is.

(1:11:47) [Damien Blenkinsopp]: Well Andrew this has been an amazing — it’s very inspiring episode today. I can really say that — I’m totally going to take some of the things that you have been trying and start testing them out myself. I would like to ask you — where to look first if they would like to learn about this topic if they’re facing cancer or epilepsy?

Are there good books or presentations on the subject, the first places to go to, to start learning themselves about this?

[Andrew Scarborough]: I would thoroughly recommend the book, Cancer as a Metabolic Disease by Thomas Seyfried. I think that’s a great starting point. For anyone starting a ketogenic diet I would recommend, Keto Clarity, that’s a good resource to use. I would also go to www.ketogenic-diet-resource.com — that has answers to just about all the questions that you could have.

For help to a dietician, if you live in the UK I would recommend the charity, Matthew’s Friends. In the US, I would recommend the Charlie Foundation which is the sister organization of Matthew’s Friends in the UK. It has recently started to see — it’s mainly brain cancer patients that they see because they get around with that by saying that they’re treating the epilepsy.

I would also go on Clinicaltrials.gov to see what clinical trials are happening globally to do with the ketogenic diet and different cancers.

[Damien Blenkinsopp]: Right, so if they’ll just search for a ketogenic diet on there…

[Andrew Scarborough]: Yeah, if they search for ketogenic diet and cancer on Clinicaltrials.gov they can see all of the clinical trials that are currently happening in terms of ketogenic diets for different cancers. It’s very exciting that more and more of these are popping up, and I hope to — I have a meeting on Thursday to discuss having proper official ketogenic diets, using the right approach in this country, and that’s really exciting new development.

[Damien Blenkinsopp]: Is that with the government, NHS or some other body that’s going to help promote it.

[Andrew Scarborough]: This is in conjunction with brain tumor research, they’re one of the very few cancer charities that actually are going all at it with this metabolic research, and they’re doing that with Imperial College London. It’s a small charity that’s doing this, it’s quite incredible what they are able to do being such a small organization.

[Damien Blenkinsopp]: It’s great they’re starting to be – some grounds building from the bottom and up.

[Andrew Scarborough]: Yeah, and I’m going to start-up my own individual research with a few of my lecturers at my university because I want to get these things happening much faster than if it’s going through clinical trial protocol. I want to do this myself with lower grade gliomas, so that we can see a long-term response to try and shrink these tumors hopefully, because they are not as aggressive, but, they still are incurable.

I want to see what effect that we can have on them rather than having to go through all the standard treatment to go through clinical trials. I think that’s very exciting going forward.

(1:15:25) [Damien Blenkinsopp]: That sounds really exciting, and I’m sure anyone who – maybe affected would be very interested to know more. What are the best ways for people to connect with you and learn about you, and keep up with you when you’re doing these things, they can stay up to date on them. Are you on Twitter, you mentioned you had a YouTube channel?

[Andrew Scarborough]: Yeah, my Twitter name is @ascarbs, and I’m on Facebook if people want to add me on there, Andrew Scarborough. I also am working on a website at the moment which is www.metabolictherapy.co.uk, and that has a holding page at the moment, but it should be live shortly. I have a YouTube channel, Andrew Scarborough, and I have a blog, My Brain Cancer Story that’s the title of it.

People search for Andrew Scarborough and My Brain Cancer Story, they should find it.

[Damien Blenkinsopp]: Excellent. We’ll put all those links on the show notes of course also, make sure all of that is there. Is there anyone besides yourself you’d recommend to learn more about the stuff that you mentioned, Thomas Seyfried, is there anyone else that people should look to?

[Andrew Scarborough]: I would look at the research by Dominic D’Agostino, also I would recommend Dr. Colin Champ, I’ve had various discussions with him online which are very interesting. He’s very interested in my approach and he is very unique, he’s a radiation oncologist who is very supportive of this metabolic treatment. Very similar to my oncologist who – it’s quite a rare thing to find – but it’s very encouraging.

There’s Dr. Adrienne Scheck, who I’m having a meeting with on Thursday she’s coming overseas from the Barrow Neurological Institute in the US, and she’s the one that does the rodent studies using the ketogenic diet. It’s great to be able to discuss with her.

(1:17:29) [Damien Blenkinsopp]: Great, great, thank you for those. Some quick items on your – just a personal approach on what you would advise people to get started with – are you still tracking any biomarkers, on a routine basis?

[Andrew Scarborough]: Only occasionally with MRI spectroscopy but we’ve stopped doing that now just because it looks a bit boring and nothing’s really changing. It all looks really good, that’s why we’re not monitoring it anymore.

[Damien Blenkinsopp]: So maybe once in every six months or once a year?

[Andrew Scarborough]: Yeah, just to keep an eye on it, but everything that you would expect to be elevated but would be a bad thing isn’t showing up – it sounds like a good thing. It’s very new research, we don’t know too much about it, but it’s very promising for the future.

Because if we can see these things before they show on the scan, in terms of enhancement or just showing in an obvious way then it’s – that can only be good for the patient really. Then we can intervene in a non-toxic way.

[Damien Blenkinsopp]: So if you were to recommend one experiment, basically you’ve done many experiments to get to this point – they’re not proven recommendations by doctors and so on. What would you recommend that someone with brain cancer or potential other cancer – what would be the first thing they should try, the biggest payoff from all of the things that you’ve mentioned, what should their first step be?

[Andrew Scarborough]: The first step should definitely be reducing carbohydrate intake. The second step would be reducing protein intake to maintenance levels, and therapeutic fasts are very important. But the main thing, I would say is the omega 3 to 6 ratio, I believe that they should be an omega 3 to 6 index, just like with the glucose-ketone index, and they should work together, as a synergistic therapy.

Because you could even argue the ratio of omega 3 to 6 is even more important than the ketones. I would also say, the magnesium is very important with that too, those three things. Therapeutic ketosis, the omega 3 to 6 ratio and the magnesium I would say are very important for brain cancer patients.

[Damien Blenkinsopp]: Great, thank you, that’s some great takeaways for people at home. Andrew, I’ve got to say this has been really amazing interview – it’s amazing all of the different avenues you’ve run-down and all of these different aspects that you found to improve your situation. I know it’s going to be an inspiring story for the audience.

Thank you very much for being on the show.

[Andrew Scarborough]: No problem, we did cover a lot but we got there in the end.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

itunes quantified body

What You’ll Learn

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

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

Tim Omer, Hypo Diabetic Blog

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

Biohacking CGM Devices

Tools & Tactics

Interventions

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

Tech

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

Diet & Nutrition

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

Supplementation

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

Tracking

Biomarkers

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

Lab Tests, Devices and Apps

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

Other People, Books & Resources

Organizations

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

Full Interview Transcript

Click Here to Read Transcript

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Tim Omer]: Yes, that’s correct.

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

[Tim Omer]: Um-hum.

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

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

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

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

[Damien Blenkinsopp]: Yes.

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

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

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

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

[Damien Blenkinsopp]: Okay.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Tim Omer]: Yes.

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

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

[Damien Blenkinsopp]: Yeah, great.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Tim Omer]: That is correct.

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Right.

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

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

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

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

[Tim Omer]: High blood sugar levels.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: A bit more flexible.

[Tim Omer]: Exactly.

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

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

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

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

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

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

[Damien Blenkinsopp]: Right.

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

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

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

[Damien Blenkinsopp]: As with everything.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: How deep does it go?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Tim Omer]: Absolutely correct.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Tim Omer]: Definitely.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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A look at how to accurately quantify your cardiovascular fitness in order to optimize endurance sports or your cardiovascular health. Is VO2Max the gold standard? Are the metrics in the current “fitness trackers” useful for this goal?

In this episode we look at different ways to track fitness. Previously we have talked about VO2 max and Heart Rate Variability (HRV), along with the trackers (ex. Fitbits) which are used to quantify such physical activity markers.

This episode highlights difficulties and advances in translating physical activity data into meaningful information. We seek to understand what tracking fitness actually tells you about how fit you are? How is your fitness evolving due to training and other changes you are possibly making to your lifestyle? Ultimately, can we usefully quantify cardiovascular fitness yet?

Aiming to accurately capture this, our guest has developed his own approach to analyzing fitness and this is the main topic of this episode.

There is an opportunity.. to quantify what the fitness levels [are] that you can have. You can have feedback… from a health point of view, to see if exercise is having any impact.
– Marco Altini

Our guest is Marco Altini, a PhD Data scientist and entrepreneur working in the middle of the quantified self area. He has spent a lot of time working on heart rate, HRV, fitness, and physical activity analysis via wearable sensors.

Marco has published over 25 papers on the topic. He has a popular HRV4Training app, which is available on the iTunes store. I have used this app myself for over-training monitoring. So he has really done a lot of work in just this specific space.

If you’re in the quantified self community you probably know Marco already because a lot of his posts are widely circulated as these are normally rigorous and interesting. Today he heads up Data Science Activities at Bloom Technologies, where he is using technology and data to help women have healthier pregnancies. We also touch on that.

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

  • Marco’s research interests and the science behind personalized fitness (3:49).
  • Interpreting accelerometer, heart rate, or calorie meter device data (8:31).
  • Modeling physical activities and normalizing body data to accurately determine energy expenditure (9:54).
  • Using the VO2 max test as a marker for quantifying cardiorespiratory fitness (15:49).
  • The VO2 max test in tracking for performance or health benefits of exercise (19:24).
  • Interpreting VO2 max test results and the drawbacks of normalizing (25:13).
  • Using technology for normalizing results and improving accuracy of quantified fitness (25:54).
  • How to track individual fitness changes (30:23).
  • How Marco’s StayFit app works and distinguishing features from other similar apps (30:38).
  • Key points of analyzing energy expenditure as a fitness marker (33:44).
  • Because fitness improves over long periods, accurate tracking should aim at long – term benchmarks (37:14).
  • The complexity of the relationship between HRV and quantifying fitness levels (38:45).
  • How Marco tweaked his app to adapt measuring heart rate in overall fitness equations (42:28).
  • Normalizing fitness metrics and allowing for un-biased comparison between people (43:26).
  • The importance of context when considering what normalized fitness metrics actually mean for an individual’s results (44:12).
  • Comparing the advantages and limitations of tracking HRV vs. heart rate as fitness biomarkers (46:37).
  • Tracking HRV and fitness parameters in order to prevent pregnancy complications – a Bloom Technologies project (48:22) .
  • Discussing near-future market products and collaborations with major clinical research centers (51:54).
  • How to obtain more information on the topics of this episode (52:50).
  • How best to connect with our guest (53:36).
  • Marco’s recommendations for learning about cardio fitness (53:52).
  • Marco’s approach to tracking his body data on routine basis (54:34).
  • Caveats and useful insight into tracking HRV as a cardiovascular fitness parameter (55:45).
  • Marco’s number one recommendation for improving health, performance, and longevity (57:41).

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

Marco Altini (PhD), Bloom Technologies

Fitness Apps developed by Marco

  • HRV4Training: This app is useful for preventing over-training by measuring HRV and providing personalized feedback on your physical condition. Learn more on their website.
  • StayFit: This app from Marco is based on a novel method for quantifying cardio fitness, known as the Fitness Index developed by Marco Altini. Some of the research backing this up was just recently (after this interview took place) published in the Artificial Intelligence Journal here.
    Note: StayFit is not available on the Apple Store any longer. Marco has integrated the Fitness Index into his main app HRV4Training.

Tools & Tactics

Supplementation

  • Lypo-Spheric Vitamin CLiposome Encapsulated Vitamin C for Maximum Bioavailability; 0.2 fl oz. – 30 Packets | 1,000 mg Vitamin C Per Packet. Damien suggests taking this supplement in response to particularly low HRV test scores. As such, it can be used to prevent potential colds in a timely manner.

Tracking

Biomarkers

  • Maximal Oxygen Consumption (VO2 max): This marker reflects the ability of your circulatory-respiratory system to provide oxygen to your muscles for sustaining exercise. Research has confirmed that low cardiovascular fitness is associated with higher disease risk, including heart disease. A running VO2 max test is more indicative of cardiovascular fitness compared to a biking test which does not require you to carry your entire weight forward. We have previously discussed this marker in the context of wearable devices which estimate VO2 max with Troy Angrignon in Episode 24.
  • Heart Rate Variability (HRV): HRV is the measure of the change in the heart’s rhythm, measured as variations in para/sympathetic stimulation to the heart muscles. HRV is not an ideal marker for tracking fitness improvements because of day to day variability in results. Previously we covered HRV in the context of optimizing training in Episode 1 with Andrew Flatt, longevity in Episode 20 with Dr. Joon Yun. and using HRV to reduce stress in Episode 35 with Richard Gevirtz.
  • Heart Rate: The speed of the heartbeat – measured in beats per minute (bpm). Lower heart rate is associated with stronger cardiovascular ability. Marco recommends tracking resting or active heart rate for tracking overall cardiovascular fitness. Heart rate increases by 10-20 bpm during pregnancy – an important factor to consider when quantifying fitness or risk for pregnancy complications.

Lab Tests, Devices and Apps

  • Basis Peak: A watch functioning as a fitness and sleep tracker.
  • Moves: An exercise tracking app which can detect the type of exercise being performed.
  • FitBit: This company offers wearable devices which include cardiovascular fitness tracking. The FitBit Surge is a fitness watch that offers GPS tracking, heart rate monitor, all-day tracking, and sleep tracking. The FitBit Charge monitors physical activity and sleep quality.
  • Runkeeper: An app which tracks running, walking, cycling, workout, pace and weight and which also lets you manually enter the activity you are performing.
  • MyHeart Counts: A personalized tool that can help you measure daily activity, fitness, and cardiovascular risk developed at Stanford University.
  • Steps: A pedometer and activity tracker app with measures how far you walk and how many steps you take.

Other People, Books & Resources

Organizations

Full Interview Transcript

Click Here to Read Transcript
[03:49][Damien Blenkinsopp]: Now Marco, thanks so much for joining us on the show today.

[Marco Altini]: Thank you, my pleasure.

[Damien Blenkinsopp]: So I wanted to get first into a story about where you are at, and how you got into measuring fitness and looking at that specifically. What’s your background, and what’s your interest in this area?

[Marco Altini]: So basically I’ve been doing a PhD all around using wearable sensors to monitor energy expenditure. Well, let’s more say on their machine [04:12 check ‘machine landing’] aspects, so integrating multiple data streams [04:16 unclear] to accurate measurements of physical activity. Which is normally what we focus on is energy expenditure. So basically the intensity of the activity.

And taking a step back, let’s say most of the research in the field focused on the component of energy expenditure, which is due to physical activity, right? So body movement, because energy expenditure is actually composed of three elements. So we have diet induced thermogenesis, which is the energy expenditure we expend due to digestion, for example. And that’s something we consider as a sort of standard component, about 10 percent.

Then we have our basal metabolic rate, which is basically the calories we burn at rest. So if we take a bit of a simplistic view, this is what we would consume if we were not doing any activity. We lie in bed all day, and we still consume actually most of our energy which is due to this component. And then the third component is physical activity energy expenditure, which is the calories we burn when we move or exercise.

So by working a lot around this component and trying to estimate this more accurately using accelerometer and heart rate data, then I started focusing on aspects like personalization. Because when you use physiological data like heart rate to estimate energy expenditure you basically rely on parameters which are very well correlated with energy expenditure at the individual level. So for a single person, because of course heart rate is directly connected to oxygen uptake, which is also what we measure when we want to get the reference for energy expenditure.

At the same time there are individual differences between people so you need to try to understand how to model this difference between people in a way that your energy expenditure estimate coming from heart rate is accurate. And while working around this, basically you’ll get the work on what is the problem of basically normalizing heart rate between individuals, which is directly connected to fitness.

Because everyone tends to know that lower heart rate means better fitness. This is true at rest but even during exercise, which is, as a matter of fact, the principle behind, for example, sub-maximal fitness tests.

So, people are brought to the gym and they do an exercise to a certain intensity, and then based on what their heart rate you get, basically a surrogate of their fitness level. And all of that came back as something that you need to account for also when you measure energy expenditure because the whole reason behind normalization is that our metabolic response to exercise is not affected by fitness.

So just as an example to clear this up, if we think about, let’s say two individuals which are the same in terms of age, body weight, body mass, pretty much the same anthropometric characteristics. Then when they do a certain activity, they consume the same energy. So it’s the same kilocalories per minute because that’s mainly driven by the type of activity and the body mass.

However, these two individuals could be having a very different fitness level. So let’s say that one is very fit and while doing this activity their heart rate is very low, and the other one is very unfit and the heart rate is much higher. Then if you use heart rate to estimate the energy expenditure, you would be over or under estimating for one of these people.

[Damien Blenkinsopp]: So the one with the fast heart rate is over estimating?

[Marco Altini]: Yes. If you have a higher heart rate and then you don’t take into account that there is a difference in fitness, then you will assume this person is consuming more energy because the heart rate is higher with respect to the average, let’s say.

But that’s not the case because actually metabolism is not affected by fitness and there have been quite a few studies looking both at rest and during exercise, and given basal metabolic rate the component of energy expenditure.

[08:31] [Damien Blenkinsopp]: So what we’re saying is there are a lot of devices out there right now which are attempting to assess how many calories you’re burning in addition to the steps. So when you’re looking at that, actually, it’s a bit more complicated than the standards currently use, right?

[Marco Altini]: Yeah, exactly. Especially manufactures which are using, providing sensors with heart rate. They like to claim that just because there is heart rate they will be more accurate. And let’s say that using heart rate certainly is already a step forward compared to accelerometers because you can, with minimal effort already take into account energy expenditure for many activities which don’t involve body movement. Right?

For example with accelerometers we have limitations even just biking, because you might have the accelerometer in a place where it doesn’t move when you do these activities. So by using heart rate you can solve, partially, these issues. Because of course your heart rate will increase.

It doesn’t matter if you don’t move if you are doing exercise which is intense and of course requires your heart to pump more oxygen to your muscles. At the same time, due to the fact that the relation with heart rate is very personal, then you need to be able to make an extra step and model that if you want your system to be accurate during intense physical exercise.

[09:54][Damien Blenkinsopp]: Great. So in terms of the tech out there currently, would it be safe to say that a lot of it’s either overestimating or underestimating based on these restrictions or are there devices or apps out there which have tackled this problem?

[Marco Altini]: So I think what we are starting to see a bit more is, for example in the context of even just monitors using, for example movement or steps, some of them are introducing something more around context. Which is important because when you use accelerometers this first instance were probably already in the late 70s, for sure in the early 80s.

The researchers started to develop the first equations to link accelerometer output and movement to energy expenditure. however some of the imitations there are that, for example, the relation between the accelerometer output and energy expenditure changes depending on the activity. So if you are walking or running there’s a different relation. If you are at rest, of course, there is no movement, and all of that.

Recently we started seeing even commercial devices which are able to detect activities. For example, I think the Basis watch is detecting a couple of activities. Even apps like the Moves app can detect activities.

So in general I would assume even though they don’t disclose the methods they use to estimate energy expenditure, I would assume the ones that are able to detect the activity, then what they do they use this table, it’s called the compendium of physical activities. Basically it’s a table where you have almost all possible activities you can think of, and for each of them there is a value of energy expenditure normalized by body weight that people are supposed to be expending while doing that activity.

So these devices are probably mapping the activity they recognize to this level of energy expenditure. This method [11:53 unclear] like four or five years ago, to be much better than using accelerometers without context. But it’s even better than combining heart rate and accelerometers, if you don’t take extra measures like modeling context or normalizing heart rate.

So just putting together accelerometers and heart rate is not able to outperform methods where you use only accelerometer data. But with a bit more of machine learning to be able to recognize what activity is being performed, and then map that to an energy expenditure level.

[Damien Blenkinsopp]: Right. It sounds like if you have the heart rate, and you have the anthropometric data ñ what’s your weight and age and so on — and if you have the accelerometer data showing the movement, and you have an algorithm which categorizes what kind of activity it is based on the accelerometer, what’s that showing.

Which, I know isn’t always correct, based on my experience. So sometimes, for instance, I was wearing the Basis and it would say I’m on a bike where I never got on a bike. So it isn’t quite perfect yet, but we’ll assume that’s getting better. And maybe it’s already better.

Then what they’re doing is they’re looking at the activity and they’re saying, ìWell for this type of activity this heart rate is standard for this kind of fitness, and this heart rate is standard for this kind of fitness.î Is that how it works? Or is it a more basic thing right now?

[Marco Altini]: I think step zero would be simply to map it to known values, regardless of your heart rate. Let’s say, an app without heart rate, like the Moves app. So you just have the activity type, and you map that energy expenditure. Yes, like the average energy expenditure for that activity for a person.

So you are walking, and of course you can walk at many different speeds, so maybe that’s not known by the app. But still you would assume that for the average walking speed for the average person, you would consume this many calories. And when you detect walking you just map it to that and then based on other characteristics you input, like your body weight, you scale that by your body size, basically.

And then if you do a bit of more advanced work, let’s say, and you want to develop your own model for a specific activity. Let’s say you have the Basis, and at Basis they have a couple more physiological parameters together with movement, then it could develop there on regression models by collecting reference data.

So normally we do that with indirect calorie measure. So that’s a device which is a physical mouthpiece, where you breathe and it’s measuring O2 and CO2 counts. So, you compare the O2 and CO2 in body sheets, and that’s basically energy expenditure. So by having people performing different activities wearing the Basis watch, while you measure these reference calorie meter data, then you can see how all these valuables change depending on the activity.

And then you can map, let’s say heart rate changes and movement changes, the energy expenditure for a specific activity. I don’t know if they are doing that, because that would require to do all the tests with a calorie meter. I would assume, considering that they have all that physiological data that they did also this kind of development. While maybe all the other devices which are simply accelerometers, they might have simply used the values from the compendium of physical activity.

Basically the compendium of physical activity is what you use also when you, let’s say you use an app for tracking your workout, like Runkeeper, that let’s you also manually enter the activity. So maybe one day you didn’t have your phone and you want to enter it manually, then it will also estimate your energy expenditure. And that’s basically just a lookup from this table. And then it’s just scaled by your body size and for the amount of time you did the exercise.

[15:49][Damien Blenkinsopp]: Okay great. So what we’re talking about here is physical activity level, right? These are different version of it. There’s energy expenditure, and there’s Steps, which is currently what’s on the market. All these devices are looking at quantifying our physical activity level.

I guess the question is is that what people really want in terms of the end game? Because you’ve got this app out which is trying to get at something which you feel is a bit closer to the end goal of what you want to measure.

[Marco Altini]: Yes, so while I was doing research here on energy expenditure and the more I looked close to the whole personalization story, basically I was thinking what is a way to quantify not only what activity you do, right, the amount of exercise, the Steps, but also what the impact of this activity on your health, if there is any.

So this is a process in which we try to move from quantifying physical behavior to quantifying physical activity related health markers. And one of these markers, which is probably the most important one, is cardiorespiratory fitness.

[Damien Blenkinsopp]: That’s kind of well-known. That’s been the standard for a long time, in terms of quantifying fitness. But it’s only been done in laboratory contexts, as I understand it.

[Marco Altini]: Exactly. So far, as you say, it’s been really, I think 20 or 30 years that we know for sure that all these studies show that low level of cardiorespiratory fitness is indicative of higher risk of getting different sort of diseases. And even in general of just what is called [17:24 check – all cause mortitus], so you’re just most likely to live less if you have a low level of fitness.

And what is interesting here is that it is true even when it’s basically controlled by physical activity or body size. So it means that it doesn’t matter even if you are obese or if you have less levels of activity, but as long as your cardiorespiratory fitness is higher, you tend to be protected with respect of these other issues.

And indeed we know that. The research community at least is well aware of the importance of cardiorespiratory fitness, but in the general population I think we still lack awareness of this. Mainly because, as you say, there are basically no tools. So the way this is measured is in laboratory conditions. The reference is called VO2 max test.

And while VO2 is the oxygen volume and this is called VO2 max basically because the way the test works is that you get people either to do a treadmill test or a biking test in which they bike around until exhaustion. So you increase the intensity of the exercise every 5 minutes or so. And basically there is a point in which an individual is still able to keep it going at that intensity, just a bit before you drop. And then your oxygen sort of plateaus, and that’s your VO2 max.

[Damien Blenkinsopp]: What does that signify? Is that the moment when you switch to anaerobic, or what does it signify physiologically?

[Marco Altini]: Well, there is really the moment in which you cannot take any oxygen anymore. You need to stop. You cannot take any more intense activity, so that’s the max oxygen you can take.

[Damien Blenkinsopp]: Right. So it’s like your maximum ability to metabolize…

[Marco Altini]: It’s the ability of your circulatory-respiratory system to provide oxygen to your muscles for sustaining exercise.

[Damien Blenkinsopp]: Great, great.

[19:24] So showing that efficiency and when people are looking at that list, let’s talk a little bit about the decisions.

Typically when you have these meters when people are using these activity tracking meters for, whether it’s biking and running and so on, typically they want to improve something. They either want to lose weight, sometimes, or they want to improve their fitness. Or they want to improve their health.

So you’ve talked a little just there about cardiorespiratory fitness, we say that that has a protective effect against heart disease, which is one of the biggest killers. And also, if our cardio fitness is better, is more efficient, then we’re probably going to be able to run further, and run faster.

We’re going to be able to perform better, which is also something that we want. Whereas the Steps and the energy expenditure is hard to understand how that reflects either of those two cases, kind of like the use cases: health or better performance.

And with Steps and energy expenditure, you can tell that you’ve done more in terms of quantity but you can’t really tell if it’s going to give you more performance or you’ve actually got health benefits.

[Marco Altini]: Yeah.

So I think there is an opportunity in trying to quantify what is the fitness levels that you can have. You can have feedback for the ones that are interested just from a health point of view, to see if exercise is having any impact. You can have, actually even for professionals it would be, they do the VO2 max test and they know their actual cardiorespiratory fitness level, but still you cannot do that that often and it takes time.

[Damien Blenkinsopp]: It’s expensive, I think it’s like 300 dollars or something. Because I looked up, when I was in the US recently I was going to do one in San Diego and they had a gym that was actually providing it. Sometimes you can go to laboratory health centers or sometimes some advanced gyms will have the equipment to do this.

[Marco Altini]: Yes. I think there are a few limitations around the VO2 max test, apart from the cost.

Certainly you need some medical supervision and you need, again, the calorie meter to measure the oxygen. It requires a level of infrastructure. And apart from that, I think sometimes it’s even tricky to interpret the result. Because VO2 max is normally reported normalized by body weight. So you need to provide people with an easier way to understand their fitness level.

So you have these tables where basically different levels are divided by gender and by age. So if you are a person of a certain age and you’re male, and then you have your VO2 max result and it would soon [21:53 unclear]. Okay?

But however, these tables are not organized by body weight. Only by gender and age, since the results are normalized. However, the exercise type you use to acquire the VO2 max data is not part of those tables. And that has a great influence on oxygen consumption.

Because even just when you normally measure energy expenditure, even if you’re doing an activity which is weight bearing, you literally carry your weight around, like when you walk around, then the link between oxygen consumption and body weight is much stronger compared to when you just bike. Especially for stationary biking in the gym your energy expenditure is much more similar to the one of a person which is of different body size compared to you. While if you would be walking or running there would be a much bigger difference, because it’s a different impact of body weight.

Even, like in one of my recent studies through my PhD I measured VO2 max on a group of 60-70 people, and for example there I had a subject which was unfit; so all the parameters that we measured seemed to show that his fitness level was quite poor. He had very high heart rate at rest, very high heart rate during all exercises, he couldn’t finished some of the protocols. During the free living part also, his physical activity level was very low.

And the VO2 max test [23:25 unclear audio] it turned a result that he was the most unfit person as well. However, if we go to normalize the VO2 max, so we divide by body weight, this guy became the second most fit of the entire data set just because he’s very thin.

And that’s actually the result normalized by body weight, is what you normally get. Because it’s common practice to report it that way. But at that point, how do you interpret it?

[Damien Blenkinsopp]: So it’s a bit tricky to make it. So VO2 max is the gold standard in terms of measuring this.

[Marco Altini]: Exactly, but it has its own limitations. Yeah.

[Damien Blenkinsopp]: If someone was to go and take that test, what would you suggest they make sure, like to check they get a result that’s useful for them. Is there anything they can look out for or ask for?

[Marco Altini]: So in my opinion at this point, I tend to think that maybe a running test would be a better way to do it, because the relation with body weight is a bit more clear than compared to the biking test. However, normally a biking test is done also because of safety reasons. It’s a bit easier to do a maximal test on a bike; it’s a bit more of a controlled situation.

However, when you then go to normalize by body weight, the fact that your body weight doesn’t have the same impact because you’re biking and you’re not carrying your weight around, then you’re [going] to have this weird results like we did where the normalized VO2 max basically makes an unfit person the most fit person. That’s one of the reasons why I prefer to use VO2 max data non-normalized. So I use the value of oxygen consumption they reach, and that’s it. I don’t normalize it by body weight.

[25:13][Damien Blenkinsopp]: Okay. So, are there benchmarks for that? If they get a specific score back they can assume they’re relatively fit?

[Marco Altini]: Yeah, but the problem with that [25:22 unclear] is then you don’t have this [25:23 unclear] they’re not aware of, that there are these tables for matching it to something like, [25:29 unclear], like fitness is poor or average or good. These tables are all normalized by body weight. So that’s sort of a problem.

[Damien Blenkinsopp]: So what you’re saying is if you were to do this twice, you could get your relative fitness without normalization, right? If I took a test today and I took another test in 6 months.

[Marco Altini]: Exactly. You could calculate longitudinally. That’s no problem, maybe it’s more difficult to compare with other people.

[25:54][Damien Blenkinsopp]: Right. So is there any way we can get around the issue of normalization so that it works for us?

[Marco Altini]: There are some maximal tests which are not all bad.

So basically, some maximal tests, the way they work is that of course they want to predict VO2 max, and they rely on the fact that we know, as I was saying before, that the heart rate changes based on fitness.

So instead of doing a maximal test and measuring oxygen consumption until exhaustion, you do tests at a predefined speed. For example you run at a certain speed, you bike at a certain intensity, and then you measure your heart rate. And that goes into an equation that was developed before using referenced to VO2 max, which basically predicts your VO2 max based on your sub-maximal heart rate, and a bunch of other parameters like it measures your age and body weight and all these other parameters.

And the simplest of this test I actually did on [26:57 unclear audio] to measure heart rate, for example. I think something interesting is that we’re seeing now is also to bring awareness to people with [27:09-27:12 unclear audio] and we got this out from Stanford which is called MyHeart Counts, I believe.

So they measure, they ask you a lot of things and get a lot of reference points and your lifestyle and what you do. And then they track, using the phone, your activity. But since the study is all about cardiovascular health, they ask you to do this fitness test, which is one of the most commonly used because of its simplicity, I would say, where you just have to walk for six minutes.

And you have to time it, and you have to check the distance basically. So the longer the distance you go in six minutes, the more fit you are. And again, here you don’t need physiological data, and this might be probably a better test for people which are not in optimal health conditions.

But I think it’s good because the app is also targeting healthy users. So it’s a good indication that fitness should be of interest for the general population. And there is an effort here to raise awareness.

This being said, I think the potential of current technology is much higher. So you can do much better than that. And you can overcome also the limitations you had, because until now you had to either do a VO2 max test, which is expensive and has all the limitations you discussed, or even if you want to do a sub-maximal test you need still to go to a gym, you need to do an exercise at an exact intensity and then do your math to get what your VO2 max would be.

But right now, since we have phones with all sorts of sensors, and then we have wearable sensors and we have heart rate monitors and all of that, and then we have other reasons that can really automatically understand if you’re walking or running or what is your speed. You don’t even need a treadmill anymore to understand the context around the activity you’re doing.

So, some of the work we’ve been doing recently as part of our research is indeed to give people just a phone and a wearable sensor and don’t ask them to do any specific activity. They just live their life for two weeks while wearing the sensor.

And then all the other reasons we automatically understand: which location they are and what kind of activity they’re doing; if they’re walking, then then what is their speed. And then, basically you put your heart rate in a specific heart rate continuously. And by knowing that, since your heart rate still will be affected by your activity and your fitness, and you also rate the activity because you know the context. And then you can estimate the fitness level basically without requiring any test anymore.

So I think that’s quite interesting because you can finally get to something that is useable by everyone and doesn’t require any specific tests. And again, if you want to monitor them longitudinally, you don’t need to do a test every month. Because you just wear the sensor and it’s sort of being continuously updated just by wearing it.

[30:23][Damien Blenkinsopp]: So when you say longitudinally, that means testing ourselves in time, and seeing if we’ve got an improvement or decline over time.

[Marco Altini]: Exactly.

[Damien Blenkinsopp]: See if what we’re doing is actually working or not.

[Marco Altini]: Yeah. To see if there is basically changes at the individual level.

[30:38][Damien Blenkinsopp]: So this is basically what your StayFit app does?

[Marco Altini]: So basically with this app, I tried to make something where you don’t even need the sensor anymore. So [30:48 unclear] yields a research prototypes. Basically it’s a necklace, you wear it and there is, essentially you get full SG. And then we [30:56 unclear] heart rate. Then there is an accelerometer which we use for activity recognition and walking speed. Then with the phone we use GPS to understand location of that.

However, even if now you have some trackers that do heart rate like the latest FitBit or the Basis, we don’t have access as developers to all of their raw data that you would need to develop algorithms on top of these devices. So what I was thinking is, well of course if you have heart rate data during all of these activities, your fitness estimate can be more accurate.

But, at the same time heart rate at rest has been shown to be linked to fitness. So the lower heart rate at rest the higher fitness. This was the case in many studies, even interventions about physical activity trying to increase physical activity, often show that they were also able to reduce heart rate at rest.

So what I did with this app was to combine the two aspects. So using just the phone you can get activity level based on the step count, which is on the phone, and this data is transformed in energy expenditure, and your physical activity level. And then you combine heart rate. And again since you need context, the way the app is used is by taking a short test in the morning, similar to what the HRV apps do.

[Damien Blenkinsopp]: So, just to clarify, that means when you wake up in the morning you take a reading before you do anything else.

[Marco Altini]: Yeah, exactly. So that’s the easiest way to isolate context without having to go through much trouble. You just, you wake up, you take your test, that’s at least the moment we are the least affected by all other parameters and stressors.

And then you get your heart rate at rest, which goes in the system together with a bunch of other parameters to get you an estimate of fitness. And what the app is actually estimating is basically your sub-maximal heart rate, which is then transformed to a number between zero and 100.

But the whole point here is that since sub-maximal tests basically measure your heart rate at a certain intensity, because that’s what then goes into the formula to estimate the VO2 max. But if you consider that your age, and gender, and body weight will stay pretty much the same if you do two tests in a short period of time, then the actual measure of fitness is just sub-maximal heart rate.

So your VO2 max will be different only if your sub-maximal heart rate is different. So, here I removed the VO2 max step and estimate directly their sub-maximal heart rate. Which is a proxy to fitness, basically.

[33:44][Damien Blenkinsopp]: Great. And how have you seen this work out? Because you’ve been using this app for a while, and I guess you’ve gathered some user data now as well?

[Marco Altini]: Yeah, I did. Not that much, I must say. So I cannot really make any analysis yet, especially because I don’t have a reference point either.

It’s more of an individual tool that you might want to use to track your fitness, but I don’t know the VO2 max of the people using it. So maybe it’s something for future versions would be to try to add some other reference points so that I can do some further analysis like I did with HRV apps.

[Damien Blenkinsopp]: Great. So in your own case, how long have you been using the app, and have you noticed any differences in your fitness? For example, your running time, because I know you’re a runner and you developed it primary because of that interest.

So have you noticed or seen differences in your fitness level, in terms of your efficiency and your performance, and seen those correlate within the app, or has it not?

[Marco Altini]: So I used it for about two months. Something interesting I think is around the metrics that I used. So for example, I used the physical activity level as a measure of activity. So the physical activity level is a normalized version of energy expenditure.

So if you’re telling me your energy expenditure today is 4000 kilocalories, I can’t really infer anything, because if you’re severely obese that may be just your energy expenditure at rest when you do an activity, right. At the other end, if you’re a thin person and a small person, then it means that you’re being very active.

So, the total energy expenditure is difficult to interpret without knowing who are we talking about. And the physical activity level is the energy expenditure divided by the basal metabolic rate, so the component result is your metabolism at rest.

In this case you would get a value which is representative of how much you move. So if you don’t move at all it’s one, and if you move a lot it really doesn’t get much beyond two. So that’s a good indication of physical activity.

And it’s based on energy expenditure, which I think is important because sometimes, for example, I could see in my data is that I went for a trip and I did a lot of hiking, which is a lot of activity but at the same time it’s not really cardio activity or activity that I believe would improve my fitness level. It’s not like when you go running you know the intervals on track.

It’s movement but I would assume my fitness stayed more or less constant those days, right? And if I look at Steps, I see that I’ve been much more active than my average, because you walk all day and it’s much more steps than when you go training. So if my fitness was just based on my activity, I would get theoretically more fit when walking on holiday.

However, since we use energy expenditure, the normalized energy expenditure, the physical activity level, that was pretty much the same as it was when I was here and I was training. Because the activity when I train here is much more intense and consumes much more energy than when you’re just walking. So I think that’s a valuable point of using physical activity level as energy expenditure to track fitness instead of just movement or steps.

[37:14][Damien Blenkinsopp]: Okay. So for your hiking and so on, did you see your fitness level change in the app? Because it gives an index of one to 100.

[Marco Altini]: Yeah, exactly. So it stayed pretty much the same.

[Damien Blenkinsopp]: Right. So you saw basically that that case was shown in the results. Did you do anything where you saw your performance improve in your app and you correlated it to basically better times, or other things that seemed to be improving?

[Marco Altini]: For now I just saw it dropping, which is not good. So, yeah. I guess my condition is not ideal.

But I think it is interesting to track over long time. I tracked for two months, and I don’t race that often. Maybe for a professional person it would be more interesting because their life is training. For me it’s more of a hobby.

But I think looking after a year or so, then you can track it. You can look at data with respect to maybe the half marathons you did and the times you did, and then you get all these reference points, then it could be interesting.

So, you know I’ve been doing some work around HRV for example, and there it’s very valuable on a daily basis. Because there were points that you measure basically those points of this test, which can be training, and you get basically daily advice on how to train, and if your body is ready for another intense training. On the other hand this one tracks a parameter which changes much more slowly. Fitness doesn’t change fast.

[38:45][Damien Blenkinsopp]: Right.

So this one strikes me as it would be more useful to understand the effectiveness of your program. Like, the protocols you’re using to increase your fitness, for the longer term? So a lot of people will follow a set program for a while, especially if you’re a professional athlete you’ll have a set workout and timing and everything.

So you can kind of evaluate the performance of that, and if it’s increasing in the fitness one. But as you said, because a lot of people are using the HRV today. We’ve looked at the HRV in the context of stress, of longevity, and also of course the training in terms of recovery, which you just mentioned.

So, I could imagine that some people might look a HRV and be thinking, “Oh, my HRV is higher so I’m fitter.” Right? Because we’re also looking over time rather than the day to day, looking at the trend. Would you say that’s the case? Or do you think that’s not an accurate way to look at HRV?

[Marco Altini]: I think HRV is great as a day to day tool for recording and a proxy to personal activity and it is true that even at the [39:47 unclear – professional] level, let’s say athletes tend to have higher HRV, and really sedentary people tend to have lower HRV.

But, the link between HRV and fitness is, let’s say far from being clear. Meaning that there have been many studies, and some of them found some link between HRV and fitness, meaning higher HRV higher fitness, but many many studies found no relation there. Especially when doing interventions.

So, you know, longitudinal studies where you take people through a training program and then you measure their HRV at the beginning and at the end. And many of these studies found that heart rate changed and it was lower, but they couldn’t find any change in HRV, so it might be that there is a stronger genetic component there.

And also physiologically speaking, with heart rate you train, so you train your heart which then would be basically able to pump more blood. The volume changes, increases per beat, and that’s why your heart rate also decreases. The more fit you get, you train your heart muscle, which is going to be able to pump more blood and oxygen to the muscles, and then your heart rate as a consequence also decreases.

However this link, in terms of HRV, I don’t think it’s clear. So in general, even in this study I was mentioning before where I had all these people doing VO2 max test and doing also all the free living recordings, that was not a longevity study, so we just got a snapshot of these people. But there we can see clearly there is a very strong relation between heart rate and their fitness level.

And this was true for heart rate at rest, heart rate while they were sleeping, heart rate during activities. So you always see this relation which becomes stronger, of course, for more intense activities, but is there already at rest. While with HRV we couldn’t see any link with VO2 max, even at rest or sleeping or anything. So, I think in general HRV might not be the ideal tool to monitor fitness level.

[Damien Blenkinsopp]: In terms of cardio fitness?

[Marco Altini]: Yes, in terms of cardiorespiratory fitness. And basically as a proxy to VO2 max, heart rate at rest seems to be a much better parameter.

[42:28][Damien Blenkinsopp]: Right. If someone is just looking at their resting heart rate, that’s also a standard in athletics and so on, people could watch that. And then you’ve basically built up a bit more on that, through your fitness index.

[Marco Altini]: Yeah. So I basically used that one and the energy expenditure normalized value together with some adaptation due to age, so that basically the value doesn’t depend on age.

So if your other fitness index tries to predict is just maximal heart rate, basically it tries to predict, for example, what would be your heart rate if you were running, even though you’re now resting and you do these activities in your life. And then that your sub-maximal heart rate and your maximal heart rate are basically depending on your age as well, right. So it will decrease over time.

And so I applied some corrections there to allow people of different ages to get values that they could compare.

[43:26][Damien Blenkinsopp]: Right, right.

So it’s all about normalization, right? Getting normalization right so that you can use it, which would mean that you can compare it against different people. Right?

So just before this call, I was saying hey my score is 60, what it is it like? Does that mean I’m fit or not, compared to you, you’re 70 and I’m like, damn I’m less fit than you. Right? So that kind of context, which is literally what people like to do, right?

[Marco Altini]: Yeah, I think so.

[Damien Blenkinsopp]: People want to be a bit competitive about this, and you know it’s part of team sports and so on. And people are into this stuff.

[Marco Altini]: Exactly. Because for every time if you look at VO2 max, for example, then it’s basically impossible to compare unless you have a person who is basically your age, your gender, and your body weight and possibly also your body fat. Then you can compare. Because otherwise there are too many parameters there.

[44:12][Damien Blenkinsopp]: So I wanted to use this as bit of a demonstration on what’s important in a biomarker if it’s going to be useful to us.

So one of the things you brought up, which is key here, is normalization so we can compare it to other people. There are different devices out there, but sometimes we can’t compare against other people effectively, because as you say it hasn’t been normalized. That’s one part.

What other things do you feel are important? Like if you just think of a biomarker, what would you be looking for to make it effective and useful to make decisions around?

[Marco Altini]: I think in general, it’s important that we always contextualize these things and this whole thing goes together with normalization. Normalizing parameters means also understanding in which context you were measured. So that’s something important.

Try to know everything around it and take care of taking measurements in isomeric conditions, because otherwise it’s easy to make the wrong conclusions just because some other factors are influencing what we are measuring.

[Damien Blenkinsopp]: It’s important to get some benchmarks.

[Marco Altini]: Yeah.

[Damien Blenkinsopp]: So we can understand the implications for our goals. So I’d like to see in the future if you have more data with your fitness app to see if you can compare the range of readings for different users, and things like that.

[Marco Altini]: I think in general, when we make these tools and we release them, for me it’s very interesting to look and take it step by step.

First you try to look at some relations that have been proven already in research, for example with heart rate variability apps, I let the people give me some reference points. So basically they can annotate not only when they train, what’s the intensity of their training and in the next lessons they will be able to add some more text around sleep, and all of that.

And that’s interesting because afterward because then, again, you can put the whole heart rate variability story in context with respect to how they trained and all of that. And then you know from some studies in literature, on maybe 100 people, that there is an important relation between HRV and training.

But then you can just scale that at the level of 1000 people and you start to find all of these relations. And then you can start exploring maybe a new one. So I think that’s quite powerful.

[46:37][Damien Blenkinsopp]: So another thing about this measure and measures that tend to be more useful is its stability. We’ve often come back to this in our podcast in different episodes, with different markers, whether it’s laboratory testing or whatever.

If a marker is moving around a lot ñ HRV is kind of moving around a lot, which can make it more difficult to use sometimes.

So, often you’ll see a pattern where one day it’s up and a little bit down the next day. It’s always kind of a jagged reading, so you have to kind of take an average of the last three days and things like that to get a stable reading on where your recovery is. Of course where there are the extremes and it really drops, then you’re like, “Okay this is a recovery day.”

But the thing about these biomarkers in general is it does help if they’re more stable and they’re moving along more steadily over time so you can make decisions on a more even basis. Because we’re not making decisions hour by hour in these cases where it’s fitness and health. It’s more like what am I doing this week versus next week, and so on.

[Marco Altini]: Yeah, the two cases also something with HRV, I think it’s very powerful because of that, because it can react that way to some stressors. But at the same time, it makes it very difficult to interpret sometimes. Because even consecutive tests can have very different values.

So that makes it quite difficult sometimes. But yeah. With heart rate, that’s a bit less the case. So indeed that’s one other reason why heart rate at rest is better for the cardiorespiratory fitness estimate, because it’s more of a stable parameter like cardiorespiratory fitness is. While HRV is very good as a parameter which you can use to understand how you’re reacting to certain stressors.

[48:22][Damien Blenkinsopp]: Yeah, that’s great. So different contexts. So I also know that you’re now working with data to help mothers with pregnancy.

[Marco Altini]: True.

[Damien Blenkinsopp]: So I wanted to touch on that and see what you’re doing there, because it’s an interesting area.

[Marco Altini]: Yeah. Well basically I’m working at the start-up at Bloom Technologies, where we are working on different aspects and the goal is to better understand pregnancy complications, by monitoring longitudinally different physiological parameters.

Since many of these complications, like for example pre-term birth, or gestational hypertension or gestational diabetes, are poorly understand, let’s say. And even in the developed world, even in the US, the percentage of pre-term birth is more than 11 percent and the whole medical community is, let’s say a bit struggling around how to try to bring this epidemic down.

So what we are doing there is to try to add some parameters to what we are measuring today. For example, uterine activity or even heart rate variability over time. And all we discuss now basically becomes important again because during pregnancy there are even more challenges because all these parameters change also because of pregnancy.

For example, heart rate increases by, let’s say, 10-20 beats during pregnancy because of course their heart needs to work harder because it needs to provide also for the fetus while it’s growing. So you have the additional context of knowing at which stage you are of the pregnancy, and trying to understand how all these parameters change.

So what we hope there is to be able to use this physiological data contextualized longitudinally over time, and try to get a better understanding of what is the impact, for example, of uterine activity and physiological stress, physical activity in all of these complications together with the variables which are already known to be affecting pregnancy.

[Damien Blenkinsopp]: So it strikes me this could be pretty interesting, because you might be able to alert someone to an issue over pregnancy. What kind of outcomes do you expect once this work is completed? What kind of goals would you have?

[Marco Altini]: So I think the first part would be to try to understand better what parameters are influencing some of these complications. And then for some of them there are interventions.

If you consider hypertension or diabetes, you can reduce activity or [51:02 unclear] and you need to know to be a bit more under control. Others are more complicated, for example pre-term birth; there is really no intervention there.

So still by understanding better what are the pathways there, and what is causing the issue, you could then after the second step try to see what is possible to do in terms of, for example, behavioral changes.

It is, for example, known that high stress has an influence on some pre-term birth rate, and on pregnancy outcomes in general. So if you can measure physiological stress, you could also have an intervention around some mediation practice or whatever it is that could lower stress, and then try to reduce complications around pregnancy with these kind of feedback loops.

[51:54][Damien Blenkinsopp]: Great, great, thank you.

I’m guessing it’s quite a ways off in terms of bringing something to market or things like that.

[Marco Altini]: Yeah we hope to have a product by the end of the year, around contractions. But again, let’s say more limited but at the same time that would allow us to collect data and work with hospitals and doctors to start to explore a bit more around this using also the power of having consumers with the device.

And consumer inserted data and data sets can grow much faster than with regular clinical studies while still providing clinically accurate data. So, we’ll be looking into that with some collaborations also here, for example with UCSF in San Francisco where they have a pre-term birth initiative that we are collaborating with.

[Damien Blenkinsopp]: Great, great thanks.

[52:50] So, where should someone look first to learn more about the topics we’ve talked about, VO2 max, or are there any presentations on cardio fitness or anything like that you know of, or maybe a book, that if someone was interested in this to get a better idea of this they could look up?

[Marco Altini]: There are some good resources, maybe I’ll just provide you some links. More on the physiological aspects. I think in general I’m happy to see the whole thing moving forward with this Stanford study.

So even just the website of this study, the MyHeart Counts study would be a good starting point to understand better these things. Because indeed we target as well healthy people. So giving a look at this up, it would be a good starting point for your cardiovascular health.

[Damien Blenkinsopp]: Great, we’ll put those in the show notes then.

[53:36] What are the best ways for people to connect with you, and to learn more about what you’re up to?

[Marco Altini]: I would say through my website. I try to keep it updated. Normally I’m very active. So if they just drop me a line or an email or something, I’ll get back to them for sure.

[53:52][Damien Blenkinsopp]: Is there anyone besides yourself you’d recommend to learn about cardio fitness and these area we’ve been talking about today?

[Marco Altini]: From the HRV stories, for sure all the people you had already on your show are great experts. For the fitness, I would need to think about it, because the research I’m doing, being a researcher now it means it’s going to take some time before it’s out. So I’m sure there are a couple of other groups that are doing great work there, but I haven’t seen much yet.

[Damien Blenkinsopp]: Okay. Well we’ll be linking to your stuff in the show notes of course, so people can check that out.

[Marco Altini]: Maybe I’ll think of something and I’ll get back to you on that.

[Damien Blenkinsopp]: Great, thanks.

[54:34] I’d also like to learn a bit more about your personal approach to body data. Do you track any metrics or biomarkers for your body on a routine basis, whether they be labs, and so on.

I know currently you’re using your own fitness index, correct? What are you doing in your life, or what have you been doing over the last year?

[Marco Altini]: So basically I’ve much of a maker approach. I use this stuff all the time when I make it because I want to try things first and it helps me understand the limitations a lot and where things can improve. So I’ve been using HRV for a long [time] because I have these apps around HRV and now I’m using also these ones about fitness.

In general, the only things I really track are my trainings. So I like to track that and see improvements there. And that’s why I also work around these variables which are connected to activity and fitness, and try to basically close the feedback loop, like with HRV, that gives you advice, and fitness that tries to quantify what your basically current level, what performance can you achieve.

[Damien Blenkinsopp]: Great, great thanks.

[55:45] Have you got any insights, like from the data you’ve collected, have you got an insights about your biology? Have you made any changes to behavior, or taken some kind of actions?

[Marco Altini]: No. I haven’t yet. It’s not that I didn’t get any insights, but I think it’s important to track first for very long periods. Meaning a year at least before you can start making changes.

Because so many other parameters affect our physiology and performance, especially if I consider training there are months where everything looks the same. Like maybe I haven’t traveled much, and I kept my diet the same, and my stress at work is pretty much the same. And I think I haven’t over-trained, but still there are some weeks where you don’t perform very well.

So it would be sometimes easy to make the wrong conclusions if you tend to make too many changes. So I think it’s good to track for very long periods, even HRV, to get all the values you see. And then you look afterward how your training had an impact and all of that. And then you try to make adjustments.

Maybe around HRV I am making adjustments, like I tend to follow now what I see there. You find something very interesting things, like sometimes you can spot you are sick before you actually realize you are sick. You do your test in bed because your HRV is like…hugely affected by that, for example like even just a fever or something.

Maybe in the morning you don’t just feel particularly well, but it seems just a regular day. And then your HRV is terribly low, and then the day after you’re sick. And that’s quite interesting to see.

[Damien Blenkinsopp]: I definitely rely on it. I’ve seen that a number of times. If it really drops, then I’m like, “Uh oh.î I’m going to get some vitamins, liposomal vitamin C and stuff like that to try and void the crash the next day. Or minimize it a bit. So I think it is pretty useful like that.

[Marco Altini]: Yeah, it’s quite interesting.

[57:41][Damien Blenkinsopp]: Okay, so what would you number one recommendation for someone trying to use data to make better decisions about their health or performance or longevity?

[Marco Altini]: Be consistent. Don’t expect short term miracles but keep doing it, keep tracking. Try to understand at your personal individual level what is affecting these variables and then slowly start to make changes and bring to mind how these changes affect the rest. Let it be, I don’t know, performance or whatever variable that matters to you.

[Damien Blenkinsopp]: Yeah, I think you make a great point because as you were saying, there are so many different variables which we can’t keep track of. Especially in our busy lifestyles today. Whether it’s travel, a different location, different food, different sleep conditions, or maybe just different supplements and other things if we’re experimenting things. There are a lot of different variables that can influence it. So that makes a lot of sense.

So Marco thank you so much for your time today. It’s been a great chat.

[Marco Altini]: Thank you Damien.

Leave a Reply

Heart disease affects 50% of the U.S. population in their lifetime. Learn how to accurately quantify your personal heart disease status and risk, and if necessary, take clear actions to reduce that risk by eliminating plaque in the arteries.

This episode presents an in depth look at heart disease because this is one of the most likely things to shorten our lifespan. We focus on the key topic of quantifying your real heart disease risk.

One in three deaths in the United States are caused by cardiovascular disease. Even worse, one of out two Americans will suffer some form of heart issues, meaning that one half of the population is at risk. The total costs for dealing with heart disease are larger than any other disease by far, estimated at 650 billion dollars in the US.

While heart disease is a big risk which is worthwhile taking a look at, it is not a big risk for everyone. For some people there are other health risks they should look at and assess. Thus it is important to know if heart disease is something you personally need to act on – in a proactive way which reduces the risk for it. Are there specific factors you need to be concerned about?

The way to approach this issue is by quantifying our risk for cardiovascular disease. Naturally, understanding of risk goes beyond the typical cholesterol numbers. We discussed some of the problems with cholesterol biomarkers in Episode Seven with Jimmy Moore which is a useful preamble to this episode. In this show we go deeper into details, looking at metrics which give you a real accurate view of your heart disease status and risk.

There is a way to be very accurate, both [by] blood work and by imaging. To really nail down your personal risk of experiencing the number one killer in the Western world, heart disease.

– Dr. Joel Kahn


DrJoelKahnNew
Dr. Joel Kahn
University Professor & Heart Prevention Doctor

Joel Kahn has focused his career on preempting cardiovascular and heart disease. His goal is to reduce risks as well as to avoid surgery and cholesterol – lowering drugs. He takes a proactive approach by using information and interventions to ensure that heart disease does not become a problem in patients.

He is a clinical professor of medicine at Wayne State University School of Medicine, and Director of Cardiac Wellness, Michigan Healthcare Professionals P.C. He is a Summa Cum Laude graduate of the University of Michigan School of Medicine and author of two books, The Whole Heart Solution and Dead Execs Don’t Get Bonuses: The Ultimate Guide to Survive Your Career With a Healthy Heart.

Joel has also recently set up the Kahn Center for Cardiac Longevity. In their institution they emphasize early imaging of arteries and extensive laboratory evaluation for the correctable root causes of heart disease. So Joel and his clinic have a very quantified and longevity focused approach to this whole area, which is great to see.

I think this is an episode everyone should listen to, because absolutely everyone is going to have to deal with these issues in their life. Inevitably everyone comes into contact with heart disease, whether it be through themselves, their family, or their friends.


The episode highlights, biomarkers, and links to the apps, devices and labs and everything else mentioned are below. I’d love to hear what you think of the episode – and if it has helped you – let me know in the comments!

itunes quantified body

What You’ll Learn

  • What led Dr. Kahn to choose a career in cardiology (4:30) .
  • A holistic view of the true causes behind developing heart disease (6:17) .
  • The causes behind heart attacks and strokes are tightly related and how both conditions are preventable (9:05).
  • How the condition of the endothelium (inner wall of blood vessels) and mitochondria affect cardiac health (10:26).
  • The biomarkers Dr. Kahn uses in his practice and ways to personalize medical and lifestyle advice (15:08).
  • Infrared Sauna treatment is proven to have positive effects on cardiovascular disease treatment (23:27).
  • Using chelation in treating disease to lower toxins levels – including heavy metals (26:03).
  • Early detection of coronary artery plaque using a CAT-scan for coronary artery calcium (30:47).
  • Because CAT scans are radioactive an ultrasound-based carotid IMT test is used for following disease progression (37:09).
  • How to get informed and decide whether to get a coronary calcium test (39:24).
  • Understanding genetic testing results in conjunction with imaging of arteries (41:04).
  • The Liposcience NMR technology platform offers the most accurate measurement of LDL cholesterol particle density (43:35).
  • Familial genetics and lifestyle when tracking lipoprotein levels as a biomarker for cardiovascular disease risk (44:07).
  • Using C- Reactive Protein (CRP) as a biomarker for cardiovascular disease risk (46:36).
  • Measuring blood vessels inflammation as part of a comprehensive heart health assessment (48:04).
  • Diet recommendations for preventing heart disease and examples of successful programs (50:00).
  • Replacing dairy products with healthy hydration is beneficial but strict ketogenic diets exhibit negative health effects by causing adrenal stress (54:19).
  • Why dark coffee is generally a health drink and the caveats to consider when consuming coffee (59:00).
  • Scientific and medical practice sources for discovering topics in this episode (1:01:32).
  • The biomarkers Dr. Joel Kahn tracks on a routine basis to monitor and improve his health, longevity and performance (1:03:50).

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

 Dr. Joel Kahn & The Kahn Center for Cardiac Longevity

Books by Dr. Kahn

Tools & Tactics

Interventions

  • Far Infrared Sauna: Sauna treatment improves heart health, especially in patients who have suffered heart attacks or have blocked arteries. As Dr. Kahn claims, repeated treatment consisting of 15 minutes infra-red sauna followed by 30 min rest helps the body sweat-out toxins and improves cardiovascular system function (See study looking at use of infrared sauna therapy for heart patients).
  • Chelation: Chelation therapy has been scientifically proven to rid the body of excess of toxic metals and is approved by the FDA for this purpose. This published study summarizes the findings of the US National Institute of Health clinical trial – specifically on using intravenous EDTA chelation therapy for coronary heart disease. We covered chelation and removing metals in greater depth in past episodes: episode 13 with Chris Shade (Mercury) and episode 19 with Garry Gordon.

Supplementation

  • EDTA: EthyleneDiamineTetraacetic Acid is the main chelating supplement discussed in this episode, and which is supported by the studies, in particular to chelate lead.
  • Niacin: Also known as vitamin B3 – is an essential human micronutrient. Supplemental niacin is primarily used to treat high cholesterol. Dr. Kahn claims that niacin is particularly good at lowering lipoprotein(a) levels – a proven risk factor for cardiovascular disease.
  • Proline / Lysine: Dr. Kahn claims that intake of these amino acids may prevent the damage that lipoprotein(a) otherwise imposes on the cardiovascular system.
  • Coenzyme Q10 (CoQ10): Helps support healthy mitochondria in cells. In turn, this maintains a robust cardiovascular system. Dr. Kahn encourages most of his patients to take this supplement.
  • Vitamin CLiposomal Vitamin C: Proponents of the Pauling Therapy from Linus Pauling argue that heart disease can be treated, and even cured, by substantially increasing Vitamin C intake.

Diet & Nutrition

  • Nitric Oxide (NO) Supporting Foods (Watermelon, Hemp Seeds, Pine Nuts etc.): Nitric Oxide (NO) is synthesized by the inner walls of blood vessels – known as the endothelium. It prevents arteries from constricting or spasming. NO prevents heart attacks in both an immediate and a long term time frame. Dr. Kahn suggests foods which support NO synthesis including watermelon, hemp seeds and pine nuts.
  • Coffee: As a drink, coffee is a rich source of beneficial antioxidants. However, it’s positive effects may depend in part on what type of caffeine metabolizer you are. If you metabolize caffeine slowly then you have a tendency to feel jittery or racing heart and there is some evidence that it may be less heart healthy than for fast metabolizers of caffeine. However, overall caffeine is considered a health food in most studies, and Dr. Kahn recommends 1 cup of black coffee per day to his heart patients.
  • Tea: The intake of tea is also an advisable health practice including green tea, herbal tea, hibiscus tea, or chamomile tea before bed – which is a source of sleep support.
  • Vegetarian / Vegan Diets: A vegetarian diet excludes meat by focusing on plants for food, but may include animal products such as milk and eggs. In addition to excluding all meat products, a vegan diet also excludes all animal products. Dr. Kahn argues that in world areas where people live the longest, and with the greatest freedom from heart disease, the populations are not completely vegan.
  • Paleo: This diet is based on the foods that paleolithic humans might likely have eaten. It includes meat, nuts, and berries, and excludes relatively – recently developed food products including animal products such as milk. Dr. Kahn described his view that there is a lack of scientific evidence to support this diet for cardiac health.
  • Ketogenic: A ketogenic diet is a diet that induces a state of ketosis in the body where the body uses ketones instead of glucose for fuel. Typically this involves a diet with low carb and low to moderate protein intake with high fat intake. Previously, we discussed measuring ketones and ketogenic dieting in Episode 7 with Jimmy Moore.

Tracking

Biomarkers

Cholesterol Based

  • High – Density Lipoprotein (HDL): The traditional measure of ‘good cholesterol’ used by doctors and healthcare. Levels above 60 mg/dL are considered protective of cardiovascular disease. Dr. Kahn stresses the importance of checking your cholesterol, even at around the age 18 or 20.
  • Low Density Lipoprotein (LDL): The traditional measure of ‘bad cholesterol’ – the type which causes heart disease. Less than 100 mg/dL is considered an optimal level, while levels between 160-189 mg/dL increase the risk for cardiovascular disease. Research has shown that LDL alone is not the best predictor for cardiovascular risk. Actually, LDL particles with the smallest sizes are most damaging to the cardiovascular system. Dr. Kahn puts more emphasis on using the LDL particle number and LDL particle size metrics.
  • Lipoprotein(a): Lipoprotein molecules carry cholesterol and similar substances through the blood. A test can be done to measure a specific type of lipoprotein called lipoprotein-a. Higher levels of this marker are associated with risk of artery damage. Dr. Kahn states that in most labs normal reference ranges for lipoprotein(a) should be under 30 mg/dL.

Blood Sugar Regulation Markers

  • Fasting Glucose Levels: A biomarker used to understand blood sugar regulation. Optimum levels are between 70 and 90 mg/dL. Higher levels indicate some level of blood sugar dysregulation, which increases risk for diabetes II.
  • Hemoglobin A1C: A form of hemoglobin which is measured to identify the average plasma glucose concentration over prolonged periods. Higher levels of hemoglobin (A1C) indicate poorer control of blood glucose levels. In turn, these are associated with diabetes and cardiovascular disease risk. 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.

Inflammation Markers

  • High Sensitivity C-Reactive Protein (hs-CRP): Elevated hs-CRP levels indicate inflammation which is damaging to inner artery walls. If your level is below 1 mg/L then you do not have a cardiovascular disease risk. Because of the proven clinical use of this biomarker, Dr. Kahn claims it is high time for cardiovascular patients to start measuring hs-CRP.
  • Homocysteine: Elevated homocysteine blood levels indicate blood vessel inflammation and higher risk for coronary artery disease. This marker has previously been discussed in episode 5 with Ben Lynch and in episode 29 with Dr. Nicolson.
  • Lipoprotein-associated phospholipase A2 (Lp-PLA2): This biomarker gives insight into inflammation of blood vessel walls and is useful as part of a comprehensive assessment. The PLAC test measures the activity of ALp-PLA2 (an enzyme) in a patient’s blood. Individuals with test results showing Lp-PLA2 activity greater than 225 nmol/min/mL are at increased risk for cardiovascular disease.

Other

  • Ferritin: Serum 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.
  • Myeloperoxidase: A very sensitive biomarker for predicting myocardial infarction in patients with chest pain. It shows added predictive value compared to measuring hs-CRP alone.
  • Vitamin D: A vitamin which is essential for bone development and maturation and prevents osteoporosis. The Vitamin D Council suggests an optimum level of 50 ng/mL. The 25-hydroxy Vitamin D Blood Test is the most accurate way to measure how much vitamin D is bioavailable to be used by your body.
  • Free Testosterone: A steroid sex hormone. Physiological effects include muscle growth, increased bone density, and development of male sex characteristics. Free Testosterone is a small portion of this hormone which is bioavailable, because it remains unbound by carrier proteins in the bloodstream. Free testosterone reference ranges for females are 1.0-8.5 pg/mL and 50 – 210.3 pg/mL for males.
  • Estradiol: This is the primary female sex hormone. For females, the levels of this hormone vary greatly because of its key role in regulating menstrual cycles. In the normal reproductive cycle, estradiol levels measure typically <50 pg/ml at menstruation, rise with follicular development (peak: 200 pg/ml), drop briefly at ovulation, and rise again during the luteal phase for a second peak. At the end of the luteal phase, estradiol levels drop to menstrual levels unless there is a pregnancy. The reference range for healthy adult males is 14-55 pg/mL.

Lab Tests, Devices and Apps

  • Coronary Artery Calcium Score (CASC) Test: This test is a type of CAT scan which determines whether your arteries contain clotting plagues by quantifying calcium presence. By measuring calcium scores, the extent of blocking can be determined. This test lasts very short (under a minute), does not require injections, and is not claustrophobic. CASC tests have been shown to predict mortality.
  • Carotid Intima-Media Thickness (IMT) TestThis test measures the thickness of the walls of your arteries and helps determine whether you have a higher risk for cardiovascular disease. Individuals with unwanted CASC Test scores should undergo IMT ultrasound as a follow up for disease progression or risk. This is because the CASC test is based on a x-ray CAT scan, as opposed to the harmless ultrasound waves used in the IMT test.
  • WellnessFX Cardio Lipoprotein Profile: This test panel includes a number of lab tests, including the comprehensive analysis of lipoprotein particle numbers and sizes. It uses the accurate direct-measurement laboratory method (NMR (Nuclear Magentic Resonance) lipoprofile). Individuals with patterns of higher counts of smaller particles have a more concerning lipoprotein profile than those with less particles with greater size.
  • Life Extension Company Blood Testing: Joel mentioned LEF as one of the organizations that provides direct to consumer blood testing that he trusts.
  • Caffeine Metabolism Genetics: Whether you metabolize caffeine more rapidly or slowly depends on the presence of a Single Nucleotide Polymorphism (SNP) genetic variation in the liver enzyme responsible for metabolizing caffeine. The company 23andMe offers a genetic test for identifying slow metabolizes who may be at increased risk for cardiac attack due to coffee consumption.
  • Toxin Concentrations: These can be measured using blood or urine tests available in specialized labs. We’ve covered this subject extensively in previous episodes – see episode 13 with Chris Shade (Mercury), episode 19 with Garry Gordon (Lead) and episode 23 with Kara Fitzgerald (other metals and chemicals).

Other People, Books & Resources

People

  • Dr. David Katz: Founding director of Yale University’s Yale-Griffin Prevention Research Center and current President of the American College of Lifestyle Medicine.
  • Tim Russert and James Gandolfini: Both men were prominent individuals in American culture, whose lives were shortened by sudden unexpected cardiac attacks.
  • Linus Pauling: An American biochemist, author, and educator as well as one of only four individuals to have won the Nobel Prize twice. During the 1990s Pauling put forward a plan for the treatment of heart disease using vitamin C.
  • Stormie Jones: Was the world’s first recipient of a successful simultaneous heart and liver organ transplant at the age of sixShe suffered from an inherited genetic condition named Heterozygous Familial Hyperlipidemia which made her liver unable to remove cholesterol from her bloodstream. In turn, this was also causing her serious heart problems.
  • Nathan Pritikin: An American inventor, nutritionist and longevity researcher. His program features the Pritikin Diet which is focused on a variety of whole (unprocessed) or minimally processed foods.
  • Dr. Dean Ornish:  A cardiologist and the founder of the non-profit Preventive Medicine Research Institute. He coaches patients towards a vegetarian diet but not a strict vegan diet. His program is defined in four specific elements of lifestyle. It is the first scientifically proven program to “undo” (reverse) heart disease by optimizing stress, diet, physical activity, and social support.
  • Dr. Caldwell Esselstyn: His proposed diet for cardiac health is strictly vegan with under 10 percent of calories coming from fats. His program for patients includes walking, meditation, stress management, yoga, and other lifestyle choices to decrease cardiovascular disease burden.
  • Dr. Neal Barnard An associate professor of medicine at the George Washington University School of Medicine. He has led numerous research studies investigating the effects of diet on diabetes, body weight, and chronic pain.
  • Dr. Garth Davis: Among the leading researchers in the field of bariatric medicine – a branch which deals with the causes, prevention, and treatment of obesity.
  • Dr. William Davis: A cardiologist and author of the Wheat Belly blog.
  • Dr. David Perlmutter: A Board-Certified Neurologist and Fellow of the American College of Nutrition.
  • Dr. Alessio Fasano: An Italian researcher who sees pediatric and adult patients in the Center for Celiac Research and Treatment at the Massachusetts General Hospital. He is carrying out important research on the health impact of eating grains.

Organizations

Books and Video

Full Interview Transcript

Click Here to Read Transcript

[04:30][Damien Blenkinsopp]: Joel, thank you so much for coming on the show.

[Joel Kahn]: My complete pleasure.

[Damien Blenkinsopp]: So, I’d like to start with a quick story about how you became a cardiologist; why did you get into, specifically, holistic cardiology?

[Joel Kahn]: Sure.

I knew really from a very young age that I wanted to be a cardiologist. I actually had a very small issue as a young child with a tiny hole in my heart. It healed, but I had the pleasure of seeing a very fine heart doctor until I was about 18 years old.

It had a very good impression on me; [there were] a few scary moments being in a big hospital as a little kid, but overall it was actually very positive. And kind of pursued a fast tract to making this my career. I’ve been doing it now for almost 26 years after training.

Holistic? I just always felt people are more than a pill. Doctors are wonderful people, nurses are wonderful people; I don’t have a chip on any shoulder. But I was exposed to some really good people. I got very involved in nutrition, nutrition lead to Mind Body, nutrition lead to Standard and Alternative Fitness, nutrition lead to supplements, Yoga, meditations.

So I just poured my heart and soul into studying and learning, and expanding my tool box for patients. And then I said, I’m going to start writing about it, because I don’t know if [they] are practicing it. So it’s all been a wonderful journey that’s far from over.

[Damien Blenkinsopp]: I didn’t realize you’d had that heart issue. Is it completely resolved now?

[Joel Kahn]: Yeah. Yeah. It’s very common, a little worrisome to the parents — god bless my mother and father. But it’s another example of if you don’t get in the way of things, the body can often heal itself. And this was a relatively minor thing, so good for that.

[Damien Blenkinsopp]: Great to hear. And it gave you the motivation to get started in all of this. It’s kind of funny who life always does that; it kind of steers us in the direction we end up going.

[06:17] I was wondering, because you’ve been looking at this holistically — and a lot of people focus on the heart, cholesterol, and things like this — could you explain what a formula to get heart disease would be, in terms of a holistic view? Because when you read through your book, it gives you a much more global view of how heart disease comes about than we’re typically used to.

[Joel Kahn]: Yes. And you know, we don’t want to throw away the basics. In essence, there’s two ways to approach this.

Our government, the United States government, has been publishing for a while, every 10 years, major causes of death. And unfortunately heart disease is at the top of that list, every list, every 10 years. But that’s not really the true causes, and starting in 1993 some very open-minded researchers said, “Let’s talk about the true causes.”

And the true causes for 80 to 85 percent of premature deaths were three activities: smoking, poor fitness, and poor diet. And those true causes dwarfed everything else. And it always dwarfed genetics. It’s a lifestyle world, baby, in terms of developing or preventing heart disease.

So, heart disease develops because we smoke too much; fortunately, under 20 percent of the population, and it used to be 40 to 50, so major inroads, it’s falling. Heart disease develops because we don’t move enough, and we’ve gone from farming and active community 150 years ago to everything being tech based, and we’re blessed with all of that. But we are paying a price.

And we now have to use, I have an app on my phone that reminds me to stand 5 minutes every hour. So we’ve come full circle, where technology was the problem and now technology will provide solutions. And desks that go up and down so you can stand at work and such.

And then heart disease develops because of the change in our diet since the Golden Arches hit California in the 50s, and all that’s followed with giant companies and processed food, and our crazy lifestyle where we don’t have time to make meals from whole foods anymore. Those are the big three by far.

A good friend at Yale, head of Preventative Medicine Dr. David Katz says, “Forks, fingers, feet.” Fork, what you do with it will determine your life; fingers what you do in terms of smoking, and feet whether you move and exercise that body. And really that accounts for the majority of it.

Sleep, stress, and love would be the other three. Adequate sleep, managing stress, and including yourself in a community to be surrounded by loving, like-minded people would round out the top six. And that’s a pretty holistic view, but it’s not very difficult, and it’s not very sophisticated.

[Damien Blenkinsopp]: Yeah, great, thank you very much for that.

[09:05] And I think when we think about heart diseases we often think about heart attacks, but is stroke related to heart disease as well? Is that one of the outcomes from the same kind of mechanism?

[Joel Kahn]: Yes. Stroke is a little bit more diffuse or widespread in terms of trying to nail down the cause. The number one listed cause of death in the United States is heart disease, such as heart attack. And number three is stroke, with cancer between the two. Therefore, if you lump heart disease and stroke, cardiovascular disease is the number one cause of death in every segment of the population over age 30, men and women.

But stroke has a shared cause to heart attacks; that is you can get clogged arteries from the lifestyle measures, and in part genetics that I just ran through. But there are other causes of stroke: bleeding disorders, heart rhythm disorders.

So the data is you can prevent about 80-90 percent of heart attacks through adopting a healthy lifestyle that’s neither expensive nor difficult, just rarely done. And you probably can prevent about 60 percent of strokes. It’s not as high because the cause is more commonly something other than atherosclerosis, or hardening of the arteries.

[Damien Blenkinsopp]: Great, thank you for that. Yeah, because I wasn’t really aware that they were so tightly related and preventable as well.

[10:26] In terms of stressors and some of the other mechanisms, could you talk a bit about the actual mechanisms behind heart disease? How this takes place? Without getting, obviously, into crazy detail, because it can get pretty detailed.

But in your book you talk about a variety of factors that we don’t often think about, such as mitochondria, and the gut, and other areas. And we don’t think about those leading to heart disease. So could you give us some kind of overview to show us how these mechanics are working to create a condition.

[Joel Kahn]: Well certainly, and one term that readers and listeners may not be familiar with but is important to grasp is something called your endothelium. And that is, essentially, inside every artery in your body — miles and miles of arteries carrying blood to your brain, your pelvis, your heart, your organs, your toes — is a one cell layer thin lining, like wallpaper on a wall.

And until about the 1980s we thought it was simply just a cell barrier between blood on the inside and the structure of the wall on the outside. But now we know that the endothelium makes many chemicals, the most important of which, or perhaps the most crucial, is nitric oxide, a little simple gas that in a healthy artery is created in abundance.

Arteries making nitric oxide because of a health endothelium will resist the clotting of blood; you want the clotting of blood when you cut your finger, you don’t want the clotting of blood when you’re on the verge of a heart attack. The nitric oxide will prevent; arteries from constricting, or spasming, which again can trigger a heart attack; the Raynaud’s blue-white-red fingers some people struggle with in the cold; leg pain on walking; and also the actual plaque, the actual build up of debris in arteries is resisted by a healthy endothelium with healthy production of nitric oxide.

So, that’s one physiology, and the good news is things that we would associate with a healthy lifestyle –eating a lot of produce, fresh fruits and vegetables, exercising your body, adequate sleep, good blood pressure, good blood sugar, good cholesterol numbers from a healthy lifestyle — are all associated with a healthy endothelium. And if you have a sick endothelium, you can make it healthier though a healthy lifestyle.

All of these things resoundingly shown scientifically. For example, eating watermelon, [it’s] very rich in chemicals that support nitric oxide. Hemp seed [is] very rich in chemicals that support nitric oxide. Other seeds and nuts similarly: pine nuts.

The other one [is] as you mentioned; inside every cell are little organelles, or little structures inside our cells. We have trillions of cells —- brain, heart, muscle, everywhere — and their powerhouse to generate function is called your mitochondria. We don’t think about them, we don’t give our mitochondria a kind of shout-out, we don’t wake up in the morning and say, “Thank you mitochondria for taking care of me while I slept seven and a half hours.”

But indeed, aging is a stress on our mitochondria where they won’t function to make energy so well. And unfortunately we now know not only bad lifestyle, which is way too common — sedentary lifestyle, food-based poor lifestyle, smoking poor lifestyle — but environmental toxins clearly affect our mitochondria: pesticides, herbicides. There’s data that genetically modified products and the herbicide roundup affects our mitochondria. Nutritional deficiency like low magnesium from not eating enough produce affects your mitochondria.

And our cells will age quicker and won’t function as well, and may produce fatigue, may produce congestive heart failure, shortness of breath. But again [it is] an area of science that is very hopeful, because lifestyle can cause our mitochondria to be much more efficient, and, probably most strongly, exercise. The actual number and health of your mitochondria in your muscles goes up when you exercise. You actually, you can be in your 40s and 50s and you can create more mitochondria by regularly exercising to a fairly vigorous degree for a while.

So yeah, those are concepts that I think are important to share. And there’s ways to boost the function of both our endothelium and our mitochondria, both by lifestyle, and not — I’m a fan of selected supplements. The supplement Co-enzymeQ10, CoQ10, which is more commonly used in Europe than the United States, helps support healthy mitochondria and [it’s] something I encourage most of my patients to be on.

[15:08][Damien Blenkinsopp]: Great. So, on this show we talk about a lot of biomarkers, and I know you have preferences for different biomarkers from the standard.

Could you, first of all, walk us through some of the very typical. I mean, when most people go to their doctor they are given the standard cholesterol markers. So could you talk through the LDL, the HDL, the total cholesterol, and if you use those, and how useful you find them.

[Joel Kahn]: First step, and I always like basics, is get your cholesterol checked, even at around age 18 or 20. Because one out of every 400 people may have an inherited disorder called Heterozygous Familial Hyperlipidemia, or FH, and you may be 18 years old with a cholesterol 450.

One out of every 400 is not all that rare. In a typical high school in this state that might be six kids. And it’s better to know it at age 18 or 17 than to find out in an emergency room at age 45 with a heart problem.

But in my practice, I do advanced cholesterol lab values. There’s a variety of different ways. For example I can see two people with a cholesterol of 220 and the LDL cholesterol of 120, and they may be at very different risk for artery damage because we can break down the size of their LDL, the number of particles in their LDL. Usually it’s a technology called NMR spectroscopy, but it’s become a very low cost lab that’s much more accurate.

So I can have two people and I can speak to them differently; that’s called personalized medicine. And say, “Nancy, your LDL is actually very favorable. You don’t have much. They’re large particles, and I think we can leave you alone and continue your good lifestyle. And Joe, your LDL of 120 is constructed largely of small, dense particles, and you’ve got way too many of them. And we’ve got to really kick that lifestyle in gear, and your nutrition in gear, and we’ve got to get that belly a little thinner.”

You know, it can help me define a more guided approach. But when we’re talking population, a standard finger prick or church-based or work-based cholesterol is a good starting point.

[Damien Blenkinsopp]: Right. It’s just a screen to see if it’s worth digging further. So basically, if LDL comes up high, you’d be like, okay I’ll look at the particle number and size to see if this is a problem.

[Joel Kahn]: It can. Yes, that’s one of the things we can do to refine if, everybody needs encouragement about lifestyle, but if they need beyond that consideration of medication or more intense lifestyle.

[Damien Blenkinsopp]: Great. So is it possible for someone to have a high LDL number, which is over the standard reference range, and it not be a problem because the size of their particles is large and small number of particles, basically?

[Joel Kahn]: Yeah. We broke up a little, but cholesterol is associated with developing heart disease. And it is causative, there’s no doubt. I mean, I reflect back when I was in cardiology training in Dallas, Texas.

I took care of a little girl, 11 years old, who was known around the world, Stormie Jones was her name, sweet girl. And she was born with a genetic disorder where she had both genes defective, that was called Homozygous FH. It’s very rare, it’s about one person in a million. But that little girl had had a heart attack, a bypass, a balloon, by the age of 12. And to argue that cholesterol doesn’t have a direct role in damaging arteries has many pieces of science behind it, animal and human, but I always reflect back on Stormie Jones.

So cholesterol is important, but there’s so much variability in human physiology. So when I’m dealing with one person, I try to find if their arteries are healthy or not. There are ways to determine if there’s any early plaque, if there’s any early endothelial damage.

And if I see somebody with a fairly high cholesterol at age 60, for example, but they have no evidence of plaque, no evidence of endothelial damage I’d have a very hard case to put them on a prescription drug, in my mind, because there must be other factors that are protecting them. And yes, they may have an additional 30 or 40 years to worry about, but I’m really going to stress to that person lifestyle — healthy diet, exercise, weight management, blood pressure management — and not necessarily write a prescription drug.

And, you know, there’s always the opposite too. There are people that have had a heart attack, or a bypass, and relatively moderate risk factors, and then we really have to go on a search. We have to go on a search for other biomarkers, like something called Homocystine, lipoprotien(a), Ferritin.

There’s a lot of people that are prediabetic that fall through the cracks, and are suffering artery damage from their prediabetes, but it’s really not been offered as a diagnosis, and that’s kind of a very common one, for example.

[Damien Blenkinsopp]: Right. With the Homocystine, for example, are you looking for the causes? Or are you trying to look a bit further back?

So if you get some high cholesterol numbers and some particle numbers that are indicative, is homocystine more indicative of a cause, so you can refine your prescription, the treatment you recommend? Or is that just a basic filter for your assessment?

[Joel Kahn]: No, I think the ultimate joy is trying to get back to the root cause. And the root cause, certainly the majority of it, is lifestyle. And we’ve talked about that, food choices, which I’ll go over carefully with patients: processed versus unprocessed, high in saturated fat versus low, high in added sugar versus low. [And also] body movement, body fitness, body exercise, adequate sleep, methods of managing stress.

For example, it’s been shown that meditation can have a significant effect on lowering your cholesterol. Kind of pieces of scientific data that are published that aren’t talked about much. When you’re stressed out your cortisol level goes up, your blood sugar goes up, your blood cholesterol goes up, your blood pressure goes up. And a practice of breathing or yoga or meditation can fairly dramatically lower blood cholesterol.

So then getting at the root cause, now the question is after those basics, which need to be addressed every visit, over and over — sleep, stress, nutrition, fitness — do we go further? We do know that there are environmental toxins, and we do know that heavy metals we’re exposed to through cosmetics, through industrial exposure, through dental fillings. We often carry a burden of mercury and lead and cadmium.

Smokers not only are ingesting all kinds of toxic carcinogens, but the ground in Virginia is said to be quite rich in cadmium, which is fine if you have it in the battery that’s powering your radio but you don’t really want cadmium in your blood stream in your body. So you can use blood analysis, hair analysis — take a little snip of hair — or urine analysis and determine if a person has greatly elevated levels of some of the pesticides, herbicides, pollutants like heavy metals.

And sometimes the course directed at identifying and removing those can really restore a person’s health to a much higher level. It’s a slow process because you accumulate those things slowly, and any plan to exit them by avoiding; if it’s an industrial exposure taking more care or changing jobs, don’t walk on your lawn the day that they spray the pesticides or look for more natural organic way to treat your lawn. Consider whether your mercury in your mouth might be a problem or not, you can get tested for that, for example. All those things.

But then there are strategies to remove some of these toxins. And of course considering eating organic versus non-organic to lower our input of pesticides. These are all strategies; and then there are more advanced strategies.

I’m a big fan based on some very fascinating and rich scientific data of the health benefits of sauna on our overall health, and specifically our heart health. And the amount of data that supports it is surprisingly rich, but very rarely taught in the annuls of medicine, of course.

[23:37][Damien Blenkinsopp]: Is that any type of sauna, or is that the infra-red version?

[Joel Kahn]: Well the infra-red is the hottest and most widely mentioned, because in Japan, starting about 20 years ago, heart patients have been treated, heart patients who’ve had a heart attack, heart patients who’ve had blocked arteries or even the very serious problem called congestive heart failure, have been treated with 15 minutes of infra-red sauna followed by 30 minutes of rest and it has been shown that they can enjoy dramatic improvements in health.

And these are all actually published studies; scientific journals, some of them involving up to about 200 patients, which is getting to be respectable size for a research project at all. So that’s infra-red sauna, which is a special kind of deeply penetrating heated dry sauna; not that common in this country at this point. People can consider buying one for their home for under $1000 up to a few thousand, or finding a spa that might have an infra-red sauna, which is growing interest in this country.

But recently, as you may be aware, out of thin [24:50 unclear] came a large research study with 2000 people that were asked how often do you get in a sauna, how long do you sit in a sauna, and all that tracked with actually survival and heart health. And the number of days a week that people used sauna, and the number of minutes per sessions were kind of linearly related to overall health, which was large, and shocking, and made the news. And that’s a slightly different form of sauna. It was dry sauna but not infra-red.

So I think there’s much hope in perusing that. And the theory is that it may have something to do with detoxification. There’s no doubt that the sweat that is generated in such a thing as infra-red sauna is rich in heavy metals, richer than your urine or richer than your blood. You’re actually exiting these toxins from your body in your sweat.

So I’m a big fan of that. Then you can get into other approaches, so called oral chelation, juicing, using green vegetables like broccoli, sprouts, oregano, parsley and other greens to accelerate the exit of some of these toxins from your body in a fairly easy and natural way.

[26:03][Damien Blenkinsopp]: So it sounds like heavy metals in particular sound like something that you think they are quite relevant and important to heart risk issues.

Did you see, I believe there’s some studies with EDTA and heart disease more specifically and the impacts on it with some of the plaque and things on it. Am I correct in that, have you seen those studies?

[Joel Kahn]: Yeah. I was not a fan of recommending chelation. And so let me just take a step back, because not everybody is going to be familiar with chelation.

But because of industrial exposures to heavy metals in the 40s and the 50s — for example a worker exposed to arsenic in an explosion, or lead — there was an interest in trying to treat those acute toxicities. And various medicines like EDTA have been shown in those kinds of exposures to be quite helpful. And they’re, in fact, approved by the FDA for use in these industrial exposures to heavy metals: heavy lead, cadmium, mercury and such.

But in the process of some of those treatments, there were reports that people with heart disease were describing that they were having less symptoms. And some sharp clinicians were observing this and started to specifically treat some people with clogged arteries of their heart and their legs with chelation. And that, to this day in the United States, is not an FDA approved treatment; you won’t get paid for it, and in your charting you could be subject to some exposure for saying that’s why you’re treating them. Using i.v. EDTA for the reversal of atherosclerosis as opposed to heavy metal toxicity.

So, all of that was kind of subject to derision from the standard medical community, including myself. If you would have asked me four years ago, can we talk about the science behind chelation — I know there’s people that say they feel better, but do we have much science? You would have been very hard put.

So again, very forward thinking people about 10 years ago approached the National Institute of Health and said we need to resolve this; is this witchcraft, is this good care, and let’s do a study. And surprisingly the United States government came up with about 30 million dollars and designed a trial using kind of standard i.v. chelation protocols in, ultimately, 700 people that had survived a heart attack — that’s what was required to be entered in — and they were supposed to show up for about 40 weeks.

Some of them got EDTA based intravenous infusions, some of them got some vitamins, but there was no EDTA in there. And at the end of that study, which took a little longer to complete than hoped, was a little bit more difficult to recruit patients, but the overall trend of the study favored an improvement in outcome, like the combination of being alive, freedom from a heart attack, freedom from needing a bypass and hospitalization in those that got the active chelation.

And specifically two groups, if any of those 1700 people were diabetic or any of those 1700 people had actually experienced a fairly large heart attack in the background in their history, they had a dramatic improvement. It was a 40 percent reduced chance of having a bad outcome. And if you had a pill that within about four to five years reduced those bad events by 40 percent, you’d have a blockbuster new pill.

So chelation looked good, actually, and the combination of i.v. chelation plus potent multivitamins — because that was another aspect of the trial, it’s called the TACT trial, Trial to Assess Chelation Therapy — that the combination of i.v. chelation once a week and potent twice a day multivitamins had the biggest impact. But that was announced, I think it was around November 2012, so more than two years ago.

And there’s really been no movement since to seek out reimbursement, or FDA approval. Most doctors clearly are not set about to offer intravenous therapy. There’s a very small chance of harm. You can lower blood calcium levels because it’s going to chelate minerals, and calcium is one of those so very often the mixture has to have some nutrients and mineral support in it. But I have referred patients to colleagues of mine in the area that are experienced and certified in chelation.

[Damien Blenkinsopp]: Great, great, thank you for that, because the connection is appreciated by a lot of us.

[30:47] So I wanted to look at some of the, because I know you recommend some more accurate tests. For someone who really wants to know for sure their heart disease risk and where it’s at, if the status of their plaques, what do you use to accurately and directly see what the picture is looking like?

[Joel Kahn]: Yeah, well thank you for asking that question, because that’s really my passion. My passion is to teach people that there is a way to be very accurate, both by their blood work — and we talked about that — and by imaging, which we’re going to talk about right now. To really nail down your personal risk of experiencing the number one killer in the Western world, heart disease which can come on suddenly, without warning, and the next day there’s a funeral tragically leaving spouses and children and parents wondering how did nobody pick up that there was a burden of disease.

I’ll just give you a quick example. Sadly a friend of mine lost her husband, who was a prominent businessman in my town, who was a very fit person [who] ate healthy, looked good, wasn’t overweight, enjoyed athletics, and a little over two years ago went out for a bike ride on vacation and never came back. And was found at the side of the road and shown by autopsy to have a 99 percent blocked Widow-maker artery. And that shouldn’t happen.

My passion is to say, that’s tragic and we need to circle around that family with a lot of love, but let’s not let the next family and the next family and the next family, you know the Tim Russerts and James Gandolfini from Sopranos and such. We just had a bank president in my town, about three or four weeks ago, who experienced the same tragic end to his life, a man I’m sure was getting good medical care, absolutely.

So, there is the most accurate way right now to [if] you’re 45, 50, 55 years old, you’re concerned that this this number one killer in America could be creeping up inside silently; And you should be concerned, particularly if you’re overweight or sedentary, or [have] blood pressure, cholesterol, blood sugar issues, smoked in the past, [have a] brother, sister, mom, dad with heart disease.

There’s a CAT scan that takes 10 seconds, 20 seconds. You lie down, you’re pushed into a tube, a CAT scanner. It’s not around your head, it’s not claustrophobic. No i.v., no injection of medication. The CAT scan is done, you go home, you get a report. It’s called a coronary artery calcium scan, or coronary artery calcium score, CACS.

You can see the three heart arteries on the CAT scan without any injection of contrast material. Your arteries should contain no calcium; calcium should be in your bones and your teeth. If your heart arteries have calcium, your heart arteries have plaque. And you’re going to have that way before you ever need to have your bypass, your stint, or your heart attack therapy. So you can find out.

And there’s a number associated with it. If your score comes back zero, you have youthful arteries that are free of calcium, and your 10 to 15 year risk of a heart event are extremely low. Keep living healthy, but you can take a sigh of relief.

And if your arteries are prematurely calcified, you’ve got plaque. You may not be 80 percent blocked, you’re probably not going to need a stint or a bypass, but you need to see somebody about it. So that number could be 20, or 100, or 200.

I get people that show up, I saw one yesterday, totally good looking guy 61 years decent lifestyle, his calcium score was 1,100, mainly in the one artery we call the widow-maker. That’s a ton of burden of abnormal artery that we need to deal with by identifying why, and we’ve talked about some of that search.

He had already had a stress test that was normal, so he doesn’t need an angiogram, stint, or bypass, but now he needs a cardiologist who cares about lifestyle and all of the things we’ve talked about. We talked about yesterday about sauna, and heavy metal assessment, and advanced lipid blood work, and a daily aspirin. He’s a heart patient now, so I plead with people now.

[Damien Blenkinsopp]: Right. Yeah, I guess in that situation you would kind of throw everything at it, because it does sound like you were pointing out the worst case scenario, the worst score you’re likely to see.

Would you kind of throw everything at that case? Should he be really worried, and say, “Whoa, I’ve got to really change my lifestyle. Heavy metal chelation, everything I can.”

[Joel Kahn]: Yeah, that person needs to become a good student of the disease, reading my book, reading a book by Dr. Dean Ornish, a book by Dr. Caldwell Esselstyn. Many many good resources: Dr. Neal Barnard, Dr. David Katz. There’s plenty of good resources online for free, or books, or watch the DVD Forks Over Knives. I mean, many good resources, and I encourage my patients to do all of that.

But we ordered up a pretty in-depth analysis, and we’ll sit down in a few weeks and design a personalized plan. Now on the other hand, I see people all the time, they’re carrying extra weight, their cholesterol is 250, their diet isn’t exactly what I’d called in-line with nutritional goals, and their calcium score is zero at age 65. They’ve gone through six decades of life and are identifying no calcified plaque in their arteries, and their risk is very low.

And I don’t want them going to fast food places and eating their french fries, but I can cut back a bit on their medical treatment and focus on lifestyle with a great sense of joy and relief. And I see that a lot; a brother died at age 44 and the sister is zero and is going to smile for the next few years that she isn’t also carrying a burden of life-threatening plaque.

The oddity about the test is in the United States it’s not covered by insurance in about 48 states; 10 years ago places were charging 700 or 800 dollars. It’s very easy now to find that test under 150 dollars, sometimes under 100 dollars, which makes it very reachable for most people.

[Damien Blenkinsopp]: Is it quite widely available, like a lot of hospitals have these machines?

[Joel Kahn]: It’s just a standard CAT scanner, you do have to have special software to calculate that score, but it’d be very surprising if [in] most medium or large towns at least one of the hospital systems, or all of them, don’t offer it.

[37:09][Damien Blenkinsopp]: Okay. As it’s a CAT scan, is this something you shouldn’t do to often because of the radiation? With your patients, if someone’s got a score of 1000 or above, I guess you’re tracking progress over time to make sure it’s not increasing and you’re reversing some of that damage. But are you concerned at all about radiation, and do you do anything about it?

[Joel Kahn]: Well it’s an excellent question. I am a bit hesitant to repeat the CAT scan to follow their disease for two reasons: every time you do it it is some additional radiation, and number two there is not much data that you can drive that calcium out of the artery.

For example, the TACT trial, the chelation trial didn’t, unfortunately, assess calcium score. It would have been nice if we actually knew. So I don’t know the natural history. I know the natural history tends to go up if you do nothing; there are some studies that your calcium score may go up 30 percent a year. So if your score is 100 this year, it may be 130 next year. That’s just an average; it’ll be less for some, more for some. But I’m not so sure what I’d do with a repeat calcium score, because I fear they all go up.

There is an alternative test, called a Carotid IMT, intima-media thickness. This is an ultrasound. So ultrasound, of course, is no radiation; ultrasound can be repeated. And there’s about 700 medical studies on the value of having a special ultrasound machine with special software, that measures the thickness of the wall of your carotid artery.

And that is something you can track every year, every six months, compared to databases that have thousands of people age matched and sex matched, to make sure your arteries aren’t rapidly getting thicker and more plaque ridden. And hopefully actually seeing some improvement. So, if I have somebody with a bad calcium score, I’m probably going to use an ultrasound technique to follow them so I don’t need to keep exposing them to radiation.

That’s kind of a high level approach, but we’ve got the disease that’s the number one killer in America. So we’re throwing all kinds of high pollutant, expensive technology at other issues, it’s about time and way overdue that we try and prevent a million heart attacks in the next couple of years in this country so families don’t get ripped apart.

[39:24][Damien Blenkinsopp]: Who would you recommend takes the calcium scoring test?

[Joel Kahn]: Thank you for asking that. Not people who know they have heart disease. So if you’ve had a stint, a bypass, if you’ve had a previous angiogram that showed you’ve got 40 percent blockages, you already know you have a problem and you need to be working on it with somebody that can direct you.

However, it would be somebody aged 40 to 45 and up who has risk factors; brother, sister, mom, dad with early heart disease; high blood sugar; high blood pressure; smoker. Or maybe around age 50 to 55 just because you’re halfway through life and you’ve got the number one killer in America lurking around.

The American College of Cardiology, a fairly conservative group, gave very high endorsement of this coronary artery calcium score for people with risk factors. So if you’re 50 years old and you’ve got high blood pressure, boom: American College of Cardiology endorsed, and unfortunately not covered by insurance. They would leave it in a gray zone.

If you’re perfectly healthy 50 year old, do you need it? Well, I think that’s a personal decision between you and your doctor. I tend to favor getting one because it’s a very low dose of radiation and we still are dealing with the biggest silent killer in America.

There’s a very interesting documentary that came out two months ago called The Widowmaker. And it’s available online, about 90 minutes. I’d encourage anybody to watch it. It’s all about this topic of coronary artery calcium scoring and why is it not more available to make inroads into the health of Americans and identify those at risk.

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

[41:04]There are actually a lot of other blood markers. If you look at WellnessFX — I don’t know if you know the WellnessFX lab for consumers?

[Joel Kahn]: Which blood test is that, sir?

[Damien Blenkinsopp]: It’s not a specific blood test, it’s a lab which is directed at consumers. So it’s a company called WellnessFX, and some people are using those for blood panels.

[Joel Kahn]: Right.

[Damien Blenkinsopp]: So they have a large array. There’s a few companies like this, but WellnessFX is the best known at the moment. So it’s direct to consumer. They have a cardiovascular panel, which is why I bring it up. And there’s quite a few things on it.

So I wonder if you could just comment on some of the values that they include in their panel, if you find them useful. Because it seems like to me that there are so many markers linking to cardiovascular disease it makes it more complicated.

Because we have all these markers, and I’m sure someone like you could maybe get more data and get a better picture, but for the majority of us, it builds up this kind of complex mass of data. And maybe some of them would be out of range, some of them aren’t out of range, and we’re like, “Okay, so where does this put me? I’m not really sure.”

[Joel Kahn]: Yeah, I agree. I am familiar with WellnessFX. There are some others — I have no financial ties to any of these. There’s an organization that I very much like called LifeExtension.org. They’ve been in Fort Lauderdale for 35 plus years, and you can directly get a kit and blood work — a male panel, a female panel — and they’ve got hundreds of thousands of data points built up over the decades.

So you’re right, I think it is worth [it]. I have not seen the advanced lab test we talk about, the particle number, particle size. I have not seen that available in a direct consumer way; I’m not absolutely certain if that’s at WellnessFX. But you’re going to get a good screen, and you can learn quite a bit.

But I do go back to the idea that imaging arteries remains the kind of litmus test. You can have a lot of abnormalities in your blood stream, but you really need to know if you’ve either got thickened carotid arteries by the ultrasound, or if you have calcified, hard arteries by the CAT scan. You need to know that at least once to make sense of the blood work.

These biomarkers are all associations, where the imaging studies are direct imaging. So I favor the coronary artery calcium scan. In some places [it] requires a prescription, but since it doesn’t involve insurance, not everywhere, you can often arrange it on your own.

I encourage people to pursue these direct blood tests, like you said.

[Damien Blenkinsopp]: Yeah.

[43:35] I just wanted to go through a couple of them. You mentioned the NMR, which is, as I understand it, the most advanced blood test if you really want to understand your heart disease risk. Is that kind of the best one you find, in terms of accuracy and getting the closest to the same bar as the calcium score, if you’re just looking at blood?

[Joel Kahn]: Yes, in terms of blood, that LDL particle number which is most commonly obtained through the Liposcience NMR technology, is at the present, I believe, still the most accurate particle in the blood you can measure.

[Damien Blenkinsopp]: Yeah, Great.

[44:07] So WellnessFX, they have something called LPa, or lipoprotein(a). Are you up to speed on that one? Do you find that one useful? Because it’s a little bit similar in that it’s looking specifically at low density lipoprotein, I understand.

[Joel Kahn]: Yeah. Lipoprotein(a) is a cholesterol particle that a smaller number of the public has heard about. A very large amount of science saying it’s a blood test, the higher your level, the higher your risk of artery damage. It seems to be a highly inherited abnormality.

So I get it basically in pretty much everybody once, but I’m particularly aggressive in people that have a family history of early heart disease in their relatives, because that may be the factor. Usually in most labs lipoprotein(a) should be under 30, and in some patients of mine it’s over 200; it’s seven, eight, or nine times elevated above normal.

What is still lacking a bit is an absolutely clear cut trial that shows that lowering it — we can talk about lowering it in a minute — but lowering it makes a long term difference, just because there hasn’t been such a trial designed and carried out long term. Lifestyle can lower lipoprotein(a), hormonal balance of female and male hormones can lower lipoprotein(a), Niacin is particularly good at lowering lipoprotein(a).

And there’s some work going back all the way to Linus Pauling that you can minimize the effects of an elevated lipoprotein(a) by taking Vitamin C, strengthening the wall of your artery, taking some amino acids called Lysine and Proline, and that they may prevent the damage that lipoprotein(a) may do otherwise.

So there is, finally, there actually is a very strange therapy where, much like dialysis, you can get your blood cleansed through a filter. And this is an FDA approved treatment of people like that little girl I mentioned, Stormie Jones, if she were still alive today. That’s a therapy that would be used for somebody with a familial super high cholesterol.

But that filter also takes out lipoprotein(a), so if somebody has a very high level and vascular disease, that’s an option. So, it’s important, I believe, for people to measure their lipoprotein(a). And again it’s genetic, but I mentioned some things you can do.

[Damien Blenkinsopp]: Great, great.

[46:36] So one that I’ve been using for a long time is high sensitive TCRP. Is that something you find useful?

[Joel Kahn]: I do. We’ve been measuring C-reactive protein for decades, because we were measuring it to assess rheumatic fever, so it has a history going back literally decades and decades. But then along came a patented test, the high sensitivity test, and that seems to be more reflective of artery wall inflammation.

And inflamed arteries are more prone to suffer heart attack, stroke, clot and the rest. So you do not want an elevated high sensitivity C-reactive protein. And you want to measure it. And it is highly correlated with increased risk.

So then I’d get on a search for why it might be elevated, and most common would be abdominal obesity, poor nutrition, a lack of exercise, poor sleep or sleep apnea. But you can also look for occult causes like gum disease, periodontal disease and such, unsuspected prostate disease, prostatitis, and probably a diseased gut. Our Western processed foods, high in salt, sugar, and fat causing gut disorders. Lack of adequate microbiome health probably causes inflammation.

So you’ve got to work on the entire patient in a holistic way.

[48:04][Damien Blenkinsopp]: And so I don’t think we’ve really covered this properly, but inflammation is directly related to heart disease as well? Or is it a bit more of a wavy line?

[Joel Kahn]: Yeah no it’s prime time to measure inflammation and high sensitivity C-reactive protein. There’s also a number of other markers out now, like myeloperoxidase, and a test called the plaque test that give insight into inflammation in vessel walls and can be quite useful in a comprehensive assessment.

[Damien Blenkinsopp]: Great, great.

So in terms of some of these indicators, like CRP, the lipoprotein(a) , they’ve got others like alpolic protein, the HDL, the LDL, none of these are binary, as I understand them.

So if someone has a high CRP score, say it’s four or something like that, is that a sure thing that they have some kind of heart disease risk as well? Or could it just be related to some inflammation, or something like that.

You’re really using these as indirect indicators and you can’t trust the picture from that, but it’s just kind of a notice [that] I should go see a physician and investigate maybe if it’s calcium score.

[Joel Kahn]: Yeah. If it’s elevated, it should prompt a search into lifestyle, it should prompt a search into, as I say, gut health, gum health, prostate health, any other. Even though it’s felt to be largely a vascular marker, it’s a marker of the disease and it participates in, actually, vessel damage. But sometimes it can be very frustrating and unclear. I’ve had people with very high C-reative proteins: 40, 50, 60, 70, 80.

There’s a very limited experience with using a shotgun approach, after searching for every possible cause, an antibiotics like minocycline in the tetracycline family. I have been taught that, and I’ve had rare experience to do that with patients after a very thorough evaluation for every other kind of cause of elevated C-reactive protein. And it came down dramatically and stayed down.

[Damien Blenkinsopp]: Great, great.

[50:00] I wanted to tackle one thing. Could you go over the diet you recommend? As background, I’m Paleo and we’ve often talked about ketogenic diets and high-fat diets on here with people like Jimmy Moore and so on.

So could you give your perspective, where you come from with respect to heart disease; what kind of diet and lifestyle are you recommending?

[Joel Kahn]: I like to stay, in every aspect where I can, grounded in the science that’s available. And in terms of artery health, heart disease, survival and heart disease, the weight of the data is not in the ketogenic or Paleo world, the weight of the data like by 100 to 1 in terms of science at least, is in the world of nearly or completely plant based diet.

[Damien Blenkinsopp]: Okay, so is that a vegan diet?

[Joel Kahn]: Yeah. Well vegan, I’ll distinguish those very briefly.

But you can look at epidemiological studies like the Blue Zones, five areas in the world where people live the longest with the greatest freedom from heart disease, none of them are completely vegan. Except actually Loma Linda, California is one of those five Blue Zones, the longest lived community in American, and ten percent of that community is strictly vegan, the other 40 percent are vegetarian, and the remainder are omnivores. They are the longest lived people in the United States and they have the highest percentage of vegans in the United States of any community, because of the Seventh-day Adventist Church there.

So you can look at epidemiological studies like that, or you can look at the data on heart disease reversal, which is a concept that is scientifically sound. Two centers started studying [that], actually three, Nathan Pritikin in what’s called the Pritikin Longevity Center in Florida. He was an engineer, not a physician.

But Dr. Dean Ornish, a cardiologist, began in the early 1980s a lifestyle that is a largely vegan diet. If you really read between the lines its a very low oil, no added oil diet; so less than 10 percent of calories are from fat. He does allow his patients to have some non-dairy fats and some egg whites. So by strict definition it’s vegetarian not vegan.

And he has now pursued that dietary research for more than 30 years. It’s actually approved by Medicare, because the data is so strong that for heart patients it can halt and reverse their symptoms and disease, and minimize their need for medical care.

Dr. Caldwell Esselstyn began the same research project at the Cleveland Clinic in the 1980s, and has similarly shown [with] follow up catheterizations [and] follow up on patients’ health, dramatic reversal of heart disease without stint, without bypass. And his diet is strictly vegan and again under 10 percent of calories are from fats. Kind of the opposite approach to many ketogenic diets.

And, very compelling, Dr. Ornish has taken his program, which is more than diet —- Dr. Ornish emphasizes 30 to 60 minutes of walking, an hour of stress management by meditation or yoga, and group support — and has shown that in prostate cancer you can halt and reverse prostate cancer with his program. And he’s embarking now on a program in breast cancer, which I suspect, but we’ll have to wait, the results will be positive.

So it’s dramatic research, it’s not out of date. I hear some of my colleagues say, “Oh, Dr. Ornish’s data is aged, it’s old.” Well, he’s working with Nobel Prize winning scientists and continuing to put out some of the most cutting edge data on nutrigenomics and epigenetics. And his diet is one that if all of America were to follow to a large part we’d have a tremendous drop in the burden of chronic diseases like dementia, diabetes, cancer and heart disease. Without question; it’s been scientifically proven.

So my recommendation, I lead in Detroit a patient’s support group for people striving to stick to Dr. Ornish, Dr. Esselstyn, the Pritikin program, the Dr. Neal Barnard, you know, reversing diabetes program. And we have about 1000 volunteer people in the area that get together for meetings and group sessions, and it’s been profoundly effective in improving their health at very low costs, very grass roots.

[54:19][Damien Blenkinsopp]: Yeah. So what do you think of the Paleo principles of dairy and grain avoidance? Would you include those in your recommendations, or are those not relevant?

[Joel Kahn]: Sorry, the question was about grains?

[Damien Blenkinsopp]: Yeah, grains and dairy, in general.

[Joel Kahn]: I’d love everybody to stop eating dairy. I don’t view it as a health food in any setting, and it’s a tremendous burden on animals and the environment. And if somebody is not willing to eliminate animal products from their diet but would be willing to eliminate dairy, it’s one of the most frequent food allergens that people react to. It may be involved in the pathogenesis of Type 1 diabetes in children and young adults.

I wish we could legislate a dairy free world. Even the Harvard School of Public Health has advised greatly minimizing your dairy intake and replacing it with healthy hydration, like water, teas, and coffee, unsweetened; even alcoholic drinks, to a limited degree.

But grains, I know it’s contentious. I have had the pleasure of spending time with Dr. Bill Davis of Wheat Belly, Dr. David Perlmutter of Grain Brain, and I think also a name that’s not as well known, Dr. Alessio Fasano, who’s an Italian scientist now at Harvard who’s really doing amazing research on what grains do to Celiac patients and what’s the actual molecular pathways.

And I tend to favor Dr. Fasano, who I think I’m fairly quoting that one percent of the population is showing signs of Celiac disease, six to seven percent of the population if tested shows signs of gluten sensitivity. And that leaves over 90 percent of the population that neither has Celiac nor documented gluten insensitivity and if they’re reacting to grains, they’re reacting very briefly in a way that’s not a big deal.

And they should be part of a healthy diet. If you look at the scientific data, which I just reviewed and published a blog on in the past six weeks, even just in the last two years the data on whole grains and health is an amazingly strong body of data for survival, for freedom from heart disease, freedom from diabetes, freedom from cancer.

And it’s always a question, what’s it substituting? If you’re eating whole wheat pasta, whole wheat bread or wheat germ you’re probably not eating donuts and fried food and vending machine food because you’re exhibiting an intelligence in a selection on the healthier part of the spectrum.

So, I always encourage my patients that are having problems, take a four week elimination diet from gluten. If you’re having runny noses, rashes, if you’re having unexplained headaches, maybe even for an unexplained cholesterol elevation it could be that it’s inflaming your gut, and four weeks would give us some input on how you’d feel and biological markers.

But I eat whole grains consistently and recommend to my patients they do the same if they’re not in that small percentage.

[Damien Blenkinsopp]: Great, thank you for that clarification.

So if someone is on a Paleo diet or ketogenic high-fat diet, is there a test they could take? Would it be the calcium score, would you recommend that they take that if they want to assess if it’s having some impacts?

[Joel Kahn]: Yeah, well my comment and advice for those that are following a ketogenic diet is if you’re doing it for 10 days to fit into a tuxedo for a wedding, it probably will work and you’re probably not going to do yourself any harm. Long term, again I have to go to science, which there were at least two or three major studies saying long term low-carb ketogenic diets are associated with increased risk of death.

These are studies involving tens, and tens, and tens of thousands of people; yes, they’re databases, yes they’re association studies, but they are strong because there is no data that you live longer with a ketogenic diet. And in the last nine months there’s been specifically a study that ketogenic diets after heart attack are associated with the increased risk of dying.

So I strongly advise my patients not to follow ketogenic diets, and if they choose to, yes I think they should have all the biomarkers. If they don’t know of atherosclerosis then they should be having calcium scoring and possibly the carotid ultrasound testing. But I would advise them against it.

I know it’s all the rage, but it is a stress on the body, it’s a stress on the adrenals. And the healthy carbs found in vegetables, even starchy vegetables and whole grains, are adrenal pleasing sources of nutrition.

[Damien Blenkinsopp]: Great, great. Thanks for the clarification.

[59:00] Winding up, this is kind of a thing that affected a lot of my friends in their 20s. People were working very hard and were taking a lot of caffeine and generally very stressed, [and] we were getting a lot of pains around the heart area.

One of my friends went to a doctor and he said it was just stress and caffeine. I don’t know if you’ve come across this before; is this an issue, or is it just a symptom which isn’t really that important? Maybe too much caffeine or something.

[Joel Kahn]: Yeah. Caffeine in general, I mean it’s interesting. There is some genetic variation, and there is even a blood test you can get that’s a SNP, single nucleotide polymorphism, it tells you if you metabolize caffeine rapidly or slowly. If you metabolize it slowly, it’s going to hang around longer and give you more tendency to feel jittery or racing heart. And if you metabolize it rapidly, otherwise.

But with that aside, if it doesn’t bother you, caffeine is, in most studies, a health food. Now of course, like everything, you dump in some manufactured whitener and sugars, and you don’t have coffee anymore you have some modified, processed, anti-health drink. And certainly a frappuccino isn’t a cup of coffee.

But black coffee, dark roasted coffee two or three cups a day is generally a good boost in the morning, a good brain support. I always would cut it off about two in the afternoon so it doesn’t interfere with sleep. It’s a rich source of antioxidants.

There’s a little concern that your readers may know about that some coffees may be contaminated with mycotoxins, fungal toxins. You don’t really know it because it’s not measured and reported on American coffee sources; it is in Europe, and in fact there’s limits in Europe where they can’t be sold. Coffee beans sit outside and they can get moldy, and the mold can get into the coffee beans.

So you can ask around where you buy your coffee; it’s not a topic that a lot of people know about, and it may be a source of some illness for some people that are sensitive or are drinking lower quality coffees that may have mycotoxins.

With those couple of comments aside, I am pro-coffee. My heart patients ask me, I tell them enjoy a cup of black coffee. I certainly also urge them to enjoy green tea, or any of the teas actually; herbal teas, hibiscus tea, chamomile tea before bed [is a] wonderful source of soothing and sleep support.

[Damien Blenkinsopp]: Right. So it doesn’t sound like there’s any specific mechanism there which would be giving people heart pain from just coffee. Maybe something more like stress?

[Joel Kahn]: Right. There should be no heart pain.

[Damien Blenkinsopp]: Okay, great.

[1:01:32] So, where should someone look first to learn more about your topic? Are there any good books, your books, or presentations on some of the subjects you referenced?

[Joel Kahn]: Sure. I [1:01:41 unclear] appreciated that, and I probably do need to get back to some hospital rounds here. But I do have an active website at www.drjoelkahn.com. And all the blogs and TV interviews and podcasts and things I’ve done over the last few years are there. I encourage anybody to take a peek.

I do have two books out. Last year The Whole Heart Solution, published by Reader’s Digest. And this year a self-published book — but they’re both on Amazon — it’s got the title, Dead Execs Don’t Get Bonuses: How to Survive Your Career With a Healthy Heart, which I think is an important topic and the title has caught a lot of people’s attentions. It’s a real plea to not be one of those dead execs, or dead anybodys, for as long as you can.

I would encourage anybody to read anything by Dr. Dean Ornish, Dr. Caldwell Esselstyn, Dr. Neal Barnard, Dr. Garth Davis in Houston. All active scientists, researchers, clinicians that I think are speaking from the heart about overall health and sort of bucking the trend that all fats are good and animal products are benign.

We just don’t speak about the environment enough. We just don’t speak about animal rights enough, and we have to have a holistic approach to our plate; our plate represents an impact on forests and impact on our waterways and impact on our grandchildren’s world. And our plates represent a process that is very often extremely cruel, extremely unfair to beings that feel and sense pain and terror. And it’s as if we can’t talk about that.

We have labels — Paleo, Mediterranean, Ketogenic — but that’s only partial descriptions. I like to eat a kind diet and my plate is filled with kindness. So I hope that spills into my life as much as possible.

[Damien Blenkinsopp]: Thanks so much for all of those references. That’s a lot of material for people to get through. We’ll put all this stuff up on the show notes, of course.

[1:03:50] One last question. In your own personal life, are there biomarkers that you track on a routine basis? What do you do in terms of collecting data for yourself, for optimizing health and performance, or whatever?

[Joel Kahn]: Yes. I mean, I’ll do inflammatory markers like C-reactive protein, advanced lipid tests like LDL particle number and size. I’ll look at my Vitamin D levels. I’ll look at my male sex hormone, estradiol, total and free testosterone; I try and keep those optimal through natural ways, exercise, weight loss, weight lifting and such, healthy diets, toxin free diets that don’t interfere with the process. Blood sugar and insulin sensitivity, fasting glucose, hemoglobin A1C, important markers. So those would round out the majority that I’m doing: homocysteine level

[Damien Blenkinsopp]: Great, thank you very much for that.

Well Joel, it’s been really great to have you on the show. You know, we’ve covered a lot of ground today and a lot of markers, and I’m sure it’s going to clarify a lot for the audience.

[Joel Kahn]: Well there’s so much people can do. They’re in control of their health. And it starts with realizing that, and realizing the power of food, the power of fitness, the power of abstaining from smoking, the power of sleep, the power of friendship, and then getting credible information. And your podcast has done a wonderful job [with that], and I’m very honored to be able to share with your audience.

[Damien Blenkinsopp]: Thank you.

[Joel Kahn]: Have a great day, sir.

[Damien Blenkinsopp]: You too.

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Meditation – ever more popular as studies pile up proving its benefits. However, how do you assure yourself that you gain the same benefits with your meditation practice? Muse Calm is a neurofeedback device that promises accurate feedback on the quality of your meditation.

In this episode we talk about improving your focus and meditation practice with the Muse Calm app. There are many benefits to meditation. Some find that it helps increase their calm. Other benefits include reducing stress, and changing the structure of the brain.

In spite of these benefits, many find it hard to either start or continue meditating. People wonder if they are doing it right, if they are making progress, or if they are getting results.

Muse is a meditation tech device that tracks your brain waves. Using the Muse Calm app, you get feedback on how focused your mind is. Users can see if they are getting the results they want. It also helps you refine your technique in the moment. This feedback and reward system makes it easier to practice long-term.

When you have the ability to know about your own internal state and your own internal motivators…those subparts that truly are the motivations for your actions, you can live a much better, much happier, much more pleasant, calmer life.
– Ariel Garten

Today’s guest is Ariel Garten. She is the CEO and co-founder of InteraXon, the people behind Muse. She has an unusual background as a neuroscientist, a psychotherapist, and a fashion designer. Called the “Brain Guru,” she’s known for integrating art and neuroscience.

Her research at Toronto’s Krembil Neuroscience Centre focused on regenerating the brain’s hippocampal tissue. She’s lectured about neuroscience and meditation at many events, including TED. Recently, Ariel was selected as one of the nation’s top entrepreneurial women by Ernst & Young.

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

  • Ariel help found InteraXon to allow consumers to see into their minds (11:10).
  • The Muse device is a consumer EEG to track brain waves and comes with Muse Calm, a mediation app (12:23).
  • There are numerous other applications being developed for the Muse device, including for anxiety and ADHD (14:00).
  • Doctors can incorporate Muse into their practice to help patients (17:18).
  • The Muse device is easy to use, but electricity and movement can cofound the readings (20:20).
  • The Muse Calm app was specifically developed as a focused attention training tool (22:07).
  • By tracking four types of brain waves associated with different activities, the Muse device can give feedback on your focus (24:41).
  • Brain wave activity depends on the person and the time of day, so Muse has you calibrate your baseline every session (26:55).
  • Focused breathing is essential to developing a better meditation and mindfulness practice (28:35).
  • Muse Calm can benefit both experienced and new meditators (30:25).
  • Long-term data from Muse users show that people get better at meditating, and that the device helps with a variety of issues (33:07).
  • Self-awareness lets you know yourself in a more meaningful way (34:54).
  • The skills learned through using Muse Calm can benefit you in other areas besides meditation (37:46).
  • Caffeine can either increase or decrease your ability to focus (39:10).
  • Athletes use Muse Calm to calm their anxiety and improve their performance (40:27).
  • Ariel personally tracks the time she spends doing certain activities, blood oxygen levels, and heart rate (44:44).
  • Her biggest recommendation on using body data is to focus on your goals and choose data metrics that will let you reach those goals (46:15).

Thank Ariel Garten on Twitter for this interview.
Click Here to let her know you enjoyed the show!

Ariel Garten and InteraXon

Tools & Tactics

Tech

  • Muse Device and Muse Calm: The Muse solution combines the Muse brain sensing headband – a consumer EEG (electroencephalography) device – with the Muse Calm app. The app provides direct feedback on your state of mind as you use either its guided meditation exercises or practice your own mindfulness or other form of meditation. The app is intended to reduce stress, increase focus, sharpen concentration, and relieve anxiety. Muse Calm works best on iPhone 4S or later, IOS 8 or higher, and Android OS 4.0.4 or higher. The app does not work on desktop or laptop computers.

Walkthrough How-to and Tips on Optimizing the Muse Calm Score

Screenshots from Damien’s Muse Calm App Results

Example Muse Meditation Session Stats
muse-score-one-session
Session Overview Stats Screen
muse-screen

Supplementation

  • Nootropics: Sometimes called “smart drugs” or “cognitive enhancers,” nootropics are drugs or supplements that enhance mental function. The most commonly known are stimulants, including caffeine.

Exercise

  • Mindfulness Meditation: Mindfulness meditation is the practice of sitting meditation. The ultimate goal is to be unconditionally present in the moment. Research has shown that mindfulness-based meditation can help alleviate anxiety, pain, depression, anger, and promote well-being.

Tracking

Biomarkers

  • Brain Waves: The brain produces a range of waves, each associated with different activities and levels of consciousness. Delta waves (0.1 – 4 Hertz) are seen when you are asleep, and theta waves (4 – 7 Hertz) are seen during dreaming or relaxed states. Alpha waves (7 – 14 Hz) can be seen during both relaxed and focused states, while Beta waves (15 – 30 Hertz) are seen during focused cognitive processing. Gamma waves (30 + Hertz) are associated with consciousness and potentially cognitive process.
  • Blood Oxygen Levels: Blood oxygen is the amount of oxygenated hemoglobin in the blood compared to non-oxygenated hemoglobin. Blood oxygenation is important for physical performance and cognitive function. The normal range of blood oxygen levels at sea level for a healthy adult is 96 – 99%; anything less than 94% indicates that you may have a health condition.
  • Heart Rate: Heart rate is measured in beats per minute. For most adults, normal resting heart rate is between 60 and 100 beats per minute. Better cardiovascular health is associated with a lower heart rate.

Lab Tests, Devices and Apps

EEG Devices

  • Biosemi EEG: An EEG system designed to be used specifically in research settings.
  • Brain Vision actiCHamp: A research amplifier that combines components for all electrophysiological research into one componenet.

Personal Fitness Trackers

  • Pulse Oximeter: Used to assess levels of blood O2. An example of one of these devices can be found here.
  • Up by Jawbone: This product tracks sleep, activity, and nutritional information.
  • Misfit Shine: A waterproof activity logger, the Misfit Shine can be used to track various activities.
  • FitBit: The company makes a variety of different personal activity loggers, including the Fitbit Charge.

Other People, Books & Resources

People

  • Sam Harris: Sam Harris is a neuroscientist and an author on meditation and spirituality.
  • Brian Orser: A Canadian skating champion and Olympic silver medalist, Brian Orser currently coaches competitive skaters.
  • Javier Fernandez: Winner of the 2015 World Championships and the 3-time European Champion. Javier represented Spain in the 2010 and 2014 Winter Olympics
  • Nam Nguyen: A Canadian figure skater, Nam was the 2014 World Junior champion, 2014 Skate America bronze medalist, and 2015 Canadian national champion.
  • Jon Kabat-Zinn: Dr. Kabat-Zinn is the founding Executive Director of the Center for Mindfulness in Medicine, Health Care, and Society at the University of Massachusetts Medical School. He is also the founding director of the Stress Reduction Clinic. He teaches mindfulness and Mindfulness-Based Stress Reduction (MBSR), is the author of numerous scientific papers and books.
  • Daniel Goleman: An internationally known psychologist, Daniel Goleman writes about the brain and brain science, including for the New York Times.
  • Dr. B Alan Wallace: Dr. Wallace writes and lectures on incorporating Buddhist contemplative practices with Western science to advance the study of the mind.
  • Dan Harris : Journalist and author on the topic of his personal journey to understand the benefits of meditation.

Organizations

  • Mayo Clinic: a nonprofit medical practice and medical research group based in Rochester, Minnesota. The Mayo Clinic is currently using Muse Calm to reduce stress in cancer patients.
  • Baycrest Health Sciences: A global leader in geriatric residential living, healthcare, research, innovation and education, with a special focus on brain health and aging. Baycrest is currently doing a study on the effect of Muse Calm on blood pressure

Books

  • Waking Up: Recommended by Damien, Sam Harris’ book talks about spirituality without religion.
  • 10% Happier: A book about Dan Harris’ (described by our guest as a “self-absorbed journalist”) as he changes through meditation.
  • Search Inside Yourself: Chade-Meng Tan, one of Google’s earliest engineers, teaches readers the same skills in mindfulness and emotional intelligence that he teaches Google employees.
  • Emotional Intelligence: Daniel Goleman’s book about the importance of emotional intelligence in success.

Full Interview Transcript

Click Here to Read Transcript

(11:07)[DAMIEN BLENKINSOPP]: Ariel, thank you so much for joining us.

[ARIEL GARTEN]: My pleasure, happy to be here.

[DAMIEN BLENKINSOPP]: Could you share a little bit about how you became part of InteraXon and you got to do what you’re doing today?

[ARIEL GARTEN]: Sure. I’m so lucky to be doing what I do today, I have to tell you, I’m really, really thrilled. I founded InteraXon with my co-founders Chris and Trevor about six years ago, it’s actually our sixth birthday tomorrow. Prior to that I was working in a research lab where we used primitive brain computer interface software to allow people to create comfort with their own mind, so they’re actually creating musical experiences.

From there we went on to allow people to control physical stuff with their mind in a very basic way, and this entire time we recognized that we had this amazing technology that allows you to literally peer inside your mind, connect your mind to a device and then do something. So we created InteraXon to really find out what that “something” is that we could do with it and bring a product to market that was ultimately going to help people by.

[DAMIEN BLENKINSOPP]: So, is the innovation with InteraXon, as I understand, it’s because you’re enabling consumers to get in touch with this, whereas a lot of the devices beforehand have been clinical – they’re not exactly very accessible. Is what you’re doing based on trying to make this more widely available, or are there some other specific innovations involved that you’ve brought?

[ARIEL GARTEN]: There are a lot of innovations involved and certainly being more widely available is one of them. The Muse is – for people who don’t know about Muse – a clinical-grade EEG, its seven centers that deliver four channels of data, two on the forehead and two behind the ears. It tracks your brain activity in real time and sends it to your smartphone or tablet.

From there, the application that Muse comes with is basically a meditation tool – focused attention training tool – that teaches you to improve your attention, decrease your stress and learn to self-monitor and self-regulate.

In terms of the innovation, it uses clinical-grade EEG. It’s a dry system, so it’s very sleek, very fun, very easy to wear, and it’s mobile. Our innovation’s around getting EEG to fit easily on any head, getting something that really is just a part of your daily life and it looks like any other wearable device, like a Jawbone UP or a Fitbit.

It’s a little device that you wear as part of your daily life or at home. I sometimes wear mine to parties and people think that it’s actually part of my outfit!

[DAMIEN BLENKINSOPP]: So are you actually using it to track your brain waves while you’re at a party or is it more for decoration?

[ARIEL GARTEN]: I have to admit that I sometimes do that, yes, because I am a neuro-nerd.

(13:34)[DAMIEN BLENKINSOPP]: Well, I’d be interested if you’ve learnt anything about yourself, because I’ve been using it, of course, just for the meditation, with your app Calm since September now. So I’ve been using it specifically for that.

This is basically a consumer EEG device that you’ve made available to people. I understand that you’re going to be able to add other different applications on top of it. Today we have the meditation app called Calm, but there’s potential to add different apps also?

[ARIEL GARTEN]: Yeah, we actually have an ecosystem of hundreds of developers. The SDK is open so anybody can build on top of the Muse platform.

We have people doing things like drowsiness detection, building simple game-based interactions, using it for more complex healthcare needs that are also game-based. There’s a group out of Europe that is doing beautiful applications for kids with anxiety, there’s two groups that are creating lovely applications for kids with ADHD and through gaming they actually improve their ADD/ADHD symptoms. The first one has gone through the first trial.

Then we have over probably 50 different research institutions that we’re working with that are using Muse. Mayo Clinic for example, are just beginning to study the Muse to decrease stress during cancer care; NYE has been using it to look at learning and memory, so true variation across the board – some of them are just fun gaming things, some of them are really serious medical applications.

Then, of course, there is our application that we’ve built called Calm, that comes shipped with the device, and that is a beautiful experience that helps you to understand and improve your own mind.

[DAMIEN BLENKINSOPP]: That’s excellent, I didn’t actually realize that you had as many projects out there. I guess a lot of these we don’t hear about because they’re done more in very specific niche areas, so unless you’re actually looking into the clinical applications…Are these with doctors or are these in universities primarily that it’s being used at the moment? Are there any doctors taking interest?

[ARIEL GARTEN]: We have quite a number of doctors that actually use Muse as a part of their practice. We have a pediatrician who has a Muse room and when kids come in, she can send them to the Muse room to do focused attention training. We have other doctors that recommend the Muse for issues like sleep anxiety and depression. In North America, if you have a naturopath in your clinic, the naturopath can actually sell Muse at the front desk.

Then we have health care institutions that we’re working with to do broad scale studies. Baycrest, it’s a geriatric care facility in Canada, they’re doing a study on Muse’s effect of blood pressure and affect; Mayo, as I said, is doing their study on stress in cancer care patients; I’m trying to think what other ones I’m allowed to mention, but there’s quite a number of them going on.

(16:13)[DAMIEN BLENKINSOPP]: Yeah that’s a lot. I want to talk more about the meditation one now, because that’s the one that’s more widely available to people right now.

For some of these applications, like some of these things other people would be interested in – just like increasing focus and attention, things like that – will these be more widely available or are they going to stay in these niche applications, like with physicians working with them? I guess you’ve got a more private program working with those or is there somewhere someone could go to download these and use them with the Muse headset?

[ARIEL GARTEN]: These are all in very early prototypes that people are building themselves. So from a year forward, you’re going to start to see these things enter into the Muse ecosystem. Some of these studies that are running, like the Mayo Clinic study for example, they’re fusing Muse Calm, using the existing software that comes with Muse, and they’re applying it to these various health care settings.

When a doctor recommends Muse, he’s recommending the existing application, Muse Calm, to help his patients with sleep or anxiety or depression.

[DAMIEN BLENKINSOPP]: So they’re using Muse Calm and then seeing what the impact is on insomnia and some of these outcomes. Is it mindfulness techniques they’re using?

[ARIEL GARTEN]: Yeah, Muse basically teaches you how to meditate. The doctor, if somebody comes in with heart disease, one of the main prescriptions for them is actually change your diet and learn how to meditate so you can manage your own mind and decrease your stress.

Patients will then say, “Okay, how do I do that?” and they walk away and absolutely nothing happens. So now they can come into a doctor’s office and the doctor will say, “Well you should meditate” and frequently they’re saying, “you should meditate and you should use this device. This device is going to teach you how to calm yourself, improve your focus, manage your urges and your cravings, manage the stress in your life, and I will know that you’ve used it because you can come back, you can show me your data, you can show me how you’re improving, we can talk about how this works for you” and it becomes a really actionable tool.

(18:06)[DAMIEN BLENKINSOPP]: Right. The reason I approach this is as soon as it came out, it was because meditation is one of those things that everyone would like to do and everyone would like to do it properly. I’ve been doing it for many years, and honestly, I found it difficult to know how effectively I’m meditating.

I think this is something that a lot of people struggle with when they’re trying to meditate, so it was really, really an interesting device for that reason for me to get hold of.

I want to talk to you a little bit about, first of all, the EEG, you said it’s clinical EEG; so has it gone through specific tests to show that it’s exactly the same output as the bigger contraptions that people are used to when they go into hospital for example, or are there slight differences? What does it mean that it’s clinical EEG?

[ARIEL GARTEN]: We’ve had third parties, hospitals, go through the processes, comparing Muse to Biosemi and to Brain Vision actiCHamp – these are 30 to 50,000 dollar systems that are clinically used – and their analysis came back that it is not statistically different from a clinical-grade EEG.

To be fair, there are only four channels. In those four channels you’re getting the same readings as you would get from a clinical EEG. We can’t see the rest of your head, where you may in a clinical EEG also have sensors on the top of your head and the back of your head.

[DAMIEN BLENKINSOPP]: Typically how many channels are there on a hospital-based machine?

[ARIEL GARTEN]: It depends. There can be anywhere from 19 channels, 32 is common, or all the way up to 128 or 200 and more depending on the application.

[DAMIEN BLENKINSOPP]: Right. So is it sensitivity? What would be the difference between having more or less channels?

[ARIEL GARTEN]: It really depends on where on the head you need to measure and what you’re trying to do. More of anything is typically better, but we found with four channels you can actually get really great data. We’re able to look at the difference between left to right, back to front, we can do some very basic mapping on focal localization – where is the signal coming from in the head – once you have four channels.

For the applications that we’ve been building, this is the perfect channels for the perfect head for the outcomes, and no goopy gel and no wires and no doctor on the other side of the room looking at your data.

(20:20)[DAMIEN BLENKINSOPP]: Right, exactly. I think that’s the important thing to emphasize here, that it’s a lot more convenient than the standard EEG systems – where you have to put gel on your head and it’s kind of messy; this thing, you can just put it on and take it off as you want.

One interesting thing that I noticed: I was wearing headphones – I don’t know if you know this too; I imagine you do – so obviously with a wire, and I found that sometimes I wouldn’t be able to get a signal when I was wearing the headphones and it was irritating me. Then I realized it was because it must have been an electrical signal coming through the wire in the headphones. I’ve got these other air ones now and I don’t get that, so I don’t know if that’s something you’ve seen before?

I just wondered, what kind of confounders could people come across, or things that they should avoid? I think another one is that you shouldn’t be moving, right? You have to be still.

[ARIEL GARTEN]: Yes. EEG is very sensitive. EMG – muscle activity – is much, much louder than EEG, so in order to use an EEG, you have to remain quite still and relax the muscles in your face and neck. That’s the main confounder.

Then if you’re in an insanely electrical environment, you may find that your signal’s having some issues, but overall that should be fine because the electrical lines would be affecting both the ground and the reading channel, so ultimately that should cancel itself out.

But in most environments, it’s pretty good. You can even do it on airplanes. Sometimes when it starts to get really turbulent, then your signal has an issue, but overall, you can use it on the plane.

(21:47)[DAMIEN BLENKINSOPP]: Great. So it sounds like its best suited for meditation, where you’re really not doing anything. If you wanted to increase your focus, like say attention on a task, are there applications that are potentially coming out later that we’ll be able to use to do that?

If you’re working on your computer, you’re moving your head a little bit, from side-to-side, probably not thinking about it much.

[ARIEL GARTEN]: Yeah, actually the best thing to improve your focus on a task is to do the existing application with Calm. It is literally a focused attention training tool; that’s what it’s been built for.

When you Muse, you focus your attention on a single object, and as soon as your mind wanders, you get a notification and then it’s your job to bring your attention back to the single object. The more you’re able to maintain that state of focused attention, the more you’re rewarded by points and birds and all sorts of fun stuff.

I joined a study that we had internally really early on, and after my first two days of Musing, I was doing a long form essay. Typically, these things take me three or four hours to do because I’m distracted, I think about something else, I obsessively check my emails – and this time I started typing and kept typing and I had a slight urge to do something else, now I’m coming back to what I’m doing. It was just phenomenal for my focus.

(22:58)[DAMIEN BLENKINSOPP]: Yeah, there’s a lot of research on the benefits of mindfulness meditation for increasing these things.

I’m wondering, when you wear you device in other scenarios, have you learnt anything interesting from it? You said you would sometimes wear it to parties or anything like that; have you learnt any insights about yourself or anything you’ve learnt from it?

[ARIEL GARTEN]: There’s a couple of really funny examples. I’ve noticed the correlation of my brain activity over the day and with weather. Prior to it raining and when there are changes in pressure systems, I see big decreases in my data activity, decreases in my down activity. I’m like a human barometer in some ways, it’s quite cool.

Another pretty fun story: I was actually on stage and projecting my brain waves live during a presentation that was in Paris. The presentation was in English and then it came to Q & A. Somebody asked me a question in English; my focus spiked a little, I answered, it was not a big deal. I then tried to answer another question in French – being Canadian I marginally speak French and I thought I could show off to the audience – and the audience started to rustle and giggle and I didn’t realize why.

It wasn’t my French, it was my brain activity: my level of data activity had just shot straight through the roof as I was trying to figure out how to answer in French. Then as I started to answer, you could see it come back down again as I’d gone through the processing.

The audience figured this out well before I did – it was behind me, I couldn’t even see it – and so then they started asking me questions in French, playing with my brain activity! Hacking my own brain on the stage, it was really cool.

(24:41)[DAMIEN BLENKINSOPP]: Taking a little bit of a step back; you described a few different waves there, so the Muse is tracking four different types of waves? Could you give a bit of background for the people at home who aren’t used to these different types of waves and what the purposes of them are?

[ARIEL GARTEN]: Sure. The Muse tracks full spectrum EEG activity, from about half a Hertz, which is as low as the EEG is ever going to go, up to EEG that we tend to talk about ending in around 50 or 60 Hertz. 60 Hertz or 50 Hertz when you’re up with activity from the electrical activity in the room, like your lights, etc.

Muscle activity tends to be from 40 Hertz up to hundreds and hundreds of Hertz. EEG is typically broken up into different bands. Delta activity is the lowest wave of activity – that happens predominantly during sleep. Theta activity is from about 3 to 7 Hertz – that happens when you are dreaming or highly relaxed, and also during sleep. Alpha activity is from 8 to 12 Hertz, and that is both a relaxed state and a focused state. Then beta is from 13 up to 35, that’s intense cognitive processing – so if you’re thinking about something, your brain is working.

Then from 35 up, and there’s debate up to how far that up goes – some people say it goes even up to 200 Hertz – we have gamma activity, and gamma is associated with consciousness and a bunch of other very fun things. Sometimes also seen in the meditation literature.

When you go through and you get an EEG, often it’s broken up into these bands. Somebody will say where you’re falling asleep, you know we’re seeing an increase in delta activity, or you’re processing, we can see a lot of beta activity right here, so me trying to speak French, it was very beta. And me relaxing is very alpha.

When we run our algorithms for Muse and we use Calm, what we’re looking for is a state of focused attention and we’re looking a little bit at this band-based activity, but we’re also doing machine learning on your brain activity, and so we’re not saying, “Okay, well, you are in beta activity so you must be focused”; we’re saying, “alright, let’s look closely at what your brain is doing and let’s build a model for your brain that we can then apply much more settled times of thinking and interactions around, rather than just ‘are you in beta? Are you in alpha?'”

(26:55) [DAMIEN BLENKINSOPP]: Right, that’s interesting because I wanted to ask you about how the algorithm worked, just for the people at home. When you first put this application on and you’re going to start a meditation session, it asks you to calibrate, so it asks you to think about some things – so you’re trying to generate beta, I guess, at that time, or the equivalent of beta, like basically, a lot of thinking activity – as a control, and then you try to compare that.

Is it because brains are very personal, is that why you have to take that approach?

[ARIEL GARTEN]: Yes, absolutely. You do a calibration, so we’re looking for the baseline that day. We’re not just looking at beta; we’re looking at all sorts of different things in your brain at that moment. Then we’re seeing how that compares with two sessions that you’ve done previously and to the session that you’re about to do.

We’re able to see a real snapshot of your brain at that moment in time, because not only does your brain differ from day-to-day, it also differs at different points of the day, it differs based on how much caffeine you’ve had, how much sleep you’ve had, the environment around you at that moment.

So we take all of that into account looking at your brain activity, and deciding how you’re going to respond to the algorithm experience.

[DAMIEN BLENKINSOPP]: Basically, it gives you a score – it gives you percentages of calm. Would that vary, would it be relative for each session? Is that what you’re saying – say it was a different time of day or something like that, it will say “for this time of day you’re basically doing well”?

[ARIEL GARTEN]: Yes. Your calm score is relative to your calibration.

[DAMIEN BLENKINSOPP]: The immediate calibration immediately before?

[ARIEL GARTEN]: Exactly, you do calibration every session.

(28:35)[DAMIEN BLENKINSOPP]: Right. I guess the important thing there is like when you’re given the instructions to think about things, you have to do that properly, otherwise that won’t work as effectively?

Mindfulness-based meditation is a type of meditation that has the most research on it. I don’t know if you’ve compared it to mantra or some of the other types of meditations and if you specifically chose mindfulness because there was more research? Could you talk a little bit about why you made the decisions to design the application the way it is?

[ARIEL GARTEN]: Sure. The application that you’re getting is specifically a focused attention training focus, focusing on your breath. This action of focusing on your breath tends to be a really first-line thing that you learn when you learn mindfulness and you learn to meditate.

Once you build your state of focused attention, you can then start to apply it to anything, and you can move your attention around your body and do a body scan for example, or you can move your attention around your environment and do open monitoring, or listen for your own thoughts and put your attention on your own thoughts.

With Muse you’re really doing a core exercise that teaches you this muscle of attention and builds it so that you can then go on through the range of experiences. The application offers a range of teachings that are available in mindfulness and meditation.

The application that we’ve built works very specifically with the focus on your breath, so it doesn’t work with the body scan, it doesn’t work with the mantra meditation, though we will have more exercises like body scans being added to new Calm.

(29:57)[DAMIEN BLENKINSOPP]: Great, and you’ve just actually come out with an upgrade of the original app. The thing I noticed, it used to have difficulty levels, and I think they’ve disappeared now. Is that correct? Or are they still there and I just can’t find them?

[ARIEL GARTEN]: Yes, difficulty levels have disappeared, and I think we’ve replaced it with volume on the wind.

[DAMIEN BLENKINSOPP]: Oh really, that’s interesting. So are there some things you’ve learnt over the past six months that you integrated into the new app which were interesting?

[ARIEL GARTEN]: Absolutely. There are two classes of people who love Muse: one is experienced meditators, and we would hear things from them like, “We don’t want the volume, we don’t want the real time feedback, we just want to see after the fact how we did.” So we now have a volume switch so you can turn off the different sounds, so less to be rewarded by a sound or it’s going to your score at the end.

The other class of people who love Muse are people who kind of know they should meditate but really have no idea about how once they’ve started and it’s really hard to stick to a practice. One of the things that we’ve really learned from that audience is about motivational architecture and what’s required to encourage them into the experiences of meditating with Muse and how you create an experience of motivating and sticking – you just want to come back and do it and you just want to do it every day, and before you notice, you’ve built yourself a meditation practice and that thing that you know you should do is a thing that you’re actually doing.

[DAMIEN BLENKINSOPP]: Yeah, so you’ve integrated a little bit of gaming in there. The birds are still there, as well as the win?

[ARIEL GARTEN]: Yes.

[DAMIEN BLENKINSOPP]: Okay, great. So you had these birds come along when you were being really good and you were being calm for a while and they start chirping, so I think that’s one of the things you’re saying you can turn off the volume on the birds – is that it?

[ARIEL GARTEN]: Yes.

[DAMIEN BLENKINSOPP]: Because some people were saying that was a distraction for them, the way they like to meditate; whereas other people need that feedback to know they’re doing good, as you say, for motivation.

[ARIEL GARTEN]: Exactly, so the vast majority of people love birds, and I will get random texts out of nowhere like, “My grandfather just tried Muse. He got 87 birds,” which is a lot. And people just get very excited about birds. Then every now and again, I hear somebody say, “I hate those damn birds. I’m really, really calm and then they start going.”

[DAMIEN BLENKINSOPP]: Right. Because there is just that little temptation to start listening to the birds, which I guess is starting to interfere with the mindfulness. But in order to add neurofeedback, I guess you need…

[ARIEL GARTEN]: If we’re talking about the birds for a second, because that temptation to listen to the birds is actually part of the experience. Everybody who complained and said, “Those damn birds,” it’s kind of funny because those damn birds are actually part of what’s challenging you.

The goal of mindfulness and meditation, you will ultimately be triggered by something, you might be rewarded by it, and then you get really excited about this reward and then the reward leaves. You’re trying to move to a place of equanimity, where you are not pulled either towards the positive reaction or negative reaction towards something. So these birds are actually there to subtly reinforce these lessons of equanimity.

But if somebody’s not ready for them, you can turn off the volume.

[DAMIEN BLENKINSOPP]: Right. As you get better and you get more birds, you’ll basically be more challenged?

[ARIEL GARTEN]: Yes, and more rewarded, which is also your challenge to not get excited by those rewards.

(33:07)[DAMIEN BLENKINSOPP]: Yeah. I was wondering have you learnt things from using the app, because it’s been out for a while now and I guess you have a lot of data from people. I don’t know if there’s anything you can talk about that you’ve learnt in terms of how people learn and how long does it take to learn to get better at mindfulness-based meditation, or anything like that.

[ARIEL GARTEN]: One of the things that we’ve learned is that people get better. We can see people’s Calm scores and how they improve over time and track those improvements. It’s astonishing; people really stick with it and get better.

We’ve done some fun diagnostics, which is the Calm City. I will check back and send you an email and let you know which city it was. That was a fun little study that we did.

We’ve also learned of the different ways that this can make an impact in people’s lives. I’ve gotten tremendous emails from people. The first one I ever got was a girl who was 27 years old with ADHD. She’d stopped taking medication four years ago and she said within three or four days of using it her parents had noticed a difference. Then within three weeks of doing it, this to her was not a game changer; it was a life changer.

When you give people this small ability to learn that they can actually manage and direct their own mind, extraordinary things start to happen in their lives. If you go and look in our Amazon comments, there’s a woman’s husband with cancer and she was using this to manage the stress of his cancer. There’s another woman who had heart palpitations and was using Muse to manage her heart palpitations and she stopped having them and stopped taking her medication.

When I hear those things, I strictly say, “No, keep taking your medication. It’s not a medical device. It’s not indicated for this.” The things that people are discovering about themselves and how they can learn to manage themselves through non-medical easy to implement tools is pretty amazing.

(34:54)[DAMIEN BLENKINSOPP]: I know from your TED presentation that you’re a big believer in building self-awareness. Could you talk a little bit about that and what it means to you?

[ARIEL GARTEN]: Self-awareness is about being able to know yourself in ways that are meaningful to you. There’s a whole lot of navel gazing that one can do that’s not necessarily useful, and quantified self tends to get very caught up in data. To me, the data is not the important thing, it’s our own human experience. I think data often takes us away from that human experience, which is why we wanted to create a tool that just was based on real time feedback so that you can learn about yourself in real-time in this way that’s really intuitive, really quite emotionally lovely.

As a psychotherapist, and with the [psychotherapist part starting to interact on –??], my job is to help people understand themselves. We have so many things that govern our reactions every day that we have no idea about.

A cliché example, that fight that you had with your boyfriend that comes in and causes you to snap at your boss or your co-worker or your child; you don’t know why is the thing that causes stress and grief and strife and undoes the lovely world that most people are trying to build for themselves. When you have the ability to know about your own internal state and your own internal motivators – these motivators that previously had been secret motivators, hiding deep in your subconscious and below the surface, and just guiding your actions without you even realizing it – when you have the ability to begin to dig in there and to decompose your actions into those subparts that truly are the motivations for your actions, you can live a much better, much happier, much more pleasant, calmer life.

You’re not creating drama and distress and perpetuating discomforts that are your own internal discomfort by putting them on somebody else in ways that you may not have previously realized.

(36:55)[DAMIEN BLENKINSOPP]: Thank you for that because it’s something I feel is very important too, and obviously the Muse device can help to give you these kinds of insights. Do you recommend people do it at a specific time in the day?

One of the things I’ve noticed is that my morning sessions are always a lot calmer than my evening sessions, basically after I’ve been working and doing things like that. Is that very typical? Is that the kind of thing that you would expect?

[ARIEL GARTEN]: Often people’s morning sessions are calmer than their evening sessions, yes. You can do Muse anytime, so the right time to Muse is anytime when it fits best into your day. Some people do it in the morning and set themselves up for the day; other people take it to work and will use it when they have a little break and they need to focus, or when they’ve had an issue and they just need to calm down; and then another set of people do it in the evening to shed the day, or right before bed to improve their sleep.

(37:46)[DAMIEN BLENKINSOPP]: You were talking about it earlier, if something upsets you in your life and maybe you’re not that aware of how much of an influence it’s having on you. Have you heard of case examples where people are using it just to get back in touch with themselves after something? It could be maybe they had a big dose of caffeine and they’re not sure how much of an effect that has on their ability to focus and relax and so on, or maybe it’s when they’re in contact with a certain boss which they find a bit disagreeable – have you heard of examples where people are using it just to touch base with themselves?

[ARIEL GARTEN]: Yes, and to be clear, Muse is not going to tell you that you’re sad, or Muse is not going to tell you that you don’t like your boss; all you’re getting is this feedback of focused or not focused.

But it’s that action of learning to quiet your mind and look inside yourself, and that action of knowing that you can actually observe your own thoughts and take the time and space internally to focus on your own thoughts, that leads to those insights.

And that leads to this state that in the past where your boss had said something really annoying and then you feel the anger rise, you don’t just immediately jump on him and respond the way that’s probably going to threaten your job; you’re able to take the time to then recognize what’s going on internally and respond appropriately.

But we have a bunch of quantified selfers who do fun things like track their neuro response to caffeine, etc.

[DAMIEN BLENKINSOPP]: Are there other thing, like caffeine, which you would say typically disturb it that people should be aware of? Because if they’re using this and they’re upset with their scores because they’re not getting what they should be, are there other things that they could be doing in their life that might be interfering?

[ARIEL GARTEN]: Caffeine – we actually have a relatively personal interactional score. It’s not only the bad thing, and for some people, caffeine really helps you focus. For other people who are over-caffeinated, caffeine makes it very difficult to focus. So it’s not yes or no caffeine, it’s the dose that is actually making you productive.

[DAMIEN BLENKINSOPP]: That would be interesting. Potentially your score in Muse might translate to productivity in some areas as well, so they could tell if caffeine was having a positive.

We all take caffeine and we think it helps, but I think it could help in some situations for some people, and for others it may not be helping – like making us more distracted. So that could be a correlation there.

[ARIEL GARTEN]: Yes, potentially. It’s something to think about. A fun experiment for somebody to run.

(40:11)[DAMIEN BLENKINSOPP]: Great. Are there any others that you can think of offhand, which people could be aware of that might interfere or have an influence?

[ARIEL GARTEN]: Anything that has really aroused you that day, so if your heart is beating and you’re anxious about something, it’s going to show up in your Calm score and that’s what Calm has been teaching you to calm back.

(40:27)[DAMIEN BLENKINSOPP]: How about exercise? Would that have an impact?

[ARIEL GARTEN]: I haven’t run an experiment looking specifically at the effect of exercise on Muse. But, we have quite a number of athletes who use Muse, so we know a lot about the experience of Muse on exercise.

We’ve done programs where you Muse prior to your workout, and people report significantly better workouts – they’re able to push themselves further.

Then we have a good handful of Olympic athletes who’ve been using Muse. Most recently I was talking to you may not know him, he’s a Canadian skater – it’s really valid, and it’s exciting here. Brian Orser is a Canadian Olympic skating championship and he’s been training two amazing young skaters, Javier and Nam. They have been using Muse prior to the World Championships, which just happened a few weeks ago. Javier came in gold in the World Championships after Musing, which is amazing.

[DAMIEN BLENKINSOPP]: It’s competitive advantage!

[ARIEL GARTEN]: Yes, definitely a competitive advantage. And Nam is 15 or 16 years old and I went and I spoke to him after his World Championships. We sat down and he was telling me, I’ve no idea how he’s been using it, but he said that he Mused every day. Prior to Musing and prior to being introduced to me, he would be really distracted and nervous and felt all these incredible social pressures on him being so young and having to perform.

He’d be Musing all the time to get that down and to learn to manage his own anxiety. He’d Mused 15 minutes before every performance, and he Mused 15 minutes before his performance at the Worlds, where he came in fifth at the age of 15 or 16 in the World Men’s Skating Championship.

I heard this a week ago and I was overwhelmed, kind of beside myself.

[DAMIEN BLENKINSOPP]: That’s amazing. There’s so much research on mindfulness proving these kinds of things. It’s great to hear examples where it’s actually happening in the real world.

For the people at home, I guess there are a few things that could be influencing that. First of all, neuromuscular control is basically driven by the brain, so even people lifting weights, they can do better. Or people using nootropics for example, as well – if you’re improving your brain, you’re going to have more control and you’re going to be basically stronger.

Then you’ve got all the coordination and these complex sports and everything like that, which obviously is a lot more brain driven as well. So, there’s definitely a very direct relationship there.

Thank you for those examples, it’s really interesting. If someone was looking to learn more about your topic, are there any books or presentations on the subject, like your TED talk for instance, or is there anything else related to the Muse and some of its applications we could look up?

[ARIEL GARTEN]: You can always go to our website, choosemuse.com. We’re going to go through a website rebuild pretty soon with more and more information and resources there for you.

Then of course there is the entire canon of mindfulness and meditation research. I’ve loved talks by folks like Jon Kabat-Zinn, he’s got a good-old [unclear 0:43:26] school pep talk that teaches you about learning about mindfulness and the impact it can have in your life.

If you’re looking for something really, really accessible, Dan Harris’ book “10% Happier” is really fun. It tracks a journalist, narcissistic, self-absorbed journalist who changed through mindfulness, so lots of really interesting stuff there.

[DAMIEN BLENKINSOPP]: Right, thank you for that. If people want to connect with you, are you on Twitter? What’s the best way to connect with you and follow what you’re up to?

[ARIEL GARTEN]: You can find me on Twitter, @ariel_garten. If you type in Ariel Garten you’ll find me. And Muse is on Twitter @choosemuse.

[DAMIEN BLENKINSOPP]: Okay, great. Is there anyone besides yourself you’d recommend in this area, basically like you’re saying, I guess those references you already gave out would fit that.

[ARIEL GARTEN]: Yeah, sure. Meng from Google wrote an amazing book, “Search Inside Yourself.” It’s sort of an engineer’s perspective on mindfulness. Alan Wallace is always a great one to look into. Daniel Goleman has a great book on focus that ties neuroscience and mindfulness and focus. I can keep going!

[DAMIEN BLENKINSOPP]: It definitely sounds like you’re passionate about this stuff. I’m also interested in just more general, like whether it’s with Muse and meditation or in more general, are there metrics or biomarkers you track for your own body on a routine basis, and things that you use to keep an eye on yourself and you take an interest in?

[ARIEL GARTEN]: For myself, as I said, I’m not into data-driven quantification in the same way because for me it’s about having an actual human experience and data is there to support it. Definitely I’m aware of the amount of exercise that I do, I don’t count my steps but I count the amount of time that I spend in activities like walking, dancing, ice skating, climbing, etc.

[DAMIEN BLENKINSOPP]: Is that through a device?

[ARIEL GARTEN]: I just have weekly goals for myself, and I just do it on a calendar basis.

[DAMIEN BLENKINSOPP]: Are there any lab tests or anything like blood markers that you look at from time to time? Or is that awkward for you?

[ARIEL GARTEN]: Oxygen levels was one I was having fun with for a while. I began very interested in a relationship between oxygen and both cognitive and physical performance. I have a CO2, just a little blood oxygen reader that you clip onto your finger that connects to my iPhone. I’ve tracked my blood oxygen levels in really fun places, including up in planes, and it’s also interesting to then start to look at people of different ages in the same situation and track their blood oxygen levels and see how they’re doing relative to myself. And of course, I’ve got the ones like heart rate.

[DAMIEN BLENKINSOPP]: Yeah, I’ve played around with that a little bit as well. I didn’t really find a lot of change in myself; did you find some interesting things about that in different situations? I didn’t try on the plane one though, which would be the more extreme one, right?

[ARIEL GARTEN]: Definitely with altitude the change becomes very, very clear. Then when I’m fatigued, I see a change in my blood oxygen levels.

[DAMIEN BLENKINSOPP]: What would be your number one recommendation to someone trying to use data to make better decisions about their health, performance or longevity, whatever they’re interested in?

[ARIEL GARTEN]: I would say focus on your goals and choose data metrics that are going to directly lead you to those goals. If fitness is a goal, your step counting is definitely the easiest and simplest way to start. And for absolutely any individual who wants to motivate themselves to lose a little weight and get a little fitter, get a Fitbit, Jawbone UP, Misfit Shine, any of the above and just start to engage in the understanding of your activity and have an impact on your life and simply be active, beginning that correlation will be motivating you to improve.

[DAMIEN BLENKINSOPP]: Yeah, it sounds like you said the greatest benefit is accountability, like a motivation for a lot of these devices.

[ARIEL GARTEN]: Yes, for level one, yes. If you are an athlete in the 90th percentile, you’re well beyond motivation and you’re really trying to optimize. For the vast, vast majority of individuals, motivation is the thing that’s most required to get you to engage in any these mindfulness activities.

[DAMIEN BLENKINSOPP]: Great Ariel, thank you for that, it’s interesting. I certainly agree; a lot of it’s about motivation and accountability, making sure you’re moving in the right direction.

Thank you for all of your tips on Muse and for giving us some insights into how it works.

[ARIEL GARTEN]: My pleasure. Thank you very much for the time. I’m happy to be on the podcast with you.

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What is genetic testing able to do and not do with current services? We talk with one of the top genetic lab services to understand how technologies differ in accuracy and where it is working, where it is not yet ready and why.

In this episode we look at the impact that genetics has on our health and wellness. With rapid discoveries in epigenetics, the picture isn’t as clear as when we thought genetics was everything. Epigenetic factors regulate which parts of our genetic blueprints are actually active and working for us at a given time.

As previously covered throughout this show, the typical “cookie cutter” approach to genetic testing often doesn’t lead to results. We look at the potential for genetics to give us precision medicine and precision health, where people get targeted advice and care fit for individual needs. You are an individual; you are an n=1 experiment.

In which areas does modern day genetic testing give actionable information? For instance, what drugs should you use? What diet may best fit you? Which health complications are you most at risk for in the long term – so that you can strategically manage these and put the effort in where it’s really going to count for you?

We put a team together to really go after genetics as a solution for patients, and using genetics and genomics as a solution for patients, and also physicians, for risk assessment or to give them insight into personal issues and to try and take some action against it.
– Michael Nova

Today’s guest is Dr. Michael Nova. He is Chief Innovation Officer and Founding Executive at Pathway Genomics. The company is an accredited clinical laboratory that offers genetic testing services from screening for cancer and other disease predispositions – to precision health and medicine advice. These services differ and are broader than those of 23andMe, which you probably know about as you listen to this show – that’s the genetic testing company that most people have heard of and used.

Pathway Genomics is the first company to bridge artificial intelligence and genetics-based precision medicine or a health mobile app to consumers. It does this in partnership with IBM, and notably IBM Watson which is IBM’s artificial intelligence machine learning platform.

Dr. Nova is the inventor of many of Pathway Genomics’ solutions. He has over 30 patents and many studies published in peer-reviewed journals. He is also a winner of the World Economic Forum Technology Pioneer Award. Finally, he’s a serial entrepreneur and is on the board of advisors for IBM, which is a pretty big deal.

I hope you enjoy this interview with Dr. Michael Nova and it helps you to understand how genetics can be valuable to you personally.

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

  • Dr. Nova’s roots in genetics and how Pathway Genomics differs from 23andMe in structure, technology, staff, and interpreting testing results (06:12).
  • Why reporting on genetic tests varies between companies; why testing does not produce ‘black and white’ interpretations of tested parameters (15:22).
  • The meaning of personalized / precision medicine; current applicability and future prospects, as numerous testing technologies become cheaper (17:46).
  • How genetic test panels are researched and converted into actionable information for physicians and individuals (20:40).
  • The complexity of genetic and epigenetic tests and why professional guidance is required when making health decisions based on results (29:30).
  • Why epigenetics is more complex than genetics and how genes are switched on / off by interactions with the environment or due to behavior (33:50).
  • Pathway Genomics and IBM’s Watson collaboration – integrating extremely diverse and data-dense medical information into meaningful outputs (36:11).
  • How genetic testing improves pharmacological prescription decisions and why increasingly complex data is even more useful (39:20).
  • Optimizing exercise for individuals using genetic information (46:04).
  • How to access information about personalized medicine and genetic testing (47:33).
  • What information Dr. Nova tracks on himself and why it is crucial to be aware of your genetics (49:46).

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

Michael Nova, Pathway Genomics

Tools & Tactics

Diet & Nutrition

  • Mediterranean Diet: All diet recommendations at Pathway Genomics are generated based on a Mediterranean diet. Based on personal genetic information, diets can be modified towards a low-carbohydrate or low-fat diet.

Tracking

Biomarkers

  • BRCA genes: There are two BRCA genes, BRCA 1 and 2. Certain mutations in these genes are associated with a high risk for developing breast and/or ovarian cancer. Full gene sequencing and results interpretation is offered by the Pathway Genomics BRCATRUE test. Angelina Jolie underwent preventative breast surgery because of her positive BRCA 1&2 status and her family history with breast cancer.
  • Maximal Oxygen Consumption (VO2 max): The maximum rate of oxygen consumption as measured during exercise, usually on a motorized treadmill. VO2 max reflects the aerobic physical fitness of an individual. The Pathway Genomics PathwayFit test includes sequencing of genes which are relevant to VO2 max in individuals.

Lab Tests, Devices and Apps

  • Pathway Panorama (Not Yet Available): This will be a genetics-oriented mobile health application. It is intended to integrate personal genetics with publicly available scientific medical information from trusted sources. Using the IBM Watson engine, the app will compare this information to the standard of care and provide personalized feedback on health and well-being.
  • Fitbit Charge: Fitness watch with automatic monitoring.
  • Pathway Genomics: Genetic Testing Panels

  • BRCATrue: A genetic test that searches for mutations in BRCA1 and BRCA2 genes.
  • PathwayFit: Analyzes over 75 genetic markers known to impact metabolism, exercise, and energy use within the human body. Provides insight into how your body may process sugars, fats, nutrients, and vitamins. This is the most popular test of Pathway Genomics.
  • Healthy Weight DNA Insight: One of the most comprehensive weight-related genetic tests available. Unique combination of nutrigenetic, medication, and general health information.
  • Mental Health DNA Insight: Identifies genetic variants that affect the metabolism and efficacy of psychiatric medications. More than 30 common antidepressants, mood stabilizers and antipsychotic medications included.
  • Pain Medication DNA Insight: Identifies genetic variants that affect how an individual will respond to the analgesic effects of certain types of commonly prescribed pain medications.
  • Cardiac DNA Insight: Tests for the genetic risk of a variety of heart-related health conditions. Examines eight classes of drugs that affect the cardiovascular system.
  • Genetic Testing Technology Platforms

  • Fluidigm Assays: Pathway Genomics uses Fluidigm assays with high precision and whole gene sequencing to detect ALL Single Nucleotide Polymorphisms (SNPs). These are variations in DNA code which are usually associated with predispositions towards health-related conditions. In comparison, the company 23andMe does not use Fluidigm technology.
  • Illumina Chip Seq Assays: In addition to Fluidigm technology, Pathway Genomics uses this technological platform for genetic testing. The company 23andMe also uses this type of genetic testing technology.

Other People, Books & Resources

People

  • Prof. Roger Guillemin: Dr. Nova started his career in genetic at the laboratory of Prof. Guillemin – who was awarded the 1977 Nobel Prize for Physiology or Medicine for his work with hypothalamic hormones.
  • Jim Plante: Founder of Pathway Genomics.
  • Eric Topol: An American cardiologist, geneticist, and digital medicine researcher. Mr. Topol is a leading voice in the field of personalized medicine and putting the consumer in charge of his/her own healthcare.

Organizations

  • IBM Watson Health: Overview of healthcare applicability of the IBM Watson’ artificial intelligence platform.
  • 23andMe genetic testing A popular and accessible genetics testing service company. The 23andMe model is focused on testing for subsets of SNPs (Single Nucleotide Polymorphisms) across various genes.
  • GeneMed: The company provides cancer and infectious disease diagnostic reagents for different instruments and technology platforms. This company also provides development and commercialization services to partners for improving In Vitro Diagnostic (IVD) products.
  • Lab Corp: Laboratory Corporation of America provides lab testing and services, with expertise in esoteric testing, genomics, and clinical and anatomic pathology.

Other

Full Interview Transcript

Click Here to Read Transcript

(06:12)[DAMIEN BLENKINSOPP]: Michael, great to have you on the show.

[MICHAEL NOVA]: Thank you, it’s my pleasure.

[DAMIEN BLENKINSOPP]: How did you first get into the area of genomics, and now it’s personalized medicine, but was there an evolution towards that? When did this first start for you?

[MICHAEL NOVA]: I was a research associate at the Salk institute a while back in a Nobel Prize winner’s laboratory – his name was Roger Guillemin. It was a very large laboratory; it had a lot of different technologies and scientists that were involved with it, as you can imagine.

The overall function of the laboratory was to study growth factors, and so we were studying everything about growth factors. We were studying how the proteins worked, tissue culture, how they interacted with each other, the DNA and RNA genetics of these growth factors, everything you could think of.

[DAMIEN BLENKINSOPP]: When you say growth factors, what exactly would that be for?

[MICHAEL NOVA]: Things like human growth hormone and thyroid releasing hormone and corticotropin-releasing factor, every kind of growth factor.

[DAMIEN BLENKINSOPP]: Okay. Things that stimulate growth in the human body?

[MICHAEL NOVA]: Yeah, in one way or another. He got the Nobel Prize for the first person to isolate TRF, which was a growth factor that was released in the hypothalamus. A signal that is released in the hypothalamus goes to the pituitary and then turns on all these thyroid hormones. That’s what he got it for, and so we were just peeling back the onion on a lot of different growth factors using different technologies.

I got into genetics there and then I started a couple of companies and took one public in the biotech area. We’ve almost used genetics as part of the technology, but it’s only been recently when we started (with Jim Plante, the founder of Pathway Genomics), we put a team together to really go after genetics as a solution for patients, and using genetics and genomics, I guess, as a solution for patients, and also physicians, for risk assessment or to give them insight into personal issues and to try and take some action against it.

I think it’s really been within the last ten years that the technology has been inexpensive enough that we could even try to use it directly for patients.

[DAMIEN BLENKINSOPP]: Great. First of all, I think a lot of people have heard of 23andMe, but they haven’t necessarily heard of Pathway Genomics, so could you give us a comparison of how the technologies compare and how the service is different? I know Pathway Genomics kind of evolved over time, so potentially a bit of that back story would be helpful too.

[MICHAEL NOVA]: Sure. First of all, the major difference is we have our own laboratory; 23andMe doesn’t. We have a big laboratory staff and scientific staff and curators and all that. All the tests come back to our laboratory and we do the DNA isolation and we do the reading of the mutations on different types of machines and then develop a report that goes back to the physician, which is the second difference: we’re only a physician’s ordered test; we’re not direct to consumer. So there has to be a physician in the loop or some kind of health provider in the loop, certainly on the ordering side, but also on the interpretation of the test.

All our tests are covered by insurance in the United States – that’s a third differentiator. We sell our tests in 44 different countries…

[DAMIEN BLENKINSOPP]: So just on the insurance angle; I understand it that you’re targeting a much smaller range of genetics, and basically you’re targeting specific arrays of things that you want to look at, like pharmacogenetics and other areas of the human body, whereas 23andMe is very, very broad in terms of what they look for?

[MICHAEL NOVA]: Yeah that was going to be my fourth!

[DAMIEN BLENKINSOPP]: Oh sorry.

[MICHAEL NOVA]: You took the wind out of my sails with that one, that was going to be the fourth big differentiator. We offer, like you said, panels of genes. We have a test for fit, nutrition and exercise, which only covers those two elements and then some eating behaviors and some metabolism.

Then we have another test for pharmacogenetics, like you mentioned. And one which is specifically for psychiatric, and another one that’s specifically for pain medications. Then we have a cardiovascular test, a cardiovascular risk, which also has some diet and exercise components in it.

So we have about 12 different product lines, 12 different types of tests, including BRCA. We do whole genome sequencing or next generation sequencing for the entire BRCA gene, if you know that gene. It’s the one that is prominent in certain ethnic groups for hereditary breast cancer. It’s the same gene that Angelina Jolie had. So we test for that as well.

We’re the only comprehensive genetic testing company that has health and wellness products all the way to hardcore next generation sequencing products for risk assessment for things like breast cancer.

A new thing that’s coming is we have an alliance with IBM, who’s an equity partner, and we’re building a mobile application that will basically put an artificial intelligence super computer in a handset to help with managing patient information and giving recommendations back directly to the user. That will be a direct to consumer type of product, but at this point we don’t sell any of our genetic tests direct to consumer.

[DAMIEN BLENKINSOPP]: I’d like to take a little step back because 23andMe and you are really very different propositions. There’s also the technology and the accuracy of the tests, and you have a different price point as well. Whereas I think for 23andMe for the whole thing right now, it’s $99; per array, yours is roughly $199 per different panel. So why is that, what’s the difference in the technology and what you’re delivering?

[MICHAEL NOVA]: It depends on the genetic tests. We do Fluidigm assays for our smaller arrays of up to about 80 different genes; 23andMe doesn’t do that. They basically take an Illumina chip that’s got a certain number of markers on it and run that chip for their $99 test. We also have that chip-based technology and then we also have the sequencing technology, which 23andMe doesn’t have.

So we have, the sequencing technology is basically more expensive than the Fluidigm or TaqMan assays, which are probably the least expensive.

We run every different type of genetic testing in here, but some of our reports require more than one platform. Some of them require the Fluidigm platform plus either maybe a sequencing or plus an Illumina chip, so the cost varies on a particular report based number one, on the technology that we’re using – it could be more expensive to run that particular report.

Then the way we do the reports is also different. We have a physician that reviews the results, we have a dietician that reviews the results, we have all those people that are on staff that are patient and can access at any time, so there’s a little bit more cost that’s embedded into the test or tests, depending on which one the clinician orders from us.

[DAMIEN BLENKINSOPP]: Right. Are your tests 100% accurate, so we could run them one time and we’d know for sure which gene SNPs we have?

[MICHAEL NOVA]: Sure. We have our own laboratory and it’s CLIA certified, CAP certified, it’s New York State certified. We’re the only comprehensive genetic testing company that has a health and wellness panel that’s been certified by New York State, which is very difficult to get.

23andMe can’t sell in New York State; they can’t sell in certain countries because direct to consumers is illegal. It’s illegal in places like Brazil and Singapore.

Our accuracy, since we’re licensed by three or four different licensing bodies, they come in here and inspect us all the time, at least once a year on all of them. So, we have to be extremely accurate.

[DAMIEN BLENKINSOPP]: I guess what I’m getting at also is the chip set that 23andMe is using is pretty reliable but it’s not 100% accurate, as I understand it. So in the past when I’ve done tests – I’ve done the 23andMe and I’ve done some other more specific genetics tests – and the answers weren’t the same. As I understood it, it was related to the technology that 23andMe uses, which is very economical to get a lot of data – which is interesting, so look at a variety of risks – but if you want to actually get clinical based information where you’re going to make decisions, you should run with the sequencing technology that you’re using with your panels to be 100% certain. Or am I looking at the wrong things there?

[MICHAEL NOVA]: No, I think you’re right on one aspect or a couple of aspects of what you said. I think that for things like the BRCA test, which is a very serious type of genetic test, 23andMe only reports on a couple of variants on the BRCA mutations, whereas we run the entire sequence. So the doctors come to us for that particular test; they would not necessarily go to 23andMe, even though the mutations that they provide and the way they do it are probably accurate, but they, just by definition, miss stuff.

It doesn’t mean that their technology is bad, which it isn’t; it doesn’t mean that the way they run the Illumina chip is not sufficient. That’s not correct. For what they’re reporting on, it’s perfectly adequate.

[DAMIEN BLENKINSOPP]: So everything you get reported should be correct with their technology as well – the Illumina chip?

[MICHAEL NOVA]: Yeah and I think it’s a good company. 23andMe is a good company. There are good companies like us and 23andMe and some of the other ones – we’ve been at this for eight years or seven years; we know what we’re doing. We just happen to have our own laboratory and so we’re under a lot of different kinds of governance that 23andMe isn’t under.

(15:22)[DAMIEN BLENKINSOPP]: Do you use blood samples as well, or is it saliva samples?

[MICHAEL NOVA]: Sure, we can use blood, saliva…

[DAMIEN BLENKINSOPP]: Is there a difference in the quality, or is it exactly the same, it doesn’t really matter which one you use?

[MICHAEL NOVA]: Both samples have different pluses and minuses, but trying to get to the same endpoint you still have to conform to what the governing bodies and what the licensing groups want us to report on. So we don’t have any choice but to make them equal in the end – if you gave us a blood sample or a saliva sample. But the way we do each one… in some respects it’s harder to do saliva because there are more contaminants in it and whatever, but then it’s a much easier test. People don’t necessarily want to get needle stick all the time.

[DAMIEN BLENKINSOPP]: I guess I’m trying to understand like I had a blood test run through DNA sequencing and a couple of the SNPs were different compared to my 23andMe. What would be the cause of that or is it a mystery?

[MICHAEL NOVA]: We can’t do that necessarily. We would certainly have to report on the same SNPs in the report in the same way so I don’t know. It could be a number of different things.

23andMe, again, has been around for a long time and so I think the accuracy of their reports and what they’re reporting on is really good. It’s hard for me to make a kind of black or white decision on something like that.

[DAMIEN BLENKINSOPP]: No, no, I’m not talking black or white, I’m just curious if there was a technological basis or something like that.

[MICHAEL NOVA]: There might be.

[DAMIEN BLENKINSOPP]: Yeah, I just figured it was the slightly different configuration of the technology.

[MICHAEL NOVA]: I’ll give you a really good example here and I think people don’t realize it: If you went and got a SMAT panel or a CAM panel from one company, like LabCorp, or you went and got one and put in the same sample to Quest, there’s no question that there will be a little bit of difference in what each one of these things reported on, but just a tiny bit of difference. That doesn’t mean that they’re wrong – either of them.

People think that genetics is black and white and the laboratory results are exactly 100% supposed to be the same all the time; that’s not necessarily true. And then we don’t know a lot more about the genetics either: There are 25,000 different genes, and we probably know what about 10,000 of them actually really do, but then they have to work with each other and all this kind of stuff.

I think getting the information on the particular SNPs is not necessarily the hard part; the hard part is interpreting what it means and giving that information back to the patient.

[DAMIEN BLENKINSOPP]: So it may be just a different reporting basis, that’s what it sounds like.

[MICHAEL NOVA]: Yeah, it could be.

(17:46)[DAMIEN BLENKINSOPP]: Taking a little step back, because I know this is basically your area, what does a shift to personalized or precision medicine and health mean versus where we are currently in the world?

[MICHAEL NOVA]: As a physician, we’ve always kind of practiced personalized medicine. When somebody comes in and they’ve got some condition they’re worried about, we give them their medications or help based on them as a person. But now, we’ve got a lot more tools. There’s a lot more granularity in what we can actually see that might be affecting this individual or even preventing things from happening.

Genetics is just one of those tools. So there’s genetics, there’s epigenetics, there’s transcriptomics, there’s all these different types of technologies now that are becoming less and less expensive. They’re kind of getting weaved into the management, if you will, of patients, and that’s what doctors are doing, basically, with our reports.

Precision medicine is just another name for personalized medicine, but I think one of the reasons there’s a much bigger push for it now is that we’re really seeing some major advances in cancer-targeted therapies using genetics, we know cancer is a genetic disease, a molecular disease. We’re now starting to target individual mutations in these cancers to give better results.

We’re now getting a clearer understanding of things like obesity – there are 97 genes that are related to obesity – they’re all different metabolites. It’s not necessarily going to be one size fits all and now we just have technologies that are getting less and less expensive to weave in information for the physicians to make decisions on. That’s where it’s at right now.

This is going to be an ongoing process forever; there’s going to be some sort of genetics or -omics or precision medicine technology that we’ll be able to use to really personalize individual therapies or prevention regimes or whatever you want to call it.

b>[DAMIEN BLENKINSOPP]: I guess one of the things about personalized is, if we take a comparison: If you have a cough today, you’re given the same drug no matter who you are; but in the future – and you have a panel which is pharmacokinetics – you could look at the impact of the drug on you – depending on your genes, drugs have a different impact. So it’s taking it up to a much more personalized level than what is possible today by just looking at someone.

In some cases, maybe you’ll see they’re different and maybe have got some blood test that is slightly different, but the genetics adds another layer of personalization.

[MICHAEL NOVA]: This is standard knowledge in the industry that anywhere between 40 and 50% of all drugs that are prescribed fail for the user, and especially the first time around. That’s a huge number.
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If we can add some way of tailoring those drugs – maybe you take this antidepressant instead of that antidepressant or you take this cough drug versus some other cough drug because your liver is metabolizing it different based on your genetics – you’re more likely to get a much better result.

Again, that is certainly where everything is headed in this whole precision medicine area.

(20:40)[DAMIEN BLENKINSOPP]: Great. So I also just wanted to talk to you – your tests are insured compared to the other ones, so I guess that the extent of research done on the specific panels is quite deep to get to that level where now tests can be insured.

[MICHAEL NOVA]: Yeah it depends. I’ll just take Medicare as an example because they’re kind of the gatekeeper for insurance coverage and our tests are covered by Medicare. The way that Medicare does it now in the United States, it looks at a panel on a gene by gene basis, and some genes have more clearly defined outcomes and predictability than others. So, on a panel of 80 genes, they might only cover three or four of them, but that’s enough to cover the entire cost of the panel.

There are three big levels of gene coverage in America. There’s a) genes that are covered automatically, like methylenetetrahydrofolate and some of the genes for warfarin metabolism. These are covered automatically, it’s an automatic payment, and since the technology on the panel is cheap enough, at least for us, to get over the cost of doing just that one gene, whatever Medicare decides to pay us, we make enough money to cover the panel. That goes for all the other insurance companies too, whether it’s United Healthcare pays on certain things, Aetna pays on certain things. Some insurance companies don’t pay at all on genetics, one way or another, so it really is not just based on whether the data is good enough, but it’s also based on whether a certain insurance company thinks it’s relevant enough to pay for it.

[DAMIEN BLENKINSOPP]: Right, right. As you’re saying, only part of your panel will necessarily be covered by that, and then there’s other things you’ve added, which you feel are relevant too. How’d you make those decisions? What kind of level of research has to be done?

[MICHAEL NOVA]: Yeah. We have a very strong curation. We have, I think, 15 PhD level geneticists and genetic counselors, and myself and a number of MDs, and we basically go and we grind through the literature. We look for human clinical studies and see if the data is relevant enough or there’s enough human clinical studies to put the gene into the panel and then report on it. We can only report on what the human clinical studies tell us.

There are plenty of genes and plenty of studies out there that we never would report on because we don’t think it’s relative; we don’t think that the data is strong enough. So to give you an example, in our healthy weight and fit test – which is our most popular test by far – we rate the science level in the test.

A really good clinical scientific study, let’s say on thousands of patients, and it has to be replicated in the same ethnic group, showed the same results and hopefully over multiple times, then that gets four stars.

Then there are other studies that aren’t quite as well validated but we think that there’s relevance because it might only have been done in two or three clinical studies of 500 patients each, which isn’t necessary a thousand patients but it’s 500 and it does show the same phenotype or it does show the same direction for what the genetics is reporting on. That’s a pretty good study so that gets put in the test too.

[DAMIEN BLENKINSOPP]: Great. I was going to actually ask you which was your most popular test but you’ve already brought it up.

So in terms of what that test gives people, who’s asking for the test and in what conditions are physicians looking for this kind of test? Is it someone who’s had a recurrent obesity problem for a very long time? What are the kinds of conditions and what’s actionable about that information for the physician once he gets it?

[MICHAEL NOVA]: For that particular test, we have a lot of different types of physicians that order it. Some are obviously looking for weight management, weight control in their population. But we also have people that are diabetics that are trying to use it to control their sugar levels or hemoglobin A1c levels, so we have a whole group of anti-diabetic groups that are using the test.

We have cardiovascular groups: many cardiologists think that most cardiovascular disease can be prevented by diet and exercise changing, so we have a lot of cardiologists that order the test and try to put people on more balanced types of diets, more personalized types of diets. Not necessarily to lose weight but to cut down lipid levels and other things that cardiologists worry about.

Then we have performance groups: we have performance athletes, we have gyms like Equinox health clubs that order our tests for a lot of their gym members to either increase performance or put on muscle mass, depending on what exercise.

So basically we have a lot of different types of groups, not just one type of clinician or group that orders the test.

[DAMIEN BLENKINSOPP]: Great. Is there an example you could walk us through of one of the most actionable genes in that area which people look at?

[MICHAEL NOVA]: Well, on that particular test… or do you mean all our tests?

[DAMIEN BLENKINSOPP]: The most popular one, because you said this was the most popular, if there’s one specific gene that people watch out for more than others.

[MICHAEL NOVA]: I don’t think it’s one particular gene. There are about 80 genes that we report on and we chop up the test into basically seven different sections. One section has to do with what is the best diet for you if you’re trying to lose weight and we have four different diets. That’s based on 50 different genes and how they interact with each other. Then we give you a diet recommendation, whether it’s low-carb, low-fat, standard Mediterranean or balanced diet. All of our diets are based on Mediterranean, but some have lower carbohydrates than others; some have lower fats.

Then we also give diet plans along with. So that’s a very popular part of the test, that section.

Another popular part of the test is we have a behavioral section, which looks at things like eating disinhibition – “I can’t stop eating.” Those genes around “When I start eating, I can’t stop eating.” Those genes in your dopamine pathway. We look at sugars – “Do I have a sweet tooth? Do I tend to like sugars more?” So this whole behavioral section is a very popular chunk of the test as well.

Then we have a standard metabolism section – we look at things like do you have a tendency to have increased insulin? Do you have a tendency to have increased lipid levels? Those types of genes, and there are multiple genes in that section – 20 or 30 genes in that section, so that’s also a popular part of the test.

[DAMIEN BLENKINSOPP]: Right. One of the interesting scenarios I think is the diet, the high fat versus the low-carb and the low-fat. Because a lot of the dietary recommendations today, it’s basically which crowd do you want to go with? I’m with the low-carb crowd; I’m with the high fat crowd, high protein…

Some of the genes can be pretty significant in that area, like the APOE gene. Could you talk a little bit about that and how that influences your diet and whether fats are going to be good for you or are basically going to be problematic.

[MICHAEL NOVA]: Let’s go back and look at diets in general. Most people, if they got on a diet and it was less calories than they usually intake and they stayed on that diet for years, they would probably lose weight. But it’s very difficult to get people to do that for a number of reasons.

So what we try to do is we try to look at particular genetics around fat metabolism – and APOE is one of them, and PPARgamma, and even FTO and some of these other genes – and not only how you process fats but also how you taste things. You have bitter taste receptors that we look at.

People don’t eat things that they don’t like, so we try to tailor the diet based on a number of these big subsets, whether it’s how you metabolize lipids – and people that have two copies of the FTO gene, there’s no question that they have trouble metabolizing fat in a low carbohydrate diet than somebody that doesn’t have those. That gene has been very well characterized and is a known obesogenic gene along with MCR4. If you put those two genes together, people that have those two genes tend to be about ten pounds overweight than people that don’t have them.

So we take that information, then we go back and we design a diet that’s based around not only what your metabolism is but also what you potentially would like to eat and make it a diet that isn’t too rigorous, that you’ll never stay on, and then try to give you direct diet plans – basically what to eat, literally, on a daily basis: Breakfast, lunch and dinner, this is what you should eat.

Then we have diet specialists and nutritionists and exercise physiologists and all that stuff, that if you really need help with that kind of stuff, we have ways to get you that as well.

I guess what I’m getting at is we don’t like to look at genetics in a vacuum. It’s one part of a big puzzle, and the more pieces of the puzzle we can put together, the more success we have for personalizing things for the user. That seems to really work.

We have other 20,000 physicians in the US that are ordering our tests and they keep ordering it over and over again, along with our diet plans and whatever information we give them, and the results speak for themselves – they’ve shown that what they get out for their patients is really working.

(29:30)[DAMIEN BLENKINSOPP]: Can we just go back to a distinction that you made was that you’re not doing genetics, you’re more doing genomics, right – the interaction of all of the genes together? Is that what you mean by you were saying?

[MICHAEL NOVA]: That’s a little bit of a slicing that onion really thin.

[DAMIEN BLENKINSOPP]: So what is the approach? You’re saying that it’s not a good idea to look at just one specific gene on its own?

[MICHAEL NOVA]: Yeah, very few things are one gene and then you have something bad happen. Even then, even for things like BRCA, it’s still only a relative statistic. Even if you have BRCA and you’re Ashkenazi Jewish and have the mutations that are relevant, there is still only a 80% probability that you’ll end up having breast cancer. So that means there’s 20% that you wouldn’t have breast cancer.

So very few things are one gene, one bad outcome, fortunately. It’s usually multiple genes. Again, we talked about obesity – there’s at least 80 or 90 different genes that have something to do with making somebody obese. And how they all work together? That’s the gold nugget in all this business is how to figure out how they all work together.

[DAMIEN BLENKINSOPP]: The BRCA gene is interesting because they’re pretty extreme decisions, or as you say, very rational decisions, but a lot of people see it as an extreme decision that Angelina Jolie has taken and it’s been in the press and everything.

One factor into that is that there’s genetics versus epigenetics and how we approach genetics in practice when there’s potential for some epigenetic influence and where the gene’s not actually turned on or off, right? You don’t know which one it is – is it turned on or is it turned off? Were Angelina Jolie’s BRCA genes – were they turned on and, therefore, they did represent the risk?

So, just based on what you said there, you said there was an 80% chance – I don’t know if that was a real statistic with a certain BRCA gene, but would it be in that kind of order that they were looking at BRCA?

If you took your BRCA panel, even not looking at the epigenetic influence, is there an 80% chance that that risk really exists, without taking into account the epigenetic influences?

[MICHAEL NOVA]: Correct. And remember, BRCA was first isolated in the Ashkenazi Jewish population – that’s where it’s most relevant. Angelina Jolie had family members who had breast cancer. So her decision to have surgery was based not only that she was BRCA1 and BRCA2 positive but also the fact that her mother, I think, died of breast cancer, and she’s half Ashkenazi Jewish.

So there were a number of factors that went into her decision to have surgery, not only to have her mammaries resected but also to have her ovaries taken out. I think she went down that path as well because there’s an increased risk, potentially, for ovarian cancer, which is still a very serious disease.

So you have to take all the information in total. If there was no breast cancer in her family and she wasn’t part Ashkenazi Jewish, then there might be a reason to not potentially go down that path. But that’s up to her and her clinician to work that out.

That’s why we don’t think a test like that, which is a very serious test, should ever be direct to consumer. That, for us, is something that really needs some guidance along with trying to make decisions about that.

[DAMIEN BLENKINSOPP]: Right. Excellent. I think the epigenetics area – how do you approach working with your physicians and advising them?

Do you ask them to look at factors like you were just talking about hereditary? – what’s the situation with your parents, your grandparents; other things you can look at in conjunction with some of your tests in order to capture the epigenetics? – whether something’s actually taking place or not: Do you say, “You should run these blood tests if you get these genes, and thus you could make a better decision based on that,” or do you tend to keep it to the genetics themselves?

[MICHAEL NOVA]: We tend to keep it to the genetics at this point because epigenetics is fairly new. There’s not enough data – although I do totally believe in it – in a lot of respects for us to weave that in to the process of, “You’ve got this gene but it’s not turned off.” We can do that from a technology stand point, but there’s not enough clinical data to make really informed decisions around that.

[DAMIEN BLENKINSOPP]: Right. I was talking more, at this point, as you say, epigenetics is relatively new and it’s probably quite expensive at this point for you to be integrating that type of service.

[MICHAEL NOVA]: Those kinds of expression assays – although Illumina has a methylone chip, but I don’t think it’s a clinical grade thing – it’s definitely more expensive than the genetics.

(33:50)[DAMIEN BLENKINSOPP]: I was thinking more about metabolites and lipids and things like that. So for example, we were talking about the APOE, so if your cholesterol markers are off, that would be an indicator that that gene is switched on – correct?

[MICHAEL NOVA]: Yeah, something is definitely not working correctly or you’ve got something in your diet, also, that’s not the correct diet. Maybe you’re eating too much of X, you should be eating more of Y. So there’s, again, a number of different factors – genetics, epigenetics, proteomics, metabolomics.

The metabolomics and the proteomics and looking at lipid panels, those give you a snapshot, an immediate time of day, this is what your lipid level showed. What genetics does is give you a tendency towards where potentially the lipid levels in the long run will go if you don’t take certain actions doing certain things.

[DAMIEN BLENKINSOPP]: Yeah it does. I think the area of epigenetics is potentially very confusing to people because there is this aspect of genes potentially staying switched off. Say, for instance, exercise is an important mechanism for turning off – I’m not saying this is true – but the APOE gene, right?

[MICHAEL NOVA]: There’s been data that’s shown that FTO gene for obesity can be mitigated with certain exercise and diet regimes; those are known facts. There are starting to be really hardcore data around using the environment, and epigenetics is all around using the environment – what you do in your environment to turn genes on and off – and there is data around that.

That would be one example of something that in the near future we might end up reporting on. You can change how genes are expressed by something in the environment.

[DAMIEN BLENKINSOPP]: I’m sure at this stage it’s just at a discussion level with you and colleagues and other people that you know, but how far out do you think these kinds of things are, like being able to take the next step and understanding the epigenetic aspect of it and making decisions based on that as well as just the genetics?

[MICHAEL NOVA]: Epigenetics in some respects is even more complicated than the genetics because there are so many different things that can turn genes on and off: there are methylation patterns, there are acetylation patterns, there are phosphorylation patterns, which means molecules that actually bind the DNA, or histones or whatever, and modify things and turn genes on and off.

And then there are all the microRNAs. There’s thousands of different microRNAs, the junk matter in DNA that will turn genes on and off if they’re expressed or not. So it’s extraordinarily complicated!

(36:11)[DAMIEN BLENKINSOPP]: IBM is an equity partner in Pathway Genomics?

[MICHAEL NOVA]: Yes.

[DAMIEN BLENKINSOPP]: Right. I wanted to talk about Pathway [unclear 36:16] but I think it’s also relevant to what we’re discussing right now, it being so complex and everything. Are you looking at bioinformatics and things like that potentially in the future?

[MICHAEL NOVA]: See that’s what computers are really good at. They’re good at taking noise, basically. Whereas we would look at it and not come up with any pattern; a computer’s really good at making patterns out of things. They’re not necessarily sentient, but they’re really good at taking databases and huge amounts of information and then telling you that these two things are linked together – that’s what the information is. That’s basically what we’re starting to build with IBM.

We have a very strong bioinformatics group and engineering group, and this is an artificial intelligence. Basically, it’s the Watson artificial intelligence that can play chess and was on “Jeopardy!” the show in the United States. So we have to train it.

We like to say it’s a little bit like a dog: you train the dog by lobbing it a question and seeing what answer you get back and seeing if it’s relevant. 99% of the time to start with it’s not relevant, then you have to tell it why it’s no, and go back “It should be this instead of that.”

It’s a huge process to train, especially around health care, because there’s nothing that’s more data dense than health care data. It’s not just genetic data we’re interested in; we’re interested in your electronic health record, your lab results, your wearables – your Fitbit data and all that other stuff. We want to take all that information and then compare it to the standard of care that’s what’s going to be in the Watson engine, and then give you back a recommendation that’s really personalized.

If you asked a question like, “I’ve got a nose bleed” – if you have our mobile app Panorama – “I’ve got a nose bleed, what should I do?” you would get a different answer potentially than what I would because I’ve scanned all this different information about you and compared it to what is the standard of care, and since you’re a little bit different in this gene and your latest lab result is a little bit different over there and maybe you went for a run and fell on your face, all of those bits of information are really important in order to give you a decision or some sort of recommendation about what to do.

[DAMIEN BLENKINSOPP]: Right. That sounds incredibly ambitious.

[MICHAEL NOVA]: Sure.

[DAMIEN BLENKINSOPP]: But you are going to release something relatively soon, aren’t you, so what will that be when it comes out?

[MICHAEL NOVA]: We will have public beta, sometime September to October time frame this year. We’re going through trials right now with the alpha version.

Like you said, it’s a very complicated problem because it deals with a lot of different types of data, and then getting that data so Watson can understand it, which is a whole engineering task on its own, and then getting the right information into Watson – or IBM, the super computer, the artificial intelligence – and then getting the right and curated information in there so it has the state of art in what people are thinking in terms of health care.

So you’re right, it’s extremely ambitious, and we’re really, really excited about it.

[DAMIEN BLENKINSOPP]: Yeah I can imagine. It will be fun to use it when it comes out. Is it going to be sold through iTunes or something, how’s it going to work?

[MICHAEL NOVA]: Yeah, we’ll go through the iStore and all that, and whatever Android is.

(39:20) [DAMIEN BLENKINSOPP]: Okay great. One of the other things we touched on that I wanted to get a bit deeper into because I think a lot of people don’t realize how varied this is, is pharmacogenomics.

You have several panels; it’s quite extensive the number of panels, it seems, under that area, because you have mental health areas and other areas. Is it extremely varied the impact a drug can have on each and every person? Is this very common that drugs have very different impacts per person?

[MICHAEL NOVA]: I’ll start with the panel. We have two or three different panels for pharmacogenomics. One is what you mentioned, it’s a mental health panel that has things like anti-depressants, antipsychotics, mood elevators, 30 or 40 different drugs and they each are metabolized in your liver a little bit differently.

One drug is metabolized differently to another drug, and we look at those mutations in your liver enzymes – they’re called cytochromes.

Then there are also transport proteins that have variance in how the drug is transported from the blood into the cells. There are a couple of drugs in there that have different transport kinetics. Then there are some of them also that get excreted by your kidneys, and they have a little bit different kinetics.

So we put that whole panel together on mental health based on a lot of this genetic information, or the best that we could find. Doctors use it to try and start somebody out on a drug rather than guessing what this person should have, or they’ll change a drug based on the genetics because they’ll understand why this potential drug isn’t necessarily working.

Then we have other panels. We have a pain panel, which does the same kind of thing but around pain medications – the codeines, oxycodone, morphine, tramadol, things like that – they get metabolized differently.

[DAMIEN BLENKINSOPP]: When you say metabolized, it means processed by the liver?

[MICHAEL NOVA]: Yeah, processed by the liver. There’s also transporters and uptake and excretion that are a little bit different for some of these drugs. Again, we use that information on a broad panel of different genes to tailor what potentially would be better for somebody than something else.

That kind of data is getting better. The good thing about genetics in general is that the data just gets better and better; it doesn’t get worse. It’s not like cold fusion – it’s not going to go away. It’s just going to be integrated more and more into the practice and pharmacogenetics and, obviously, drug metabolism is a huge deal.

To give you a good example: in the Asian population, there’s a drug called carbamazepine and it’s used as an anticonvulsant. There are genes involved around the metabolism of carbamazepine that if you have these particular genes, you will probably have a very high likelihood of going into Stevens-Johnson Syndrome if you take carbamazepine, and that’s a very serious disease.

[DAMIEN BLENKINSOPP]: Stevens-Johnson Syndrome; could you just describe the effects of that because I don’t think it’s very common but it’s pretty horrific, right?

[MICHAEL NOVA]: Yeah, it’s an allergic reaction basically, an immune reaction against this particular drug and you can basically end up dying from it – you go into anaphylactic shock and your skin starts to slough off. It’s a really nasty way to go if you want to call it that way. But again, it’s not very common.

But it is common more in Asians, and so screening for carbamazepine is 100% done in South-East Asia, Taiwan, places like that that are still using the drug as part of an anticonvulsant regime. They won’t put anybody on it if that person comes up with that particular variant.

That’s a really good example of how using a genetic test will really literally dial out a lot of drugs or dial in a drug based on your genetics.

[DAMIEN BLENKINSOPP]: Right. Currently though today, it’s a little bit of a trial and error process if you see a physician. Even with antibiotics sometimes, unless you’ve had tests done, it’s trial and error. We’re working hopefully towards a place where there won’t be any of that trial and error, it will be eliminated over time by these kinds of tests.

With the caveat that epigenetics sometimes will have some influence, so it’s not 100% fallible. In terms of the pharmacogenomics, there’s still some potential that basically says “This drugs better than this one for you”. It’s not 100% fallible, correct?

[MICHAEL NOVA]: No. Again, what we try to do in the genetics business is report on what the literature tells us – period; that’s the bottom line – and is that result valid.

We know, in pharmacogenetics, that across all drugs, 40 to 50% of them fail when they’re first given, so that’s a huge problem. So, dialing in the right drug, even though it might not be 100% correct… although the Stevens-Johnson issue, with this particular gene and carbamazepine, is almost 100%, so there’s nobody in their right mind if they knew that that patient had those particular genes would put somebody on carbamazepine because that’s one of those issues that is almost really one gene, one effect – you just don’t do it!

[DAMIEN BLENKINSOPP]: Yeah, right, when the risk is so high. What other high risk ones are there? Is warfarin a big one?

[MICHAEL NOVA]: Yeah warfarin potentially could be a big one for a couple of reasons. A dosing of warfarin to begin with is a little bit difficult, you have to have really strong expertise in doing that. The way it’s done is it’s done over a period of time to figure out what your INR is and how you’re metabolizing it and then getting the right dose.

Warfarin is a serious compound; you don’t want to mess around with it. It’s basically rat poison and it’s a very serious anticoagulant, as are some of the other ones like Plavix. But if you can figure out initially which dose of warfarin is better for that individual based on its genetics, that’s a good thing.

Warfarin tends to be used when a problem arises, like potentially a stent or you’ve got some sort of other issue that needs anticoagulation so you need to put them on warfarin immediately. I think that having a point of care warfarin test for pharmacogenetics is probably the way that that is going to go. Nobody wants to sit around and wait for a day for some sort of genetic test to come back before they put them on a drug like warfarin if they need it immediately, if they’ve got an embolic stroke or something like that; you’re just going to do it anyway.

[DAMIEN BLENKINSOPP]: Right. That kind of information is helpful to have it already pre-done. That is why – it’s pre-empting the need for genetic data on you. In some cases it’s worthwhile doing, right? Cancer…

[MICHAEL NOVA]: Yeah, and then the holy grail in a certain period of time it will be 500 dollars or a thousand dollars to get a whole genome sequence of all your genes, all your DNA. Then everybody gets it done, insurance will probably pay for it, and it just gets put in your record at birth. That’s probably where it’s going.

If you look at the long-term goal of getting everybody genetically tested, that’s probably where it’s going to end up. Then you’ll just pull down the information when you need it – it’s already in your file, it’s in your electronic health record. Does this patient respond to carbamazepine? Does he respond badly to warfarin? You’ll just know that because you’ll just drop down the information electronically.

(46:04)[DAMIEN BLENKINSOPP]: Great, thanks for that. One other thing you mentioned, which I’m sure is going to be interesting to some people, is the athletics aspect and the performance there. Have you got any specific examples of genes you’re looking at and reporting that are useful for training or changing/optimizing there?

[MICHAEL NOVA]: Yeah, there’s a lot of genetics on VO2 max. Some people tend to have a tendency to have a higher VO2 max than other people based on their genetics. How do you use that information in order to tailor your workouts? Maybe you’re one of these people that has a low VO2 max, maybe you need to do more X exercise than somebody that has a tendency to have a higher VO2 max. So there are genes around that.

There are genes around power and endurance: some people tend to be more power people, which means that they respond better to power athletics or power sports than people that are endurance runners. There are some pretty famous genes in that power area – actin is one of them and ACE and some other genes.

Then there are genes around exercise and insulin response, exercise and sugar response. Our panel covers a lot of these and gives you a broad snapshot of what potentially would be a better type of exercise for you than somebody else.

[DAMIEN BLENKINSOPP]: Right. so the type suggestions would be resistance training versus endurance aerobics, cardiovascular kind of work – these kinds of recommendations?

[MICHAEL NOVA]: Yeah, and then a sophisticated personal coach – we use an Equinox personal coach – uses that information to tailor what types of exercise regimes, along with their diet, potentially would be better, you’d get more response around than something else.

(47:43)[DAMIEN BLENKINSOPP]: Great, thank you. Where would you recommend someone look to learn more about personalized genomics? Are there specific books or presentations of the subject that you know are good resources to learn more about this?

[MICHAEL NOVA]: I think we have a couple of them on our website, pathway.com. There’s a lot of them out there. The University of Utah has a very comprehensive genetics database.

If you really want to get down to hardcore genetics, all the genes are listed in certain databases such as GeneMed and NIH has a database of all the genetics and all the genes, all the variants and what they mean.

You can Google in “Genetics textbook” and there’ll be 50 of them that come up. Hospital groups like the Mayo Clinic has a really good genetics site, Harvard’s got a good one, Stanford and UCSF, they’ve all got really good information on those websites about genetics.

[DAMIEN BLENKINSOPP]: Great, great, great, thanks. How could people best connect with you and learn more about you and your work? Are you on Twitter or are you active anywhere else?

[MICHAEL NOVA]: Yeah, people lob in stuff to me all the time. I figure my email is usually the best way to get hold of me, or Twitter – we have a Twitter account from Pathway Genomics. A lot of information gets disseminated through the usual media outlets.

[DAMIEN BLENKINSOPP]: Alright, great. Is there anyone besides yourself you would recommend to learn more about this, for personalized approaches, whether it be pharmacogenomics or anything else?

[MICHAEL NOVA]: There’s a lot of academic groups, every major university has somebody that’s doing it. I could certainly give you a list of…

[DAMIEN BLENKINSOPP]: It sounds pretty broad. I don’t know if there’s anyone more in the populous base, potentially working with big companies like IBM or doing some similar work, potentially different in some areas to you that would be of interest?

[MICHAEL NOVA]: One person that’s been pounding the genetics drum bag for a long time has been Eric Topol, you’re probably familiar with him. He’s one of the leaders in personalized and putting the consumer in charge of his own health care. That’s basically what we’re trying to do here from a number of different angles.

(49:46)[DAMIEN BLENKINSOPP]: Great, excellent. A couple of questions now just on your own personal approach and view of body data; what kind of things have you had tracked for yourself, whether it’s genes or other biomarkers or fitness activity trackers? What kind of things do you track on your own biology?

[MICHAEL NOVA]: I’ve had my genome completely sequenced, so I know as much about my own genome as probably is available. So in that respect, I know what’s good for me. Then I’ve certainly changed around my diet a little bit and the types of exercise that I do based on what my genetics have shown me.

I do wear one of these Fitbit tracking gadgets, and there’s a lot of them; there’s a lot of different types. Then I’m going to for sure use Panorama, this health care app that we’re going to come out with, because it will be integrated into your cell phone. You type in “What shall I do for my exercise today?” and it will tell you, “Based on your genetics or lab results X, Y, Z, you should do this. You’ve already done a thousand steps, you should do this now. You can eat this. There’s a store around the corner, you can buy it there.”

There’s a whole bunch of different parameters that I think will be very, very useful in terms of tracking where you won’t know what’s really happening. I think that’s another thing that users will like about Panorama is there’s not going to be a lot of input; you don’t have to do a food log.

Users don’t want to do that kind of thing. We live in 140 character world!

[DAMIEN BLENKINSOPP]: Yeah, there’s a burden to collecting information.

[MICHAEL NOVA]: There’s a total burden. That’s a very good word to use. There’s a total burden and we’re trying to make it very easy for it to be done automatically, so you feel as though you almost have a guardian angel on your shoulder, in some respects.

[DAMIEN BLENKINSOPP]: Are you integrating it with existing sources of information or are you just making the app very easy to integrate? A bit like Evernote, which you can upload all sorts of things into it.

[MICHAEL NOVA]: Yeah, it will be both. You’ll be able to take what you want, or we’ll go out and find it. We’ll go get your Fitbit data, we’ll go get your electronic health record, we’ll go get whatever lab result, provided we get permission from you to do it, obviously. There’s consent that’s going to be involved in this whole thing.

We’ll try and make that, as you said, that burden or that bar really low. We’ll make it very easy for you to get a very inexpensive genetic test through the application.

[DAMIEN BLENKINSOPP]: So you’ll be able to buy a Pathway genetic test through the app and it will get integrated automatically?

[MICHAEL NOVA]: Yeah, or anybody else’s genetic test. Whether you’ve got 23andMe’s; we’ll integrate that information in there.

[DAMIEN BLENKINSOPP]: Great, great. Okay last question – I always ask this of everyone – what would be your recommendation to someone trying to use some data, any kind of data, to make better decisions about their health?

[MICHAEL NOVA]: Knowledge when it comes to preventing things from happening and to changing your behavior when it’s based on real science is a very powerful thing. We hear that all the time – “Oh, that’s why I didn’t like X or Y. Now I know it’s not all my fault. Now I can change it and stick to some potential diet regime with a lot more confidence and I’m going to get a better outcome.”

So for us, knowledge is power in order to change behavior, and that’s the name of the game for a lot of us is trying to change your behavior. Because you have a lot of power to be able to do that. Giving the consumer more information about themselves is a very powerful thing.

[DAMIEN BLENKINSOPP]: Right. It’s like once someone understands something more clearly, it gives them more clarity, it gives them more confidence; it makes it a lot easier to keep that behavior on board.

[MICHAEL NOVA]: Right.

[DAMIEN BLENKINSOPP]: Well Michael, thank you so much for your time today. I really enjoyed the chat.

[MICHAEL NOVA]: My pleasure.

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

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

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

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

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

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

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

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

itunes quantified body

What You’ll Learn

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

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

Dr. Rob Knight

Tools & Tactics

Interventions

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

Supplementation

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

Diet & Nutrition

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

Tracking

Biomarkers

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

Lab Tests, Devices and Apps

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

  • uBiome: This test can be ordered and used by anyone in their home. The test allows collection of microbes from your gut, mouth, ears, nose, or genitals.
  • Electroencephalogram (EEG): EEGs record electrical activity in the brain. The frequency of waves can indicate whether brain function is normal or disturbed. Alpha (8-13 waves per second) and beta (more than 13 waves per second) waves are the most common in healthy, awake adults.
  • Magnetic Resonance Imaging (MRI): MRI scans are use pulses of magnetic energy to visualize internal organs and structures. It can be used on almost any area of the body and provides information on tumors, bleeding, injuries, blood vessels, or infection.

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

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

Other People, Books & Resources

People

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

Organizations

Other

Full Interview Transcript

Click Here to Read Transcript

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

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

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

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

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

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

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

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

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

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

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

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

[Rob Knight]: Yeah, sure.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Very, very interesting.

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

[Rob Knight]: Correct, yeah.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Rob Knight]: Yes.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Great.

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Yes, absolutely.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Right, so again, in that case we’re kind of hoping that no one tries to do clinical trials with the probiotics in products. It’s kind of no-win situation in that respect.

[Rob Knight]: Well it is a bit of an issue. It’s sort of like the issue with dietary supplements for athletic performance. So any time one tends to actually be effective, like say steroids, for example, it gets banned immediately. So you can draw your own conclusions about the effectiveness of the ones that are still on the market.

[Damien Blenkinsopp]: I guess one of the nicer things about that is currently when we take antibiotics it’s not really acknowledged that it causes any specific disease, although people may have gut upsets and any issues like that.

So I guess if these supplements continued to be marketed, and perhaps trials are just done on the basis of changing microbiome, that wouldn’t interfere because it’s not a disease endpoint. A specific disease endpoint, as I understand it, would be a specific classified disease, which is currently basically regulated today. So as long as they stay out of those disease areas, is it not a problem?

[Rob Knight]: Yeah, that’s exactly right. And that’s in part why as a consumer, it’s often very frustrating to see what claims are being made because those claims are now typically very carefully worded and very carefully negotiated.

[41:05][Damien Blenkinsopp]: So I know that you’re also involved in the Ancestral Microbiome Project.

[Rob Knight]: Uh-huh

[Damien Blenkinsopp]: Could you give us a quick update on how far you’ve got with that, and also what it is for the people at home.

[Rob Knight]: Sure, absolutely.

So the goal of this project is essentially to compare the microbiomes of different people living relatively isolated lifestyles and seeing whether they contain microbes that we as Westerners have lost with the hygiene or antibiotics. Or diets perhaps, that cause us to lose some of those kinds of microbes that could be beneficial.

There was a paper that just came out two weeks ago led by Cecil Lewis at the University of Oklahoma on the Matses who are a group of hunter-gatherers in Peru. There’s another one coming out soon that I can’t tell you about because it’s embargoed. But there’s some ongoing work that we’re doing with the Hadza in Tanzania, and the project that’s led by Jeff Leach.

So the Hadza are the last hunter-gatherers in East Africa in the Rift Valley where, of course, humanity evolved. So they’re the last group that’s still exposed to the microbes and to the mammals and to the plants that we would have evolved with during our early evolution. And so they’re very exciting to look at from that standpoint.

But basically the idea is to compare different groups and to understand first there’s still anything that they have in common that we might have lost more recently. And then the second thing is that try to understand similarities and differences in different human populations in terms of their microbiomes and how those microbes relate to different lifestyle features, to human genetics and to other factors.

It’s going to be incredibly fascinating from a science point of view. And from the point of view trying to figure out how our microbiomes should be shaped to optimize health.

[Damien Blenkinsopp]: Yeah, this is great.

I understand that Jeff — have you spent time with the Hadza as well, or has it just been Jeff that’s spent the time with the tribe?

[Rob Knight]: I went there for a week last year. It was just a spectacular experience.

[Damien Blenkinsopp]: I understand that Jeff, at least just spending time there, his microbiome changed. And he also used a fecal transplant from the Hadza to see a more extreme change.

But what I thought was interesting was just living amongst them and spending time with them, he saw some changes in his microbiome also. But I guess you haven’t had your sequenced yet, but potentially over that week you would have seen the same changes.

[Rob Knight]: Possibly. We don’t have the sequence data for that, although that would certainly be interesting to look at.

I should note that’s also true if you start living with a new partner, for example. You’ll converge on their microbiomes relatively rapidly. And one thing of interest at the moment is trying to figure out how much your microbiome records about the people you’ve lived with and the places that you’ve lived.

We don’t really know the answer to that at this point, but it’s certainly interesting to think about.

[Damien Blenkinsopp]: Well it is, just from a health perspective as well. Especially as it’s getting quite common to have IBS and things like that these days. It kind of makes you question these kind of things. How communicable is it, or not? I guess there’s a lot.

[Rob Knight]: Yeah, that’s a great question. I don’t [think] there’s been done a lot on communicability of IBS, but there are some probiotics that have done pretty well in clinical trials for IBS.

[Damien Blenkinsopp]: Yeah. So we’ve got a solution anyway.

[Rob Knight]: Yeah, and it has been linked to the microbiome by a number of different studies including some work we did with [unclear 44:25]. So yeah, it’s definitely a fascinating area. And the potential that some of these conditions could have microbial cures as well as microbial causes is very interesting.

[Damien Blenkinsopp]: Great, thank you very much Rob.

[44:40] So what are the best ways for people to connect with you, and learn more about you and your work?

[Rob Dunn]: Well, my TED Talk is a really good starting point. There’s a book associated with that Talk called Follow Your Gut, which is going on sale tomorrow actually.

[Damien Blenkinsopp]: Is that on Amazon?

[Rob Knight]: Through Amazon, and also I think it’s available as an iBook through the Apple Store. That’s a good way to find out more. It’s a relatively short book. The idea is to make it a friendly general introduction rather than going into a lot of technical detail about a whole lot of names that you’ve never heard about.

And also it’s got an Appendix that gives you a good overview of how you should interpret your American Gut results, and what things you can and can’t learn at this stage, and what we hope to be able to find out from us in the future.

[Damien Blenkinsopp]: Great, we’ll put links to all those in the show notes.

[45:22] Are there any other good books or presentations for people interested in the microbiome in general, and learning more about it? Are there any references that you commonly give out to people, which are good resources to check out?

[Rob Knight]: Yeah, Marty Blaser’s book. So Marty Blaser’s book Missing Microbes is fantastic, and really gets into a lot of detail about how hygiene and antibiotics may have led to the rise of a lot of autoimmune diseases, and other chronic diseases that are a problem today. And also one specifically about the dangers of over prescription of antibiotics. So I definitely recommend that one.

Ed Yong’s blog, Not Exactly Rocket Science, routinely covers microbiome topics. As do Carl Zimmer’s columns. Michael Pollan wrote a very nice piece in the New York Times in 2012 called “Some of My Best Friends are Germs,” and he’s continued to cover the microbiome on and off since then. Those pieces are all very good.

Jonathan Eisen and Jessica Green both have talks that are available through TED. Jonathan’s talk gives a very good introduction to what microbes are and what they do out there in the world. And Jessica’s features, it’s focused more on the built environment. And it’s talking about the relationship between the microbes in our bodies, and in the spaces we inhabit, and how we might want to design buildings that are green not just in terms of the plants, but also in terms of the microbes. So not just energy, but also microbial use.

So those would be some really good places to start. There’s definitely a lot of more technical resources out there, but you can probably get to those from the ones that I mentioned. And especially the references in Marty’s book and in my book are a good place to get started with more technical material.

[Damien Blenkinsopp]: Great, thank you so much for that. That’s very extensive, clearly.

[47:11] So I’m also interested what your personal approach is to body data, whether it’s for your health, your longevity, or your performance. Do you track and metrics or biomarkers for your own body on a routine basis?

You’ve already said that you take stool samples every single day. Is there anything else you do? And those stool samples, just by the way, for instance if you go to the toilet twice per day, do you take two stool samples, or are you taking one per day?

[Rob Knight]: Initially I was taking one per day, and I’m trying to capture all of them to the extent possible.

So in terms of auxiliary data I must admit that I’m not nearly as diligent as some other people who are interested in this sort of thing have been at tracking every single thing they’re doing every day. In part that’s informed by some of the studies where people have tracked a tremendous number of measures and not seen a lot. So that’s been relatively difficult to justify that level of additional time commitment.

Mostly what I’m tracking are things like, so periodically I’ll do a food and dietary inventory. Tracking things like travel is important. I would track medications except I essentially haven’t had any during that interval. But it’s the sort of thing that I would keep track of if it became relevant. That kind of thing.

[Damien Blenkinsopp]: Great, great. I’m guessing that most of these things are something that you’re doing in the realm of science, because you’re exploring the specific subject.

Do you think you would control for any of these if you weren’t involved in the science itself, out of a personal interest? How would you kind of modify that, if you weren’t currently studying you as an n=1 experiment to further the science? On a personal level, what kind of things do you think you would be doing?

[Rob Knight]: All kinds of things are interesting, it’s just a matter of how much time you’re willing to put into it, and how much money. So it would be very interesting to do blood and urine metabolites frequently, perhaps even daily.

It would be very interesting to get finer grade resolution on fitness, like with an activity tracker, that kind of thing. Given what we’re now starting to find out about brain microbe links it might be really interesting to, for example, track EEG readings over time and draw those microbial data.

You could even imagine doing like an MRI of yourself every day to see whether that complex multifarious specs tracks what the multifarious specs to find biomarker biome. Although that’s definitely a level of efforts and expense that it’s just not worth it at this point.

But what I think this is one of these things where the more data you have, the more potential you have to find out something really interesting that you wouldn’t have expected.

[Damien Blenkinsopp]: Great, thank you so much.

[49:44] The last question, what would be your number one recommendation to someone who is trying to use data in their life for better decisions about their health, their performance, or longevity? Something about their body. What would be your number one recommendation on how to use data effectively?

[Rob Knight]: There are a lot of different ways that could answer that question, but I guess my number one recommendation would be that what’s in the literature, like randomized controlled trials about what works and what doesn’t, are probably a really good guide as to what you should do initially.

Now, you might want to modify that based on observations of your own body, because anything that’s in the literature has got to be based on population averages. And one thing we know about people is that there are tremendous amounts of variability. So what works on average in the clinical trial is not necessarily going to be what works for you individually.

So, start with solid evidence from clinical trials, especially randomized placebo controlled trials, and then modify that based on your own observations about your own health whether it’s meticulously recorded, and you have over a long enough period of time that you have reproducible observations, not just off one anecdote.

[Damien Blenkinsopp]: Thank you there for some great insights into randomized controlled studies, and the averages also, which comes up sometimes on this show. Averages don’t necessarily mean you. So thank you for reinforcing that point.

Rob, thank you also for making time available today. I really enjoyed this show. You’ve obviously got a very, very deep background in this stuff, and we covered a lot of material. Looking forward to read your book also.

[Rob Knight]: Okay, great. Well thanks Damien, and thanks again for your interest in this, and this is only going to get more exciting as we find out more and more about the microbiome.

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Water fasting or ketogenic therapies may be effective with some cancers, and not with others. Learn about the PET scan and how it can provide insights into whether a cancer is likely to be responsive or not to the water fast tactic we’ve covered in previous episodes.

In this episode, we return to look at ketosis and water fasts as a tool to help treat cancer. This builds on the previous episodes looking at Ketosis with Jimmy Moore and the impact of water fasts on cancer with Dr. Thomas Seyfried.

In this episode, we dig deeper into the cancer topic looking at how ketogenic or low-carb diets may contribute via mechanisms related to insulin and ketones to inhibit cancer growth. We look at why only some types of cancers may benefit from these types of ketogenic treatments, and the data behind it. The data backing up this episode, is that of the PET scan — Positron Emission Tomography. PET Scans can be used to understand what type of cancer a person is dealing with and more importantly, whether it is likely to respond to ketogenic therapies or not.

For cancers that are dependent on glutamine more than glucose… They can be aggressive… and they may not show up on a PET scan, and they also may not be responsive to a low carbohydrate diet.
– Dr. Eugene Fine

Our guest is Dr. Eugene Fine. He’s currently a professor of Clinical Nuclear Medicine at the Albert Einstein College of Medicine. Most recently, in 2012, he published a study in the scientific journal of Nutrition on 10 cancer patients treated with a low-carb diet. He’s currently expanding his research by working on the use of low-carbohydrate diets combined with chemotherapy in animals.

This is all linked through his area of specialism, which is PET scans — positron emission tomography — where he has been identifying and monitoring cancers for the use of this type of scan. We’ll also touch on some of his studies looking at the impact of ketones, in vivo, on normal cells and malignant cells, and how that differs compared to glucose.

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

  • Reducing carbohydrates in diet and reducing insulin secretion in the body may inhibit cancer growth (4:06).
  • How ketones inhibit cancer cells (10:06).
  • Why are cancer cells over-expressing uncoupling protein 2 and reactive oxygen species (12:35)?
  • Dr. Fine explains how he uses PET scans to identify many different types of cancerous cells and severity by using fluorodeoxyglucose, or FDG (17:32).
  • If the cancer does not show up on the PET scan (as is the case with prostate cancer and glutamine dependent cancers) it may not respond to a low carbohydrate diet (23:57).
  • Dr. Fine discusses quantitating the PET scans (30:50).
  • Any inflamed area might also show up on the PET scan associated with the FDG (32:36).
  • This research is in the beginning phase and needs to be studied on a larger scale as the next step (34:11).
  • Dr. Fine describes his “recharge trial” where cancer patients were put on a low carbohydrate diet to observe the effects of the diet (35:00).
  • During the trial the patient’s blood levels were measured to determine whether they were ketotic (37:42).
  • Dr. Fine discusses the results of this recharge trial by identifying that inhibiting insulin may have effects on cancer progression/remission (40:31).
  • Cancer may adapt to the environment where it “grew up”. So if you develop cancer already on an low carb diet, will not be affected by a low carb diet as an intervention (45:05).
  • Damien and Dr. Fine discuss other ways to change ketone/insulin levels (49:44).
  • High calorie versus low calorie diets are discussed (53:13).
  • The biomarkers Gene Fine tracks on a routine basis to monitor and improve his health, longevity and performance (1:03:29).
  • Gene Fine’s one biggest recommendation on using body data to improve your health, longevity and performance (1:09:14).

Eugene J. Fine, MD

Tools & Tactics

Drugs & Supplements

  • Metformin: A drug which is used to improve blood sugar regulation in diabetes. Researchers are looking at its wider applications with cancer treatment as it has been found to inhibit insulin secretion.
  • Ketone esters and salts: A new range of supplements making ketone bodies directly available to the body and thus inducing ketosis. There are various forms including Beta Hydroxybutyrate Monoesters (BHB monoesters), and Beta Hydroxybutyrate mineral salts (BHB combined with Na+, K+, and Ca2+). One available for purchase is Ketosports KetoForce and Ketosports KetoCaNa.

Diet & Nutrition

  • Low-carbohydrate diet: this programme limits carbohydrate consumption to increase ketosis. This was the main discussion point for this episode.
  • Ketogenic diet: The ketogenic diet is a low carb diet which also raises the level of ketone bodies in the blood.

Tracking

Biomarkers

  • Beta-Hydroxybutyrate/β-hydroxybutyrate (Blood ketones): Ketone bodies can be used as a source of energy, similarly to glucose, for most cells in the body. However, now it is recognized that ketone bodies might inhibit the growth of cancer cells instead of fueling them. Some information about testing ketone levels can be found here. Normally, there should be little to no ketone bodies in the blood or urine. However, ketone bodies increase during a low-carb diet. The most accurate way to measure ketone bodies is through a blood draw but urine tests are also available. More information on ketones and ketogenic diets can be found in episode 7.
  • Insulin: Insulin is a hormone produced in the pancreas and released in response to blood sugar levels and metabolism of carbohydrates and fats. This hormone controls the glucose blood levels to attempt to maintain normal levels. Fasting insulin levels are normally less than 25 mlU/L. After a spike of glucose in the system (after eating) insulin levels will rise but should normally not reach levels higher than 275 mlU/L. Glucose production in the body is inhibited when more insulin is released. Hyperinsulinemia occurs when there is too much insulin circulating in the body.
  • Hemoglobin A1c (HbA1c): Measure of glycated hemoglobin, or hemoglobin to which glucose has become attached – a process that occurs when blood sugar levels become excessively elevated. A proxy measure used to assess your average blood sugar over time. Since hemoglobin is part of the red blood cells it is exposed to blood sugar over the lifetime of the red blood cell, thus giving a measure of exposure over the cells average lifetime (approx. 3 months). As such this measure is used to identify blood sugar control issues. Standard lab reference ranges show anything below 6% as fine, however this already represents blood sugar dysregulation. Optimum HbA1c levels are below 5%. HbA1c has been well researched.
  • Blood Glucose Levels (mg/dL): A measure of the level of glucose in the blood at one point in time. Fasting blood glucose levels are specifically taken when you have not eaten for at least 8 hours and optimally would be between 75 and 85 mg/dL. Health concerns with blood sugar regulation such as diabetes risk start to rise over 92 mg/dL. Levels can be measured at home using a glucose monitor and glucose testing strips (an explanation for the use of glucose monitors can be found in this episode).
  • Cholesterol-HDL and LDL: The cholesterol biomarkers include lipoproteins and triglycerides which are found in the blood. There are standard markers that all doctors and labs will run, and some newer specialist labs that are more specific and accurate. There are two main types of lipoproteins, HDL and LDL. We covered these markers extensively in episode 7.

Lab Tests, Devices and Apps

  • Positron Emission Tomogrophy (PET) scan: A PET scan is a functional imaging technique used to image body processes. As described in this podcast, a PET scan can be used to identify cancer presence and severity. A radioactive tracer, fluorodeoxyglucose, is used to tag these cancerous cells. As discussed by Dr. Fine, the cancerous cells identified in this way may be treated using a low-carb diet as a supplement.

Other People, Books & Resources

People

  • Steve Phinney, MD, PhD: Dr. Phinney has completed research regarding low carb diets.
  • Jeff Volek, PhD: Dr. Volek has also participated in research about low carb lifestyles. Together, Dr. Phinney and Dr. Volek wrote a book called The Art and Science of Low Carbohydrate Living.
  • Douglas Spitz, PhD: Dr. Spitz is a radiation oncologist who has studied the ketogenic diet as an additional treatment for cancer. His research can be read here.
  • The Caveman Doctor: Colin Champ, MD is a radiation oncologist who has researched the role diet plays as a supplemental treatment for cancer.
  • Otto Warburg: Warburg hypothesized in the early 1900’s that aggressive cancer growth is due to energy generated by the breakdown of glucose.
  • Thomas Seyfried, PhD: Dr. Seyfried is interested in fasting and diets used to treat cancer. More information can be found in The Quantified Body podcast.
  • Valter Longo, PhD: Dr. Longo has published many articles regarding fasting benefits for cancer patients.
  • Dominic D’Agostino, PhD: Dr. D’Agostino is well known for his research with ketogenic diets and performance. More information can be found here.
  • Richard Feinman, PhD: Dr. Feinman is a professor at the State University of New York. He has collaborated multiple times with Dr. Fine. Dr. Fine wrote two blog posts on Dr. Feinman’s site: Part 1 and Part 2.

Full Interview Transcript

Click Here to Read Transcript

[Damien Blenkinsopp]: Gene, thanks so much for joining us on a call today.

[Gene Fine]: Oh sure. Good to be here.

[Damien Blenkinsopp]: To give a better background, we spoke to Dr. Seyfried about his ideas and his work on ketogenic diets, fasting, and cancer. And what I found interesting about your work is you’ve dug into different areas, and you’ve differentiated cancers and I wanted to get up to speed about what you’ve been up to. And potentially, also, you’ve got some slightly different views on the whole thing.

So, first of all I wanted to talk about what do you see as the mechanisms of effect behind, if we’re inducing ketosis to inhibit the cell growth of some cancers. How is that working from your perspective?

[Gene Fine]: There really are three linked mechanisms, I believe, that have the potential to inhibit cancer growth. And two of them — well actually all three of them — one is that by reducing carbohydrates in a diet. And we have to realize that most of the carbohydrates we consume are sugars and starches, which digest the sugars — about 90 percent of them.

[And] that if we strictly limit carbohydrate to very low values, we’re inhibiting insulin secretion. And insulin alone is a stimulus to cancer growth. So, if you inhibit insulin you’re reducing one of the important stimuli to cancer growth through that alone. The insulin receptors on cancer cells will be inhibited, and so the growth signals will be inhibited.

[Damien Blenkinsopp]: Is that differentiated? Normal cells have uptake of insulin and they respond to insulin also. Is it that the cancer cells respond to a greater degree? Or what’s the difference there, if there’s any?

[Gene Fine]: No, not at all. In fact, I think the concern would be that the cancer cells may respond to a lesser degree. However, the important thing is that as adults we need some insulin. Without any insulin, we’re Type One Diabetics, but we don’t need much insulin at all.

We need insulin when we’re kids, because kids grow up when they have carbohydrates and protein and insulin helps them grow. When you’re an adult and you eat too much carbohydrates it tends to make you grow sideways. So excess insulin in an adult is not such a good thing; it contributes to obesity and to diabetes.

[Damien Blenkinsopp]: I guess we would throw in body builders in there as well, because they’re always trying to stimulate insulin to stimulate greater muscle growth.

[Gene Fine]: Yeah, well I mean if you’re extremely physically active, you probably can eat whatever you want. I’m not talking about recommendations for body builders; I haven’t studied that. I know that others have. Jeff Volek and Steve Phinney have looked at athletes, and they recommend low-carb diets for them as well.

But the main group that I’m really talking about is the average person who is, unfortunately, a little bit more sedentary than they used to be. And in this group we really don’t need very much insulin to go about our normal activities. And so carbohydrate restriction is probably safe.

[Damien Blenkinsopp]: Right. So would you put protein in there as well? Because protein also can stimulate insulin.

[Gene Fine]: Yeah, that I think is an interesting and maybe more controversial area.

Protein certainly can stimulate insulin. And the question about how much protein to consume in a diet is really an important one, but an independent question which I think has not been answered. I mean, if you look in the literature recommendations for protein in the diet are all over the page; they vary from 20 grams a day to 150 grams a day.

So I don’t know that I’m really in a good position to comment on that because it hasn’t really been adequately studied by anyone, including us. In our own study we didn’t limit protein, so we might have done better than we did if we had.

But nonetheless, our human study did show that the patients that had the highest level of ketosis were the ones who did the best in terms of stable disease or partial remission of their cancers. And those who had the lowest levels of ketosis had progressive disease.

[Damien Blenkinsopp]: So you’re talking about how insulin inhibition mechanism, are they basically opposite correlates? So when insulin goes down [it is] in response to ketosis going up? Is that basically the rough mechanism, so that you could map those to each other? That’s why with a low carbohydrate diet, ketosis goes up and insulin goes down.

[Gene Fine]: Yes. I didn’t actually clarify that. I was saying, yes, that’s the general idea.

I didn’t quite complete the thought that really there are three mechanisms by which a very low carbohydrate diet could inhibit cancer growth, and one of them is, as I say, by reducing carbohydrates in the diet and reducing insulin secretion.

Insulin by itself is a stimulus to cancer growth, but very low insulin will at least have the potential to slow that. So insulin by itself would slow the cancer growth. And there are two cellular mechanisms, so I could insulin twice.

But in addition, there are systemic effects in the whole body, and very low insulin causes mobilization from fat cells — in fact, that’s how you end up losing weight — and the fat gets broken down in the liver. And increased breakdown of fat in the liver leads to production of ketone bodies and ketosis. And ketosis independently, we’ve shown at least in metabolic studies in cell culture, that ketosis itself can cause inhibition of cancer cells. So it can inhibit cancer cells; it leaves normal cells alone. And as I say, we also showed that in our human study.

[Damien Blenkinsopp]: Yes. Yes, thank you. So there’s three mechanisms.

[Gene Fine]: Yeah. Well two of them I consider to be insulin, because there are two different insulin pathways that could be inhibited. And the third mechanism is the systemic effect of low insulin causing ketosis in the liver.

Increased fat mobilization causes ketosis in the liver, and the ketone bodies circulate in the body. Normal tissues tolerate it very well and can use ketone bodies as a fuel, but the cancer cells — at least that we’ve shown in vitro — can be inhibited by them.

[Damien Blenkinsopp]: Great. It’s interesting to look at the mechanisms, just in case later on people discover different tactics for modifying insulin, for example. I mean, like there’s drugs and stuff. Or, for introducing additional ketones or something.

So, we were talking just before the call about the study where you were actually looking at how ketones inhibit some of the cancer cells. Could you talk a bit about that? Because I know there was some glucose and ketones involved, and it was interesting how it’s done.

[Gene Fine]: Yeah. In cell culture studies, when we started this a few years ago, we studied three different normal tissue lines that were fibroblasts, which are normal connective tissue that we have in our body. And we also studied seven different cancer lines. Five colorectal cancer line variants and two breast cancer lines.

And what we found was that all seven of the cancer lines — well we grew all of the tissues for four days in a cell culture in glucose medium. And we saw how much they grew. But in parallel with that, we also grew the same cells in glucose medium but with added ketone bodies.

And, as I mentioned before, ketone bodies are a nutrient for normal cells, so we didn’t expect there to be any problems in the fibroblasts, and in fact the fibroblasts continued to grow normally when we added another nutrient.

However, all seven cancer lines showed growth inhibition. And they had differing degrees of growth inhibition when we added the ketone bodies. And we found that the degree of inhibition of the cancer lines was proportional to how much they over-expressed a particular protein called uncoupling protein 2, which actually reduces the efficiency of the cell in producing ATP.

So it turns out that the cancer cells were producing less ATP than they ordinarily would when we added ketone bodies. So the ketone bodies were metabolically inhibiting ATP production, and in proportion to their over expression of this interesting protein.

And the degree of ATP inhibition was exactly proportional to the degree of growth inhibition, which makes a lot of sense. That it requires ATP to grow. So that seemed to be pretty good evidence that we had at that point that it could be metabolic inhibition of cancer cells by these ketone bodies.

[Damien Blenkinsopp]:Yeah, that’s interesting, because, like you said, you’re actually adding something, you didn’t change [anything else]. You’ve got the same amount of glucose, so theoretically, even if cancers couldn’t process the ketone bodies very efficiently, they have the same amount of glucose there. So, in theory they could have been okay. But you’ve actually shown that somehow the ketone bodies are inhibiting that.

Would it be fair to say that the cancer cells are trying? It’s like they’re taking in the glucose and the ketone, and that they’re trying to process that. But because of the inefficiency, they’re not able to. Because it’s kind of interesting that it’s got this inhibitory mechanism there. It’s like they’re trying to, but they’re not very successful at it.

[Gene Fine]: Right, and one of the big questions is, of course, why are the cancer cells expressing uncoupling protein 2. And this has been observed that cancer cells were expressing uncoupling protein 2, for at least 10 or 15 years. There were studies in the early 2000s that I first saw that got me clued into the fact that they were doing this. And I thought well what could uncoupling protein 2 do to a cancer cell, and why would they do that?

The general explanation that I’ve adopted is that cancer cells also overproduce, what are called reactive oxygen species. And reactive oxygen species are chemically active molecules that are produced in all tissues, normal cells as well. But they’re higher in cancer cells than they are in normal cells.

And the thing about reactive oxygen species is that they actually act as sort of a two edged sword. They’re required for normal cell signaling. They’re a signaling molecule that helps cells grow, and develop, and proliferate, and so forth. However, they also are very chemically active and can cause mutations.

And mutations are also somehow the life-blood of cancer cells. Cancer cells become cancerous on the basis of mutations, and in fact they’re sort of evolutionary masterpieces in that they continue to evolve because of mutations. If a particular cancer mutation kills a singular cancer cell, well that’s fine, that cancer cell dies. But if another mutation that happens to be caused in another cancer cell makes that cancer cell even more aggressive, well then the cancer becomes more aggressive.

So, reactive oxygen species when over-expressed in cancer cells actually provide a mechanism for continued growth and continued development as an aggressive cancer. The problem, of course, is much too high reactive oxygen species will kill a cancer cell, as they will kill any cell. In fact, it’s very high levels of reactive oxygen species that are caused by chemotherapy, and are caused by radiation therapy.

So there has to be a limit on how much reactive oxygen species a cancer cell can actually produce. And what I believe, and I can’t say that I’ve proven this at all, is that the increased expression of uncoupling protein 2 — uncoupling protein is in fact, or believed, to limit reactive oxygen species. So it makes sense to me, but without proof, that the reason — quote unquote reason — for the increased production of uncoupling protein 2 is to provide a natural limit. A higher limit than a normal cell, but a limit on the amount of reactive oxygen species that the cancer cells produce.

So that’s my my overall belief. UCP2 is there for a reason. But it happens, it just happens, that that reason, which is important for the cancer cell, may actually be exploitable in terms of diet, because it also reduces the efficiency of production of ATP. I don’t know if that exactly adds up, but that’s what I believe.

[Damien Blenkinsopp]: Yeah, my understanding is — I’m just trying to re-summarize from what I understand and how it fits in — mitochondria create reactive oxygen species, and they tend to do that more with glucose fuel than with ketone fuel at a higher rate. And also when they get damaged they tend to create more reactive oxygen species, so they’re not as efficient. Does that fit in with what you just said?

[Gene Fine]: Yes.

[Damien Blenkinsopp]: Okay, great. So, somehow it seems like when the ketone bodies are being used though, in this scenario it’s potentially creating more reactive oxygen species via ketones, because of the protein change there?

[Gene Fine]: I think that’s not really clear. I don’t believe the ketone bodies… Other people who have looked into this a little bit, I think, are somewhat ambiguous about it as well.

I don’t believe that ketone bodies cause increased reactive oxygen species, but I can’t say that I know that for certain. I do believe, from at least the mechanisms that we’ve explored, that ketone bodies provide a complementary way of inhibiting cancer growth metabolically. If they also produce increased reactive oxygen species, and therefore contribute to higher levels of reactive oxygen species that are cell killing, that would be interesting.

But I don’t have direct proof of that. I believe that’s been suggested by others. Possibly Doug Spitz who’s a radiation oncologist, and I don’t know but Colin Champ, who is also a radiation oncologist. He’s written about this, but I’m not sure he’s described increased reactive oxygen species production through ketone bodies. It’s possible.

[Damien Blenkinsopp]:Alright, so great. There are some mechanisms you’ve been looking at there.

And another that’s been interesting about your work is that you’ve been looking at the differences between the different cancers in your studies with PET scans, which is of course your background and your area. Could you talk a little bit about the PET scan and how you use it to assess the cancer?

[Gene Fine]: Yeah, sure.

Most cancers — most aggressive cancers I should say — end up becoming, well first of all they begin to outstrip their blood supply. Their blood supply becomes erratic, and instead of having blood vessels well supplying nutrients to the cancer cells, the cancer cells become relatively hypoxic; they don’t usually have enough oxygen. And hypoxia will interfere with the ability of a cell to use the Krebs cycle as a means of developing energy.

So most cancer cells actually depend on glycolysis, which is anaerobic glucose metabolism, in order to develop their ATP. Now, because they’re using so much glucose and they over express glucose transporters and glycolytic enzymes, because they’re using so much glucose, if you inject a glucose like tracer — a radio tracer — whether it’s carbon-11 glucose, or another one that we liked to use in general nuclear medicine, fluorine 18, fluorodeoxyglucose.

This is a glucose analog, and it gets taken up very avidly by cancer cells that are aggressive. These aggressive hypoxic cancer cells take up FDG very avidly. There’s also something called the Warburg effect, which Otto Warburg, famous biochemist, demonstrated 100 years ago that aggressive cancers, in fact, they may be hypoxic but that even if you expose them to normal oxygen conditions, they still retain this glucose and glycolytic dependence.

In any event, the result is the same that aggressive cancers light up on a PET scan if you inject a patient with FDG, with fluorodeoxyglucose. And a PET scan is basically a nuclear medicine study. These radioactive tracers give off emissions, which allow you to see where the radio tracer goes.

So FDG distributes through the body. Glucose is used by a lot of tissues, so you can also see the heart, you can see the brain because these are often glucose utilizing structures. However, you don’t expect to see FDG in locations where it shouldn’t be. But if you have metastatic disease, which these kinds of hypoxic glucose dependent cancers, FDG will go to those sites as well.

And in fact this one image can be used, or a total body PET scan using FDG can be thought of as a one step metastatic workup, because you can actually see the full distribution of cancer cells throughout the body.

[Damien Blenkinsopp]: So is this the gold standard for assessing the severity of cancer? Could you give us an idea of when you would use this kind of scan?

[Gene Fine]: Yeah, everything in medicine really is very empiric. So if it works, it works. And certain cancers are particularly avid for this kind of tracer, where they do become hypoxic glycolytic cancers. And it’s turned out to be useful in management of cancers in one way or another.

For example, in a solitary pulmonary nodule, you’re trying to determine if this is likely to be a cancer or not or if it’s a benign module. Benign nodules don’t tend to take up glucose that avidly, but the malignant ones do. So an FDG scan can be very useful in just a diagnosis of whether a lung nodule is in fact cancerous.

But PET scans are useful in the management and decision making processes of breast cancers, of uterine cancers, actually a variety of lymphomas, in particular, are usually quite avid and PET scans can be quite helpful. Esophageal cancers, gallbladder cancer, colorectal cancers, PET scans can be quite useful because they light up, and they show you not only where the tumor is, but where the metastases are.

[Damien Blenkinsopp]: And the other thing, I guess it would simply appear bigger if it’s getting worse? So on your PET scan, if you did one every three months with a cancer patient and it was getting worse, you’d see it getting bigger and potentially spreading to other areas of the body. Is that how it comes back?

[Gene Fine]: Yes, you can definitely see how it spreads.

And nowadays I should actually say that most PET scan devices are actually two devices in one. They’re PET and CT, CAT scans. So you actually can get even better information, because the CT scan is really a computerized three-dimensional x-ray. So you’re actually able to see exactly where in the body.

The PET scan doesn’t have a road map of the anatomy, it’s just where the fluorodeoxyglucose goes. But on the CT scan, it gives you the underlying anatomy, so you get the anatomy as well as the functional arrangement at the same time and in the same locations. So you can identify exactly where you’re seeing it. And that’s very helpful.

I should actually mention that there are certain cancers that PET scans are not useful for. For example, pretty notoriously, prostate cancer is an unusual cancer. It’s unusual in a lot of ways.

Actually 80 percent of prostate cancers are rather slow growing and indolent. And probably for at least that reason, that may be one expression of the reason why they don’t actually take up glucose that avidly. It’s usually the aggressive [cancers] that take up FDG.

But also some other cancers, such as mucinous cancers that are filled with so much mucin that you lose out the effect of what you see on a PET scan. So mucinous cancers of the colon and the of the lung often don’t take up much fluorodeoxyglucose.

Squamous cell carcinomas of the lungs of course are very avid, but these mucinous ones are not. And endocrine tumors, very functional, they’re often not as glycolytic. They often operate on oxygen and they can have a normal Krebs cycle and normal metabolism. So thyroid cancers, unless they’re extremely aggressive, are not this slow growing, and they take up much less FDG. So PET scans with FDG are not as useful for certain kinds of cancers, such as these.

[Damien Blenkinsopp]: That’s important because — tell me if this is over simplifying — anything that doesn’t show up in a PET scan, would it be less likely that any type of low carbohydrate diet or inhibition of insulin and up-regulation of ketone is going to have an impact on it, as we’ve been talking before?

[Gene Fine]: Yes, true.

In fact that’s very interesting because — I was mentioning prostate cancer before — prostate cancer actually, it’s not even approved for PET scan use, I should mention. Because they say 80 percent of prostate cancers don’t take up FDG. But in fact prostate cancer is also not associated with obesity. It’s not associated with hyperinsulinemia. It’s not associated with high glucose levels in the blood.

In fact, interestingly, there’s an inverse association of diabetes with prostate cancer. Patients with diabetes — it’s a little bit odd to use the word, because I’m not sure that it’s accurate, it may not be cause and effect, but it’s at least an association — are so called protected with diabetes against prostate cancer.

Now I don’t want to recommend getting Type 2 Diabetes to protect yourself against prostate cancer, but the point is that not all cancers would respond to a low-carb diet either. It doesn’t seem to have anything to do with the mechanism of that particular kind of cancer.

[Damien Blenkinsopp]: Right. The mechanism you described earlier was higher insulin would lead to more aggressive cancers, but in this case you’ve described, Diabetes 2 you’d have higher insulin, but it’s actually reducing the likeliness of getting prostate cancer. Is that correct?

[Gene Fine]: Yeah, it appears to be. As I say, at least epidemiologically, it fits the mechanism of the — I should also mention that 20 percent of prostate cancers are actually very aggressive.

So this is a distinct minority of prostate cancers. I don’t know that anyone has done much study of whether these aggressive prostate cancers, this subvariant, which grow much more rapidly, actually are glucose dependent. They may well be, but I don’t know that they’ve been studied this way. So I can’t comment on those. But they might be FDG avid.

The other thing though is that actually aggressive cancers, very aggressive ones, not uncommonly develop a taste for, not glucose, or not just glucose, but also an abundant amino acid that circulates in the blood called glutamine.

For cancers that are dependent on glutamine more than glucose, they might have even bypassed. They can be aggressive, and they may be glutamine dependent, so they may not show up on a PET scan, and they also may not be responsive to a low carbohydrate diet. So there are other subtleties here that have to be explored before knowing exactly what to do in these kinds of situations.

[Damien Blenkinsopp]: Well I’m guessing potentially restricting glutamine might have a kind of impact there. I guess there’s no studies that have been done on that.

[Gene Fine]: That’s hard. It’s hard to do that, because glutamine is synthesized by the body, and it just comes out of ordinary metabolism.

Glutamine and Glutamate are products of protein metabolism. Glutamine can actually be synthesized, glutamate can be synthesized from alpha ketoglutarate, which is a product of ordinary metabolism. So it can actually be synthesized, and is, and then circulates in the blood steam in high concentrations. And you can’t really restrict glutamine in a diet and expect glutamine to go away; it won’t happen.

I think there are approaches that are trying to figure out how to limit glutamine in the blood, but I’m not sure how successful they are. It seems to be an important metabolite and substrate for a lot of different mechanisms. It’s actually used by the brain, indirectly at least. And so, there really are glutamine restrictions, I think, is something still for the future.

[Damien Blenkinsopp]: In summary out of everything you’ve been saying, that the fasting approach or the low carbohydrate approach is, in your view, only applicable to some types of cancers, and typically the most aggressive ones.

[Gene Fine]: Yes, I would agree with that.

The other thing I should mention is that the fact that there are plausible mechanisms where cancers could be inhibited by a low carbohydrate diet, cancers of the types that we’ve been discussing, doesn’t guarantee that it would be inhibited.

And I should also mention about the PET scan, that a PET scan in the way we used it in our clinical pilot study in 2012 with 10 patients was that the PET scan indicates that we can at least identify a cancer that is glucose dependent. We can do that on a PET scan. So those, from the perspective of our hypothesis are carbohydrate, or at least have the potential to be carbohydrate restriction sensitive.

It doesn’t guarantee it, because we don’t actually know which cancers will have the appropriate characteristics and qualities. Maybe not all cancers will express uncoupling protein 2, or whatever other mechanism we were describing earlier. So we can’t guarantee it.

And in fact, if I would describe the hypothesis that I believe, it’s that — I actually have this on a slide in front of me because I like getting the wording exactly right — that large cohorts of individuals with cancer in the developed world do not experience sustained ketosis, or other features common to the insulin inhibited very low prone state. We’d expect many cancers to express a range of plausible vulnerabilities, and accidental adaptations to this unfamiliar metabolic microenvironment.

So, I think that’s the broadest statement that I feel comfortable making, that we can’t guarantee that an individual cancer is going to be responsive to this, even if it has a positive PET scan, because we don’t yet know all of the characteristics that are required. But we do believe that those kinds of cancers are at least eligible for that possibility.

[Damien Blenkinsopp]: Right. Well so it sounds like at the moment there’s nothing really concrete on this, but we think there’s a higher probability of some types of cancers, so that the most likely cancers to respond to this would be ones which tend to be more glucose dependent.

[Gene Fine]: The ones that show up on PET scans would be the ones that would have eligibility. So, we actually treated in our 10 patient study a range of patients, and there were several with lung cancers, there were several with breast, several with colorectal. There were a couple with esophageal [cancer]. So those were the ones that we actually treated.

This was a very small study, so it’s a little hard to generalize from them. But in addition, as I say, the ones that are associated with hyperinsulinemia and hyperglycemia could also be eligible, I would say; endometrial, uterine cancers, perhaps pancreatic cancers, and others have actually begun studying that as well. Possibly kidney cancers, and maybe gallbladder cancers as well.

So these are the ones that I would consider to be at least potentially eligible for this, depending on what else we learn.

[Damien Blenkinsopp]: Great, great.

Particularly in those cases, if I have cancer I’d probably want to get a PET scan to see if it lights up.

I don’t know if you have an index there or if it’s just something visual you use. Do you have any kind of index you use with PET scans to understand the severity, like how much is lit up?

[Gene Fine]: Yeah, there are ways of quantitating PET scans, and you can eyeball the uptake, which is often done for purposes of saying whether the cancer has spread to a location or not. If you have a primary.

But if you have a, I like using the solitary pulmonary nodule because so many of them are benign and others are also malignant. And so people have attempted to develop quantitation, and there are a variety of different ways. One of the common ones is called the standardized uptake value.

And you compare the uptake there, essentially, to the average uptake in the whole body. And a value has been assigned by a number of investigators as a cut off that can be useful, and that’s an SUV of 2.5. That’s two and a half times the average value in the body is assigned as being a cutoff for cancers.

Now all these cutoff values have overlaps, and some of them turn out to be benign, but the frequency tends to be much higher. And the higher the SUV the higher the likelihood for cancer.

The reason that there can be uncertainty in this is that the uptake of fluorodeoxyglucose can also be seen in inflammatory tissues, and inflammatory situations, for example even in pneumonia. You can see pneumonias take up FDG. You can see benign granulomas take up FDG, although they usually take up less. But in fact you can get false positives.

[Damien Blenkinsopp]: Oh, so could this be any type of inflammation in the body? Basically where white blood cells are active?

[Gene Fine]: Yes.

[Damien Blenkinsopp]: And there’s a lot of inflammatory conditions in the gut these days. Is that something that would potentially influence it?

[Gene Fine]: Yes. You do in fact. With the colon there are also patterns of uptakes, so the thing is inflammatory conditions in the intestines and the colons, for example, usually there are patterns of uptake, and you actually see an outline of the colon with FDG distributing itself throughout the colon and basically showing the shape of the colon.

Whereas cancers usually have a site of origin and they can be somewhat irregular. But they generally have a round or a spherical type of initiation and shape. And come in clumps. So there is usually quite a big difference between what you see intestines and that as well.

But these are non-invasive diagnostic tests, which are absolutely marvelous because things used to be much more invasive. But they do have false positives. Your goal in a non-invasive test is to be able to screen well, and therefore identify those patients who may have this condition.

And if it’s negative it can be extremely helpful because then the patient doesn’t have it. But if you do have it you may still have to, in some cases, go on and do a invasive biopsy in order to determine what’s actually there.

[Damien Blenkinsopp]: So I guess, just to be practical for anyone at home that might be related to some cancer case or perhaps working with cancer patients. So if it does come up a positive PET scan, it may be worth using a ketogenic diet, a low carbohydrate diet as one of the tools. Could you just confirm more, and tell me that that’s not correct. And then talk a little bit about your recharge trial, where you were actually looking at this.

[Gene Fine]: Sure, okay. I think that it’s hard to generalize. I have spoken, patients have found me on the internet and have called me and discussed their particular cancer situation. And I don’t consider myself explicitly an advocate for this, simply because a 10 patient study — which I’ll talk about in a minute, our recharge trial — is a very small study, and it’s pretty hard to generalize from a study of 10 patients.

But it’s not appropriate to make a scientific conclusion when generally the standard of evidence is that you have to do large, randomized controlled trials. However, that would be the direction I’d like to go to find out more information. And also the fact that it certainly is uncertain whether this works in all patients with PET positive cancers.

But I can talk a little bit about the recharge trial, as preliminary as it is. And what we did was we studied 10 patients with advanced cancers, which is to say they all had PET positive studies and they all had failed several rounds of chemotherapy and were still progressing. So they had had chemotherapy, they were therefore eligible for an experimental trial of the diet, because nothing really was working anyway.

And these patients signed informed consent and they were told that we didn’t know what the outcome was going to be, but we were going to put them on a 28 day trial diet of very low carbohydrate. And so the patients agreed to this, and for 28 days under nutritionist and dietitian guidance they were taught to change their diet.

They had a two to three day trial diet, just to see if they hated it, to make sure. If they didn’t hate it then they could go ahead, but we didn’t want to have people who were clearly not going to be able to complete the diet. We limited it to 28 days because change in diet is hard for anybody. It’s not easy. However, just about anyone can stay on a diet for a month.

So we figured that this would give all the patients a chance to succeed. And principally, the first goal we had to have was safety and feasibility. Was this actually safe? There wasn’t really a lot of reason to believe that it wasn’t safe, but you still have to try that out before you can do anything else.

And it was, there were no unsafe adverse effects. The worst effects that sometimes were reported in this, that we did see were some patients had some reversible constipation — as I say reversible — and reversible fatigue within a couple of weeks. And that’s generally the worst that happened.

So the patients were able to span the diet. Half the patients stopped a little short of 28 days, like 26 or 27 days. We considered that really a successful completion. They didn’t stop because of the diet, they stopped because these were patients with advanced cancers who had planned before they had heard about this trial to go on vacation.

They had bought tickets and thought this might be the last vacation they would be taking. So we weren’t going to interfere with that, and we got the PET scan two days earlier than we had expected and they then left the next day for vacation. So really everyone completed the trial without any adverse effects.

Now, what we did see was that, and we measured ketosis as the standard for how compliant they were. Patients would report their food intake and they would tell us what they ate, and the dietitians would record that. But food recall can be inaccurate.

The most reliable way we could determine whether they were on a ketogenic low-carb diet would be to measure ketone bodies in the blood. And we did find that all of the patients were ketotic. In fact all of them became ketotic — and we measured this weekly for four weeks, a baseline and then four weeks — patients became ketotic really by the end of the first week. So we know that they were ketotic for the period of the four week trial.

[Damien Blenkinsopp]: Were you measuring blood levels?

[Gene Fine]: Yes, these were blood levels. We felt that that was going to be a more accurate measure because urine levels can be influenced by hydration state. If you’re very hydrated you’ll dilute your urine, if you’re dehydrated you’ll concentrate it. So this is more accurate.

[Damien Blenkinsopp]: Yeah, absolutely. We discussed this with Jimmy Moore, who you know well, in a previous episode.

[Gene Fine]: Oh yeah, that’s right. And he actually interviewed me one time as well. That’s right.

So the goal, as I say, was the 28 day diet. And what we did find was that, one patient we actually had to exclude from analysis because, it took us four years to recruit 10 patients. Most patients are on chemo and they don’t really have this opportunity.

And we also didn’t want patients who were too thin because that would have trouble getting past the investigational review board. These are thought of as weight loss diets and you don’t want a cancer patient to lose too much weight. So we had to restrict our patients to patients who were normal weight or above.

Now finding patients with advanced cancer who had not lost too much weight took a long time to get this group of patients together. It took four years to recruit them, there was a lot of time in that.

So beggars can’t be choosers, and we didn’t notice that one patient had had advanced breast cancer with chest wall invasion, but she’d had it for 14 years. And this was different from all the other nine patients, who had failed multiple chemotherapies. She’d had this for 14 years and had never sought any treatment for it at all. She had no surgery, she had no radiation therapy and she’d had no chemo.

So in retrospect we realized, oh my gosh, this patient clearly has much more indolent disease. Even though it’s advanced, it’s progressing so slowly we would have to exclude this patient from analysis because in one month she wouldn’t show change.

She was stable from that point of view, so we couldn’t show progression of disease in this patient in a one month diet. And it turns out she wasn’t very compliant with the diet anyway, and she showed very little change. So the reality was we had to exclude this patient. So we really only evaluated nine patients.

Anyway, getting to the gist of that, of the nine patients the results on the face of it were really not terribly impressive; five patients showed, well four patients showed stable disease, one patient showed a partial remission on the PET scans. We had a baseline PET scan indicate the patients had glucose dependent cancers, and we had a follow up PET scan to monitor the change in the PET scan as an index of whether these patients responded in some way.

But four patients had continued progressive disease. So on the face of it, this is really not that impressive. However, the interesting thing about the difference between these patients is that the patients who had the stable disease or partial remission had three times the levels of ketosis compared to those who didn’t.

So the fact was that whether this was an issue of compliance or metabolic effect, whatever that was with the level of compliance they achieved, the reality was that the patients who showed the best responses were those who had the most ketosis. So that was also consistent with our hypothesis that the ketone bodies and the effect of low insulin levels, which would include ketosis, would have some varying on the outcome.

[Damien Blenkinsopp]: So did the same thing show up? The higher the inhibition of insulin the better the result?

[Gene Fine]: Yes,that’s essentially what we’re saying. That the more it was inhibited, it’s effects were best measured by measuring ketone bodies. Insulin itself varies so rapidly that unless you time it exclusively the same way, timing after a meal and so forth, you have to be very careful. So we use ketone bodies as a more robust measure of the effects on insulin inhibition.

[Damien Blenkinsopp]: So is that pretty concrete then? That there will always be an inverse correlation? That that’s been established very well in science?

[Gene Fine]: An inverse correlation between ketone bodies…

[Damien Blenkinsopp]: Because as you say, insulin can go up and down very quickly so it’s kind of difficult to know where it is. But in scientific studies it’s been pretty well established that insulin is inverse to ketone bodies, so then it’s okay to assume that.

[Gene Fine]: Right, but they act on different time scales. Insulin spikes very rapidly after a meal, and ketone bodies gradually build up over a period of days after chronic low insulin levels.

So you can go out of ketosis fairly quickly, but not as quickly as you can spike. You can spike an insulin level pretty level and the ketone bodies will decrease over a period of hours, the insulin levels change rapidly over a period of minutes. It’s a little bit different time scales, but yes there is a general inverse relationship for chronic insulin levels and ketosis.

The other thing I wanted to mention about this is that the patients who did show progressive disease also showed evidence of, which we weren’t really looking at, we wanted patients who did haven’t coincident other diseases, particularly diabetes because we didn’t want to be treating two conditions at the same time. So we basically made sure that the patients were not diabetics and were not taking diabetic medications.

However, in retrospect we did notice that the patients who showed progressive disease had evidence of pre-diabetes. That these were patients who were the four heaviest, they actually were the four heaviest of the group of 10 patients. They also had baseline glucose levels 100 and above.

There was more evidence of pre-diabetes in this group than there was in the group that showed a response. And there were lower levels of ketosis. So, overall, we don’t know for a fact that this is the way to screen patients, whether this is actually a biomarker. I would suggest that it makes sense that in patients who have pre-diabetes, pre-diabetes is marked by high insulin levels, and it takes quite some [time].

So that in this group, a low-carb diet didn’t seem to have much benefit. In fact, it didn’t have any benefit at all, they had progressive disease.

Now of course the way you want to treat, at least the way I like to treat patients with pre-diabetes, is put them on a low-carb diet. But I think that that would take several months to improve their insulin insensitivity, and if they already have cancer that’s probably not what you want to do in this particular group. If they have cancer and they have pre-diabetes, you’d probably have to treat the cancer as a separate entity.

[Damien Blenkinsopp]: Right, because it’s going to take a longer time to have the metabolic impact that you want.

[Gene Fine]: Right, and you don’t want the cancer to be progressing during that time, so you probably have to make your choices in that case.

[Damien Blenkinsopp]: So, from your study I remember one thing you were doing was in order to assess the better performers was you were looking at the relative ketone change.

[Gene Fine]: That’s right. And we actually, we used relative ketosis, interestingly, rather than absolute. Now, the absolute ketosis was not very different in the two groups. But I actually believe the relative ketosis is more important, mainly because — let’s see if I can describe that succinctly.

When you looked at the baseline ketosis, baseline levels of ketone bodies, absolute values.

[Damien Blenkinsopp]:: So this is before you start the low-carb diet?

[Gene Fine]: Fasting levels, right.

There were some patients who had issues of values, who had like 0.04 millimolar. And then there were others who had 0.4 millimolar. So that’s factor of 10.

Now, the absolute levels of ketosis rose in most patients to about 1.0 millimolar. A patient that only went from 0.4 to 1.0 went up by a factor of just two and a half. A patient that went from 0.04 to 1.0 went up by a factor of 25. So there is a much bigger change in the overall metabolism, and the change of the metabolism in a patient that started at a lower value.

I would propose — and this is what I actually believe — is that the patients who were living with a baseline ketone body level of 0.4 were actually acclimating their cancers to a higher level of ketosis during the period of the cancer’s growth, initiation, and development. And in fact that these cancers may be well acclimated, in other words adapted to, that they grew up in a level in which they were used to these levels.

And so that you can’t expect — well, put it this way. Whereas I do believe that people who live in environments where they eat mostly meat and fat during the year — let’s just say Inuits for example that haven’t been exposed to McDonalds and Laps living in northern Finland and live on reindeer meat all day long — that people who live under those conditions I would suggest, and I don’t know what the evidence is exactly, that they will have lower incidences of cancer.

However, should a person under those circumstances develop cancer, you know you sure as heck would not put them on a low-carb diet, because you know that they developed cancer already on a low-carb diet.

So that’s what I’m basically saying. If you have somebody who already is in a state of higher levels of ketone bodies and cancer develops in a person like that, then you certainly wouldn’t expect that patient to be as responsive to a low-carb diet.

[Damien Blenkinsopp]: It’s interesting because there’s a lot of things in biology, like somatic signals, where, like if you think about the treatment of antibiotics, right, you basically have to pulse it. You have to pulse it and do it one go has to be done effectively. If you get chronic antibiotics for a while then it stops having it’s impact, and you don’t get the benefits, and so on.

So it’s interesting that you identified this mechanism where a body could be a lot more beneficial to, let’s say do something. I mean I’m sure you’re aware that Dr. Seyfried recommends a five day fast, which is a more extreme version of what you did in your study, and potentially may be more beneficial because it is more extreme. As you said, and maybe there will be a higher therapeutic value.

[Gene Fine]: Yeah, that’s right. And Dr. Seyfried is one, also Valter Longo in California has recommended calorie restriction and fasting as well. And I think that those methods may have some other unique benefits that carb restriction may not have. They also may not be as easy to implement, but I think that they’re all in the ballpark, and there may be values for all of them.

[Damien Blenkinsopp]: So one thing I did want to bring up is when we were talking to Dr. Seyfried he mentioned he’s using an index now, which is called the glucose ketone index. I don’t know if you’ve spoken to him about that, or come across it.

It’s simply glucose divided by ketones in millimolars. And he’s been using that to look at his approach to metabolic therapy and see if it’s effective. I’m just wondering if you could compare that to the relative ketones. Would that make sense for you, or you haven’t looked at this?

[Gene Fine]: I haven’t done that, so I really don’t feel up enough to comment on it. I didn’t do that. I actually might want to go back and calculate that as well in these patients to see if I can get those numbers and make some correlations. But I haven’t actually done that yet.

[Damien Blenkinsopp]: Yeah, it strikes me it just might be interesting because, as you said, some of the diabetic patients went up, potentially high glucose. So you might see something similar there. Based on it.

[Gene Fine]: Yeah, that’s right. I was just thinking about that.

[Damien Blenkinsopp]: Great, great.

There’s a few things I wanted to bring up here in terms of the other tactics people might use. Which I don’t know, you may not have an opinion on these. But there are other things that can change the levels of ketones in our body. You can use MCT oil, or ketone esters, exogenous ketones basically, or a high fat diet.

My personal experience with these, for instance, is I’ve been on a high fat diet for a while and in my fasting insulin tests, my insulin is pretty low compared to the average. And I understand that that’s pretty standard. So I was just wondering what you thought of these kind of approaches. Also, if you’ve seen anything that might say there would be similar impact. Because they’re basically mimicking the effects of a low carbohydrate diet.

[Gene Fine]: Well yeah, I actually don’t know what way a high fat diet is distinguished from a low-carb diet. There are three macro nutrients, and basically a low-carb diet is a high fat diet. I don’t know if a high fat diet necessarily is also a low-carb, but it must be lower in carbs because you don’t really make up the difference in protein.

[Damien Blenkinsopp]: Right, you’re right. The question is the protein. That’s the missing…

[Gene Fine]: Right. And as I say, I haven’t tested the protein values. We didn’t restrict protein in our group. I think we could have.

We were dealing with patients who, as I say, had advanced cancers, and we were getting them as through referrals from their oncologists as volunteers, and we really didn’t want to give them something too complicated to do, so we just tried to [simplify it]. But yes, protein, certainly restriction might have had further benefit.

But as far as inducing ketosis with medium chain triglycerides, coconut oils and the like, ketone esters, I think these are interesting approaches. They can certainly, possibly offer more convenience, rather than going through a low-carb diet. And that I think has value.

The other thing to note is that they don’t actually mimic the full effects of a low-carb diet because they don’t inhibit insulin. So, there is that aspect of it. While there may be value, I’m not sure that they’ll produce the full effect.

[Damien Blenkinsopp]: Great, great. Thanks for the commentary.

Now the other thing I wanted to just bring up was metformin, I don’t know if you’ve looked at all at that.

[Gene Fine]: Well, yeah. I mean, I’m aware that this is being used, at least in trials, as another potential mimicker. And it has it’s own value. I think what it does for me is it illustrates the value of low-carb diets, because what it really does, metformin, is it limits glucose and thereby insulin secretion. So, it’s fine. To me it’s major mechanism is the same mechanism as a low-carb diet.

It has some independent mechanisms. It seems to up-regulate AMP kinase, which happens also to be done by low-carb diets. So metformin may have some advantages. It’s a drug. It’s a very well tolerated drug, but it’s not a universally well tolerated drug.

There are some side effects that have been reported. Not frequently, but some patients develop lactic acidosis, which can be very serious. And some patients develop hypoglycemia. So, I think overall it would be considered a very safe approach, it just has to be tested, like everything else.

[Damien Blenkinsopp]: Great. Thank you.

I was wondering if you had any opinion on calorie deficit versus high intake of calories. I could be on a high fat diet, or a low carbohydrate diet, and still have a surplus of calories versus a deficit. Do you think that’s anything that could be either affecting your results, or something to look at?

[Gene Fine]: Yes, it is something, definitely, to look at. The calorie restricted approach has been advocated…well, it’s just been advocated. I can’t say exactly whether the mechanism is the same, overlapping, or somewhat different.

But I can just say this, that in our study we actually wanted patients to not lose weight. We encouraged them to overeat. Overeat a low-carb diet, but overeat. So to eat as many calories as they needed to sustain their weight.

So the only comment I can make about this is that all the patients lost weight. We did not intend for them to lose weight, that was not our goal. We encouraged them, we would be weighing them weekly and we’d tell them, “Eat more, eat more. You’re making these shakes, add more cream to it. Add more oil to your foods. Put butter on everything.”

Well anyway, whatever it is that we encouraged them to do, all 10 of them lost weight. They lost on average about four percent of their initial body weight. The interesting thing about that, I just suppose that this is why these diets are effective as weight loss diets.

No one knows exactly why they work, but you certainly can speculate some pretty plausible mechanisms. One is that ketosis may inhibit appetite. Another is that your inhibiting insulin, and insulin, as I say, under the influence of carbohydrate makes you fat and keeps you fat. The absence of insulin does the opposite. It releases lipids from your fat cells, and metabolizes them in the liver. So the fact is that low-carb diets intrinsically may be weight loss diets.

We believed in our study that it’s possibly to defeat this. That there’s such a thing as overfeeding, and maybe if one is particularly conscious about this, one can do this. But the other interesting factor is that seven out of the 10 patients were above a body mass index of 25, which is to say they were overweight. Only three of them were in the normal weight range, between 20 and 25.

And as it happens, the patients who lost the most weight were the heaviest. Frankly they were delighted with their weight loss, even though we were trying to maintain weight just for the principles of our study.

The patients who were in the normal weight range, the two who were the higher two in the normal weight range — I should say, the heaviest patients lost about five to six percent of their body weight. The patients who were in the normal weight range, the two heavier of them — 25 BMI and 23 — lost about three percent of their body weight. And the patient who was 20 lost no body weight at all.

So what this tells us is something we all know also, which is that the closer we approach our ideal body weight, the harder it is to lose weight. I don’t know whether you’ve observed that yourself, whether you have gained, lost or are stable in terms of your body weight, but I believe that high fat diets do not necessarily cause weight loss, particularly in people who are approaching their ideal lean body weight.

[Damien Blenkinsopp]: I’ve been on this diet for many years, just as an n=1 experiment. I think I lost a bit of weight when it first started, but ever since I’ve been really stable, ever since. And I’ve never paid attention to the number of calories. Sometimes I’m sure I’m eating a lot of calories, and sometime I’m not eating so many, for whatever it’s worth.

[Gene Fine]: I should also mention one other thing, which is that in our study, when we calculated what the calorie intake was on the basis this is of course on the patients self-reports, that all the patients reduced their calorie intake as well. Now, we didn’t want them to, but the measured calorie intake on the basis of their self reports was reduced, in fact by about one third.

The other interesting thing though is that the stable disease effect and partial remission, those patients who showed stable disease or partial remission had three times the ketosis. But the degree of weight loss in the two groups was the same. They both lost about four percent. So although there was weight loss in all the patients, weight loss, or calorie deficit, did not appear to correlate with the effects that we saw.

[Damien Blenkinsopp]: Well that’s a great point then.

I think the other point you illustrated, if we’re talking about your studies, is how difficult it is to set a good cancer study up, given the situation with the patients and you’re trying to control for a lot of things. So, as you say, it took you four years to recruit the patients for the last study. So I think it gives us a much better appreciation of how difficult it is to do these types of studies.

[Gene Fine]: Yeah. I think it is the fact that physicians are trained to treat with drugs and that’s very understandable. Drugs generally work well. And in cancer, it would be naive to start off with the assumption that diet is going to be a successful therapy. It has to be tested.

And so, whereas there was some reluctance, there wasn’t entirely, and many of the oncologists were very helpful and cooperative and referred patients when they were on a chemo holiday, or chemo break. That’s what was needed to get this study done. And also the fact that I didn’t want patients who were too thin and too sick.

But I think going forward, I think that we can count on, perhaps, some additional support. And we are actually aiming for human studies going forward as well. Right now, as I say, we’re also trying to couple diet with drugs in animal studies. So this combination, we hope, will lead us somewhere.

[Damien Blenkinsopp]: Yeah, Great. So is it the first time someone’s been trying to couple chemotherapy with diet? Or are there existing studies that you’re basing your current work on?

[Gene Fine]: Coupling a low carbohydrate diet with other therapies has been done. I know that Colin Champ and Doug Spitz, I believe, have coupled low-carb diets with radiation therapy. As far as coupling with drugs, I’m not actually immediately aware that anyone has done that. I think that we may be the ones who are looking at that right now.

[Damien Blenkinsopp]: Great. Wrapping up a bit, thanks so much for your time today.

Where could we learn more about this subject? Are there other people you would look to to learn more about this? Perhaps people you’ve worked for who are doing a lot of studies in this area. You mentioned Valter Longo, of course who was mentioned in Dr. Seyfried’s as well. Or are there any books or presentations on the subject that are good?

[Gene Fine]: I’m trying to think, other presentations. I know that there are some other people working in the area that I know have been doing good work.

Dominic D’Agostino in Florida. I think he has a website, and it would be interesting to look at some of the work that he’s done. A somewhat, I hope, accessible discussion of what we’ve talked about.

I have a couple of guest blog posts that I wrote. My colleague Richard Feinman has a generalized biochemistry and metabolism web blog, and he invited me to write some guest blog posts for his web blog. So I wrote two.

One which is on the general hypothesis, which I didn’t even discuss today. I mean, I discussed it in the broadest forms, but I didn’t discuss some of the details. And the other one is more on the clinical trial, on the recharge trial. So it gives more detail on that.

And I think Colin Champ has an interesting website as well, Caveman Doctor. I think I’d look at that. These are other resources. I think I’ve mentioned most of those that I know.

[Damien Blenkinsopp]: Great, great. So, we’ll put links to all of that in the show notes, thank for those.

Well how about you? What are the best ways for people to connect with you? I mean you mentioned the blog posts, which we’ll put in. Is there anything else? Do you have a website, or are you on Twitter? Is there anywhere you are active where people could learn more about what you’re up to?

[Gene Fine]: Let’s see. The website that I have is my website at Albert Einstein. You can also, through the blog posts that I mentioned it gives other links to papers that I’ve written as well as to my website. So I think that probably the most complete portal, you can look me up just at Albert Einstein and find my website there. And that will also link me to the dietary studies and the blog posts and the papers. They all connect to each other.

[Damien Blenkinsopp]: Great, great. We’ll put those on the show notes.

Something we spoke about just before the interview, your perspectives are a little bit different to Dr. Thomas Seyfried that we’ve already had on the show. Could you briefly summarize where you think you might have a different opinion?

[Gene Fine]: Well, I just think that we really are in the same camp. I think that we both believe in metabolic therapy, as do the other people that I’ve mentioned. I think that he believes that when he describes cancer as a metabolic disease, he believes that the fundamental problem is it starts as a metabolic disease in abnormal mitochondria. That may be true.

The only thing that I think that I would differ is that that abnormality in the mitochondria, I believe, is a genetic abnormality, even in the mitochondria. That you still have, what’s happening in the mitochondria is that, to me the fundamental problem in cancer is actually a genetic mutation that leads the cells to increased proliferation and growth and unlimited growth and immortality, and so forth.

The source of these mutations, I believe, could certainly be in the mitochondria, but in fact if it is, and that would make sense to me, it would be increased reactive oxygen species. And increased reactive oxygen species can cause mutations in the genetic portions of the mitochondria, and that would cause abnormal mitochondria. Or it could cause mutations in the DNA of the cell. Certainly hydrogen peroxide, peroxide can migrate over distances and can migrate into the nucleus.

So, I actually believe that the fundamental problem that leads to the cancer may initiate in the mitochondria with reactive oxygen species, but nonetheless results in the fundamental change of cancer is in a mutation. So I think that [in a] certain sense we’re describing the same phenomenon, but we have a different emphasis on which syllable we’re emphasizing.

[Damien Blenkinsopp]: Right. Potentially where it starts and where it finishes, and so on.

[Gene Fine]: Yeah, yeah.

[Damien Blenkinsopp]: Great. Great, thanks for that clarification.

Before you go, I just wanted to look at a bit of what you do on a personal level with your body data. I was just wondering if you track any metrics at all for your own health, biomarkers, or anything like that on a routine basis. Maybe yearly, or more so?

[Gene Fine]: When I started studying this in, around 2003, and I got interested in it, by the way, from my friend and colleague Richard Feinman. He’s a biochemist, and he’s been interested in this principally from the point of view of the effects on metabolic syndrome, diabetes, lipid disorders, and so forth.

However, I came in from the nuclear medicine background, and PET scanning and Warburg effect, and hypoxic cells. For me it was attractive for the possibility that this may have some effect, low-carb diets in inhibiting glycolosis, and as I mentioned earlier through the uncoupling protein 2 having a unique inhibitory effect on cancers while sparing normal cells.

So in 2003 when I got interested in this, and I decided that — you know, I never really had a weight problem, but I had gradually put on a few pounds over the years. And I have a small frame, so I’m about five foot nine, and 165 pounds. For me that was carrying excess fat.

So I figured well, you know, if I’m going to study this in others I might as well experience what it’s like for myself. And maybe I’ll even have some benefit in terms of overall body composition.

To make a long story short, I’ve been on a low-carb diet of various degrees of strictness over the years. In some cases I’ve been ketogenic, I’ve been very strict. In other cases, I’ve just been low-carb, but not likely ketogenic. I haven’t been under 50 grams a day, I’m not quite sure.

But the short story is that over a period of now, what 2003, really 2004, about 11 to 12 years, I’ve lost 33 pounds. Sometimes it’s been in fits and starts, but I’m very, very happy and comfortable with my weight right now. I like myself at 132. I have a small frame. I feel that for me I am lean and fit, and that’s a good thing.

There’s that aspect of it. In terms of other biomarkers, the numbers that I like to look at, in particular, are those that have risk profiles for, well my glucose and my hemoglobin A1C has dropped. In addition, my fasting blood glucose.

[Damien Blenkinsopp]: So if you remember, where did they start and where are you at now? And are you happy with the numbers now?

[Gene Fine]: Well yeah. I mean, I think I’ve been stricter lately and more consistent, so I’ve only been monitoring them really. I don’t think I’ve really been taking very close watch of them.

But I think over the past year or two my blood glucose, a couple of years ago had actually been at 100, and my hemoglobin A1C I think at one time was around 5.7. I’m sorry, this was only about one year ago.

The hemoglobin A1C changes slowly, but in two successive measurements, I’m about to come up with a third, it’s dropped to 5.7 to 5.6 now to 5.5, and I’m expecting it will continue to be going down because I’m doing this. And my fasting blood glucose is now about 94. So it’s dropping, and I’m satisfied with that.

I used to eat what was recommended. I used to eat a low fat diet, which of course means a high-carb diet, and I think I suffered the consequences. But little by little that has been reversing.

From the point of view of my lipid profile, the things that I’m most interested in are those that are atherogenic, that contribute to risk of cardiovascular disease. And I think the current thinking, which makes some sense to me, is that it’s not so much LDL which is targeted by the cardiologist, because LDL is a mixed bag.

Low density lipoproteins really consist of two major fractions. One of the light, buoyant LDL, which is really not harmful, and the other is the small dense LDL, which is. And what happens on a low-carb diet is you reverse the ratio. You reduce the amount of small dense LDL.

And the good measure of that, because it’s hard to get that measurement directly. There are only a few labs in the world that actually measure small dense LDL directly. You have to send away to specialized testing for them. However, there’s a good index of it and it’s the ratio of your triglycerides over your HDL.

[Damien Blenkinsopp]: So there’s a proxy?

[Gene Fine]: There’s a proxy for small dense LDL, yeah.

[Damien Blenkinsopp]: Oh, great.

[Gene Fine]: And so when I started, I guess when I first measured my triglycerides to small dense LDL when I had been not very compliant at all, my triglycerides at one point were about 150, and my HDL was about 50. So the ratio was about three. And since going on a low-carb diet, my triglycerides fell in half, to 74, and my HDL went from 50 to 75. So basically my ratio is now one.

[Damien Blenkinsopp]: That’s pretty high.

[Gene Fine]: So all the things went in the right direction. I’m very pleased that the HDL went up, without any major increase in exercise, just the diet alone. And my triglycerides fell in half. So those are both just exactly what you would expect on a low-carb diet, and what you want.

[Damien Blenkinsopp]: Great, thanks for those.

They’re very useful, especially the triglyceride HDL ratio. Because it is difficult to get the, I guess you were talking about the NMR, nuclear magnetic resonance. We spoke about that in a previous episode. And then there’s the LDLP to get the number of particles. But as you say, there’s only a few specialized labs, so it’s not as accessible. So it’s great to know that there’s a proxy to use also.

Last question here. What would be your number one recommendation to someone trying to use some kind of data to track, whether it’s biomarkers or something else, to make better decisions about their own health?

[Gene Fine]: Yes, well I mean it depends on what aspect of the health you’re talking about. But I don’t know if ketosis is necessary.

As I mentioned, any change of diet can be difficult to sustain over the long term. I don’t even know what it takes. Willpower is something that, what is it. So, it’s hard to know how to do that.

And by and large the reason I would say it’s hard to change diet is people eat what they like. And you want to eat what you like, and so changing your diet means you’re, by definition, changing it to something that you didn’t prefer. So it seems as though there’s a fundamental issue there.

On the other hand, I think that if you have a weight issue that you’re not happy with, or your doctor reports blood lipid markers or glucose markers that you’re not happy with and evidence of pre-diabetes or diabetes, and you’re on meds, so forth — let’s not consider meds yet. Let’s just talk about without being on meds. Because low-carb diets, if you can actually go on them and you’re also on meds, you have to do that under supervision because you might actually become hypoglycemic, and you have to be careful about that.

But without considering meds if you just want to, say, improve your health in terms of obesity or aspects of metabolic syndrome, lipid disorders, blood glucose levels, pre-diabetes. Without going on a strict low-carb ketogenic diet it’s not as hard, I think anyway, to reduce the quantity of carbohydrates that you eat.

You can have a breakfast where, you can cut out, well cut in half the size of the desserts that you eat. You can cut in half the amount of mashed potatoes that you eat. You can eat one slice of bread instead of two, or you can not eat bread. Although that sometimes is hard for people, but if you eat the bread and don’t eat the mashed potatoes, you’ve reduced the number of carbs that you eat.

So if you just start by reducing certain portions of carbohydrates. And I actually found I still have carbohydrates a little bit now. I have a sort of modified Atkins Plus, I call it, or South Beach Plus. I have a little ice cream at night. It’s my treat.

Overall, I probably eat about 60 grams of carbs a day. But, I treat myself to a little bit of ice cream at night. I’ll find out what that’s done to my lipid profile, by the way. But I don’t think it’s going to have a major effect. I think that overall it’s going to be still pretty good.

So the idea of reducing the overall quantity of carbs, I think, is actually important. I think that with the average American diet, I don’t know if the same is true in UK but probably, that overall consumption of carbs is 300 to 400 grams a day. And that’s really quite a lot. And if that could be cut in half to 150, that would be a big improvement.

So, I think that that would be lower stimulation of insulin secretion. Yeah, I think that that would be my principle recommendation in terms of health.

Now as far as exercise is concerned, exercise is also something that many people do but can’t stick to an exercise regime. And overall, I think that even if you look at the overall impact on insulin sensitivity and improving metabolic profile, there’s no question that exercise helps. But it really comes a distant second to diet in terms of having a dramatic impact on insulin sensitivity and these other biomarkers of lipids and glucose and so forth.

So that, while you’ll never hear me discourage anyone from wanting to do exercise, I think that if you want to have an immediate and more dramatic effect, the thing to do would be to reduce carbohydrates in the diet somehow.

And that’s probably the best I can say at the present time, because as I say, I don’t think anyone has a magic bullet as to how to help someone go on a diet. It’s never easy, but if you can find a way to reduce carbohydrates, you’re off to a start.

And if you feel encouraged by the results that you see, you tend to continue it.

[Damien Blenkinsopp]: Absolutely. Thank you for bringing that up, because we’re introducing changes here, new habits. And as you say, it’s super difficult.

I feel one of the things that helps people is making it clearer how helpful it can be in different areas of their life. Once you’ve heard it 10, 20 times from different people who are studying these things, like yourself, in different areas. I think it makes it easier for people, just because of the repetition, for the clarity in their heads.

I think part of the problem is the mystery and the misunderstanding, especially in the media and the press. The more times you’ve heard five different stories, the less you feel like taking action against any one of them, because you’re just not sure, you’re hesitant.

So thank you for your time today, because it’s certainly helping with these type of things.

[Gene Fine]: Thank you. I’m glad that you have this program, really, to spread the word through interviewing people who are active in the field.

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