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

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

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

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

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

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

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

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

itunes quantified body

What You’ll Learn

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

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

Robb Wolf

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

Recommended Self-Experiments

7-Day Carb Test

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

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

Damien’s 7-Day Carb Test Results

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

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

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

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

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

carbohydrate-tolerance-glucose2

Blood Ketone Response to 50g of Effective Carbohydrate

carbohydrate-tolerance-ketones-2

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

Sleep

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

Tracking

Biomarkers

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

Lab Tests, Devices and Apps

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

Tools & Tactics

Diet & Nutrition

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

Interventions

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

Tech & Devices

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

Other People, Books & Resources

People

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

Books

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

Other

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

Full Interview Transcript

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

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

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

[Robb Wolf]: Awesome, awesome.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

First of all you were talking about insulin resistance.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

And there are some other methods for tracking that. There’s looking at fasting blood glucose, but there are limitations to that. There are ways that that can be misinterpreted both on the up and the downside. Fasting insulin is similar, it’s helpful but there are ways that can be circumvented. A1C [is another].

So we do like looking at several of these numbers, in the beginning in particular, and then checking back on them periodically, because it provides a lens. In particular a lens to help us better understand that 7 Day Carb Test. Because those carbohydrate numbers just in isolation can also be a little bit confusing.

But with that lipoprotein insulin resistant score, what we found in the police and fire populations that we work with – I’m on the Board of Directors of the Medical Clinic here in Reno, Nevada – we found that with the other methods for tracking insulin resistance we were missing people, particularly folks that were sleep-deprived and/or hyper-vigilante.

So they had consistent adrenal cortical response, some HPT axis dysregulation. Those people were insulin resistant, and often times significantly so, but we didn’t see it in fasting insulin levels. Specifically blood glucose levels may not have been that bad at that point, but we were seeing some really consistent long term insulin resistance when we looked at that LPIR score.

(0:24:28) [Damien Blenkinsopp]: So it sounds like it could be uncovering people that we normally miss.

How about the waist to hip ratio? That’s a nice easy thing that anyone can do at home. Did you also find the same thing, that it doesn’t necessarily capture people? Like you can be pretty thin and slim and have these same issues.

(0:24:53) [Robb Wolf]: Absolutely, and that’s where again we use it to build a case, but you can’t hang your hat 100 percent on anthropometric measures like that.

[Damien Blenkinsopp]: Great. Have you looked at how people can basically recover carb tolerance? Or have you seen that kind of period, the timeline?

Any indication of, say they did a 7 Day Carb Test now, when would it be useful to retest? Maybe 6 months after following a clear Paleo diet and all of your proscriptions. You talk about all of them.

[Robb Wolf]: That’s a really good question. Part of the inspiration for even doing the 7 Day Carb Test came out of research from the Weizmann Institute in Israel, and it was looking at personalized nutrition by tracking the individual glycemic response.

And what they did in these folks is they had them wear a CGM, a continuous blood glucose monitor – just a little disk that gets slapped on the back of your arm – and it measures your blood glucose levels once a minute, every minute for the duration of the test. I forget, but it was two or three weeks and they had 800 people signed up on the study.

So it was a massive amount of data; they had over a million blood glucose samples. They then did a gut microbiome sequencing on these folks, they did a full genetic analysis, and the standard kind of lipidology based blood work. And then they started feeding these people different meals. And the blood glucose responses were all over the map.

It was similar to myself and my wife, where one person would eat white rice and [their] blood glucose would go to the moon, [whereas] another person would eat white rice and they had a barely perceptible increase in their blood glucose response.

And then there were wacky things like hummus. Even though I’m the Paleo guy and legumes are theoretically problematic, hummus is protein and fat and fiber. There’s hardly any carbohydrate to it, but hummus was about a coin toss as to whether or not you had a good or a bad blood glucose response.

And the one thing that they did figure out with this was that if you determine the amounts and types of food that kept your blood glucose within lower bound levels, then your gut microbiome tended to improve and your inflammation and insulin sensitivity tended to improve over time.

So I don’t know that I have an exact timeline on this that I could relate, but what appears to happen is if you eat in a way where you’re not consistently deranging your blood glucose, which seems to have knock-on effects with the gut microbiome. There are some interesting theories around how acellular or processed carbohydrate can shift the way that our gut microbiome is existing. It’s a pretty interesting and elegant model.

But if you keep things within good bounds, then things tend to improve in kind of a virtuous cycle, and then conversely if you are consistently driving blood glucose out of what we would consider to be healthy bound, the gut microbiome tends to shift towards a more pro-inflammatory state. We see elevated inflammatory cytokines on circulation, we tend to see elevations in insulin resistance.

And in the book I make a recommendation that maybe quarterly. We don’t necessarily need to do a full reset as far as a 7 Day Carb Test, but I really recommend sitting down and just paying attention.

“Hey, how long can I go between meals and still feel good? If I do a little bit of fasting training, how do I feel with that? How’s my sleep? What’s my creakiness in my joints, what’s my subjective measures of inflammation?”

I am fairly geeked-out on the quantified self stuff, and I find a lot of it valuable, but I still like to get people back in their own skin so they can get a sense of where things are going right or potentially going wrong.

And a quarterly recheck, at least on the subjective level, seems to be frequent enough that if things are sliding sideways we haven’t slid so far that it’s terribly hard to get things back on a good track. But it’s also not so frequent that you just throw your hands up in disgust and you’re just done with the whole process and don’t pay attention to anything anymore.

(0:29:39) [Damien Blenkinsopp]: Yeah, absolutely. On my own journey I’ve quantified so much stuff, but at the end of the day it’s how you feel that matters. And you can even improve a whole bunch of biomarkers, but if you don’t feel better or feel less inflammation it’s not that helpful. It can be insightful and give you clues, but we’re still at quite a rudimentary level yet.

I actually interviewed Eran Segal in just the last episode of this podcast, actually. He inspired me to get into CGM, amongst some other people. So ever since I’ve been playing around that and have found it very instructive.

And not just for the food intake, but also sleep, which you talk about a lot in your book, and stress.

How important do you think those are in your experience, compared to the food? Because we always talk about the carbs and the food.

[Robb Wolf]: Even though I’m the food guy and we used to run a gym, so you would think that I would say that exercise is most important, or exercise and nutrition, but sleep is it. I mean, sleep is it. And here’s my argument for that.

You could eat the most wretched diet imaginable, and it’s going to be hard for you to kill yourself in anything short of a couple of decades. Some people can do it, but it takes a pretty Herculean effort to do yourself in with even the worst dietary practices you can imagine.

But sleep-deprivation is so injurious to our physiology that the Guinness Book of World Records, they will let you jump a rocket motorcycle across the Grand Canyon, they’ll let you juggle chainsaws that are lit on fire, but they will no longer entertain people trying to do unbroken longer periods of sleep-deprivation. The last two people that have tried it, they got right around that 9 to 11 day mark and they just died. And they don’t know why, but they are dead rather quickly.

So the sleep piece is just so incredibly important. The stress piece is important too, but there was a great book that I read and I interviewed the author, it’s called the Myth of Stress. It was really a fascinating reframing of this whole stress story. And so much of what we experience in day-to-day life that we perceive to be stress is completely generated between our own ears.

It’s anxiety about finances, it’s anxiety about how this meeting is going to go with our boss. It’s all these different things that really at the end of the day, we have an opportunity to either let this stuff eat us alive, or we can reframe it and just say that’s not actually a real threat, and so I don’t have anything to be worried about. So there’s actually comparatively little in the modern world that is in fact a legit stressor.

Now the caveat with that, we do a lot of work with police, military and fire, and those folks legitimately live in hyper-vigilant states a lot, because they have life-or-death scenarios that they’re dealing with every day all the time. So there are caveats to that.

But a shlep like me, where I live out on a small farm, we have some animals, I have two kids, I do the business stuff that I do, I can let myself get spun up and feel stressed out. Like, oh my god, one of the goats got bit by the neighbor’s dog.

This did happen this time last year, and the poor goat it’s eat got peeled off. But it was fine, we had a vet come out and gave it some antibiotics. We had to catch the little bugger and wrap it’s ear up for about a week, and then he was totally fine.

But when it first went down, I was like, why did we ever move out here, what are we doing, this is a waste of my time. And all this just internal dialogue and stress. Then I stopped and I was like, well I love living here. The kids love the animals.

There’s sometimes pain in the ass elements to this, but I’ve turned this from an acute event into what is now for me a long-term stressor, but I did it to myself. So I would throw out there that a lot of what we perceive to be stress is mainly self-generated.

And again, circling back to the sleep part, I just can’t think of a greater return on investment than trying to go to bed a little earlier, sleep a little longer, within the boundaries of what’s normal for you. Just blackout your room, have a really solid sleep hygiene process where you go to the bed at the same time each night.

It may not do wonders for your social life, but then again maybe it will because you may not be a cranky cantankerous prick because you’re actually well rested. So it’s hard to tell. And it’s liable to pull 5 years of aging off of you in just a matter of a week.

[Damien Blenkinsopp]: Yeah. Sleep is the hardest part.

Just curious, do you use anything to track your sleep? To try and keep a bit more responsible, or have you seen anything that works for people?

[Robb Wolf]: Really HRV is kind of the best thing that I’ve seen. Some of these actigraphy things are interesting. It is interesting, again, even though I’m a biochemist, I don’t know if I’ve weighed and measured so many things that I’m just like, oh my god I don’t want to do it anymore.

But I’ve just gotten into a point now, and it’s interesting. Folks like Tim Ferriss and some other folks I’ve interviewed with, they were like, “What’s your morning ritual?” And because I have kids, the morning ritual is super variable. I don’t know if somebody pooped their pants, and they’ve got poop from their earlobes to their toenails. That’s a way different morning than if that doesn’t happen.

But what I have found is I tend to have really good control over my go-to-bed ritual. So when the sun goes down – and this varies with the seasons, our days get longer so we stay up later – but when the sun goes down then, we installed dimmer switches in our house when we did our remodel last year and we drop the lights down to a super low level. We put on some blue blocker Swannie sunglasses.

Usually not too long after that I do a little bit of reading and I just fall asleep. And it’s like a ninja blow dart hits me. And when I’m consistent with that, and if I also happen to be tracking my HRV pretty consistently, I just see that HRV score improve. And then if I do have an off-night of sleep, we see some pretty immediate impact on that.

But the actigraphy, I haven’t found to be super helpful. If we had someone that was waking up in the middle of the night or something like that and we had some HRV score feedback. The thing about HRV is it tells you something is up, but it doesn’t tell you what that thing is.

It could be that we’re having a low blood sugar response in the middle of the night, so we get some cortisol release, and that suppresses melatonin production, so it pops us up out of sleep. So maybe we need more calories overall, maybe we need more carbs near dinner. Maybe we need fewer carbs near dinner, because some people are experiencing that rebound hypoglycemic event.

There’s not a one size fits all answer with it, but in general I just kind of gauge [when] I wake up in the morning, I stand up [and see] do I feel clear headed, do my joints ache because of jiu-jitsu and being 45, or do I feel good? And if all of that stuff feels good, then I’m pretty good to go. And particularly if that HRV score just stays nice and consistent.

(0:36:41) [Damien Blenkinsopp]: Yeah. I’ve been a fan of HRV also for a long time. I’ve been tracking it.

I also find it difficult, the same way you do. It captures everything, and if you’re someone who’s got some kind of chronic health or some issue like that on top of potentially not sleeping correctly, over-training. You’re doing Brazilian jiu-jitsu, so I’m sure that’s happened a few times.

And there are these different factors and you have to kind of piece the story together. But it can give you that overall number.

I’m just curious, what do you use, do you use a sort of an app or is there something specific you like because of convenience or something?

[Robb Wolf]: Yeah, I’m just kind of old school. Joel Jamieson hooked me up with the BioForce platform and I’ve pretty much just like hung out on that.

I know there are a lot of cool stuff out there and I do have a few others but I’m again, a little busy and kind of lazy with that stuff. I’ll check in on it occasionally, but it’s generally a deal where once I get a baseline established, and it’s a thing again that I know if I’m getting into bed, falling asleep, and waking up feeling good, everything else is fine.

And then on my training side I do a little strength and conditioning, a little bit of weight work, gymnastics, and also some low level cardio to support the Brazilian jiu-jitsu. I just keep my volume and intensity really modest on that. 80 percent of my rolling is more in a drilling and aerobic fashion, and about 20 percent is that white buffalo in the sky.

Like the 20 year old three stripe white belt is trying to take my head off my shoulders, and so it’s a battle for survival. But I don’t do too many of those. Maybe one day a week that there’s some pretty hard training that goes on.

And so long as I do that, everything is good. Everything is really, really good. I just try to make very small, incremental progress, in mainly the jiu-jitsu side, and so all of my strength work, all my conditioning work, all of that is of a remarkably low volume and intensity for the most part. Just to support jiu-jitsu.

If I feel the least bit knackered after a cardio session or something, I went too hard. Because I need to save that energy for rolling, and not for getting better at the Airdyne or something like that.

[Damien Blenkinsopp]: Yeah.

So when you’re talking about volume, how many hours are you doing of exercise, jiu-jitsu, and all kind of mixed together?

[Robb Wolf]: So jiu-jitsu is between three to five days a week, and usually an hour to two. Shorter classes if I’m time pressured, then I get the one hour class which is a mix of drilling and then a little bit of live rolling.

A couple days a week I usually will stay for a half hour to an hour of just continuous live rolling. I try to grab partners where we don’t set a timer and we just try to roll. We just try to keep moving, and it forces a pace that you could maintain for about an hour straight. And I really, really like that. You get lots of repetitions in in that regard.

And then as far as the weights and gymnastics stuff, I just drop in a little bit of gymnastics bodies, mobility and strength work during the course of my work day. Usually once a week I either squat or deadlift. Once a week I might do some heavier weighted press and pull weight room style stuff for the upper body.

But those weight room workouts, I warm up and I’m done in less than 20 minutes. Occasionally a little longer than that if I’m doing a lot of mobility work in between, but even then it’s not like I’m doing a CrossFit work out.

I have two minutes of rest between sets. I’ll do a set of weighted chins, a set of weighted dips, and then some weighted shoulder dislocates to work on my thoracic mobility in between those sets. So it’s not a frenetic pace.

And then the recovery cardio, I will go longer on that if I can. It may be 40 or 60 minutes occasionally, but a lot of those – my oldest daughter now is five years old and has gotten pretty good on her little dirt bike. So I will drive her and and myself over to a park right next to our house that has some dirt trails and she’ll ride her bike and I’ll run at a nice easy pace. So I’m outside and I’m spending time with my kids.

So there’s like somewhere between three and maybe eight hours a week of jiu-jitsu, there’s maybe two more hours total a week of weights and cardio. But I do try to do a ton of stuff. I’ll stick the younger kid in a backpack and go for a hike for as long as she will put up with it. We have a three acre farm where we have animals to deal with, and we just run around playing hide and seek, and stuff like that.

So I do a lot of physical activity running around with the kids, but in the gym stuff between jiu-jitsu and strength and conditioning and all that is less than 10 hours a week, for sure.

[Damien Blenkinsopp]: Yeah, so you keep the intensity monitored.

I just looked up the Myth of Stress. Was that Andrew Bernstein?

[Robb Wolf]: Yeah, Andrew Bernstein.

[Damien Blenkinsopp]: Okay. Bernstein. Cool. That sounds really, really interesting.

Does that tie in with the gratitude stuff? We hear a lot about gratitude and I’ve been practicing it for a little while. I think a lot of people have. Did he mention that at all?

[Robb Wolf]: Yeah. He would be a great interview. He’s a solid guy, a really, really good guy.

(00:41:35) [Damien Blenkinsopp]: Yeah. Excellent.

Okay. So I thought we’d also jump into a little bit of ketones, ketosis, and fasting, because I know you’ve played around with this yourself and your levels of carb. And it’s such a big topic at the moment.

You’ve spoken a bit about you can’t really do the really low carb and the Brazilian jiu-jitsu and that you can’t get away with it. What’s you overall feeling on the whole ketones and ketodiet?

[Robb Wolf]: Yeah, the last chapter of the book is called Hammers, Drills, and Ketosis: the one tool your doctor will never use. Fortunately, that story is changing. Therapeutic fasting and ketogenic diets are incredibly powerful as potential adjuvants or adjuncts to things like epileptic treatments, potentially working in synergy with conventional cancer therapeutics.

Just huge potential there, but it’s crazy because you don’t see people get into huge pissing matches about whether or not you should use a hammer, a screwdriver, or a handsaw to get something done. If you’ve got a 2×4 and you want to cut it cleanly into two pieces, a hammer and a screwdriver are terrible options, the handsaw is a great option. There’s just not a lot of drama around that.

But then whether or not you should be higher carb or lower carb becomes this religious doctrine thing. And there is a little more nuance to it, there is a little more depth. But just empirically we’ve seen people do pretty well at the power athlete end of the spectrum, the real short time indexing end of the spectrum, and quite low carb.

And we’ve also seen some people doing this ultra-endurance work at a pretty good level going very low carb. And interestingly that looks like catering to the ATP creatine phosphate pathway and also mainly the aerobic pathway.

Where we have a kind of deadzone, a no-man’s land, appears to be these really glycalitically demanding sports like soccer and MMA and CrossFit and jiu-jitsu. And there’s just, man you don’t see a lot of just empirical success there. You see people like me that try, and try, and try.

There are a few examples, there are a few people out there that are figuring out how to do it. Probably the highest level, most sophisticated person I’ve seen looking at this problem is Alessandro Ferretti. He’s in the UK. Man, that guy is smart.

And he is just doing some shockingly interesting work looking at [it]. And he does Judo and Karate, so not exactly the same as Brazilian jiu-jitsu but he’s found he runs great on a ketogenic diet, he has great energy, he can fast, and he’s lean. All the stuff is great, but then he will get kind of adrenalized and burned out in the process of doing too much high-intensity activity.

And what he’s done is just try to map out the volume and the intensity of the training he will be doing, and then match that with a maltodextrin solution or maybe a maltodextrin plus fructose, because there are some arguments for repleting some of the hepatic glycogen preferentially. And he does some really amazing work.

Now, for me, because I’m kind of lazy, it also looks a little bit like a calculus problem. Alessandro is like six times smarter than I am, and he runs a really well done clinical intervention, where they’re just collecting tons of data on people.

I’m kind of a knuckle-dragger. So where I’ve arrived out with all the stuff is I just tend to eat between 75 to 120 grams of carbs a day. Higher end on training days, lower end on non-training days.

But the overall story I think is ketosis and fasting hold enormous therapeutic potential. Potentially some great performance enhancement under certain circumstances, but it’s also a powerful tool. And like any other powerful tool it can be misused, or inappropriately used.

[Damien Blenkinsopp]: Yeah, Absolutely. I know Alessandro, I talk to him quite often too. He’s a great guy. I have to get him on this show soon.

[Robb Wolf]: Yeah.

(0:45:35) [Damien Blenkinsopp]: So thanks for all of this. Last thing on this carb thing is it doesn’t sound like you time your carbs at all before or after training, or anything like that. It sounds like you’re very much focused on the practical, which is probably 80 percent of society who aren’t super self-disciplined and robotic about this.

[Robb Wolf]: Yeah, I do time it a fair amount, in following a guy Bill Lagakos. He’s a professor of Biochemistry, I believe, in the East Coast, and really super sharp on circadian rhythms. And he kind of alerted me to this idea that time restricted feeding, the shortened feeding windows, seem to be quite beneficial for a variety of reasons.

But he made a really strong case for this idea that we would do better to eat more of the calories and more of the carbs earlier in the day. And I know there’s carb backloading. This becomes, again, if you want to get a contentious pissing match on the internet, just throw one of these concepts out there.

But Bill made a really interesting case that there’s an argument based off of circadian biology that we should eat more carbs, more calories earlier. And that is one thing that I’ve focused on.

So I will do, whereas before I might do an 18 hour fast, I’ll just do 14 and 16 hours now. And I will do a really robust meal, and then maybe 2 to 3 hours after that I have a Jiu-jitsu session. And then that meal ends up being much higher in carbohydrate. And I again kind of base it off the volume and intensity.

But then usually my dinner… I do two to three meals a day. Probably 80 percent of the days it’s three meals, 20 percent of the days it’s two meals, and that tends to be more the weekends when I’m just hanging out with family and I just want to be lazy and I don’t want to cook yet another meal for myself and all that.

I do partition closer to the pre-workout period but I’m not like taking a maltodextrine drink right before and one right after, and all that type of stuff. There might be some upside to that, but I have noticed for my digestion that the digestive process, for me, does much better with less frequent feedings, and less refined foods and all that type of stuff.

So I’ve had a pretty darn good degree of success with that so far. And I mean it is dead simple. I would be hard-pressed to think of a more simplistic way of eating and fueling. It is really, really simple.

But at 45 years old, I just got my purple belt last Saturday and I’m doing great on that. And body composition is good. My wife is still willing to sleep with me with the lights on most nights. So life’s pretty good in that regard.

[Damien Blenkinsopp]: Congrats, I saw that purple belt. It’s quite an achievement.

[Robb Wolf]: Thank you.

[Damien Blenkinsopp]: So is there anything we’ve missed that’s important about your most recent thinking on this subject?

[Robb Wolf]: No, I don’t think so. You did a great and thorough job asking this stuff.

Again, I would just encourage people to think about, if they feel off-put by this idea of Paleo diet type stuff, just give some thought to this. Is there any merit looking at biology and thinking about the evolutionary underpinnings, particularly when we see things go south?

If we don’t see health or other parameters that we would ideally like to have, if something significant is changed in that organism’s environment, do we have any insight from looking at what the environment preceding that event? So that’s kind of the totality of my greasy used-car salesman pitch on this stuff. Is there anything we can learn from that?

And it’s not just around food. It’s around sleep, and photoperiod, community, gut microbiome. All of these things really, when we see problems popping up, it’s this discordance model again. And modern medicine is shockingly well-suited for dealing with acute injuries and infections, and it has been an appalling failure with regards to chronic, degenerative disease.

And people may get their back up about that and say we work very hard. I don’t doubt that people do, but if you simply look at disease rates and incidence – Type II diabetes, Parkinson’s, Alzheimer’s – they’re increasing at exponential rates, yet we know more about the disease process than we’ve ever known in history.

Our iPhones, iPads and computers get cheaper and better every single year, and it’s because we properly apply the technology and knowledge that we have around that topic to improving the product and the outcome. We do not do that in health and medicine, and it’s because we do not start the story from this evolutionary biology perspective, and start having the conversation from there. Because if you do that, chasing symptoms no longer works, and filing people into these arbitrary buckets of disease or not-disease doesn’t really work anymore.

In the 1900s, the previous century, was the century of eradicating infectious disease, for the most part. This century is going to be about dealing with chronic, degenerative disease due to affluence. And it is not going to be solved by a pill or a potion. It’s not going to be solved by telling people to eat less and move more, everything in moderation. Because all of that completely ignores every element of our fundamental evolutionary biology.

[Damien Blenkinsopp]: Thanks, so much for that roundup.

To learn more about this, they can go and get your book. That’s available at Amazon. There were some bonuses or stuff. Is there anything like that still available?

[Robb Wolf]: The bonuses might pop back up again, but most of that was for saying thank you for people who were early adopters on it. But we’ll see. Maybe a couple of months down the road we might pop the bonuses back up.

(0:51:39) [Damien Blenkinsopp]: Okay, cool. Are there any other good books or presentations on this subject that you’d recommend?

[Robb Wolf]: Oh, man, if people are not following Chris Masterjohn, they’re really missing out. That guy is brilliant.

And he’s been doing a deep dive on kind of a series of different nutrients that you need to pay attention to. And he kicked the whole thing off, actually, with iron. Both the iron deficiency, anemia, stories and also the iron overload stories.

So he gets into the biochemistry and the pathophysiology of when things are right and wrong. And then he also starts off at whole food solutions and also makes supplement solutions, and man he is just doing brilliant work.

Who else is doing great work? The folks at Nourish Balance Thrive are doing phenomenal work. Marty Kendall over at Optimizing Nutrition. They’re just some brilliant people.

It’s funny a lot of them had an engineering background and either they got sick or spouse got sick, and then they got in and started looking at this stuff. And it’s interesting. They come in with no medical training biases, and after they start retro-engineering, literally, the disease process, they arrive at something that looks like kind of an appropriate carb, Paleoesque looking nutritional intervention with a focus on sleep and gut microbiome and all that.

I don’t know if that’s just confirmation bias, or really smart people applying their training to figuring out a process. But it certainly caters to my confirmation bias, so I tend to like that stuff.

(0:53:14) [Damien Blenkinsopp]: Cool.

What are the best ways for people to connect with you, and learn more about you and what you’re up to? Twitter or Facebook?

[Robb Wolf]: The blog and podcast live over at Robbwolf.com. The bulk of my social media time I spend on Instagram these days. My handle there is @dasrobbwolf, and I answer just about every single question that is shot across the bow there. So I do the best job I can to stay on top of that.

(0:53:45) [Damien Blenkinsopp]: Excellent.

Just a few more details maybe on our personal approach through using any tracking. I know we’ve already spoke about them, so just really to see if there’s anything else.

I was wondering if there’s anything you track yearly, or every six months, or anything like that that we haven’t already spoken about.

[Robb Wolf]: So, I do check-in on my lipoproteins, that LPIR score, or LDLP, LPPLA2. There’s kind of a suite of somewhat obscure lipoproteins which I keep an eye on about once a year.

And part of that is because at the end of my last book, I was pretty beat up from that. Then I went on a Discovery Channel reality show, called I, Caveman. And we had to live like Stone Age hunter-gatherers. We had stone tools, we lived at 8,500 feet in the Colorado Mountains while there was still snow on the ground.

We basically starved for 10 days until I killed an elk with a hand-thrown spear, and that was the first food we ate. But the long and short of that is I lost 18 pounds in 10 days, and was super beat up. And I ended up with some HPTA axis dysregulation. My thyroid was super low, I had adrenal issues, testosterone was kind of tanked out.

And so an interesting sideline with that was that my lipoprotein numbers were sky-high. My LDLP was 2,800 or something like that. Really, really high. And the clinic that I’m on the Board of Directors of here, we do tons of lipidology work. And the doctors were freaking out, you need a statin. And I said no I don’t, I’ve got other stuff going on.

So we did some poking around, and I actually went on some Nature Throid, which is kind of like armor but a T3/T4 thyroid deal. And I did kind of a classic adrenal restoration story, high dose Vitamin C, some licorice, some adaptin. And I quit traveling, and I started really paying attention to my sleep.

And within three months I was off the thyroid medication, testosterone had more than doubled, both free and total. And I felt remarkably better after that, shockingly. And my lipoprotein number, my LDLP, had gone from 2,800 to, I want to say, 1,100. And eventually it settled out at 800 or 900.

I do check back in on that every once in a while though, because that combination of super low testosterone and disordered thyroid. The low circulating T3 that really down-regulates your LDL receptors in the liver. So you just don’t clear LDL particles, so they accumulate in circulation. And once they start accumulating, then the potential for them to oxidize is much greater.

And then I also potentially have a little bit of iron overload going on. So I had a really kind of nasty situation brewing there. So I do check in on that, just to make sure everything is bumping along good. So I do a really thorough thyroid assessment, which is TSH, T3, T4, reverse T3, thyroid uptake, and then some of the just kind of background iodine status. And that gives me a pretty good benchmark about where that is.

And then I’ll check testosterone, estrogen, estrodiol, DHT, to kind of see where that part of the hormonal axis is. Because again, based off inflammation, fatty acid ratios and what not, you can start pushing more testosterone towards the DHT pathway, which can be problematic for the prostate under certain circumstances.

So I pay attention to those things, but it’s usually about once a year. But again, I’m a lazy cuss when it comes to that stuff. I know some people test it like once a month. I’m more of a once a year, maybe once every six months on some things. But more of a once a year deal.

(0:57:58) [Damien Blenkinsopp]: Thanks for that, very, very interesting. And the fact that you recovered, and you obviously see that as an actionable metric that you can keep up with.

I’m just wondering, which labs were there? If there’s any specific place, or are these just standard Quests, or something like that?

[Robb Wolf]: We tend to go through LabCore because LabCore ended up purchasing LipoScience, which is the [unclear 58:09] that developed the NMR technology around looking at lipoproteins. There’s other ways of looking at it, and they have pluses and minuses to them, but in my opinion that NMR spectra that looks at the LPIR score and lipoprotein count is head and shoulders above everything else out there.

The guy that largely developed it, William Cromwell, he was a physical chemist, a believe a PhD, which is basically a physicist who studies chemistry. And then he went to medical school, and he got into this NMR spectra jockeying type stuff, and developed this whole technology around looking at these lipoproteins. They have some really interesting correlation studies that they’re doing.

There’s a biomolecule called glycA, and by looking at glycA in relationship to some other lipoprotein fractions, they’re claiming that they can see things like Parkinson’s, Alzheimer’s, and insulin resistance decades ahead. And they’re still awaiting FDA approval on that. But it’s really interesting. So I tend to really put some pretty heavy weight on that lipidology side with regards to that LPIR score and that whole NMA spectra technology.

(0:58:28) [Damien Blenkinsopp]: Thanks very much, that’s very, very interesting stuff.

I think I know what you’re going to say here. If you were to recommend one experiment someone should try to improve their body health, performance, longevity, chronic health issues, whatever, with the biggest payoff, what would it be?

[Robb Wolf]: Sleep.

[Damien Blenkinsopp]: Okay.

[Robb Wolf]: Sleep. I mean, maybe a blood sugar deal I can make an argument for, but if we improve your sleep, there is nothing else that you could do that’s going to improve everything else more.

And the one caveat with that, if we have say a shift work population – police, military, firefighter, new parents, medical caregivers – who can’t control their sleep, then they really need to get a handle on the glycemic load of their diet and get it to a level that’s non-toxic for them.

But even then, the shift-workers, they need to pay even double attention to the sleep. When they do sleep, they need to sleep well. When there is sunlight, they need to get out into the sunlight at appropriate times. It becomes doubley important for them.

But the greatest return on investment anybody’s going to get on any of this health and wellness stuff is putting more emphasis on their sleep.

[Damien Blenkinsopp]: And should they just track hours slept, something simple like that?

[Robb Wolf]: Hours slept is good, but it’s more the ritualized process. When the sun goes down, then you dim the lights. And if you’re still on the computer, you flip on the f.lux, and you put on some Blue Blockers, and you set up a ritual.

To the degree that we set our lives up that we have to live and die by self-control, we’re mainly going to die. We’re going to fail. And so we have to set up a kind of a habituated process so it really takes the thinking out of it; it’s just what we do. So I would tend to focus more on that.

And then certainly if you want to keep an eye on approximate duration in bed, but that’s a whole other interesting feature too, is when you start paying an over the amount of attention to those things, then you start getting anxious about it. And I just see this damnable downward spiral in the quantified self space, where I just want to put a black bag over these people’s heads, drag them out into the woods and stick them in a tent.

And it’s like, there’s a creek full of fish. We’ve got them trapped behind a fish weir, you need to get them out by hand and gut them and cook them. Here’s the kit to make a fire. We don’t make it ridiculously hard, but you’re going to have to work to get your dinner, work to stay warm. And when the sun goes down you’re going to make a decision, do I want to sit up in the dark, feeding this fire on the limited firewood I have, or am I going to go crawl into my sleeping bag and go to bed.

They’re not quantifying a goddamn thing under those circumstances. And all of a sudden, all of the digestive issues disappear, and the sleep disturbances disappear, and they’re three body fat percentage point is lower after a week and it’s not because they’re hypocaloric, it’s just because they’re not inflamed and insulin resistant.

And so again, I try to get people to just live. I’ve really been harping on this thing of track what matters. And the longer that time goes along, I’m just finding fewer and fewer things that matter, relative to the experiential process. Be in your body, experience what is going on. Be in contact with what your emotions are, and develop a little bit of a zen and stoic process, where you can see these things occurring, and then you can choose to how you respond to it.

Whereas if we’re so tied to external devices for every little bit of feedback, then we’re essentially dependent on that. And I hate dependency of any variety.

[Damien Blenkinsopp]: Thanks so much for that, this is really, really interesting. It’s been a fantastic episode. And thanks for being so open, just giving all these details of your own experiences and your life. It’s a great, great show. Thank you.

[Robb Wolf]: My pleasure. It’s a huge honor being on. Thank you.

References:

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Is your glucose metabolism driven by your personal microbiome? Recent research reveals how the microbiome influences blood glucose, weight gain and weight loss. And how the new company, “Day Two”, is using microbiome sequencing data to provide personalized nutrition recommendations.

In this episode we discuss how personal your blood glucose response and regulation is. We look at how glucose metabolism can differ from one person to another, and how it differs based on typical measures, such as the hypoglycemic index. Most research studies try to understand what a diet or food does to an average person. But the question is whether you or any of us is an average person? Will your body respond to inputs in the same way as it will for an average person?

I found out that collecting personal data for myself is more useful than following the recommendations that come out of the studies that are looking at a statistical human person, rather than a real individual person. Data which is unique and personalized is usually most helpful to act on, especially when the derived conclusions differ from the mainstream nutrition studies proposals.

In the past, we have covered several aspects related to this episode. You may find it helpful to do some background listening on previous episodes before digging into this one. These include the blood glucose metabolism episodes, Episode 43 on Continuous Glucose Measurement and Episode 26 on Biomarkers of Aging – in which we discussed blood glucose as a biomarker of aging.

On microbiome testing and its use, we have had episodes that are relevant to this one. There is Episode 9 on Quantifying the Microbiome with uBiome and Episode 37 on Health Impacts of the Microbiome with Robert Knight, a well-known researcher.

“We study many different aspects of the microbiome as it relates to our health. This is another study where we studied another very basic phenomena, the yo-yo diet. What we showed there is actually that even after you complete a diet and lose weight, your microbiome doesn’t go back to what it was.
– Eran Segal

This is a two part episode with two guests. We have Eran Segal who heads up the Segal lab, which undertakes research in computational and systems biology focusing on nutrition, genetics, microbiome and gene regulation, and their effects on health and disease. This lab has released a series of studies over the last years on microbiomes and how they may be impacting blood-glucose regulation.

These studies have been heavily featured in the mainstream press because they put into question lots of our assumptions of how diets and food work, and how they impact blood glucose. Eran Segal earned his Ph.D. from Stanford in 2004, and in 2011 he was made a professor at the Weizmann Institute of Science, which is very well-known in Israel.

“What we do is give you a mobile application. So you get a personalized mobile app that you download, and it’s tailored just for you. It gives you a microbiome report, because we did it and we have it… We’re giving you your top food and meal recommendations. You have your top breakfast, your top lunch, your top dinner, your top fast food, because even when you eat fast food once in a while, you can still choose healthier fast food than others.”
– Lihi Segal

Our second guest is Lihi Segal – same last name but, no relation. She is the CEO and Co-Founder of DayTwo, which is the new microbiome lab-testing and personalized diet and recommendation service that has licensed, and is applying the research from the Segal lab, on the microbiome. Lihi has held a series of CFO and COO positions in start-ups over the years. Previously, she was COO and CFO of Sisense Limited, a provider of business intelligence and analytic software. She holds an MBA from Northwestern University.

itunes quantified body

What You’ll Learn

  • Studying the glucose response as a quantifiable effect food has on our bodies (05:43).
  • Post-meal glucose levels represent direct tracking of response to different foods (13:00).
  • Tracking glucose spikes and quantifying the body’s post-meal blood glucose regulation (14:17).
  • The accuracy and usefulness of continuous glucose monitoring – new devices and helping research (14:55).
  • Constructing multifactorial algorithms for personalized prediction of blood glucose response (18:53).
  • Using high-resolution microbiome sequencing to detect specific strains of microbiome bacteria (20:31).
  • Compared to BMI or blood tests, the microbiome is a more significant factor in predicting glucose metabolism in a personalized way (22:55).
  • Different microbiome features contribute to the overall prediction of response (22:56).
  • The propensity to gain weight and the effects of artificial sweeteners (26:11).
  • The microbiome’s acquired ‘memory’ regulates weight gain mechanisms (26:53).
  • Relapsing weight-gain is regulated by the microbiome, including by regulating genes involved in energy expenditure (26:53).
  • The microbiome remains stable over time, such that consistent long-term diet changes are required for profound health effects (30:20).
  • Unlike micronutrients, small fibers are digested solely by gut bacteria – but consumption of either has sustained effects on glucose metabolism (33:38).
  • Artificial sweeteners currently being examined by Segal Lab (34:52).
  • What DayTwo does as a company and personalized services to expect in near future (35:20).
  • Providing actionable information for glucose management (42:00).
  • The basic data inputs for using the DayTwo service and integrating lifestyle into personalized diet feedback (43:26).
  • Instead of being a diagnostic company, DayTwo offers recommendations under a predictive model (45:52).
  • Where DayTwo microbiome testing and output to users stands out – comparison with competition companies (46:38).
  • DayTwo collaborates with the Mayo Clinic to replicate the Israeli microbiome study on US population – calibrating the algorithm for American foods (50:59).
  • DayTwo’s success story in Israel, public recognition, service available for pre-order in the US (53:15).
  • Plans for bringing DayTwo to the UK and European markets after first tackling the US market (55:24).
  • DayTwo US release is not dependent on the Mayo Clinic trial, but more data means continuous predictive algorithm improvement (57:34).
  • Reasons why numerous lab testing companies operate in Arizona (58:53).
  • Pricing of DayTwo services and a lower US pre-order price (59:42).
  • DayTwo takes a direct to consumer approach – offering customizable nutrition advice delivery for different individuals (1:01:51).

Thank Eran Segal and Lihi Segal on Twitter for this interview.
Click Here to let them know you enjoyed the show!

Prof. Eran Segal, Segal Lab

Lihi Segal, DayTwo

  • DayTwo: A microbiome lab-testing company and personalized diet recommendation service. Lehi co-founded DayTwo where she currently serves a CEO function.
  • MyNetDiary: LabTwo’s database for the American market is on this network’s nutrition database featuring 400,000 different US-based foods.

Tools & Tactics

Diet & Nutrition

We discussed the studies that reveal several tactics with respect to weight loss and weight gain, as well as optimizing blood glucose metabolism towards health impacts. Important aspects from Prof. Eran’s team’s research include:

  • Predicting Diet Response: We discussed the health effects and potential benefits of various diet types. A key takeaway is that nutrition can be personalized based on predicting post-meal blood glucose responses.
  • The Microbiome & Artificial Sweeteners: Segal Lab has tested for the effects of non-caloric artificial sweeteners (NAS) – namely saccharin, sucralose and aspartame compounds. They determined that artificial sweeteners induce glucose intolerance by altering the gut microbiome. Xylitol and stevia are chemical formulations currently being examined by Segal Lab.
  • Post-Diet Weight Regain: Eran’s team have shown that persistent microbiome alterations modulate the rate of post-dieting weight re-gain. As a general rule, a low carbohydrate diet is most beneficial for weight loss because this diet prevents post-meal blood glucose spikes. Compared to a meal which spikes blood glucose levels, low response meals are associated with more fat burning and with losing weight over time.

Tracking

Lab Tests

  • DayTwo: This test offers analysis of your blood glucose metabolism as a response to particular food types or complex meals.
    • The most novel feature is microbiome sequencing with the greatest resolution offered on the market – known as ‘shotgun sequencing’. This method covers the entire genetic content found in a stool sample.
    • Current price in the US is $299 pre-order, but will later cost $399 as a standard price for the US market. This is cheaper compared to Israel, where the price is $500. In Israel, DayTwo incorporates continuous glucose monitoring for all users, thus requiring more for the glucose monitor everyone receives.
  • uBiome: A company which offers microbiome testing services, using 16S sequencing technology for microbiome analysis. We covered the applicability of uBiome’s service in Episode 9.
    • While it is cheaper than DayTwo sequencing, 16S sequencing does not allow looking below the genus level of bacteria. 16s sequencing looks only at one small region of RNA rather than the whole sample and for this reason does not provide the same resolution or ability to differentiate between different species for lack of information. 16S sequencing is the most popular today for cost reasons.
    • Differentiating between specific species of pathogenic vs. benign E. Coli is not possible with 16S sequencing, but is a standard with shotgun sequencing (DayTwo testing).

Devices & Apps

  • DayTwo Food & Activity Logger: A mobile application providing personalized day-to-day nutrition and diet recommendations.
    • The app offers analysis of your microbiome in report format, based on the required LabTwo testing.
    • Additionally, it features your top breakfast or lunch food components, allows searching through a food database, and makes recommendations on alterations – e.g. substituting rice for pasta whenever fit for your body’s blood glucose response.
    • Over time, the impact of using this app should be improved health by consuming food with the aim to optimize your blood glucose metabolism.
  • Freestyle LibreThis device is used for continuous glucose monitoring and the obtained data is used to determine trends in glucose metabolism. The FDA approved this product for the US market in 2016.
    • Contains a glucose sensor and a reader displaying the glucose data collected by the sensor.
    • Segal Lab is switching to this device partly because it offers greater user convenience by avoiding the finger pricking technique for obtaining analysis-blood.
    • Eran claims the device is at least as accurate as the company states, possibly even more accurate.
  • Fit Bit Charge: A device from the FitBit company was used in Segal Lab research to track and integrate lifestyle (sleep, meditation, exercise) into predictive algorithms for personalized nutrition recommendations.

Biomarkers

  • Post-Meal Glucose Response: Measuring blood glucose levels for the two hours following a meal.
    • The most important measured phenomena by Segal Lab and subsequently used by LabTwo for making nutrition predictions – are glucose spikes following a meal.
    • Glucose spikes are sudden rapid increases in blood glucose concentrations as a result from particular meal types, or more broadly a result of your diet.
    • Glucose spikes are associated with disease (e.g. diabetes and types of cancer). Thus, avoiding such responses is important for optimizing blood glucose metabolism.
    • Other times we have discussed post-meal glucose response is Episode 7 on optimizing ketogenic dieting and Episode 43 on continuous glucose monitoring.
  • Hemoglobin A1C: This is the most used marker for diagnosing diabetes. Its interpretative power is derived from the connection between glucose and hemoglobin – the protein in red blood cells (RBCs) which carries oxygen. Because RBCs live approximately 3 months, Hemoglobin A1C reflects the average blood glucose levels over this period.
    • The results are reported in percent (%). Higher levels of hemoglobin A1C indicate poorer control of blood glucose levels.
    • Prediabetic states range between 5.7 – 6.4% and diabetes is diagnosed above 6.5%. Optimum HbA1c levels are likely below 5%.
    • A caveat: Depending on your diet, your RBCs can have a shorter or longer lifetime. Since HbA1C measures glucose accumulation having RBCs with a longer lifetime than average leads to higher HbA1C readings despite average blood glucose being low. For example, Damien’s blood glucose is typically under 100mg/dL at any time point even after many meals due to his ketogenic diet. His HbA1C has ranged between 5.1% and 5.3% during this time however low carb diets are assumed to lead to longer RBC lifetimes. Higher carb diets are typically assumed to have average RBC lifetime.
    • Both guests share the opinion that collecting HbA1C and other blood marker data is not useful for making nutrition predictions once you have microbiome sequencing data. This is because sequencing provides sufficient data when combined with an algorithm to predict an individual’s glucose metabolism and provide personalized nutrition recommendations.

Other People, Books & Resources

Organizations

  • DNA Genotek: A Canadian company supplying microbiome collection kits for DayTwo analysis. After extensive testing, DayTwo concluded that DNA Genotek offers the best state of the art technology requiring no freezing or timing. The end result is the ability to preserve stool sample in the Day0 condition for greatest result objectivity.
  • Mayo Clinic: LabTwo cooperates with the Mayo Clinic aimed at repeating the trial in Israel at the Weizmann Institute on an American population. The aim is to obtain more data and to optimize the predictive algorithm for blood sugar response to the US population. While the trial will last for a while, LabTwo is currently able to make precise predictions for US users and the data from the trial will be used to work on similar targeted future goals.
  • FDA: The US Food and Drug Administration has placed a diabetic label on CGM technology. Thus experimenting using CGM devices with individuals is not allowed, unless diabetes diagnosis has been previously established in the test participants. LabTwo partnered with the Mayo Clinic and have successfully designed a trial including CGM devices which was approved by the Mayo Clinic institutional review board (IRB) – essentially an internal ethics committee.

People

  • Dr. Saleyha Ahsan: She traveled to Israel to take part in the study on personalized nutrition at the Weizmann Institute. Afterward, this was covered in an episode of the BBC Two Trust me I’m a Doctor show.

Other

Full Interview Transcript

Click Here to Read Transcript

(00:05:43) [Damien Blenkinsopp]: Welcome to both Eran and Lihi Segal onto the call. Thank you both very much for joining us.

So I just wanted to jump straight into your research on the glucose response, and all of the other stuff you’ve been doing in the last couple of years really because it’s all kind of related. Why did you focus on the blood glucose topic in particular?

[Eran Segal]: That’s a really good question. When we started a few years ago, we wanted to take a science-based approach to nutrition.

We thought very hard about that problem, and what we should examine. And if you think of the most common approaches in most studies in nutrition they usually consist of some dietary intervention, and then they look at weight loss, or they look at a change in some marker of a disease. And that’s great because ultimately these are the parameters that we’d like to have an effect on.

But, the challenge we found with this approach is that it then takes weeks or months for these parameters to change. You know, a parameter that measures your diabetes level, or weight. And at the end of this, you get a single measure. It takes weeks or months to change, and that measure is affected by multiple things that happen to you during those weeks or months. Both the diet intervention that you give, but also many other factors unrelated, which can be then confounding to what you’re measuring.

So, we thought that maybe one of the reasons that it’s very hard to do nutritional research, and why many researchers are failing, is because they’re looking at this single measure effected by many things. So we didn’t want to go that way. Even if we see an effect, you’re not sure you can attribute it to the diet, and if you don’t see an effect it’s very hard to troubleshoot what went wrong.

So we thought very hard about this, and that led us to look at glucose levels. More specifically, the glucose levels after a meal, what’s called the postprandial glucose response, or post-meal glucose response.

So by that, what I mean is what your blood glucose levels look like in the two hours after you eat a meal, which we can also quantify using the area under the glucose curve into a single measure representing the response that you had to that meal.

[Damien Blenkinsopp]: Right, so that’s like the total area under the curve is the total amount of glucose that was in your bloodstream during that area of time.

[Eran Segal]: Yeah, you can think of that as an approximation. I’ll tell you in a moment what we really are hoping that this is actually measuring, but that’s quantifiable into a single measure. But now we have to think about three aspects, or three features of this that really led us to conclude that this is what we want to follow.

So in a nutshell, what they are is that we were convinced by all the existing literature that this post-meal glucose response is really key to weight management. It’s really key to disease – diabetes, but not only diabetes, I’ll talk about those.

Finally, and not least importantly, that it’s very easy to measure and it’s something that, not within weeks or months but within a week, we can obtain not one, but even 50 quantitative measures of healthy nutrition in a single individual.

So first, why is it important for weight loss and weight management? This is very basic, and there’s been a lot of literature on this.

When we eat – and I’m talking about healthy people, even people who are glucose intolerant, but let’s say not insulin dependent Type I diabetics. When we eat, our body digests carbohydrates in the meal and releases them into the bloodstream.

After that, there is a response of the body by secretion of insulin, whose job is to lower the glucose levels. But in addition, what insulin signals, also, is it signals the cells to uptake the sugar that’s floating around in our blood.

And then excess sugar is converted into fat for storage because it initially is converted into storage of glycogen, but our stores of glycogen are highly limited. So very fast the remainder will be stored as fat. And this is actually known as one of the primary mechanisms by which we gain weight. In other words, this action of insulin.

So, in a sense, we would have liked to even measure directly at a continuous rate insulin, but that’s technically not possible. But in healthy people – and there’s been lots of research – by measuring glucose levels you’re actually looking at a proxy for a measurement of insulin.

And there’s been work showing, for example, that if you eat a meal that spikes your glucose levels compared to a meal that does not, then after a meal that does not you have more oxidation of fat, more burning of fat.

So the connection to weight loss is very well established. There’s also a lot of literature looking at very low-carb diets, which I think as a dietary regiment it’s incompatible with life for most people. But if you look at some of the studies when you eat a low-carb diet your glucose levels are low, and in general, those have the most beneficial effect on weight loss.

So that’s item number one why we focused on blood glucose levels because it’s very important for weight loss and management. The second is disease, and the most obvious is, of course, diabetes.

In fact, diabetes is diagnosed and defined by glucose levels. It’s defined in two or three different measures; either by the hemoglobin A1C, which measures your average glucose over a period of three months or by the glucose levels that you have two hours after you eat a meal. So something very similar to what we’re measuring.

And so, of course, you directly are playing with and improving the measures by which you diagnose diabetes. By that we can manage better the disease; manage it better in pre-diabetics, even possibly reverse it in this population. And, of course, for all the people with normal glycemic levels, we can prevent or delay the onset of diabetes.

So that’s one area where it’s important, but then separate from diabetes there’s been a lot of links to cardiovascular disease, to cancer. So in cancer, this is known as the Warburg effect. We know this for 90 years that cancer cells have a very different metabolism that much more heavily relies on glucose.

And so the thought is that by limiting the amount of glucose that you provide, you deferentially affect the growth of cancer cells compared to normal cells. And there’s been associations in the literature between blood glucose levels and cancer.

There are also been associations to overall mortality. There’s one paper that tracked over 2000 people for 30 years showing that if you responded more highly to a glucose challenge 30 years ago, you’ll live longer, basically. So there’s been links to many diseases, and so we’re very confident that it also has a strong association to disease.

And the final point is what I made before that because of the technologies with continuous glucose monitors we can now really in a single week measure 50 quantitative measures of healthy nutrition. And they’re quantitative of health nutrition because of the two points I made before.

[Damien Blenkinsopp]: So you felt that it was basically the continuous glucose monitor was a game changer because you’d be able to gather a lot more data quickly, and eliminate somebody’s potential variables coming in from the longer term studies which you can avoid.

[Eran Segal]: Absolutely. So if you think about it, we actually focused on examining the direct effect, one of the ways by which food directly affects you, and this is your glucose levels.

And from everything I mentioned before, we also believed that this is really a very critical clinical marker for weight loss and disease.

(00:13:30) [Damien Blenkinsopp]: Right. Okay, great. So you focused on the post glucose response to meals specifically, but you did mention Hemoglobin A1C. Is that something else you tracked and you found useful in these studies?

[Eran Segal]: So that’s something that we measured. We found it useful for predicting how different people respond to different foods, but it’s nothing something that you measure as a direct effect of a meal.

It’s one of those single parameters that takes many weeks to change that, again, would be very hard to develop a dietary regiment that would affect that directly because of all the confounders that I mentioned before.

So in fact, glucose levels is, as far as we know, the only reliable quantitative measure that is really super relevant that we could track, and that’s why we focused on it.

(00:14:17) [Damien Blenkinsopp]: Right. And you mentioned the area under the curve is the part that you’re interested in. So I’m guessing that you’re looking at a benchmark to what’s okay, and what goes too high in terms of that area.

You said to me when I tried to give an analogy to explain that to the audience that it wasn’t quite right. How would you explain the utility of that?

[Eran Segal]: We can just say that it’s basically looking at your glucose response and it’s quantifying how much you had spikes for glucose levels after the meal. And these spikes, as I mentioned before, is what is strongly linked to everything else.

(00:14:53) [Damien Blenkinsopp]: Right. Thank you very much. How did you find the continuous monitoring technology? Did you use a specific device, and how sensitive or accurate did you find it? There’s various monitors out.

We’ve spoken about these before, and I know people that have been using them for diabetes management and so on. So I’m just interested in your opinion on where that technology is right now, if research can be improved maybe later as it advances, or is it already as good as it’s going to get.

[Eran Segal]: So I think it was very good for our purposes. Not without problems, but I think even finger pricking is problematic, and can be variable. But, there’s also progress.

There’s a recent device by Abbot that we are now shifting to using because it’s more convenient, mainly. It’s probably as accurate, possibly even with higher accuracy – that’s what the company claims. But it’s just much more convenient, and it doesn’t require the finger pricking anymore.

But overall, they definitely capture the trends. I will say that when we measure responses to 50,000 meals you really have a very large data set, and you can afford to have some inaccuracies here and there, which all the technologies have. And still you correct for that in the algorithms.

(00:16:10) [Damien Blenkinsopp]: Great, thank you for that. Moving on a bit to what you discovered is actually driving these blood sugar regulation changes. What are the examples of the most unexpected things that you saw in the data?

[Eran Segal]: Are you talking about the factors that affect it, or even just before the surprising responses that people had?

[Damien Blenkinsopp]: I’m interested in both. If we start with what you saw that maybe you weren’t expecting, and then what you think drove that, or what you discovered drove that.

[Eran Segal]: So the first key result of the study was – and this was initially very surprising – we saw that when you give different people the exact same meal, they have very, very different responses. And this is in contrast if you eat the same meal on two different days, which is what we’ve tested on an unprecedented scale of 1000 people. This is 7000 different meals standardized that we provided.

When you eat the same meal on two different days your response is going to be very similar, but when you and I will eat the same food, our responses will be dramatically different. You can eat bread and have zero response, and I can eat bread and have a higher response than what I would have if I even ate pure sugar. So it was really all over the place.

And this was even before talking about our solution, this was very surprising. And we realized also that it has a lot of implications.

Because if we realize, again, the importance of blood glucose levels to our health and weight, then what it directly means is that general dietary recommendations are always, no matter what they are, going to have limited utility. Because for any single food that we tested, we had people who had a high response and others that had a low response.

So you can’t really make a general recommendation about food. Now there are trends. There are foods that lower glucose levels on average, for some people. And that is known; it’s what’s called the glycemic index.

I think you even touched upon that in your questions. And we also saw that in the data. So whatever foods have been reported with lower glycemic index on average they have lower responses also in our data. But if you look at all those numbers that go into making that average, they’re all over the place.

[Damien Blenkinsopp]: So there isn’t a cluster around the mean, it’s widespread.

[Eran Segal]: Exactly. It’s very spread across it. And when you measure enough people the means will be significantly different, but there is a wide spread across the means.

Meaning that we can take ice cream, for example, which on average induced relatively low glucose levels, and we can take rice, which on average, induced high glucose levels, but you will still find people that respond more highly to ice cream than to rice.

(00:18:49) [Damien Blenkinsopp]: So it’s quite surprising in those terms. So, in terms of what you’ve found or discovered that drove that. I know you tested for a lot of different things. What sort of things did you also test for in order to try and find the pattern of what was driving this?

[Eran Segal]: So we looked at many different things. We looked at body measures, anthropometries, height, weight, waist for instance and so on. We looked at several metabolic parameters in blood. We looked at questionnaires.

So we had a medical background in food frequency and lifestyle questionnaires. And the most novel component that we integrated into the study is the microbiome. So we measured all of those. In fact I will say that we found an association, a strong correlation, between variability and the response to food in all of these different groups of parameters that we measure.

And then the next step was to take all of these parameters and integrate them into rules, or an algorithm, that basically given your inputs to all of these factors, which vary from person to person, we would be able to predict how you would respond to each and every single food or food combination or complex meals.

And we showed that that actually works very well, and predicts personalized responses with very high accuracy. In fact, the accuracy that we think is even feasible because, even when you eat the same meal on different days, I mentioned your response is going to be very similar, but it’s not going to be identical.

So there is some inherent biological variability, and our predictive power is approaching that variability.

(00:20:30) [Damien Blenkinsopp]: Okay, great. The microbiome was the novel part of this. What exactly did you look at? Because there’s a few different approaches to looking at the microbiome right now.

What were you looking at and trying to map with it?

[Eran Segal]: So we looked at the most comprehensive in terms of resolution, which is just doing shotgun sequencing. So that’s basically sequencing the entire content of what we find in a stool sample. That mostly consists of bacteria, but this type of sequencing is really the highest resolution.

It allows us to identify individual genes in the bacterial composition, of which there are several millions in each and every one of us. It allows us to identify not just species, but also specific strains of bacteria.

And so there are many of these different factors that we integrated together, and used them in the algorithm.

[Damien Blenkinsopp]: Great. Is that cost prohibitive verses some of the other technologies that are used out there?

So you have the 16S, which is just looking at one part which some of the projects like uBiome are using right now to enable them to serve many consumers and make it a lower cost so people can afford it right now. Are the costs much higher for what you were doing?

[Eran Segal]: So first of all, for 16S, I will say that we didn’t want to go in that direction because science-wise I don’t think we would have gotten as predictive power.

And in fact we even showed that to ourselves in the study because it doesn’t have the resolution, and in many cases it doesn’t allow you to go below even the genus level of bacteria. So you can have the pathogenic E. coli or non-pathogenic E. coli will have identical 16S; you won’t know what’s in there. Just to give an example.

So we went for the shotgun sequencing. It is indeed much more expensive. If you talk to researchers they’ll tell you that it’s way more expensive.

I will say that what we have been working on in our labs for many years prior to this study, and then as part of the study, is to optimize this process very extensively using automation and using robotics.

We’ve substantially reduced the cost; it is still significantly more expensive than 16S. But I think our margins of error are much smaller than other researchers, and this is probably also why we were able to profile at that level.

(00:22:53) [Damien Blenkinsopp]: Okay, great. So, in terms of the microbiome – because we’re talking a lot about the microbiome and the other factors – is there a stronger weighting of the variability? Are there variants associated more with the microbiome, or are there some other factors that are really important?

The other thing that is interesting is the microbiome actually does change, and we’re trying to change it and improve it and so on in many clinical situations now. Whereas your height, age aren’t changeable.

So if you could give me a bit of background on what you found is the biggest weighting there, and maybe which is most actionable?

[Eran Segal]: Those are two very good questions.

Related to what is most important, every component that I mentioned before we can show has significant predictive power. Now of course, in terms of predictive power, some of these components are somewhat redundant with each other.

So for example we found that when you add the microbiome and some other components, then we can do without all of the blood tests, and in fact we don’t need them at all for the predictive power. They add really something negligible.

Of course we think that blood parameters are predictive; it’s just that in the context of many other parameters, they’re somewhat redundant because they can be explained and correlated with several other parameters. And so likewise with the microbiome we found that actually unlike blood, in every context that we apply the algorithm, the microbiome always had a significant contribution to the prediction.

I will say though, that of course the microbiome has the most significant contribution when you add it by itself. As soon as you add more and more parameters, this is expected. It’s marginal contribution. And also, I believe this is an area where with additional research we can dramatically improve in the future.

We already have started this process because we have a lot more information and a lot of smarter ways by which we can handle this data, which is not true for BMI, weight, blood parameters, which are very limited in the amount of information they have.

[Damien Blenkinsopp]: Right, because there is basically truckloads of data we’re going to be taking out of our microbiomes, because there’s so much in there.

[Eran Segal]: And when we and others continue to research and identify key genes in the microbiomes that are helping in the breakdown of certain products, production of different metabolites that affect us, and we know better how to zoom in on different features, we’ll be able to improve the predictive power from it.

(00:25:25) [Damien Blenkinsopp]: Great. So in terms of the level, you mentioned that the technology that you’re using goes right down to the strain level, and the species, and genus, and so on. But where do you see the patterns?

Is it on the genus level, the species level? Is it just one species that can completely change how we respond? Or is it at a very high level like bacteroides, or something like that?

[Eran Segal]: So there are significant associations on all levels.

And I can say that it’s not a single species that is really dominating. We actually have this in our paper; we have many different features from the microbiome each make a contribution to the overall prediction, but together there’s dozens of these features. Together they make a significant contribution.

[Damien Blenkinsopp]: Right. It’s really a multifactorial analysis.

[Eran Segal]: Yeah.

(00:26:10) [Damien Blenkinsopp]: Okay. You did a paper before 2014 on the artificial sweeteners, which also got a lot of coverage. That was interesting also.

And in that one I believe it was the high bacteroides and the lower clostridiales which showed that you had a higher propensity to gain weight, wasn’t it? Rather than just blood glucose regulation.

[Eran Segal]: Yeah. So yes, we did see an overall effect there. But also there we developed an algorithm that could predict susceptibility, in that case, to consumption of artificial sweeteners. And that was also multifactorial basically using dimensionality reduction of essentially all the species that we had in the sample.

(00:26:53) [Damien Blenkinsopp]: So the most recent paper you are looking at is also looking at regaining weight after dieting.

For example, if you go on a diet and there’s this typical yo-yo effect where someone goes on a diet and they just regain it all back. I’m wondering is that related to the microbiome or what’s going on? So if you could relate what you’ve been looking at there and what you found?

[Eran Segal]: Yeah.

So we study many different aspects of the microbiome as it relates to our health. And this is another study where we studied another very basic phenomena, the yo-yo diet that you mentioned. And what we showed there is actually that even after you complete a diet and you lose weight, your microbiome doesn’t go back to what it was.

So it’s very well known that as you gain weight your microbiome changes, and what we showed is after you lose weight your microbiome doesn’t revert back to the original state. And that memory, if you will, of the microbiome is in fact sufficient to induce and enhance weight gain once you stop the diet.

So I would say it’s another work further establishing the causal link, and providing more insights into mechanisms by which the microbiome plays a key role in our health, and specifically with respect to metabolic states and diseases; in this case relapsing obesity.

[Damien Blenkinsopp]: In that study did you find any mechanisms? Is it specific species? I think you were talking about metabolites in there as well.

[Eran Segal]: Yes. So this work was in fact work in animal models; this was work in mice. And the advantage of is that we can really go deeper into mechanisms, unlike in humans where it’s much harder.

And so there, we also did a metabolomic profiling, and we identified metabolites that were missing after you lose the weight. And when we administered these molecules back, we in fact were able to cure the mice of the phenomena of relapsing obesity.

[Damien Blenkinsopp]: Wow.

[Eran Segal]: And more important we actually showed that these metabolites in fact regulate genes in the host, in the mouse, and they regulate genes that affect energy expenditure. So these mice, when they have less of these metabolites which are broken down by bacteria, when the bacteria break them down, these mice are going to have less energy expenditure and therefore more weight gain.

[Damien Blenkinsopp]: Wow. So I guess you don’t understand why that energy expenditure is going on. There’s probably quite a complex downstream process that follows.

[Eran Segal]: Right. That’s quite complex, but we also had some insights in the paper as to that as well, and we found some genes that regulate that process in brown fat tissue that are directly affected by these molecules. And these molecules are made less available because the bacteria in mice that had a previous history of obesity, in fact, were breaking down and taking away these molecules more.

[Damien Blenkinsopp]: Wow, so it’s actually the introduction of new bacteria for the weight gainers, which is taking away these substrates.

[Eran Segal]: So in this case, it was metabolites. So there are specific metabolites that are broken down by bacteria, which we showed here, we call that post-biotics as opposed to pre-biotics.

[Damien Blenkinsopp]: Right, by adding the bacteria that’s missing or making taking away the ones that are causing the problem.

(00:30:17) [Eran Segal]: Yeah. Those can be technically more challenging in some cases, but in general yes.

I also want to relate to, you asked me before about the stability, or how much the microbiome changes. And we have several studies on that; in fact, some are not even published. What we find is in fact the microbiome is actually much more stable, perhaps, than most people think.

So in fact your microbiome, unless there is very dramatic change in health or weight, is probably going to be very stable even across many years. We have data on that. And what I mean by stable, it means you will still look more similar to yourself even after following some dietary interventions, at least in the short term, than you will to other people.

Now, having said that, we also found that short term dietary interventions in fact do change the microbiome, also in consistent ways, across different people. So while you’ll still remain in the neighborhood of what your microbiome is, still some functions will go up, some will go down. Those can be consistent across multiple people who consume the same type of dietary intervention.

[Damien Blenkinsopp]: Right.

Just as a takeaway from that, do you think the microbiome is going to be an important area of work? Basically learning how to modify it, push it in another direction in order to solve things like weight gain, blood glucose regulation. Is that your hope?

[Eran Segal]: Absolutely.

So the more we find causal effects for the microbiome on our health and weight the more this should be a target for intervention. But of course that will require further studies to understand what is casual and also how to change it.

And I do believe that with – and this has also been shown – that with long-term changes in diet, you will in fact achieve changes in the microbiome. But with short term dietary intervention the changes will be consistent, but they will be more subtle and you’ll still remain in your own neighborhood.

And what that means in terms of the research that we did, it means the algorithm is going to give you essentially the same predictions, even in a very stable fashion, across even some small, short term dietary interventions because your microbiome is essentially going to be very much the same.

[Damien Blenkinsopp]: Right. So if I test one month, and then I test six months later after doing a series of interventions – maybe not too intense, something like courses of antibiotics, things like that might be more intense.

[Eran Segal]: Antibiotics is probably a different story. That can have a dramatic effect.

I’m talking about even if you change your diet for a few months, your microbiome is not going to change a lot. If you maintain a very different diet after a prolonged period of time – I can’t give you exact numbers, but a long time – then you will see change.

And at some point, those changes may be large enough you may want to test yourself to make some modifications to the diet. But, for a very long period of time, without dramatic interventions it should stay pretty much the same.

[Damien Blenkinsopp]: It might be interesting if you do a course of antibiotics, because people have to from time to time, to redo the test and see what it predicts afterwords. Maybe some of the food responses are going to be different.

[Eran Segal]: Absolutely. And I think after antibiotics you will have very significant changes, and those could affect the prediction.

(00:33:37) [Damien Blenkinsopp]: Yeah. So the last thing, just going back to the artificial sweeteners we spoke about. Because they did see that those had an impact on the microbiome over time.

Do you think smaller things like that, basically micronutrients or small fibers, not necessarily macronutrient profiles, but those kind of things could have longer term impacts on the diet?

[Eran Segal]: Absolutely. I would say some of them could even have bigger effects than macronutrients. So fiber, for example, is something that is digested solely by our gut bacteria, so definitely could, and this is known, have alternations and will overtime have sustained effects. So yeah, absolutely.

I think the way we think about it now, and even drugs. We and others have shown that the drugs that you take actually also affect your microbiome. Any substance that you intake, although depending on the substance, might just go through your gastrointestinal track, meet the trillions of bacteria that are there.

They have 100 times more genes than we do. They could definitely break down these products, they could convert it into other products. I would think of it right now, anything that you intake could definitely affect your microbiome.

(00:34:50) [Damien Blenkinsopp]: Yeah. Alright. Thank you very much for that. Just a last few things.

A lot of people take xylitol and stevia. It wasn’t in your original study, and I was just wondering if you knew anything about that. Because the other ones, aspartame, saccharine, and there was another.

[Eran Segal]: Sucralose.

[Damien Blenkinsopp]: Sucralose. Yeah. It was a bit of a negative view on them in terms of what they were doing to the microbiome. Have you got any information or did you see anything on the other two?

[Eran Segal]: We are studying those now.

[Damien Blenkinsopp]: Great.

Eran thank you so much for your time. It was really useful.

[Eran Segal]: Okay, great.

(00:35:19) [Damien Blenkinsopp]: Excellent. Okay, Lihi, let’s talk about DayTwo and what you’re doing there.

So basically you’re taking the work done by Eran and his co-researchers and you’ve been turning that into this algorithm service to help optimize people’s diets. Could you give me a bit of an overview, how you look at it? What the company’s doing and how you see it going forward over the next year or so?

[Lihi Segal]: Yeah, so we licensed the technology in an exclusive way about a year ago, in the summer of 2015.

And then what we’ve been doing since then with the help of both scientists, because our founders are scientists and they’re on the management team and very deeply involved in the company. And so there’s a lot of hand-holding in that sense on the scientific level as well.

But what we’ve been doing, we built a team up of machine learning experts in DayTwo and also developers, and we really dove into the algorithm.

As you heard, on the research level the first thing they took 30 metrics in the blood, they did the microbiome, both 16S and the full shotgun. What we really tried to do is once we have all the results is really look into the algorithm and see what is that minimum set of features that we need, and write it to consumer. We don’t want to send them to get anything that is redundant.

So looking into that features into the algorithm, and looking to see what we really need, how to commercialize this. So we went through a kind of learning period when we’re looking to see how we define the product, what do we need. Do we need to freeze your stool? Do we need to send you to a doctor to get blood tests, yes or no?

And where we ended up is by looking at a really minimum set; because as you heard Professor Segal say, the microbiome was very significant in any constellation that they took, and made other things redundant. So really where we ended up with on the product side is that it’s all online, almost.

So you come online and you fill in a lot of questions – not a lot, I think a 10 minute questionnaire. But, of course it has to do with your anthropometrics and your food preferences and your medical history. Any information you just fill in your questionnaire. And then we mail home a kit; just a box. In that box there is a small tube and you take a stool sample at home.

So we use DNA Genotek as our supplier of the kit. If you know them, they’re out of Canada. This is really kind of state of the art microbiome collection kit. You don’t have to freeze it, you literally just take it when you can, when it fits you. You don’t have to time it. It’s there, you take it, and then you just mail it back to us by regular mail.

[Damien Blenkinsopp]: Is it a quick swab, or are you actually taking a sample?

[Lihi Segal]: We tested a bunch of other alternatives as well, but this company really gave us the most stabilized microbiome in extreme temperatures.

It’s really important for us to stabilize it and then send it through the mail. And you don’t have to freeze it and all that. So it made it much easier on the consumer side, and it’s also very important scientifically to get the microbiome at the state it was as it was collected in Day Zero.

So we did a lot of trial specifically on that to see that what the company claims is actually right. And so we send you this kit, you mail it back to us, and then we sequence it.

We chose to sequence, as Eran said, on a full shotgun basis because we found that that resolution rate gets us the prediction into a higher level and a very good level. So we decided to do that despite the higher costs that it has.

But again, we try to put a product on the market that is very good; it’s good scientifically, we don’t really cut the corners there. So although the cost is still higher, we do expect it to go down a scale, both on the full shotgun basis and the kits.

And then what we do is give you a mobile application. So you get a personalized mobile app that you download, and it’s tailored just for you. And it gives you three things initially.

It gives you a microbiome report, because we did it and we have it. Not all our users are going to love it, but a lot of them may be curious to open it up and see. And so there’s a lot of information there.

We’re giving you your top food and meal recommendations. So what that means is that we really look into different categories. You have your top breakfast, your top lunch, your top dinner, your top fast food, because even when you eat fast food once in a while you can still choose healthier fast food than others.

We’re really trying to bring this into your day-to-day and make little changes and not turn your world upside down. And then there’s whatever alternatives with pasta, alternatives with rice. That’s really general.

And we’re really giving you your top A+ meals and scores all the way to your worst list, which has up to C-. So we’re trying to educate you through that stage. You could always go to see what your top breakfast is, what your top lunch, and all that, but then you also have the ability to search.

If we didn’t say something that you eat and you want to know what your score is, you just search for it in our database. In the US we are based on a database of MyNetDiary. So we have 400,000 different foods that are US based foods.

In Israel we are have a different database that has Israeli foods in it. So people can really find what they eat in there.

[Damien Blenkinsopp]: Right, so these are actually branded products you can buy. Is that what you’re saying?

[Lihi Segal]: Yeah, there are a lot of branded there as well, but there’s also, for example, an apple without skin.

[Damien Blenkinsopp]: Okay.

[Lihi Segal]: You also get your just general food as well, but you would find your specific brand of whatever, yogurt, that you’re eating in the specific territory. And then, so that’s the second thing. The third thing is the search and also a build your own meal kind of possibility.

So the whole point here is that we’re not scoring nutrients. We’re not saying carbs or proteins, and we’re not even going into a family of pasta versus rice. It’s very different if you eat a pasta with cream sauce or a pasta with meatballs, or you eat a pasta with macaroni and cheese.

You have to be able to score complex meals, and that is where our kind of secret sauce is, we’re really looking at your personalized response to these complex meals. And so you can just search for those meals if you want. If you’re cooking or if you’re sitting in a restaurant and you’re able to get your scores on the foods that you’re eating.

(00:42:00)[Damien Blenkinsopp]: Yeah. So just to clarify, this is just focusing on glucose management? So lowering…

[Lihi Segal]: Right. So what we aim to do is balance your blood sugar levels. So when you go on and you eat your A+ or A- foods and you eat that on a consistent basis, and you keep portion control.

So it’s not a kind of blank check to eat as much ice cream or drink as much beer as you want, unfortunately. But it does allow you some flexibility with foods that are surprising. Things you thought were unhealthy, all the sudden you understand you can eat them. And vice versa, so it’s surprising in both ways.

And then if you eat that consistently then yes, you’re going to see that we’re helping you balance your blood sugar levels.

And as Eran mentioned, balancing your blood sugar levels has an importance both in minimizing the risk for diseases of all kinds. Even as a healthy person, you don’t have diabetes but it is really important to keep your stable blood sugar levels. And also the whole thing about weight loss.

It helps you, it encourages weight loss in that sense. So you need to have a restrictive diet; you can’t eat whatever you want and think that you’re going to lose weight with this. But it does help you lose weight, it helps control your hunger, it helps control your cravings. And so it really helps you to plan and choose your foods right. That’s what we’re aiming to do.

(00:43:25) [Damien Blenkinsopp]: Okay, great. So, just to be clear. In terms of the inputs, it’s mostly filling in a questionnaire. Is there any other test apart from the microbiome sample? Or is that just the only one that they need to do?

[Lihi Segal]: No, the basic thing is that we need the microbiome and we need your questionnaire.

Now if you do have addition information, if you have your HBA1C levels then we’ll be happy to take them in. If you have more blood tests it’s always good to take in. But it’s not as significant enough so we’ll say you have to do it.

[Damien Blenkinsopp]: Yeah.

[Lihi Segal]: But on a general level, as much information as you’re willing to give us, it will always help, yes.

[Damien Blenkinsopp]: So in your algorithm, it will just take that into account as well?

[Lihi Segal]: Yes.

[Damien Blenkinsopp]: It’s just that in terms of the cost, you don’t want to add to the cost or be inconvenient.

[Lihi Segal]: Again, as Eran mentioned, it becomes redundant at some point.

And so if you have it, great, but we don’t want to get people – the cost is not that much for an HBA1C, it costs like 20 dollars in the US today. So that’s not really the issue.

It’s more just this is the basic package; you send it home, you send it back. But as we’re looking at our future products and as we interact with you throughout your day, the app is going to allow you in future versions to report to us what you ate.

And we have a lot of insight on your sleep and on your exercise. That was not published, but we have it in the data, and they haven’t published that data. He didn’t mention it, but in the research they actually had people logging in their foods, but also their sleep and also their meditations and their exercise. They had a Fitbit on everyone.

So there’s a lot of insight that we’re going to be able to give you. And when to eat your biggest meal, because people have a certain rhythm and that’s personalized as well. So when would be preferred to have a large meal of the day. In the US usually it’s dinner. In Israel sometimes it’s lunch, sometimes it’s dinner.

Certain foods that you should eat at certain times of day. So we can really interact with you over time if we have more information on how you slept last night and how much fiber you had in the past 24 hours. There’s a lot of things that go into the algorithm that, if we don’t have them, fine, but if we do it can even help us give you better results.

[Damien Blenkinsopp]: So you’re integrating these lifestyle factors as well into the computations to tell people when to eat. That’s great.

[Lihi Segal]: Your stress levels, all that.

(00:45:52) [Damien Blenkinsopp]: So I was wondering, are you able to tell the status of someone?

Say I’m glucose intolerant to an extent already, when you get the data from people without getting the HBA1C, for example, are you going to be able to know this person’s going to have to be more careful? Is any of that kind of information coming out?

[Lihi Segal]: We’re not at any point a diagnostic company, so whatever we see we will not tell you.

[Damien Blenkinsopp]: Oh, okay.

[Lihi Segal]: We don’t do health assessments on you. We’re giving you your recommendations under a predictive model.

And for example if we find things that we think you should know, then we would probably say maybe you should see your doctor, or take these results to your doctor or something like that. We would never go into actually giving you any medical advice.

(00:46:35) [Damien Blenkinsopp]: Right. The same usual thing. There’s a lot of blood glucose dis-regulation that goes on way before you get to diabetes, as Eran was saying.

So I’m just sort of interested from an algorithm perspective. I know you’re not going to publish it because there’s a medical borderline there that you don’t want to go near, but I was just interested from an algorithm perspective – can it tell how far you are along that line? Because everyone’s got a little intolerance. I’m just curious, does it offer any information?

[Lihi Segal]: I can’t.

[Damien Blenkinsopp]: Okay, fine.

[Lihi Segal]: I can’t answer that question.

But as Eran mentioned, we’re looking into on the road map for DayTwo that’s not just for the people who want to buy it right now but we are looking into various things we can do with the data that we have, the data we collect, and the things that we learn. And of course diagnostics and therapeutics are a part of that whole agenda.

And so there’s insight that we’re looking into and collecting, and can very well come out with additional products that are related.

[Damien Blenkinsopp]: So as a first stage it’s basically a food recommendation engine as the output, and of course your microbiome data.

Do you have an idea of what type of microbiome data is going to be given? I know we talked about uBiome, for instance, in the past. We had Rob Knight from some of the other tests.

We’ve looked at a few different ones in the past. Have you got an idea yet, or are there pictures or anything of what it’s going to look like in terms of the data you provide for the microbiome?

[Lihi Segal]: I can definitely go back and send you some information about how it’s going to look, more or less.

[Damien Blenkinsopp]: Alright, cool.

[Lihi Segal]: But we’re trying to go into a lot of detail. Again, we’re doing full shotgun so we have additional insight. We’re not at just a very high level; we are looking into specific types of bacteria and trying to link them. We’re looking at studies and just general information about them.

Again, we have to be a little bit careful and not tell you anything that you may be alarmed with, or if you think that you have this and you’re going to be Type II or anything like that. So of course we’re being careful in the way that we present it. But there’s a lot of interesting information.

We’re also looking to do this in a very cool way that’s going to be, at least on the web – on the mobile it’s going to be a little flatter – when you sign into your web, there’s a report that’s going to be very interactive. You can dive in and go all the way down to the strain level, and then come up. So it’s going to be really cool in that sense.

[Damien Blenkinsopp]: So is there going to be, basically are you going to give all of that data?

My audience tends to be on the high quantitative side, so some of them tend to be people who download the data and start playing around with it in Excel. So will you have that kind of data?

With uBiome, for example, they have two aspects of that. They have the raw data they provide for you to download, and then you can put it into software to actually interpret yourself, like biometrician software.

And then they give you graphs which are basically summarized. So there’s not all of that information there, it’s a bit different, and it’s according to their perspective. So in comparison, what will you provide?

[Lihi Segal]: No, I don’t know to tell you that we’re going to give you all of the raw data. We probably could, but we haven’t finalized that down to the core of it. But again, we have it.

We’re going to have, as I said, the report and the very interactive tool so you can explore it. And the infographics is really cool. People are just playing here with it when they’re too tired to code. So they go and start planning that. But we could also provide the raw data, for sure.

Again, I think our users as opposed to uBiome users, uBiome users are mainly people who purchased it because they were curious about the microbiome. Our users, most of them, if I need to kind of guess or what I see, the microbiome is what gets them to say, oh this is really interesting.

This is personalized for me, I have my personalized microbiome; these people are scientific based, it’s not just that somebody came up with a diet based on my blood type, there’s science here. I don’t think that a lot of them are going to be very interested in downloading the file of the microbiome and things with it.

But we could definitely allow that, or be able to do that, if we see that there’s a need for that from our users.

(00:50:58) [Damien Blenkinsopp]: Yeah, cool. Alright. I saw there was a mention of a Mayo study on your site?

[Lihi Segal]: Where did you see that mentioned, by the way? I’m trying to figure out how did that get to you. We didn’t publish…

[Damien Blenkinsopp]: Well I don’t know, I think it was just mentioned. Oh, I know where I found it.

I was looking through your FAQ and there were some directions for Mayo study people on how to find the information.

There’s a leak there.

[Lihi Segal]:L: No, it’s not a secret by far.

We are recruiting people in the Mayo clinic now, and DayTwo is all over it. We just didn’t issue the press release saying that yet. But that’s been approved and it’s on it’s way as well.

So, what we’re doing, I’m happy to share, it’s no secret. But what we’re doing with the Mayo clinic is a clinical trial that is very similar to the clinical trial that The Weizmann Institute has done in Israel.

And so we’re recruiting 500 people and going through the same process of putting exactly the same device that was used in the trial in Israel and giving them test foods that are American foods, like a bagel and cereal, and really having them log their foods and providing all that information, and a lot of blood tests. So we’re really replicating the trial.

We’re just going to do that because we wanted to make sure we’re providing relevant recommendations after we have a basic cohort of US people. It doesn’t have to be the entire 500 completed, but we just, as the Israeli one was all Israeli, with Israeli microbiome and Israeli food, we just wanted to make sure that we’re able to calibrate the algorithm and it also works on a US based population with US foods and all that.

So we’ve already kicked that off. It’s a great collaboration for us to do this with the Mayo clinic, obviously. So we’ve already connected people. If any of your users are Rochester or Minnesota based people they can go and be part of that clinical trial.

[Damien Blenkinsopp]: Right. And it will be literally a copy of the other study so they could look at the other study to see what it would entail as well.

[Lihi Segal]: Right. There’s a bit of new information there as well. So that’s the reason we’re doing that. And also to start a collaboration with the Mayo clinic for other things as well.

(00:53:14) [Damien Blenkinsopp]: Great. Do you have a timeline for that? In terms of when you might get results eventually?

[Lihi Segal]: The timeline for US, it’s opened for pre-order. I know you probably entered through the UK, so you didn’t see that, because it’s IP based.

But if you were in the US you would see a pre-order. If you were in Israel, you could also buy and start getting it. So we started selling in Israel already.

The US is open on a pre-order basis, and we’re going to start shipping kits out to people in the beginning of 2017.

[Damien Blenkinsopp]: Okay.

[Lihi Segal]: It’s just around the corner.

[Damien Blenkinsopp]: Okay. So there are people already using this service in Israel, and it’s functioning.

[Lihi Segal]: In Israel we started the whole process of getting the evaluation, the kits, out to people and getting them back and sequencing them. We’re just starting to get, we’re in the final stage of getting the application finalized, and then getting the recommendations for people.

But there are a lot of people already who are using it because they got recommendations, whether from the Weizmann Institute Study or through us.

They’re not using the fancy application with the ‘Build Your Own Meal’, but the results and all of that have been around and have been used. Actually the BBC had a great show – I don’t know if you’ve seen it.

[Damien Blenkinsopp]: No.

[Lihi Segal]: The BBC has a show called ‘Trust Me, I’m A Doctor’.

[Damien Blenkinsopp]: I don’t watch TV here, unfortunately.

[Lihi Segal]: Oh, okay. So anyway, ‘Trust Me, I’m a Doctor’, it’s a doctor that has a show and she features clinical trials. And so she actually participates in the clinical trials that she features on her show.

So after the publication itself, she approached the scientists. She came to Israel with her colleague and was profiled and went though it, got food recommendations. Then she went back home and only ate what she was supposed to eat, lost weight and felt great, her energy levels [were up].

She was all psyched about it, and featured it on the BBC in a great show. I’ll send you the links so if you want you can see them.

[Damien Blenkinsopp]: Yes, please.

[Lihi Segal]: So there’s a lot of people who are using it, but outside of the clinical trial setting as well.

[Damien Blenkinsopp]: Okay, great. So it’s already getting around.

[Lihi Segal]: It’s getting contracts. Yes, we see the results are there.

(00:55:23) [Damien Blenkinsopp]: Yeah. Okay, so in terms of just how it’s going to be available, you’re only shipping to the US. So is no one in Europe is going to be able to do this?

[Lihi Segal]: Well, soon. We get a lot of approach on our support.

After the show was aired there was like 10,000 people hitting the website. So we know that there’s a lot of people interested. And we really want to go into selling in the UK as well. We’re just trying to be [safe], being a start up and not to jump too far ahead.

[Damien Blenkinsopp]: One thing at a time.

[Lihi Segal]: Right. So we did Israel because otherwise people will kill us here if we don’t bring it home. But we didn’t even translate it into Hebrew, it sold in English.

And we’re opening in the US because it’s an important market to start in. But we have concrete plans to get into Europe in 2017. So, soon. At least in the English speaking countries.

Really, logistically it just means that we need to get this box to people, but it’s not that simple. We will need a local database of food. So there’s some work on the server side to give you your foods and the database that fits you. We don’t think we’re probably going to need a trial to do that.

So in terms of the microbiome what we see is that the changes are not that [significant]. So there’s changes in the territories in the microbiome, but they’re probably not that apart compared to where the recommendations are. So you and I are very different in the way the algorithm predicts for us.

The microbiome is different, but it’s not that different. Anyway, it works on people. It could work on the US even without the Mayo trial.

[Damien Blenkinsopp]: So it sounds like that’s a validation effort.

[Lihi Segal]: Right, exactly.

[Damien Blenkinsopp]: I haven’t looked at studies of comparison of different countries and their microbiomes. There are some?

[Lihi Segal]: There are, if you look at the [57:12 check, unclear] that they have their graph there. So these show the US and there’s overlaps between the US, Europe, and Israel.

There are differences as well, but the differences, the way it reflects it in the algorithm is not that significant. So it works.

(00:57:33) [Damien Blenkinsopp]: Do you know when the Mayo trial, how long that’s going on for?

[Lihi Segal]: Oh, the Mayo trial will take a while. But we don’t need to complete the trial before we’re able to give recommendations. So we just need to validate it in a smaller group. But we’re there collecting data.

It’s more, you know in the US you can’t put a continuous glucose monitor on people at all if you’re not diabetic. Except under IRB kind of trial setting. So on a consumer level we couldn’t find any provider that would allow us to put continuous glucose monitors on healthy human beings without prescriptions. It’s a diabetic label from the FDA.

So we don’t have the device, and in order to really collect that data in the US we need to have a clinical trial set up and get the appropriate IRB and all that. So part of the whole doing of the Mayo clinic is because we just want more data, relevant data with glucose monitors and logging of food.

So we don’t need that to continue to start operating. I don’t even want to stop it after 500, so we’re talking about opening Arizona as a site, and Florida as a site. It’s really good just for our internal research purposes to continue to get more data.

(00:58:53) [Damien Blenkinsopp]: One quick question. I’ve noticed that Arizona comes up a lot in lab testing. I’m just wondering, as you brought it up just then, is there any reason?

[Lihi Segal]: Because Mayo has a site there. So when I’m collaborating with Mayo clinic, they have additional sites other than Rochester, Minnesota. So they’re thinking of expanding this to there and I’m more than happy to get more data.

[Damien Blenkinsopp]: I was just on holiday in Arizona and I just noticed that there are a lot of lab testing companies there.

[Lihi Segal]: It’s probably due to relevant man power and cheap, and something like that.

[Damien Blenkinsopp]: I think there’s maybe some state regulations or something that make it a little bit easier. Something like that also.

[Lihi Segal]: But again, when you sell outside of Arizona then you’re going to have to comply with the state laws anyway. So I’m not sure if that’s going to help you. But I don’t really know.

(00:59:41) [Damien Blenkinsopp]: So right now for the US is it $299 for the pre-order?

[Lihi Segal]: The price is going to be $399 but we’re opening up at $299, that’s a pre-order discount. But once we stop reordering, we’re probably going to go up to $399.

In Israel it’s 500 dollars, but we’re also doing a premium product in Israel; we’re giving continuous glucose monitors to people in Israel. So we’re giving them a fancy report on their blood sugar levels and all kinds of other stuff. We can because the device that I talked about in Israel you can put it on humans that are not sick.

[Damien Blenkinsopp]: Right, wow. That sounds like quite a service. If someone would pay 1000 dollars or more…

[Lihi Segal]: No, no, 500.

[Damien Blenkinsopp]: Oh, and they’re getting that premium service with the glucose monitor?

[Lihi Segal]: Yeah. It’s a lot, 500 dollars. It’s just more expensive than the US because of the continuous glucose monitor that we’re putting on.

[Damien Blenkinsopp]: They’re quite expensive, those things.

[Lihi Segal]: Well, they cost a few hundred. I guess in the UK it’s about 80 Euros. And then the reader and then the patch cost a little bit more.

[Damien Blenkinsopp]: I looked into getting one for myself; not for medical reasons, just to play around with.

[Lihi Segal]: Abbott Freestyle. Just take the Abbott Freestyle Libre. Just look for it. Freestyle Libre and then just order it online. And I think it costs 100 Euros or something.

[Damien Blenkinsopp]: Okay. And it’s got consumables on it too.

[Lihi Segal]: And then you have a patch. You get a round patch that you put on for two weeks. It’s good for two weeks. And then you have a reader.

[Damien Blenkinsopp]: And this is the one that Eran was talking about earlier that they’ve started using.

[Lihi Segal]: Right. So you can get that online.

We bought a bunch of them online ourselves in the UK before we found it in Israel. And once we found it here in Israel we decided to go with this product that we can also collect from people their blood sugar managements and give them all the fancy reports on all that. So it’s cool.

[Damien Blenkinsopp]: Yeah, it sounds quite exciting what you’re doing in Israel, because you’ve got more flexibility there. Are you publishing anything, maybe a bit later, about that on your customer base?

[Lihi Segal]: Not yet.

[Damien Blenkinsopp]: Okay.

(1:01:51) Is there anything we haven’t covered about the service, that we’ve missed?

[Lihi Segal]: Yeah. I think that this is kind of our direct to consumer approach. So we’re selling to you directly, but what we’re really working on is partnerships. Because what we really believe is that the way you’re going to use this is also very personalized.

Some people, the fact that we give them a fancy application that’s really cool and has a report on it and teaches them what to eat and what not to eat. There’s going to be a diet planner at some point on this. So you can really be independent in the way you manage your food.

For some people that’s going to be great, but some people really need more support. So maybe they go to Weight Watchers or they use other weight management services. And once you know as a user that there’s specific recommendations for you that are personalized for you, you really can’t tolerate generalized information anymore.

I’m saying this for myself. I go to this Weight Watchers group – it’s not Weight Watchers, it’s a local Israeli group. But I can’t hear her say to me, you should eat pretzels as a snack. 100 calories of pretzels are your snack. I’ve been doing that for 15 years, and then I found that it was my number 1 spiking snack.

And I moved to a different, totally different corn-based snack that was much better for me if I’m eating that 100 calorie snack already. So I’m snacking on that.

And what we’re thinking of doing is really opening an API with a lot of services. And so you as a user can share your information with your doctor, or with your nutritionist, or with your weight management group. Or when you take out food you want to be able to get a score. You want to log in, connect to…

[Damien Blenkinsopp]: So you could plug into a meal delivery site.

[Lihi Segal]: Think of this. Let’s say you’re ordering take-out of your food. We do this every day at lunch, just because in Israel is how it works.

And so I want to log in and connect with my DayTwo account, into that service, then get a menu and my score, A, or B. I’m already in a great restaurant, I’m eating food or I’m taking it out, I want to be able to get a score and choose right.

In the US specifically there’s a lot of employer wellness programs. All of those wellness programs provide nutritional advice, but it’s generalized. I, as a user, want my personalized advice to go with me.

So, that’s kind of the partnerships that we’re doing. Some will bring us customers, some we will bring our customers to them. And we’re building a marketplace around this.

So literally, think of that that we’re not competing with anyone. That’s the strategy that we built. We want to enable anyone who wants to use this personalized service to use it in their application and services.

[Damien Blenkinsopp]: Great, to make the information more widely available.

Lihi, it sounds great. I’m sure there are insurance companies and so on who would be interested in that as well. I know they’re getting more interested in these wellness programs.

[Lihi Segal]: Of course.

[Damien Blenkinsopp]: Okay well thank you very much for your time today. I really appreciated it.

[Lihi Segal]: Sure. Thank you so much.

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

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

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

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

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

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

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

– Chris Masterjohn

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

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

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

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

itunes quantified body

What You’ll Learn

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

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

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

Recommended Self-Experiment

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

Tools & Tactics

Diet & Nutrition

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

Supplementation

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

Tracking

Micronutrient System

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

Biomarkers

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

Lab Tests

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

Devices and Apps

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

Other People, Books & Resources

People

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

Organizations

Books

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

Other

Full Interview Transcript

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Right. Absolutely.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Chris Masterjohn]: I do.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Wow, awesome.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Chris Masterjohn]: For sure

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Chris Masterjohn]: Oh, for testing?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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Ketone bodies, whether gained from fasting, keto diets, MCTs or exogenous ketones have many potential applications with benefits ranging from performance, to health, to longevity and mitigating symptoms and risks of certain diseases.

There is growing evidence that ketone bodies, whether they come from fasting, keto diets, MCTs or exogenous ketones have potential applications across many areas from longevity to performance, to health and mitigating some of the risks and symptoms of certain diseases like cancer and neurologically inclined deceases. As such the whole ketone body area is what I call a high leverage area due to the many potential upsides.

So I’ve personally been investing more time into experimenting in this area as the payoff for that effort, looks pretty promising. You’ll have noticed that I’ve done a fair amount of fasting and since late 2015, that also includes the exogenous ketones and playing around with the ketogenic diet. More to come on my results with all of those in future episodes.

This interview is a very in depth look at many of the applications of ketone bodies and the nuances of their use in the body.

Ketones have a unique effect of being… anaplerotic… [This] helps to generate the bioenergetic intermediates [including] the Krebs cycle intermediates… to energize the brain when fuel flow is kind of low.
– Dominic D’Agostino

Today’s guest is Dominic D’Agostino. Dominic has something that I found relatively rare but makes for extremely valuable interviews. He has a combined prospective coming from both research and self-experimentation. He has a considerable amount of lab work and research specifically done into ketogenic diets, ketones, ketone driving supplements and a growing number of applications. And he has done a lot of his own self-experimentation for many years in this area.

Dominic is currently an associate professor in the Department of Molecular Pharmacology and Physiology at the University of South Florida, and he’s also a senior research scientist at the Institute for Human & Machine Cognition (IHMC). His research is focused on developing and testing ketogenic diets, ketone supplements, and amino acid formulations for a broad range of therapeutic and performance applications.

His laboratory uses in-vivo and in-vitro techniques to understand the physiological, cellular, and molecular mechanism of nutritional ketosis and supplement formulas. His current efforts are focused on evaluating different methods for inducing and sustaining nutritional ketosis and how this can be optimized to the specific individual and applications. So, we’ll see in today’s interview that there are a lot of nuances and it’s a bit more complex than just boosting your ketones.

Dominic’s research is supported by the Office of Naval Research, The Department of Defense, Support Supplement Companies, and Private Foundations.

Special Note: In the interest of full disclosure, since late 2015 I own a company (Ketosource.co.uk) that develops ketogenic and ketone driving supplements, foods and drinks for the UK.

The episode highlights, biomarkers, and links to the apps, devices and labs and everything else mentioned are below. Enjoy the show and let me know if you want more on this topic in the comments!

itunes quantified body

What You’ll Learn

  • Using exogenous ketones to mitigate some of the impairments of sleep deprivation (all nighters, or jetlag) (5:50).
  • How the stress response from scenarios like jetlag will kick you out of ketosis (and can be compensated for via exogenous ketones) (13:00).
  • Dominic’s background research and how his career has evolved to working on ketone bodies and ketogenic diets and their applications (14:50).
  • Recent research with mice that may indicate that ketosis reduces anxiety (17:00).
  • Screening a range of different naturally derived exogenous ketone agents for their therapeutic and performance benefits (18:40).
  • A once to twice per year fast or nutritional ketosis protocol for potentially activating a range of beneficial genes (37:50).
  • The press-pulse ketone body strategy for the management of cancer (40:40).
  • The benefits of the ketogenic diet for the management of epilepsy over the pharmaceutical alternatives (49:20).
  • Using the ketogenic diet to restore normal appetite regulation (50:15).
  • The various health, performance and longevity applications for ketone bodies (52:00).
  • Potentially reducing tremors in Parkinsons and Alzheimers with the use of ketone bodies (57:10).
  • Evaluating the legitimacy of recently raised safety and effectiveness concerns related to ketone salts and MCTs based on scientific facts and their track record over the last two decades (1:01:10).
  • How racemic exogenous ketones suppress glucose more effectively than non-racemic exogenous ketones (1:13:40).
  • Using MCT oil powder as a staple product for coffee, baking and protein shakes to boost the ketogenic profile of your diet (1:16:00).
  • Avoiding liquid meals in order to be able to elevate protein intake higher while remaining in ketosis (1:18:00).
  • What a typical ketogenic day looks like for Dominic in terms of blood ketone measurements from morning to evening and how he optimizes it (1:20:00).
  • How Dominic has identified his optimum ketone and Glucose-Ketone Index ranges for mental performance (1:21:00).
  • To standardize and control for your blood ketones and glucose you need to be fairly sedentary (1:34:10)
  • Dominic D’Agostino’s recommended self-experiment with the largest potential upside with the tactic to test and biomarkers to track (1:42:00).

Thank Dominic D’Agostino on Twitter for this interview.
Click Here to show him some appreciation for doing this interview!

Dominic D’Agostino

Recommended Self-Experiment

  1. Tool/ Tactic: Start Intermittent Fasting with fasting windows of 18 hours and eating windows of 6 hours each day. Dom recommends listening to Matt Mattson’s talk on IF before you start.
  2. Tracking: Get some baseline lab tests before you start the IF and again 3-4, and/or 6-8 weeks afterwards to see the positive impacts. Your lab tests should include fasting glucose, triglycerides and hs-CRP.

Tools & Tactics

Diet & Nutrition

  • Well Formulated Ketogenic Diet: The high fat, low carb, moderate protein diet that puts you into ketosis with typical blood ketones of between 0.5 and 3 mmol/L depending on execution and the person. Not suggested for children, teens or people in their 20s with good insulin sensitivity in general.
    Foods Dominic Makes Particular Use of:

    • Coconut Cream: Combines the fats with some of the fiber from the coconut flesh. Coconut cream is also known as Coconut Butter.
    • Ghee (Clarified Butter): Butter that has had the dairy proteins removed to leave solely the fats. As such it is considered dairy-free.
    • Wild Sardines
    • Sour Cream with Live Cultures: Didn’t find a link to this – if you know a good source please let me know in the comments.
  • Fasting Protocols

  • Intermittent Fasting: Sometimes referred to as short-term fasting due to the typical 16 hour to 20 hour fasting window. Dom noted that he has spoken to a fair number of high-performing CEOs doing this routinely recently.
  • Fat Fast: A modified intermittent fasting protocol whereby you restrict caloric intake in the fasting window (e.g. 18 hours of day) to some fats, exogenous ketones and/ or MCTs instead of a pure fast (no food or calories). Dom finds this method effective and that he tends to be less hungry going into the eating window (i.e. 6 hour window).
  • Periodic Fasting: Typically refers to fasts spread out by once per week or once per month. We’ve done past self-experiments on the once per month periodic fasting protocols via a 5 day fast, 10 day fast and fast-mimicking diet.

Supplementation & Drugs

Exogenous Ketones

Dominic’s lab has looked at a variety of exogenous ketone formulations in different scenarios and applications. Amongst their papers are included improved blood lipid profiles1 and non-toxic metabolic management of cancer2.

MCTs and C8 (Caprylic Acid)

  • Brain Octane: Pure Caprylic Acid (C8) from Bulletproof Nutrition.
  • Keto8: Pure Caprylic Acid (C8) oil from KetoSports.
  • Quest MCT Powder: MCT powder that Dom is using as one of his staples mixed into coffee for example.

Dominic’s Sleep Deprivation Effects Mitigation Cocktail

  • Exogenous ketone: Take your pick from one of the exo ketones listed above. Is beneficial to combine with MCTs such as C8 or MCT powder.
  • Caffeine: Needs no introduction – use coffee or your other favorite
  • Huperzine A: A nootropic herb used for cognitive enhancement via modification of acetylcholine levels.

Drugs

  • Metformin: A drug which is used to improve blood sugar regulation in diabetes. Researchers are looking at its wider applications with cancer treatment as it has been found to inhibit insulin secretion.
  • Ringer’s Lactate: The long term use of this racemic solution was noted as evidence as to the safety of racemic ketone salts.

Tech & Devices

  • Hyperbaric Oxygen Therapy: Increasing the amount of oxygen in the body with the use of a hyperbaric oxygen tank which uses air that is more highly saturated with oxygen and which is compressed. Dominic has worked on research with Doctor Thomas Seyfried looking at its application for cancer therapy in combination with ketogenic diets3.

Tracking

Biomarkers

    Glucose/ Ketone Metabolism

  • Glucose: Dom suggests aiming to keep values between 60 and 80mg/dl and that if you can maintain this all other biomarkers should be fine.
  • Glucose Tolerance (OGTT): The Oral Glucose Tolerance Test is a glucose challenge test whereby you take a certain number of grams (e.g. the typical standard is 75 or 100 grams) of glucose and test your body’s ability to regulate glucose and bring your blood glucose back into normal range over a certain time period (e.g. 2 or 4 hours). Dom used the OGTT to assess his insulin sensitivity – the more insulin sensitive you are the quicker your blood glucose returns to normal fasting levels e.g. between 60 and 80mg/dl optimally.
  • HOMA (Homeostatic Model Assessment): An alternative method to the OGTT used to assess insulin sensitivity/ insulin resistance.
  • Glucose-Ketone Index (GKI): This index was conceived by Thomas Seyfried and discussed in detail with him in episode 16. It assesses the weighting of the metabolism towards ketone vs. glucose. Lower values are ketone driven metabolisms and higher value (especially over 20) can be associated with heavy glucose metabolisms associated with chronic disease. Dom brought a new angle to this marker with an optimum everyday target he shoots for of between 2 to 4. Previously we discussed Thomas Seyfried’s recommendation of undertaking a 5 to 7 day therapeutic water fast once or more times per year targeting a GKI value under 1.
  • Lipids

  • Triglycerides: Dom believes this is the most important biomarker to watch. Optimum levels estimated as below 40mg/dl.
  • HDL: Higher HDL levels are said to be protective and beneficial. Dom’s value are around 90 mg/dl.
  • LDL: Dom believes keeping values in the normal to normal high reference range are perhaps optimal. This puts levels at approx. 80mg/dl to 110mg/dl. We previously discussed LDL in more depth in episode 7.
  • Other

  • hs-CRP (high sensitivity CRP): CRP (C-Reactive Protein) is a very common marker of inflammation that is used to assess cardiovascular risk amongst other things. It tends to drop on a ketogenic diet. Dom’s values have been between 0.1 and 0.2 since he quit dairy (Note: Damien’s levels are also at this level).
  • IGF-1: IGF-1 was discussed in more detail in our FMD episode. Dom’s IGF-1 values dropped significantly after quitting dairy.
  • Heart Rate: Typically heart rate is measured as the biomarker Resting Heart Rate (RHR) for standardization, which is an average of the beats per minute. See episode 1 to understand the use of RHR.
  • Blood Pressure: Optimum ranges are for systolic between 90 and 120 and dystolic 60 to 80 expressed as for example 110/70 mm Hg.

Lab Tests, Devices and Apps

Devices for Measuring Glucose & Ketones

The different approaches to measuring ketones provide different perspectives on your ketone metabolism. These can be looked at in terms of the ‘window of snapshot’ that they represent. Some methods have a snapshot of a longer duration, so provide more of an average reading, while others provide a direct status of that exact moment.

Moving from the more average-based value end of the scale to the more direct status end you have:

  1. Measuring ketones via the urine (via the ketone body acetoacetate) has the longest snapshot with it representing your ketone values over the last 5 to 6 hours.
  2. Measuring via the breath (the ketone body acetone) has a smaller snapshot window of the 2 hours leading up to the measurement.
  3. Measuring via the blood (via the ketone body beta hydroxybutyrate) provides you a snapshot of your ketone level at that exact moment.

The various devices available for glucose/ ketones testing and mentioend include:

  • Urine Ketone Strips: . Both hydration status and becoming keto-adapted interfere with the measurement values provided by this. Dominic recommends starting with urine test strips as they are the cheapest and effective until you get keto adapted.
  • Ketonix Breath Meter: Currently the only breath acetone meter. If you are moderate to high on this meter you are effectively in ketosis (i.e. typically over 0.5 mmol/L). Dom recommends this in particular for epilepsy since breath acetone has been correlated with seizure control.
  • Blood Glucose & Ketone Monitoring Systems
  • Precision Xtra: The most popular meter for testing blood glucose and ketones in the U.S. Has a broader reference range than the NOVA providing values for lower blood glucose levels instead of the LOW error.
  • Freestyle Optium Neo: Freestyle Optium Neo is the upcoming replacement for the PrecisionXtra, it comes from the same company and has similar functionality – the only difference in the meters seems to be a rebranding exercise.
  • Novamax Plus: Novamax Plus is a slightly cheaper meter with some greater accuracy and sensitivity concerns than the Precision Xtra or Freestyle Optium Neo.
  • Dexcom G5 CGM: A Continuous Glucose Monitor that Dom is about to start experimenting with for blood glucose optimization. Peter Attia has also been using this tracking device recently to optimize blood glucose regulation. We discussed continuous glucose monitoring and the devices available in episode 43

Other People, Books & Resources

Books

People

Researchers

Other Mentions

  • Tim Ferriss: Has been experimenting with the breathe hold extending effects of ketone bodies via ketogenic diet and exogenous ketones.
  • Ben Greenfield: Has been experimenting with using exogenous ketones for free-diving.

Organizations & Companies

Other

Full Interview Transcript

Click Here to Read Transcript
(05:32) [Damien Blenkinsopp]: Dom welcome to the show.

[Dominic D’Agostino]: Thanks for having me, Damien.

[Damien Blenkinsopp]: Yes, it’s great to connect. So you’re just back from a trip to Budapest and you just told me that you’re doing something to bypass the jet lag?

(05:42) [Dominic D’Agostino]: Yeah. Sometimes depending on circumstances I try to prioritize sleep and try to get between six to seven hours sometimes eight on the weekends if I can. But in the absence of sleep, I like to test certain things.

Usually happens once every month or two or I’m going to have to skip one night completely and have to get thrown right back into the fire of work again. I’m doing that now, and testing some different exogenous ketones in combination with caffeine and some Huperzine, and a few other little things in a stack formula that I’m working on.

It seems to be working because I’m functioning and I’ve been able to manage my tasks in a way that allows me to get stuff done.

[Damien Blenkinsopp]: So, this could be a new jet lag formula? Or if you want to keep going on sleep deprivation and work for a night or something…

[Dominic D’Agostino]: Yeah. So, inevitably people will come to the situation where they have to meet a deadline and stay up all night to get something. I don’t recommend doing it all the time because you can get burned out. There is no pill that you can take that will substitute for sleep.

But there are ways to extend your productivity and performance with two or three days of no sleep. I don’t like when those situations arise, but I worked on ways to mitigate some of the impairments that accompany that.

(07:13) [Damien Blenkinsopp]: That’s excellent, that sounds like another application for exogenous ketones I had not thought of. I know there are a whole bunch I want to discuss with you because it seems like there’s quite a few of them. So now if you want to work all night, they can help with that.

I’m tempted actually, what is the mechanism behind that specifically for sleep, is it just a pure energy thing or?

[Dominic D’Agostino]: As far as sleep? Mitigating sleep?

[Damien Blenkinsopp]: Why would exogenous ketones help with?

[Dominic D’Agostino]: Yeah, I think there are several ways that they can help. You can formulate things to provide energy to the brain. There’s various, what we call tricarboxylic acid cycle intermediates, including alpha-Ketoglutarate, creatine – is actually something that could be beneficial to the brain when energy reserves are low, and ketones have a unique effect of being anaplerotic. So if something is anaplerotic it helps to generate the bioenergetic intermediates which include the Krebs cycle or also called the TCA cycle intermediates.

Essentially just helping to energize the brain when fuel flow is low. Many of the TCA cycle intermediates are also precursors to neurotransmitters. For example, alpha-Ketoglutarate is a precursor to glutamate, and then from glutamate through glutamic acid decarboxylase we make GABA.

So, ensuring that we have efficient energy flow to the brain and sort of stimulating anaplerotic reactions and bioenergetic reactions we can replenish the neurotransmitters. Being in a state of ketosis too, can also be glycogen sparing.
I always had the opinion that when we sleep, part of the function of sleep not only restore neurotransmitters but to also restore brain glycogen levels.

Glycogen is actually stored in the astrocytes of the brain. Astrocytes are not just for support cells they have a really important function that pertains to glutamate recycling and sort of dynamic interactions with the synapses and recycling of neurotransmitters and restoring brain glycogen levels is a function when we sleep.

I think we need to look into this more but I have a theory that being in a state of strong ketosis could prevent some of the glycogen depletion that accompanies a normal day in a person that is normally sort of carbohydrate fed.

Where the brain is sucking massive amounts of glucose but if you’re ensuring that it gets a steady fuel flow of ketones it’s going to be glycogen sparing in that way. Sort of like what Jeff Volek is doing with the athletes and it showed in a recent metabolism paper, that being keto-fat adapted and keto-adapted can actually be very glycogen sparing. If you look at the muscles of lead athletes on a carbohydrate restriction, amazingly their glycogen stores are topped off in the muscles.

I think the same thing is happening, I see no reason why it wouldn’t happen in the brain. Our energy reserves in our brain tank, adenosine goes up, neurotransmitters are depleted – we want to sleep. Being in a state of ketosis can slow that process, and exogenous ketones can be a tool in a toolbox to help with that.

[Damien Blenkinsopp]: That’s really fascinating. It’s like the biochemistry of sleep, we’re getting tired and I think we understand on a very basic level but you’ve just broken down quite a few mechanisms which lead to us needing to sleep and how to counter them.

[Dominic D’Agostino]: Yeah, sleep is a really complicated subject. I did my Ph.D. in a pulmonary critical care department that was also a sleep lab. So I sat in on a lot of rounds and meetings with residents and fellows about the mechanics of sleep.

It’s just a fascinating subject, and something I’ll probably get more into research wise. But I do teach the medical students about obstructive sleep apnea and central sleep apnea, that’s some of the research that I did in my Ph.D.

(11:22) [Damien Blenkinsopp]: Excellent, and you’re on a keto-diet as well right still?

[Dominic D’Agostino]: Yeah. I maintain that but I also like to cycle a little bit because I think a lot of the therapeutic and performance enhancing benefits can be achieved with nutritional ketosis but I also think it’s good to have relative changes.

Not to stay on something all the time, but to adjust your macronutrients a little bit, and also maybe your calories a little bit, and occasionally fasting. These relative changes can produce some pretty good performance and therapeutic effects.

[Damien Blenkinsopp]: It’s kind of like exercise like promoting metabolic flexibility, is that where you’re coming from?

[Dominic D’Agostino]: Yeah, that was what I was going to say and relate it back to a hormetic effect where relative changes are good. For a while, I just stayed on the exact same ketogenic diet for a long time and I started adjusting and playing around with different supplements and I realized it’s good to sort of adjust the diet and even adjust your calorie levels sometimes. My life is variable, it kind of fits on with my lifestyle too.

[Damien Blenkinsopp]: I feel the same way. I’m probably doing the something a bit more varied these days. So, it’s just interesting, you said you are basically stacking exogenous ketones for sleep on top of your keto diet. Does that push your levels quite high?

[Dominic D’Agostino]: At least doubles or maybe triples where I would be. I have noticed in the past that if I just stick to my normal diet and I cross time zones. I’ve been in at least a dozen time zones for the last month and a half, two months.

When I do that and I miss a complete night of sleep, coming from Southeast Asia completely flips circadian. I realized that I get a stress response from that I think my cortisol goes up, my sympathetic nervous system can be activated. And I notice that can kick me out of ketosis a little bit or I’ll have levels that are — I would predict there would be much higher based on the macronutrient profile that I’m eating and even fasting.

So, I find that exogenous ketones can sort of help in those situations where I put my body into an unaccustomed stress.

(13:36) [Damien Blenkinsopp]: That’s very interesting. I’ve started to use some of the supplements, exogenous ketones for different scenarios a bit like that situation but we can talk about that later. So, I wanted to give people a background, would you say your focus area is ketones, ketogenic diet? Is that what you’d call your focus area of research?

[Dominic D’Agostino]: Yeah. I’m classically sort of trained as a neuroscientist. I did my PhD in something very specific, it’s patch clamp electrophysiology where you measure from individual neurons and you record the membrane potential, firing frequency input resistance of individual neurons, either in cell culture or in a brain slice, and studying pharmacology and the metabolic activity. I became very interested in observing fundamental neuronal activity.

I became very interested in the metabolism that was supporting that. I realized that the life that I was seeing on the amplifier of the oscilloscope, these neurons firing was completely a result of the electrochemical and the electrical gradients between the neurons, they’re like little batteries.

That was generated completely by the metabolic activity so cells they need to maintain negative 56 kilojoules per mole of energy and they will do anything to do that. Some substrates and some means of generating ATP are more efficient than others. In my early work, I was actually looking at lactate.

I was interested in Ringer’s lactate, so racemic Ringer’s lactate is actually used on the battlefield and also in surgery when people have a lot of massive blood loss. Lactate is extremely efficient fuel, and I studied hypoxia in the brain and ischemia, and I was interested in lactate for that. That got me interested in this whole idea of developing and testing metabolic substrates to preserve and enhance brain energy metabolism in the face of extreme environments.

Our work for the last decade has been funded by the military. So I’m interested in particular situations that would accompany military operations, like a navy seal using a closed circuit rebreather with high levels of oxygen. He’s susceptible to a limitation of his mission, would be oxygen toxicity seizures so the fundamental neuroscience that I learned in my Ph.D.

I applied that to developing and testing metabolic base therapies to preserve that cognitive function and metabolic resilience in the environmental extreme of high-pressure oxygen. That’s sort of a fun thing to do because there’s many ways to do it. I’m always looking for the next, or the optimal formula, of ketones and that’s why we don’t focus on any one particular exogenous ketones. We screen a variety of ketogenic agents or formulas of them to identify the one that’s most neuroprotective or anticonvulsant.

Now, we do cancer studies and we do wound healing, performance applications – and it might be a different ketone for different applications and we’re testing that now. In Budapest, we actually presented some really interesting work on anxiety. So if we induce a state of nutritional ketosis, the anxiety levels go down pretty significantly. In a rodent model, they’ll spend more time in like an open-arm of an elevated plus maze.

Perhaps that reduced anxiety can play a role in reducing seizures too, so it’s another variable that we need to look at. I probably went off on a tangent. My background was neuroscience and now I do what I would call a nutritional neuroscience or metabolic based sort of strategies to target neuronal processes and neuroprotection.

(17:43) [Damien Blenkinsopp]: How many years have you been doing this now?

[Dominic D’Agostino]: I started neuroscience research as an undergraduate in 1997. So, it’s going on about — 1996 or 1997 — so about 20 years now I’ve been into neuroscience research. The office of navy research, post-doctoral fellowship, was the first large grant money that I’ve got, and that was 10 years ago.

It took me about four years to recognize that the most potent strategy for oxygen toxicity for mitigating that, which I was being funded to do would be a ketogenic approach. Then the ketogenic diet at that time was recognized as something very obscure even just six years ago. So the funding agency really wanted a ketogenic diet in a pill per se.

In addition, to our ketogenic diet research which I feel is also very important we have developed these synthetic and actually naturally derived ketogenic agents to mimic the effects of fasting, the ketogenic diet, and also to further augment the therapeutic efficacy of the ketogenic diet. If the ketogenic diet can only get you to one to two millimolar, and we boost it in another one or two millimolar with exogenous ketones. We’ve realized that, that can be very beneficial.

Not everyone can follow a ketogenic diet including performance applications or for therapeutic purposes.

[Damien Blenkinsopp]: People find it quite hard. I don’t think it’s relatively complex to get into it. I speak to a lot of people who think they’re in ketosis but they’re not.

[Dominic D’Agostino]: Yeah, I do too.

(19:25) [Damien Blenkinsopp]: It’s a little bit tricky I think. So, alas comes the supplementation and so on which could make it easier. I think what’s really awesome about you, you self-experiment as well in addition to your research.

You’re always looking for this stuff and I know you’ve been on a keto diet for a long time, when did you start that?

[Dominic D’Agostino]: Yeah, that’s the fun part of this research that I’m really excited about. Well looking back, I did low-carb diets for a while because I was always into powerlifting, fitness, and nutrition. So, I would experiment, and I was under the impression that being on ketosis was bad.

When I did a low-carb diet or what I call the ketogenic diet, I remember smelling like ammonia. Because it was basically a very high protein, zero carb diet, with a normal amount of fat. Then I got educated I guess, being connected with the folks at John’s Hopkins who are using this on a clinical setting. I read the book by John Freeman and Eric Kossoff at John’s Hopkins, which is a great book, ‘The Ketogenic Diet’ for epilepsy and other disorders that’s out there.

There are one or more popular books on Amazon. I realized wow I didn’t know what a ketogenic diet was. I didn’t realize it has this fascinating history. You know written with Travis Christofferson, we wrote a three part of series on Robb Wolf’s blog about the ketogenic diet the history. When I actually got into the 4:1 ratio ketogenic diet, the John’s Hopkins which is like 90% fat.

And I transitioned into a state of nutritional ketosis, it was kind of difficult in the beginning. After about two or three weeks I adapted quite well and started realizing the neurological benefits. The appetite suppression was pretty extreme it was difficult for me to maintain my weight even.

(21:16) [Damien Blenkinsopp]: In terms of losing weight?

[Dominic D’Agostino]: Yeah, because my protein level was really high. I think I was getting probably 300 grams of protein a day which is really high. So, I had to drop that down to about 100 grams of protein a day to hit those macronutrient ratios.

Probably about 120 grams a day of protein, which was a relative change that was really low. When I reduced my protein to 1/3 but elevated my fat, and I still kept going to the gym. But at the time my academic career was sort of going full steam and I was in the gym less, but still making it once or twice a week.

My weights that I was handling on major exercises were maintained so I realized that being in a state of nutritional ketosis had a pretty profound anti-catabolic effect. So, I figured I’d be wasting away if I wasn’t getting my body all these protein. But I was amazed that I could eat.

I even started experimenting and went down to like 60 or 80 grams of protein a day. Even after a couple weeks and months I was able to still move the same weights.

So it really blew my mind that shifting the metabolic physiology to being more fat and keto-adapted had this sort of protein sparing anti-catabolic effect. Which makes sense if you look at it through like an evolutionary lens.

So if we stop eating and we didn’t make ketones to fuel this big, highly energetic organ in our head. If the ketones weren’t providing fuel for our brain we would liberate a lot of gluconeogenic amino acids from the skeletal muscle, and we would quickly waste away probably in a week or two, for a lean individual. That’s important to recognize in the context of using a ketogenic diet for a weight loss strategy and also for body composition.

For example, athletes that need to make weight which many sports do — wrestling, boxing, mixed martial arts – keeping that power to weight ratio is important. We think from the studies that we’ve done, we actually just got a study approved finally for publication yesterday showing elite level athletes or advanced lifters that the ketogenic diet is quite effective for body composition alterations and preserving strength and muscle strength and performance.

So that should be out pretty soon in general strength and conditioning. We realize that the ketogenic diet has far more applications than just pediatric epilepsy, which was it’s original application. We’ve probably studied about 10 different applications now in our lab.

(23:59) [Damien Blenkinsopp]: Excellent. So I wanted to run through some of those applications. First of all taking a step back because you mentioned lactate earlier. I think the majority of us assumes that glucose is the main metabolism. Then we learned about ketones and we think maybe there’re two substrates that we’re using for metabolism.

As I understand it, it’s a lot more complicated right? That we’re using a number of different fuels at any time?

[Dominic D’Agostino]: Yeah. I think the big ones for brain metabolism, which our laboratory originally focused on and now we’ve branched off, would be glucose would be the primary fuel for most people. Then ketones are sort of a backup fuel.

If you’re on a ketogenic diet, you’re running this hybrid engine and you’re using both fuels at the same time. With ketones probably the most efficient of the two. Then lactate too.

When we exercise, we mobilize a lot of lactate and put a lot of lactate back into the bloodstream through what’s called the Cori cycle. We convert that back to glucose and then replenish liver glycogen or muscle glycogen. But that lactate can also go past the blood brain barrier across which is called the monocarboxylic acid transporters and provide a source of energy for our brains.

Lactate metabolism in the brain can also occur under conditions of oxygen deprivation, so it may be beneficial. That was also an interest in my earlier work, using lactate to preserve bioenergetic processes in the absence of oxygen. What we call hypoxia or anoxia, which is a complete lack of oxygen.

Interestingly ketones can generate more ATP per oxygen molecule consumed. In a hypoxic situation, ketone metabolism may also be able to preserve the bioenergetic state of the brain. That’s something that we’re also looking into hypoxia and ischemia protection of the brain with various fuels, ketones, lactate preventing or an alternative substrate to glucose.

In certain situations, neuropathologies and even a hypoxia, stroke, a brain injury for traumatic brain injury can cause a quick impairment of glucose utilization of the brain. By internalization of the GLUT3 transporter and also inactivation or reduced activity of Pyruvate dehydrogenase complex, the PDH complex, can be impaired under certain conditions of brain injury. Even certain viruses that cause neuroinflammation can impair this rate-limiting step for glucose metabolism.

So, alternative energy substrates are a way to bypass that glucose block.

(26:37)[Damien Blenkinsopp]: It’s like a diversification strategy?

[Dominic D’Agostino]: It is, in diving we always talk about being redundance. You need a level of redundancy to ensure safety. I think the brain does that pretty nicely. So we achieve that with fasting.

We have an alternative energy substrates being utilized in the absence of glucose. It’s interesting to be able to delve into that and understand what happens during fasting in different states. From my perspective, it’s a fascinating field of research to develop naturally derived or synthetic agents that can mimic those processes.

(27:17)[Damien Blenkinsopp]: Right. Because we are on a ketogenic diet do we also use fatty acids directly for energy substrates or do they have to be turned into ketones first?

[Dominic D’Agostino]: Yeah. Hepatic gluconeogenesis will be in a state of fasting, completely dependent upon the liberation of fatty acids from adipose tissue. Fat mobilization is directly almost correlated to a ketone production in that fasted state.

Our heart can use fatty acids more efficiently than glucose – our heart is an awesome fat burner. The skeletal muscle is an awesome fat burner especially in the keto-fat adapted athlete, the liver, various organs can use fatty acids quite efficiently. The long-chain fatty acids do not readily cross the blood-brain barrier.

Short chain fatty acids do, and medium chain fatty acids can actually cross the blood-brain barrier. So, that was actually an interest of mine and we did some brain metabolomic studies where we took out the hippocampus of some rodent models that we looked at. We saw a high level of the C8 and the CA10 MCT that we administered to the animals.

I think if you look at the ratio between the blood levels and the brain levels. I think there was a kind of like a 1:5 ratio, so that wasn’t readily getting through but a lot of it was getting into the brain. Of course, the brain was metabolizing it.

Our numbers might have not correlated precisely in a 1:1 ratio in that way. But it’s clear that our body can use fatty acids as fuels, and it’s an incredible fuel for our mitochondria. Because it metabolized exclusively in the mitochondria through oxidative phosphorylation.

(29:03) I would say ketone molecules are I’d like to call water soluble fat molecules, sort of an excessive beta-oxidation or accelerated beta-oxidation in the liver, contributes to the accumulation of acetyl-CoA which drives ketone production, and hepatic ketogenesis. So the acetyl-CoA essentially condenses to form acetoacetate. Then beta-hydroxybutyrate and these spill into the bloodstream.

So it’s interesting that the liver is a massive ketone producer but it lacks certain enzymes that prevent the liver from using the ketones as an energy source so it lacks succinyl-CoA transferase for example.

So, the liver will produce massive amounts of ketones. Then dump it into the bloodstream primarily for our central nervous system to maintain energy flow to the brain, then the central nervous system, and probably the heart too. The liver is a greedy organ, if you fast and you eat, the amino acids and glucose will basically stay in the liver and the liver will take what it needs and put whatever is left into the bloodstream.

But with ketones since the liver does not metabolize ketones it puts them immediately in the bloodstream when it’s burning fat for energy. Looking at it through an evolutionary lens, that function is to ensure that our brain gets adequate fuel flow. In the absence of food, if our brain tanked because we’re hypoglycemic, we wouldn’t be able to hunt.

So, being very lucid and having our brains energized during a period of food deprivation ensure that our species survived. The humans that weren’t able to do that did not get on and live. I think we’re sort of hardwired in a way to function optimally when we’re in a fasted state and that’s important to recognize.

Also, in the context of a society that’s programmed to give three high carbohydrate feedings per day. The metabolic program that is activated during fasting is largely silenced because of the societal norms, associated with our macronutrient profile, but also our eating pattern which is frequent feedings throughout the day.

(31:22)[Damien Blenkinsopp]: Yeah. One of the reasons I ask this is because I’ve had some fear and scared feedback about fasting for instance, which is a bit more of an extreme situation like ketogenic diet normally. One of the things I did was publish some of my own information on YouTube and I got some crazy comments from people saying I was going to die because my glucose was low.

I think it was 3.3 millimolar or something about 54-55 mg/dL. My mother’s a nurse and she saw the numbers and she was quite shocked at the time as well. Everyone thinks that we’re driven solely by glucose metabolism that’s the only thing they look at. So I think it’s really interesting that we have several various fuels that we can be going on, turns out that the glucose isn’t that important.

Someone else just sent me the numbers recently and they were the lowest I’d ever seen, like I was doing a fast and she got 1.8 millimolar with her glucose. I don’t know if you’ve seen anything that low.

[Dominic D’Agostino]: I did. Well, when I fasted for a week I tried some strategies, I probably shouldn’t talk about it here.

[Damien Blenkinsopp]: Okay. In case someone else does it.

[Dominic D’Agostino]: Yeah. After fasting a week, I was staying around the mid-fifties to low fifty’s and occasionally I would dip into the high forty’s depending on my activity and things like that. I did some strategies — I’ll label it as “strategies” — to lower it down to a level that the meter didn’t read, so it just actually was flashing low.

The lowest my meter was able to read was 25 or 26 mg/dL. I assume 25 that’s the limit. I spent a good part of the day with it flashing low and unable to read. I was using the Nova Max meter, and I was using the Precision Xtra Meter and also using the Neo Meter, so I had three different meters and I was scrambling.

[Damien Blenkinsopp]: Is that the Freestyle Optium Neo?

[Dominic D’Agostino]: Yeah. The freestyle like a lower profile sort of meter than the Precision Xtra. So I had three different meters, and I was measuring and I was like, “Oh no I don’t even know what my glucose is. All I know it’s probably under 1 millimolar range.”

I was starting to feel a little bit — using different pharmacological strategies to lower it — but I realized that I was at a level that was universally fatal for everyone if I didn’t have my ketones elevated.

[Damien Blenkinsopp]: Right. But if you had been admitted to the hospital, they’ll put you on the emergency ward most probably if you walked in like that.

[Dominic D’Agostino]: Yeah. During this particular day, I was preparing for a lecture, I was writing a grant it was really a productive day. As I was working I was doing these things and I would do measurements and work for a little bit more and it just goes to show it was a very dramatic demonstration an alternative energy source.

For me, that has tremendous implications therapeutically for someone that’s experiencing insulin shock or a neurological disease with impaired glucose metabolism. So we worked very closely with the glucose transporter type 1 deficiency association. It’s a rare disease where the brain does not have glucose available due to deficiency of the GLUT1 transporter.

There are many different diseases like that. I was also inspired by the work of George Cahill, there was a study that was published in 1967. The first author was Oliver Owen and they fasted subjects for 40 days.

In another report that wasn’t originally published with the original report. I found it in another book they administered insulin, 29 IU of insulin they gave IV. In these fasted subject they lowered the glucose down to 1-2 millimolar and kept it down there.

[Damien Blenkinsopp]: So it’s like 35 mg/dL somewhere around there?

[Dominic D’Agostino]: It’s not even that it was about that 25 range that my meter couldn’t read. So one millimolar would be 18 mg/dL. That inspired me, I was thinking if these subjects can fast for 40 days I could do a week.

It’s about five years ago or so that’s when I did the week long fast and did some experiments on myself. One of the most interesting things that happened to me was my breath hold time. So at the time I was outside a lot.

I was in and out of the pool, taking short walks and trying to stay active, keep my mind off of food. Because the main challenge was just the pleasure of eating was not there. I was swimming I was under the pool and I realized, “Wow,I had been down for quite a while”, and I wasn’t gasping for air.

I got back up to the surface and my girlfriend was there at the time, now my wife, and I started testing my breath hold time. I was like, “Keep an eye on me.” Normally I could do over a minute about 90 seconds, but I was able to stay down for three to four minutes which is remarkable.

I don’t have any kind of specialized training. I’ve been wanting to take a freediver course. I know Ben Greenfield did and we exchanged emails when he was going through that because he was trying exogenous ketones. But I found that after one week of fasting, I had a profound prolongation of my breath hold time. I think that’s fascinating to me.

Fasting does definitely start to shut down your metabolism. I think my body temperature probably went down a degree or two so the metabolic demands just weren’t there. But I think our drive to breath has a lot to do with our CO2 sensitivity.

So there’s receptors in the ventral respiratory group and the ventral surface of the medulla that sense CO2 levels and drive the urge to breathe. We also have the carotid bodies, at the bifurcation of the common carotid artery that sends oxygen and CO2 and they also mitigate or they also play a role in the drive to breath.

I think there’re interesting mechanisms going on there. A desensitization in some way or in combination to just altering our metabolic physiology. I think that has some practical benefits for different sports, maybe military operations.

I want to study that a little bit further with adaptations that happen during fasting.

[Damien Blenkinsopp]: Yes, very interesting. I’m wanting to go and test that out with freediving.

[Dominic D’Agostino]: A number of other people have, I think I might have mentioned it once or twice very briefly, not as descriptive in other podcasts but other people went out there and did it.

I think Tim Ferriss did it. I’m not sure if he’d blogged about it yet but he sent me quite a few texts and emails just saying that dramatically enhanced his breath hold time. So, I’m pretty sure it’s a real phenomenon.

(38:15) [Damien Blenkinsopp]: Very cool, to kind of round that conversation off. I get these emails, like I said, some people are scared because they get injured in fasting particularly a very low glucose levels of 30-35mg/dL.

Do you think that’s something to be concerned about or is it absolutely no problem? Typically, they have ketones like six millimolar, somewhere around there at that stage?

[Dominic D’Agostino]: I wouldn’t recommend that for a long term sustainment of life. Because there are a lot of biological processes that require glucose: red blood cells, your kidney, certain immune cells, and even biosynthetic processes like the generation of certain neurotransmitters are in some part glucose dependent. I think it’s good to get into that level and I’m going out on a limb by saying this to be a mainstream sort of medical college.

I actually think it’s very good to be in a state of nutritional ketosis with sustained hypoglycemia for a period of time, and to do that at least once a year, preferably a couple of times a year. I think what really kicks on a genetic program that activates so many biological processes that I think could be protective from enhanced insulin sensitivity to autophagy, to activating a number of different genes. There’s certain ones obviously, ampakine is activated, mTOR is suppressed.

You put tremendous metabolic stress on glycolytic cancer cells or pre-cancer cells that we may have in our body, sort of an immune activation. I know Dr. Adrienne Scheck is doing some work with the ketogenic diet and she’s doing some elegant work on the immune activation, and from the gist of it and from other bodies of literature it supports the idea that the immune system becomes hyper-vigilant, to recognizing and attacking existing cancer cells when we put our bodies into the state of fasting.

Either prolong fasting or even the ketogenic diet. I think it’s good to do that sometimes. But say if you’re on the ketogenic diet all the time in the state of moderate ketosis and then you fast.

You probably won’t get the same benefits as a person who’s on a high carb diet and did a fast. It would be a lot harder for that person who is on a high carb diet to do a fast. It would be greater stress because it’s that relative change or that pulse.

Thomas Seyfried and I we’re going to work on, it was originally his idea. We talked a lot about this press pulse phenomenon for the metabolic management of cancer. The press would just be a mild state of nutritional ketosis and the pulse could be periodic fasting or some of the things that we’re interested in. Such as hyperbaric oxygen therapy that could be pulsed exogenous ketones to further allow for a greater hypoglycemic response.

Also, you could pulse various cancer-specific metabolic drugs like 2-deoxyglucose, or dichloroacetate, or 3- Bromo Pyruvate] could be used. The press would just be nutritional ketosis and that would metabolically compromise a lot of the highly glycolytic, which corresponds to highly aggressive cancer cells.

(41:41)[Damien Blenkinsopp]: When you say press that would be like something chronic that you’re doing?

[Dominic D’Agostino]: Yeah. We know that being in a state of nutritional ketosis causes suppression of the hormone insulin. The cancer cells that light up on a fluorodeoxyglucose PET scan, a FDG-PET scan. The PET [or PET-CT] scan is really the gold standard technique.

I would say when it’s coupled with the CT scan allows you to precisely locate where that hypermetabolic activity is. So the PET-CT is an incredible, gold standard tool to assess the location and aggressiveness of existing cancer cells. The greater the standardized values that are coming out, like 2.5 would be sort of the normalized value.

If you have a PET scan showing SUVs of a 100 or 250, those cancer cells are very aggressive.

[Damien Blenkinsopp]: So they show up as the big red and yellow blotches?

[Dominic D’Agostino]: Yes.

(42:47)[Damien Blenkinsopp]: Yeah, we spoke to Gene Fine on a previous episode he was talking about the PET scan.

[Dominic D’Agostino]: Oh yeah. Actually Dr. Fine, you probably know he did a study for 28 days. He did a study with a ketogenic diet and he selected patients based on their PET scans. The topic that I was going to touch on is that insulin suppression correlates with ketosis.

I think even the title of his paper didn’t even mention the ketogenic diet, it was something like insulin inhibition therapy can be used to target cancer. It didn’t even talk about the ketogenic diet. But if you read the paper, he basically used the ketogenic diet to suppress the hormone insulin as a therapy for managing these hard to treat cancers or people who have failed the standard of care.

So, that would be the press that I’m talking about. The ketogenic diet limits glucose availability to the cancer cells. It suppresses the hormone insulin which drives IGF-1, mTOR and other factors that cause cancer cell growth and proliferation. I don’t know if Dr. Fine talked about it, but he has a number of publications.

I was inspired by his work and I actually got us to look at exogenous ketones and the effect on cancer cells. We find that if you limit glucose, suppress the hormone insulin and elevate ketones, the ketones themselves have anti-cancer effects. So, we did a study, we published in the International Journal of Cancer.

The first author was my graduate student at the time, Dr. Angela Poff, she’s now a research associate following up on this work. We gave ketones to highly aggressive cancer cells that have a glioblastoma-like origin. When we grew the cancer cells in the presence of ketones, even in the presence of 25 millimolar glucose, it inhibited, it dramatically slowed down cancer growth and proliferation.

(44:47) We did a viability testing where we looked at live cells and dead cells and the ratios of that. We found significantly more dead cells when we grew the cancer cells with ketones even in the presence of glucose. The take home was that ketones were probably turning down or shutting off a lot of some of the glycolytic mechanisms and there’s previous reports suggesting that ketone metabolism can turn down glycolytic metabolism.

So, that would be the press.

[Damien Blenkinsopp]: It sounds like a signal even for the cancer cells?

[Dominic D’Agostino]: Yes.

[Damien Blenkinsopp]: For them to switch them off even if they can’t use the ketones?

[Dominic D’Agostino]: Yeah, we think so. Now, we need to mechanistically dissect those kind of signals that are happening with the ketones because they do high-level sciences. Our lab approaches things a little different. We don’t sort of identify a target and then work up from that.

We screen a lot of things at the top and find out what works. Then, once we found out what actually causes animals to live longer or produce a neuroprotective effect then we go and try to find the mechanism.

(46:00) [Damien Blenkinsopp]: That sounds like a little bit like the pharmaceutical drug research process where they screen many many molecules for doing something. Correct me if I’m wrong. It seems like maybe it’s an efficient process to find things that work by just screening a lot of things and then focusing on the things that are working.

[Dominic D’Agostino]: Okay. So, it’s a little different, with pharmaceutical companies they actually target a mechanism or a biological kind of process and enzyme.

[Damien Blenkinsopp]: So they’re all looking for an end result right?

[Dominic D’Agostino]: Yeah. We’re testing a bunch of things, we don’t even know how they work. We’re testing various ketogenic exogenous ketone formulas and we don’t even have the pharmacokinetic nailed down yet. We don’t even know specifically how they’re metabolized.

We feel that it’s really important to get this research done so we can get these therapeutic agents out there as fast as possible. We screen a lot in various agents, first in human or first in animal, and then we identify what works. But the mechanisms, the metabolism is incredibly complex.

What we find is that it’s not working through one particular mechanism, it’s many different mechanisms working in synergy. The ketogenic diet, you have an increase in the GABA to glutamate ratio or ATP production you have a greater bioenergetic potential of the mitochondria. You have more TCA cycle intermediates.

The list goes on and on. There’s a science paper showing that ketones beta-hydroxybutyrate is a HDAC inhibitor. We published a nature medicine paper showing that inhibits the NLRP3 inflammasome and that’s independent of metabolism.

(47:41)[Damien Blenkinsopp]: So it’s like a huge dynamic system? There’s no way you can see all of the mechanisms going on there? As you’re saying you looked for the end effects and then you started looking for the mechanisms.

All of these mechanisms that you just brought up and started piecing them together to see how it worked after you’ve got the end result that you wanted.

[Dominic D’Agostino]: Yeah. The important thing is that it works and then the secondary important thing is to find out the mechanism. Because once you do know the mechanism, if the majority of the therapeutic effects or performance enhancing effects are due to a particular mechanism, out of many mechanisms. Then we can tweak the molecule of the formula, the pharmacokinetics, to further enhance that particular mechanism.

Then we can go back and tweak the formula, or the molecule to make it hydrolyze faster or to increase the sustainment of it, or deliver it in a certain nanoparticle formula to a particular tissue or something like that.

(48:37)[Damien Blenkinsopp]: So we’ve already spoken about quite a variety of basic applications, benefits of ketone based metabolism, and ketones. Could you just go through the top ones in your mind, maybe the ones that we haven’t already covered? So I know a lot of people are focused on weight loss for instance.

[Dominic D’Agostino]: That probably goes back to what they call the ‘Banting diet’. That even predates some of the work that I first got attracted to in epilepsy. So, epilepsy that would be the big thing.

The ketogenic diet, the only thing that is used for standard of care in mainstream medicine is the management of epilepsy. I always harp on this too, the ketogenic diet is grossly underutilized as a tool for managing epilepsy because it works when drugs fail.

It works in about two-thirds of the population. Imagine the efficacy of it if it was the first line of therapy. If you have a child that’s two or three years old and you load them up with anti-convulsant drugs, we know that these anticonvulsant drugs cause developmental delays. It’s even more important in pediatric epilepsy, I think to start with the ketogenic diet.

I just like to throw that out there. We’ve already talked about epilepsy. So, epilepsy would be the big one and obviously weight loss. You have the original Banting diet. Then Atkins came out with what he said was his famous diet but it was really a playoff with the Banting diet. It allows for effortless weight loss because when you’re in a state of nutritional ketosis the ketones function to control appetite.

It prevents your appetite from controlling you. We don’t really know the mechanisms that regulate appetite control, are incredibly complex. But we think that the ketones are essentially telling the brain it’s in a fed state, that’s the simplistic way to put it.

(50:32)[Damien Blenkinsopp]: Okay. Ketones get converted back into fat? Because people know that you basically pee ketones out when you first get onto a keto diet. Is that one of the mechanisms also?

[Dominic D’Agostino]: Well, yeah. If you collect all the urine of someone that’s on a ketogenic diet and then you look at how many calories are there, it’s pretty marginal. I think Atkins even advertised, “Look you’re peeing out fat, you’re peeing out calories.”

But it only came down to like 50 to a 100 calories or something like that. I think the big effect, the metabolic advantage really, is not that you’re burning more calories. I think there’re different organizations out there that we’re trying to prove if there’s a metabolic advantage to being in ketosis.

I think the big advantage that we need to focus on is appetite regulation. Our current diet of processed carbohydrates contributes to appetite dysregulation. The ketogenic diet is very effective at restoring sort of normal appetite behavior because there’s no fluctuations in blood glucose.

If we’re on a carbohydrate based diet and we go hypoglycemic that’s going to trigger an intense craving for carbohydrate re-feed to re-establish that glycemia. That’s completely abolished on the ketogenic diet.

So when you’re on a well formulated ketogenic diet, the craving that you’d have with hypoglycemia is going to be significantly attenuated if not abolished. We talked about weight loss and type 2 diabetes pretty much every disorder out there. Let’s think cancer, even kidney failure, neurological diseases like Alzheimer’s disease and many other pathologies are sort of linked pathophysiologically to the metabolic dysregulation and also obesity type 2 diabetes.

If a diet does promote a healthy weight loss and sustainment of that weight loss, it’s going to be therapeutic for many other disorders. Some of the things that we study include Alzheimer’s disease, ALS, we have a really active cancer research program in the lab. I have two Ph.D. students right now studying.

One is looking at Metformin and other cancer-specific metabolic drugs but combining it with a ketogenic diet. His main thing is to locate drugs. But we think some drugs will synergize with the ketogenic diet.

In another project is looking at the ketogenic diet or exogenous ketones and branch chain amino acids to mitigate cancer cachexia, which is muscle loss or wasting, so we’re looking at that. Exercise performance we’re looking at that. The most recent data that I’m really excited about because of the pretty robust effect as far as some of the behavioral models that we use.

One particular model is the elevated plus maze which looks at anxiety. We found that being in a state of nutritional ketosis that was induced completely with exogenous ketones stimulates in the elevated plus maze which is like a rodent going out on a catwalk. You can go into a cave or come out into an open area where you’re on a plank and you’re elevated in the air.

It’s a very anxiety producing situation. In our rodent models validate as a very useful model. We’ll spend much more time on the open arm and less more time hiding in the cave. We think that has significant implications for military personnel with PTSD and anxiety in general, and a lot of depression too is also sort of a comorbidity there with anxiety, a lot of depression, and anxiety fueled.

[Damien Blenkinsopp]: You’re saying that they’re willing to go out walk on the plank, take that risk and feel comfortable with it?

[Dominic D’Agostino]: Yeah.

(54:28)[Damien Blenkinsopp]: Do you measure it by time spent on the plank?

[Dominic D’Agostino]: Yeah. Less anti-social behavior I guess. We set up this elevated plus maze and then we have a whole video imaging system above it. We keep the animals as low stress as possible.

We have the same person working with the animals so they’re not experiencing different smells, and things like that. The room is very very quiet. We pay attention to circadian, light on light off things.

There’s a lot of variables that need to be controlled and then we image them in the absence of ketones. We see how much time they’re like in the middle, in the open arm, closed arm and our video camera system sort of can track all that. We have various programs and algorithms that do all the calculations for various things.

We do a bunch of animals just on a standard high carb diet. Then what we’ve been doing is testing various ketogenic agents, or various exogenous ketone and ketone formulas that would be administered 30 minutes prior to being put in this elevated plus maze, and being there for a couple of hours. Then we’ll track all that information, it’s all done blinded.

We have one person who’s, usually two people part of the project that’s administering the agent. The person that does the analysis does not know what the animal is receiving. We’ve got a pretty robust effect with a few of the ketogenic agents on reducing this anxiety behavior.

That’s some new data that we just presented literally less than a week ago in Budapest. That’s what I’m just returning back now. So we want to follow up on that. We used one dose, we need to determine what would be the optimal dose.

There’s a lot of work that we still need to do to optimize that and maybe think about putting together a formula that could be beneficial for people.

(56:30)[Damien Blenkinsopp]: Very cool. One of the ones you didn’t mentioned is Parkinson’s, is that something?

[Dominic D’Agostino]: Yeah. There’s an earlier study I think that was done by Dr. Theodore B. VanItallie. Dr. VanItallie is like 96 years old. We still communicate on the phone and through Email.

He was one of the original ketogenic diet researchers. He did a small sort of pilot study showing that people with Parkinson’s disease can follow a ketogenic diet and that being in a state of nutritional ketosis reduced the tremors associated with Parkinson’s disease and prevented some of the symptoms. Not a cure, but it could help manage some of the symptoms associated with Parkinson’s disease.

There really hasn’t been a good follow-up study to that. I know there was a ketone ester that was developed at NIH and a study at Oxford. There was that group that had a clinical trial open. But I think they might have had some problems recruiting people into that clinical trial, that opened a few years ago.

I know there was a clinical trial looking at the effects of exogenous ketones on Parkinson’s disease. And if we weren’t tied up with so many other projects I would be jumping on that. Because I was able to observe on Alzheimer’s patients when they took a medium chain triglyceride supplement, or even exogenous ketones. They would have pretty dramatic tremors.

And some Parkinson’s disease-like symptoms can be manifested in people with Alzheimer’s, especially advanced Alzheimer’s. I was able to observe and also got feedback from caretakers that when they induced a state of nutritional ketosis it really rapidly stops the tremors associated with that. So, that needs to be followed up on.

The pharmaceutical industry dictates a lot of what studies are done. Because you need a strong financial backing on top of a university, or chain of universities that supports this kind of research. On top of a review board, an IRB, that will prove this kind of research using these nutritional metabolic substances. There are many hurdles that need to happen.

Then you have to recruit patients on top of that and convince them that it’s not a drug but it’s a nasty tasting food that could potentially benefit you. They were like — well, it’s easier for a child, a son or a daughter [who] is bringing in their mom who is typically in a situation — 80 or 90 years old.

They’re not going to want to try to formulate some nasty tasting shake to do that. It’s much easier to just give them a pill. These are some of the things you see, the feedback that you get from people who are trying to implement these kinds of nutritional protocols in patients.

There’s a lot of hurdles. A lot of people ask me, “Well, if it’s so effective, how come science is not using the ketogenic diet or exogenous ketones to treat all these disorders?” I could write a book on the reasons why, but nutritional research is so hard to do.

Because nutrition is really tied into the lifestyle thing, and getting institutional support, getting the expertise needed, ensuring that patients are following through and complying with the protocol. All of these things are hard to do. A supplement, in theory, is a lot easier but we’re at the very initial stages. Because these are just new entities that just developed.

(1:00:16)[Damien Blenkinsopp]: Right, it’s only two and a half years you’ve had the ketone salts for instance, and the esters a bit longer?

[Dominic D’Agostino]: A little bit more than that. I would say the ketone ester was actually developed probably about 20 years ago, if you look into the animal literature. Then they were dropped because it was thought that they’re very expensive to produce and they taste like jet fuel.

Some of the people that originally developed these things, like Henri Brunengraber. He’s like a hardcore metabolic physiologist-scientist who develops a lot of remarkable things. But he kind of drops it and moves on to the next thing.

There’s also sharing the chair of his department and running a billion other things at the same time. So, I dug up some of this research and realized, “Wow, why didn’t anyone follow up on this?” Then I saw some of the work that was funded by DARPA, showing that they were the secret project.

They were using these ketone esters for warfighter performance enhancement. I found some patents and some files on that. I was like, “Well, this is what I need to explore, for use of CNS oxygen toxicity.”

Not only can the ketones potentially mitigate the oxygen seizures but the ketogenic diet was super effective. Even independent of the ideology of the seizures that it tends to work which is really remarkable. But instead of giving an anti-convulsant drug to a warfighter, which can dull your senses and impair your physical and cognitive performance.

You could be giving an anti-convulsant neuroprotective substance that enhances the physical and cognitive performance. It seemed like a win-win situation. I’d rapidly grasped this idea and just went into this manic state of writing grants and writing proposals, and digging up all the research.

Then, I was calling my program officer and I was like, “You need to hear this information and what I’m going to tell you.” We actually had a little meeting at our university and he was like, “We have to do this.” He was very generous to fund some of the initial basic science proof of concept research that demonstrated the efficacy of this ketone ester in mitigating oxygen toxicity.

It worked better than anything we had ever tested or anybody had ever tested, even drug wise. That’s going back in 2009 or 2010. From there, I’m really in safety because I’m really scared about bringing something to market that could potentially harm someone. I know there has been some discussion out there about the quote and quote dangers of a racemic beta-hydroxybutyrate salt.

People need to recognize the difference between someone’s opinion and scientific fact. The scientific fact is that racemic beta-hydroxybutyrate salts have been used for decades for treating a disorder called MAD, Multiple acyl-CoA dehydrogenase deficiency. I get Emails from the patients or from the parents that are treating their kids with this, and it’s like a miracle for them.

I also get Emails from parents that are treating their kids with glucose transporter type 1 deficiency syndrome with a racemic beta-hydroxybutyrate (sodium beta-hydroxybutyrate), which is actually a prescription you can get in Europe.

But they’re also using these commercially available ketone salt products which would be the ones that you might be familiar with. There’s KetoCana from KetoSports, Pruvit makes Keto OS, Forever Green makes Ketopia. The Kegenix product which is the one I’m testing now. It’s a really excellent exogenous ketone product.

This idea which was talked about in various podcasts, I think in Bulletproof podcasts and Ben Greenfield’s that racemic sodium beta-hydroxybutyrate was dangerous and ineffective. It is an opinion and there’s no science to back it up.

If you go back and listen to the podcast you’ll hear the speaker actually reference no actual studies. So, it has an intellectual property supporting the non-racemic, so that needs to be acknowledged and appreciated.

What is appreciated from my end, the science backing up the efficacy and the safety are really profound – like I’ve said on expert panels to approve some of these molecules. And no toxicologist or physiologist could find any evidence that racemic, which is the DL version of beta-hydroxybutyrate, was dangerous in any way.

For example, if you’re a medical doctor or a combat doctor on the field and you’re treating soldiers that have a loss of blood or you’re in the emergency room just talking to the ER doctors, use the Ringer’s Lactate and that’s Racemic lactate.

So, L-lactate would be the natural lactate that you would find in your body. The DL would be in an enantiomer or a mirror image of that lactate. Both of the lactate molecules get metabolized to energy. So, the same things happen with ketones. So the D and the L version get metabolized to ATP, to energy.

A lot of the metabolism has been worked out with very elegant tracer based fate association studies by Dr. Brunengraber at Case Western. Lactate Ringer’s has been used in millions of combat troops and emergency rooms. If there was a danger to using a racemic metabolate, there would be a lot of dead bodies around – and that has not been the case.

Actually, it’s FDA approved, it’s widely used and accepted, and it was even studied the difference between L-lactate and Racemic lactate before it became a standard of care. Actually, it was looked into, and it had exact same effect.

So, if you use the Racemic versus the L-lactate have the same effect at preserving the metabolic activity of the tissues and being protective in that way. So, that needs to be acknowledged that when statements are made, that they could be an opinion and not validated by scientific facts.

The ketone supplements that are on the market now that I’m aware of are very safe and from feedback, they’re very effective. I don’t support any particular ketone supplement that’s out there. I’ve tested all of them and they tend to elevate my beta-hydroxybutyrate and the .5 – 1 millimolar range for one dose.

So, for me to really boost my ketone levels up, I have to take a packet and a half, or a dose and a half, which I can tolerate pretty well. But I think there’s a lot of room for improvement and the products that are out there.

I hope to work with these companies, hoping that they will fund research to support the further development and evolution of these products for different applications.

(1:07:30)[Damien Blenkinsopp]: Excellent. Thanks for going through that because that’s something I have my eye on as well and wanting to get some more facts. Something else that was thrown out, a couple of things was that the racemics were less efficient or were ineffective?

We also have all of the MCTs which people are using to kick up their ketones as well. We have the C8 and C10 of the MCTs, there’re various products around. Another statement that was said they were undesirable and you should avoid those as well unless you really had to take them.

For instance, if you have Parkinson’s it was okay to take them but otherwise you shouldn’t be really taking them. But a lot of people are taking these. Right now, there’s a bulletproof brain octane. I’m sure a lot of people are taking that.

KetoSports has got their own product that I’ve been taking for a long time personally. I don’t know if you have got any comments on that?

[Dominic D’Agostino]: Yeah. I study a lot of very expensive exogenous ketone products. But the more I look into medium change triglycerides, especially the C8 oil which is digested and assimilated much differently than long-chain fatty acids. When you consume it, it basically perfuses the liver.

I mean it goes right to the liver via hepatic portal circulation. It goes right through to liver and is burned as energy. So, they’re poorly astrophied, which means they’re not re-astrophied back and packaged into chylomicrons, like long-chain fatty acids.

Once they reach the liver, it’s basically an obligate oxidation. The medium chains are almost completely oxidized to ketone bodies. Some of them will spill into the bloodstream because we find them in the brain tissue and other tissues.

But it’s independent of the various transporters too. For the medium chain triglycerides to get into the mitochondria there’s various CPT-1, for example, is not needed to get the MCT into the mitochondria. So, they bypass a lot of these rate limiting steps.

And you consume them, it goes right to the liver, you generate a lot of beta-hydroxybutyrate and some of that gets into the bloodstream. So you have the combination of ketones and the medium chain triglycerides going right to the mitochondria. And that can be very therapeutic and beneficial for many different disorders.

You have to realize that the person making that statement that MCTs are dangerous or ineffective, has some underlying personal interests in advancing the commercialization of his particular exogenous ketone, and that needs to be appreciated and understood.

From our perspective, we’re interested in testing that particular ketone formulation and 20 other, and finding out the truth, finding out which is most effective, which is safe. When it comes to the racemic, and the statement that racemic beta-hydroxybutyrate is not as effective. We have not found that out to be the case.

Actually, the first ketone ester that we studied for oxygen toxicity was a monoester of the R-beta-hydroxybutyrate we have formulated. And that did not prevent CNS oxygen toxicity, which actually was very strange to me. But the more research I did I found out that you needed to elevate both the acetoacetate and beta-hydroxybutyrate in the blood to mimic some of what happens naturally, physiologically.

The acetoacetate through spontaneous decarboxylation to acetone, or maybe it has it’s own metabolic effect independently. The elevation of acetoacetate was absolutely critical. It also in the presence of beta-hydroxybutyrate but it was absolutely critical to elevating both ketone bodies to get the anti-convulsing effect.

We published that in the American Journal of Physiology and showed the pharmacokinetics and seizure work with that. So, we screened a lot of agents and found out the particular ketone ester that we found to be most effective was 1,3-Buntanediol acetoacetate diester]. So it was 1,3-Buntanediol that was racemic, so it would make racemic beta-hydroxybutyrate.

But even the non-physiological enantiomer gets broken down and converted to Acetyl-CoA and some of that goes back to the physiological enantiomer so it all gets broken down and metabolized similarly to Ringer’s Lactate which is used in millions of patients.

But the important thing about that particular molecule is that when it’s consumed orally it gets hydrolyzed and it rapidly liberates the acetoacetate. Then the 1,3-Buntanediol gets metabolized in the liver and elevates beta-hydroxybutyrate. So you have both ketone bodies elevated in the blood. We find that it’s absolutely critical to get a certain level of acetoacetate to get the anticonvulsant effect.

(1:12:30) One thing I didn’t talk about was Angelman Syndrome, which is characterized by impairment of motor function and also drug resistant seizures. It’s extremely effective in an animal model of Angelman Syndrome.

If you look at Angelman Syndrome and the ketogenic diet, you come across case reports showing that it basically puts Angelman syndrome patients into remission, at least for seizures. So, it’s highly efficient for that.

So, the first ketone ester we studied was this R in the enantiomer, the hydroxybutyrate, and it was not effective. So it was actually the racemic version of a ketone ester that was most efficacious.

But we’re interested in exploring all different pathologies and finding out which one. So, we have not found out that the R and enantiomer is any more efficacious for any other disorder than the racemic. I think that’s important to acknowledge.

We also found that medium chain triglycerides tend to formulate really well with this exogenous ketones. Not only are they carriers but we think they enhance the transport across membranes and they improve the pharmacokinetic profile, two of many of the ketones salts. So when it’s formulated with MCTs which have the nice advantage of also being ketogenic.

One of the benefits of racemic, the other enantiomer, so there’s D and L. The L-enantiomer tends to impact the liver in a way that reduces hepatic gluconeogenesis. So, you have this hypoglycemic effect that is very well characterized by our laboratory and other peoples laboratory.

[Damien Blenkinsopp]: So you’re saying that ketones go up and the glucose goes down?

[Dominic D’Agostino]: Yeah. It’s more pronounced with the racemic and we don’t know why that is.

(1:14:22)[Damien Blenkinsopp]: Is that beneficial to some of the applications more than others? Weight loss for example?

[Dominic D’Agostino]: Yeah for weight loss, maybe for seizures too. We know that reducing glycolytic metabolism can be beneficial for seizures but also for cancer. As I mentioned, we have pre-active cancer research program.

The lower we can get glucose or glucose response to a meal, the lower we can reduce that, the better therapeutic efficacy we think the agent will have. If we formulate the agent with food, so every time our animal models will eat the food they’re getting a dose of it.

Instead of injecting into the animal or ‘gavaging’ it in the mouth for our cancer studies, we actually take these ketogenic agents and formulate it to about 10 to 20 percent of the weight of the food. Then we count the macronutrient ratio, and then they eat it.

Every time they’re eating the food they’re getting a dose of ketones with the glucose. Because we do a lot of our studies formulating with a high carb diet. Because we want to find out the therapeutic effects of the particular agent and distinguish that between the ketogenic diet.

But we also published a study, about a year ago, where we formulated the ketogenic diet with the ketogenic agent. We did this with a ketone ester and found that it further enhanced the anti-cancer effect of ketogenic diet.

(1:15:48)[Damien Blenkinsopp]: Okay. I’ve got a few questions about this. There’s some MCT powders on the market which combine glucose. Me coming from a ketogenic perspective, that’s not something I want to take with the MCT powder. There’re other powders which don’t have the glucose.

Is there anything to think about or is it not really an issue? Because there’s this effect of the ketones pushing down the glucose anyway? Would it have zero effect? I haven’t tested it myself yet.

[Dominic D’Agostino]: Yeah, the MCT powders on the market like Quest Nutrition?

[Damien Blenkinsopp]: Not Quest, they don’t. It’s basically the generic ones. There’s this cheaper one, generic one, where they’ll put glucose syrup in it and some other glycemic ingredients.

[Dominic D’Agostino]: Yeah, with my interest in the ketogenic diet and staying in ketosis, I would rather get my carbohydrates from things like vegetables, salads, blueberries and dark chocolate. Basically encompasses my carb intake there. So I would avoid that.

A staple product that I use, I have it right by me right now is the Quest MCT oil powder. I did a little bit of beta testing for them as they brought that to market. We went back and forth, and I tested that a lot.

I consumed a lot of that and I did tons of the blood work and got to the point where I was really impressed with the product. There’s not too many products that I consider staple products, maybe about a half a dozen in total that I keep with me all the time.

That MCT oil powder is great, it’s very versatile. You could use it in baking, you could put in my coffee, you can add it to protein shakes to further boost the ketogenic profile of your shakes.

[Damien Blenkinsopp]: Do you take that with you? I take this stuff as well, I’ve got it right next to me as well in my coffee [unclear (1:17:32)]. What I was going to say is that you take that on top of your ketogenic diet?

But I think an interesting thing, I talk to people and they’re taking the exogenous ketones or the MCT powder as a normal diet, or the body builder’s diet where it’s high protein, and they’re not doing a keto diet.

Then there are other people who are interested in getting keto but finding it difficult. They’re using it to ease into the keto diet. So there’re a couple of different applications people use them for different things. I’m just wondering what you’re ideas are in those scenarios.

Dominic D’Agostino]: Yeah. If I put the Quest MCT oil into my coffee or shakes or things like that. I generally try to avoid liquid meals, because liquid meals digest totally different. The only liquid meal that I have would be my coffee, and I would put in some coconut oil and MCT on top of that.

Occasionally, I put in butter or coconut cream. I’ve been using coconut cream instead of full cream. The benefit is that I can elevate my protein a little bit more. I generally eat two meals a day now that I’m home and not traveling.

My meal in the evening is about twice the calorie count. So, I get about a third of my food calories in the morning and about two-thirds in the evening, but I get a lot of fat calories during the day I guess. Because I’ll make my coffee and whip it up and then bring it in a thermos, and drink that mostly in the morning. Then I’ll have a little kicker in the afternoon maybe.

That fat balm, I guess if you want to call it that and occasionally take some exogenous ketones too during the day, if I’m testing different products. It just adds to my total fat macronutrient ratio.

I probably get — with the coconut cream, the butter, and the MCT oil powder — probably get about an extra 100 grams of fat from that. So that allows me to eat a little less fat with my meal in the evening, and that makes it maybe a little bit more palatable because I could add some more protein.

On a typical schedule, I will do my physical activity in the evening. Then I’d like to couple that with a little bit higher protein intake.

(1:19:51)[Damien Blenkinsopp]: Right. So using the exogenous ketones or the MCTs to offset gluconeogenesis? Is that the idea?

[Dominic D’Agostino]: Yeah. This morning I had three or four eggs cooked in coconut oil. I usually have sardines, oysters, chicken, or steak from the night before. Then I’ll have a little bit of green vegetables cooked in fat, and that will be my breakfast.

It will be roughly under a thousand calories, somewhere around 800 – 1000. Then, I’ll get 1,500 – 2000 calories in the evening. During the day, I might even get an extra 500 – 1,000 just of fat or ketones.

I stay semi- fasted, so if I eat 6am or 7am I feel the best when my ketones get highest between like 3pm and 6 or 7pm.

(1:20:53)[Damien Blenkinsopp]: Okay what levels of ketones would you have then?

[Dominic D’Agostino]: I say high but it’s not really that high. In the morning when I wake up it’s maybe 1.0, sometimes .5 if I ate more blueberries or chocolate the night before. Right now, approaching noon, it would start to creep up about 1.5.

Then towards the end of my work day, I’m usually approaching about a 2.0 – 2.5 or somewhere around there. If I’m lucky I budget my time where I can go to the gym so I will be typically be working out. Then if I go home I’ll do some stuff, take my dog for a walk, do some sprints, and that’s when I feel most energetic – when I’m fasted, and in ketosis.

(1:21:40)[Damien Blenkinsopp]: Right, and you’re saying your blood ketones would be 2.5 or something like that and you’d feel that’s when you’re most energetic? Or you feel your best at that time?

[Dominic D’Agostino]: Yeah. I try to subjectively do this too. Basically, I would carry my meter, and I would be like, “When do I feel most energetic, and lucid?”. Then, I would measure my glucose and ketones at that point.

And I find that basically if my glucose is about 3.5 millimolar and my ketones are about 1.5 to 2.0 is when I personally feel the best, as far as energetic. So that would be a glucose-ketone index if we use the Thomas Seyfried’s calculation, of about 2.0. When you’re approaching 1.0, you’re starting to get into that therapeutic range.

But I think for all intensive purposes, for the normal person, if you keep between 2.0-4.0. It would be very abnormal for someone in a normal society to even approach that. If you’re hitting that then you’re doing really well.

You’re in an altered metabolic state. If you can sustain that, I think you’re going to get a lot of therapeutic and performance benefits from that.

[Damien Blenkinsopp]: So 2.0 – 4.0 in the GKI — glucose-ketone index — from Thomas Seyfried?

[Dominic D’Agostino]: Yeah.

(1:22:58)[Damien Blenkinsopp]: Which we covered in his episode in the past. Yeah, the only time I’ve got below 1.0 is when I’d be fasting. I’ve tracked full days as well, every half an hour I’ve tracked, it looks pretty similar to yours.

I’ve heard you say before that over 5.0 millimolar, in terms of ketones has some metabolic downsides. So, I was wondering about the ranges. Are there ranges that people shoot for between this 2.0 – 4.0 basically? You don’t really want to be lower?

Right? Say on the GKI, you don’t want to be going down to 1.0 unless you’re fasting or doing some pulse?

[Dominic D’Agostino]: Yeah, unless you’re really in a total fasted calorie restricted, deprived state, I think between 5.0 and 6.0. I think there was a report in a 60 day fast up to 8.0 millimolar. So that it may be beneficial there for just maintaining that energetic flow to the brain.

But if you’re on an isocaloric diet not calorie restricted. I think staying between 1.0 – 2.0 is probably good. If you’re mildly calorie restricted or maybe towards the end of an intermittent fasting, the fasting portion of an intermittent fasting day, approaching 3.0 may be optimal.

I based this upon thousands of blood measurements that I’ve taken and literally hundreds of blood measurements from other people. Between 1.0 – 3.0 millimolar I think is good. We’ve even seen it in animals, once you dose them up to about over 5.0 they start hyperventilating.

You create a mild metabolic acidosis that needs to be compensated for, so that you get the hyperventilation, they start getting even drunk and sedated, when you really start getting up there and has signs of ketoacidosis. In cases where they’re sedentary, that could be the reason. If you’re approaching 5.0 or 6.0 millimolar and you’re in an all-out sprint, you’re using that.

So maybe in the case of an athlete approaching the higher numbers could be beneficial if you train for that. But say you’re not trained for that and you dose up really high. Your body perceives it as a foreign acidic-metabolic substrate that has to neutralize, your bicarbonate compensates, and you have respiratory-renal compensation that needs to compensate for that.

I just had this discussion in metabolism and physiology with some people that I really respect. They were making the argument that anything above 4.0 or 5.0 is really going to be toxic to the body. I didn’t argue against that but we agreed upon — and there’s some pretty sharp minds in the room — anywhere between 1.0 – 3.0 was probably optimal.

As you know staying in 2.0 – 3.0 range is really hard to do with diet. But staying in a 1.0 range is pretty easy to do with a diet. I do a modified Atkins or modified ketogenic diet, and that’s pretty easy.

Then if I add a little bit of exogenous ketones or some C8 on top of that. I can easily boost that up to 2.0 – 2.5. I think that would give me a metabolic, performance, and cognitive advantage. I’m pretty sure about that.

So, that’s what’s exciting to me. So, not using exogenous ketones in the place of a low carb diet — but you might be able to do that too — I’m actually thinking about doing some experiment of getting off of my ketogenic diet for a period of time.

Not going super high carb but just being out of a state of nutritional ketosis and then adding supplements back in and then doing some blood work and see what happens there. I just haven’t got around to doing it because I enjoy eating ketogenic so much.

[Damien Blenkinsopp]: Right. Once you get into it for a while it’s like you don’t have to eat very often.

[Dominic D’Agostino]: It’s almost like I dread doing it.

(1:26:51)[Damien Blenkinsopp]: I was testing some of the supplements, the different supplements. I don’t think I didn’t do it very well. But what I was doing I was eating in the evening basically a high-carb meal lots of rice to put myself out of ketosis.

I did this for about a week and then tested different supplements in the morning. For the first reason, I don’t think it was a great control because I am basically keto-adapted now. I tend to pop straight back into ketosis relatively quickly.

I’d like your feedback on that whether it’s a decent control. Maybe I’m no good as a control because I’ve been just keto-adapted for a while and also may be I’d have to go for a few days ‘carbing’ it to make it a bit more realistic. What are your thoughts on that?

If you’re trying to do some normal, the first thing is, going back to your point about exogenous ketones. You’re saying like if someone just takes it straight off as some people are doing right now. They’ve been on a carb diet the whole time.

Then they can’t necessarily utilize those because they’re not keto or fat adapted. How long does that take? Should we be taking a lot of these when they haven’t really had that much exposure?

Do they have to take them over a period of a week or longer in order to start getting more benefits from taking them?

[Dominic D’Agostino]: Yeah, that’s a good question. Interestingly, we can use exogenous ketones even if we’re not keto-adapted at all, and that was our first study that we did for CNS oxygen toxicity. It was actually rats eating a standard rodent chow which is 60-70 percent carbohydrates.

We gave a single dose not even feeding it chronically, 30 minutes prior to doing a deep oxygen dive. It worked remarkably well and that really surprised me. So, taking a little bit of a step back, we use the R-enantiomer of the beta-hydroxybutyrate, and it didn’t work.

But then when we found out the ester that did work, that particular compound worked remarkably well. That kind of changed my thinking because I approached it with the understanding or the bias that you really need to be keto-adapted. But if you are adapted to burning fat and ketones for fuel, what has been shown is that you do up-regulate the transporters and the enzymes associated with ketone metabolism.

So, you will theoretically be deriving more benefit from exogenous ketones if you have been previously adapted to a ketogenic diet. I think from a practical standpoint, say you’re on a ketogenic diet and you choose to transition to eating carbs for some reason and then you throw ketones back in. Since you’re adapted to a ketogenic diet already, I think you’ll use those ketones more efficiently even by following a carbohydrate based diet.

We have some evidence to indicate that glucose disposal is enhanced in the presence of ketones. So, it may actually be enhancing insulin sensitivity. The glucose goes does, if you have animals eating a high carb diet and you bolus exogenous ketones, the glucose goes down remarkably low. Much more than you even get with something like Metformin.

What we don’t know why that’s happening, we want to look at the liver metabolimic profile. I think it could be influencing the liver in some way, and may be decreasing hepatic glucose output. Really it’s your liver that dictates your blood glucose, it’s all happening in the liver.

So, if you turn down gluconeogenesis in the liver, you would see a decrease in blood glucose. But also if you’re enhancing insulin sensitivity you would be facilitating glucose disposal and peripheral tissues with ketones. I know Dr. Richard Veech at the NIH has written about that and suggested that ketones actually do enhance glucose uptake and insulin sensitivity.

I get the question, what if you throw ketones on top of carbohydrates? What are the cells going to use? I think the cells will use what’s available to them and we know that the brain might not be able to use the certain types of fatty acids but they can use MCTs.

If you have glucose and ketones in the blood, your cells, your muscle cells, brain cells will be using both fuels. There’s some evidence that suggests that it will be using the glucose more efficiently in the presence of ketones. Because we know ketones can lower reactive oxygen species.

Excess ROS production can decrease insulin sensitivity and cause protein nucleic and lipid peroxidation that can inhibit glucose transporter processes. Even translocation of glucose transporters to the membrane or even PDH complex could be sensitive to the Redox state of the cell.

Ketones tend to normalize or prevent an oxidative environment that could potentially impair glucose transport and insulin sensitivity.

(1:31:56)[Damien Blenkinsopp]: There’s such a wealth of information in this area. It’s not like ketones are a panacea, but there’s just so many applications we’ve spoken about today, so I could go on talking to you for absolute forever. I’m conscious of your time also.

I wanted to round off of a bit of what you do more in terms of optimizing yourself and what you think is effective. For instance, in terms of blood ketones, you said you’re tracking your blood ketones. Have you used the other methods, the urine or the breath method?

The strips for the blood can be a little bit inaccessible in the UK, in the US sometimes, and also they are really expensive. The price varies. I’m sure you have your own ways of getting them but for everyone else it can be a little bit difficult, particularly in the UK I’ve found.

What do you think of the breath? There’s the Ketonix looking at the acetone instead. Do you think that correlates with the blood ketones, and it’s an okay way to try and optimize or not?

[Dominic D’Agostino]: Yeah, it’s a good question. I get this frequently. What I would say the breath, if you’re measuring moderate to high on a breath acetone meter you’re definitely in ketosis. I like it, and I wish it was more quantitative because I’m a numbers guy.

I think we’re all sort of what’s your number? There was like a ketone competition in the lab and my friends like, “You know what’s your ketones today?”. So we like numbers and I wish the unit could be designed.

I believe [unclear (1:33:20)] who’s working on a quantified meter. I like it, and I think it’s great for kids that are trying to manage their epilepsy because breath acetone has correlated with seizure control. So if you give this to a kid and he blows in it and he sees colors and he gets excited, I think that’s great.

It’s giving you a relative level but it’s not a precise level. But it’s also a snapshot of your level of ketosis over the last couple of hours. So your blood, beta-hydroxybutyrate can change.

I’m standing here in front of my desk and talking to you and relatively sedentary. But if I was to go and take a brisk walk on the other side of campus which I do occasionally to get things signed. I’ll come back and measure my ketones, and it’ll be cut in half.

It’ll go from two to one, or below one, just from brisk walk where it should be increased right? Because I should be mobilizing fat, I’m burning fat. But I’ve burnt those ketones for fuel during my movement.

(1:34:25)[Damien Blenkinsopp]: So then it goes into glycogen? I’ve seen this before and I didn’t understand it, that’s why I’m pretty curious.

[Dominic D’Agostino]: Well, it’s burned as fuel. Ketones are substrates, so they’re going to be burned up as fuel. And yes, you may mobilize glycogen from the liver so your glucose can actually go up. You might have some lactic acid from your muscles and through the Cori cycle goes back to the liver and you get some glucose in the blood.

The stress, the sympathetic nervous system from moving and running across traffic and navigating or whatever you do when you walk, that can contribute. What I really found that’s most important is you need to be completely calm and sedentary when you make these measurements to get accurate measurements to prevent the variability.

We have this issue with our rodent studies, we need to pull the food from them for about four to eight hours, to normalize the blood glucose. Because you have some that are nibbling on food, some that have gorged, others haven’t eaten. So the glucose is going to be all over.

To standardize and normalize glucose, you need to remove their food for a little bit and the numbers are tighter. The same thing applies for measuring ketones, especially blood ketones, you need to be fairly sedentary to do it. I really like the urine ketone strips, got a bad wrap, but I like the urine ketone strips.

They’re still used by John’s Hopkins. So, before you go spending a lot of money on getting ketone strips for the meter. You want to first confirm that you’re actually in ketosis on a urine strip.

If you’re registering 15 or 40 mg/dL on a ketone strip then it’s like, “Okay, at least if I take a blood measurement now. I’m going to register something on my blood meter and it’s going to be ‘I’m in ketosis’.” I remember the other meter, I think it’s the Novamax meter, would just give you this annoying, ‘low’, it won’t even read your number on it.

One person went out and bought a couple hundred hours worth of strips and have like 17 lows on there, and have come to find out you’re just eating too much protein or they think it’s okay to drink fruit juice. I forgot what the situation was.

Well first change your diet, then go out and get some urine ketone strips. Once you’re actually in ketosis on the urine strip then go back to the blood meter. And come to find that they tweaked their diet a little bit.

They did it until they were measuring ketones on the urine strip and they went to the blood meter, and bang they get 1.2 and they get all excited. So they could’ve saved a lot of money.

(1:37:04)[Damien Blenkinsopp]: Right. Because the urine gets a bad wrap, because it stops working once you get more keto-adapted. But when you’re first on a ketogenic diet and you’re trying to check that, that’s not going to happen. Right?

[Dominic D’Agostino]: Hydration state too, also plays a role, and less ketones will spill into the urine over time because you’ll conserve them as fuel. The transporters change a little bit. But if your hydration — if you’re drinking lots of water those people who carry water around with them and drinking.

Your urine ketones may register pretty low. Sometimes I wake up dehydrated and I would check my urine ketones will be quite high, whereas my blood ketones would be quite low. So, that’s just an indication of my hydration status.

It’s also a snapshot of what your ketones were over the last four, five, six hours because that urine is collecting in your bladder over time. So it’s sort of a snapshot of what’s happening through the course of the day, whereas your blood ketone is a snapshot of your ketone level at that point in time.

(1:38:04)[Damien Blenkinsopp]: Right, just a bit of information more about you and what you do these days? In terms of tracking things, it seems like you’ve tracked a lot yourself. Are there things that have stood out for you?

Overall, the time that you’ve tracked yourself and you found really useful insights from? Any quants or anything you’ve changed something you do in your life because of that?

[Dominic D’Agostino]: Yeah, I think initially when I started doing the ketogenic diet it was very dairy based. I was taking lots of creams, a stick or two. Two sticks of butter a day. So, I had a really high intake of dairy fat, probably about 200 plus grams of fat per day of dairy.

My LDL went up pretty high and my triglycerides went down a little bit but not really low. Then, I started replacing some of the dairy fat or the whole cream with coconut cream, and just using a little more coconut oil, getting more avocado in from my fats.

I still get dairy fat, by a sour cream that has live cultures in it. I’ll probably get about 50 to 70 grams of fat per day from dairy instead of like 250 grams of fat which I was getting initially. My lab test has improved. I guess you would say, I think my insulin sensitivity is better.

My glucose I can get lower glucose numbers now after eliminating some dairy. My triglycerides are really low now, they stay at 40s to 50s, I think it was 36 at one time. My HDL has improved and better and it’s really high, like 90 something.

My LDL went from really high to normal, but normal high. Now, which I think is completely normal and actually maybe even optimal. My IGF-1 levels are really low now compared to when I was on dairy.

I think dairy may have been contributing a little bit to some insulin resistance or maybe I was just getting a surplus amount of calories. My CRP levels also are the lowest now than they’ve ever been. I mean it’s like 0.1 or 0.2.

[Damien Blenkinsopp]: Right. Basically nothing, that’s the bottom of the range.

[Dominic D’Agostino]: Yeah, it’s like totally bombed out. I just feel better. If I eat a lot of dairy, I do wake up a little bit slightly congested, stuffy in my nose but it’s not bad.

I wouldn’t call it an allergies, and it could be due to allergies. But eliminating that has sort of helped, not eliminating, but reducing the amount of dairy. I don’t get in a whole lot of dairy protein. Maybe a slice of cheese here and there but I limit that. I limit casein. I don’t take away protein anymore.

The dairy that I get is primarily dairy fat. I was actually thinking about, I get very little butter, but I was going to switch to Ghee, and do some clarified butter. The triglycerides I would say for people to look at, for physiological biomarkers, your heart rate, blood pressure, sleep is an important one.

I wear the FitBit Charged. It’s really fun to look at my heart rate during the course of the day and in my sleep, and those sorts of things. I have a Dexcom that I’m going to put in. And I want to…

[Damien Blenkinsopp]: Is that the latest one? Is it the 4 or 5?

[Dominic D’Agostino]: Yeah.

[Damien Blenkinsopp]: I know Peter Attia is playing with that.

[Dominic D’Agostino]: Yeah, the 5 I think it is. So, I’ve just been traveling I just wanted to wait until I was put it in one spot and I can test it. I’m interested in trying that, and maybe working with some companies too, to do a glucose and ketone Dexcom.

I’m hoping to try that. That would definitely fit into your show. Yeah Quantified Self, and get some data for that, that would be good. As far as looking at physical biomarkers, you want to look at blood pressure, heart rates, sleep, and all these things improved when I got on a ketogenic diet.

I think there were various reasons for that. The lab test, the simple ones are probably the most beneficial ones. Triglycerides are the things that I look at the most. My HDL I think is important, and CRP, and of course your blood glucose. If you’re keeping glucose levels between 60 – 80, and doing that pretty much all the time.

Everything else is going to be good, that’s what I find.

(1:42:35)[Damien Blenkinsopp]: You said you did an insulin sensitivity, was that the homo or was it something else?

[Dominic D’Agostino]: No, I didn’t do that. I did the glucose tolerance.

[Damien Blenkinsopp]: Okay, the challenge.

[Dominic D’Agostino]: Yeah. I did like 50 grams, 75 and 100 grams I think. I think that was like over four hours, the 100-gram ones. Yeah, you drink the nasty Slurpee glucose and look at that. I’m extremely insulin sensitive. I dispose of glucose very fast.

I can also get a little bit of a hypoglycemic effect. If I’m on a ketogenic diet, and I go off of it. For example, I get some rice, sushi, or something like that, I will dip down into the low 50s and bounce back up again – very, very insulin sensitive.

(1:43:18)[Damien Blenkinsopp]: Thanks for that. If you were to recommend one experiment. I can guess what you’re going to say. So, we should try to improve the body whether it’s health performance longevity with the biggest payoff.

What would that be? How should they track it to make sure it’s getting that payoff?

[Dominic D’Agostino]: It depends on the person really. I don’t think low carb ketogenic diets are ideal for people in their teens or early 20s because they may be extremely insulin sensitive. I know I have tons of friends and I’ve even measured their glucose levels, and they’re great.

They stay pretty low, the glucose levels and they have adapted really well to a high carb diet. They wouldn’t want to do a ketogenic diet. So, maybe you’re expecting that kind of answer.

But, I think periodic fasting would be an important thing to do. I’ve been talking to some high-level CEO people and they tell me, “Well, I’ve been doing this anyway because I’m so busy. I wake up and I just work all day, and just go home and eat at night.”

But if your pattern of eating — like my patter of eating — I was obsessed with eating every two hours especially when I was really into lifting. I felt I had this preoccupation with food, preparing my meals, carrying it with me. I think it’s very liberating to not have to do that and to realize that your performance, energy levels, are not going to tank if you eat one meal a day.

If you were to do a short term fast, initially, and to do that every once in a while. I think, not only is very good for your metabolic health. I think it’s also good for your state of mind because it tells your body. It tells your mind that you don’t have to be sort of psychologically dependent upon food.

I would go five or six hours, and I’ll be like, “I’m starving I have to eat something.” I have been around people that are like that. My wife is kind of like that, she’s an incredible carb burner.

But if we’re traveling and she’s gone four to five hours without having a meal. I could see it in her mood and in everything. But that’s fine we’ll stop and get something to eat, and usually we’ll have coffee or something like that. But it’s interesting to see, and she sees it in me, “How could you go this long? Aren’t you hungry? What’s wrong with you?”.

She understands it now. She’s watched me do so many tricks and everything. If you’re not a big fan of being hungry. If you’re not a fan of having to eat every two or three hours because you’re hungry. I think doing some intermittent fasting would be a really good experiment for you to do.

I actually interviewed Mark Mattson at IHMC. So, I’m also a research scientist at Institute for Human and Machine Cognition. We interviewed Mattson, I think you did too for a podcast. He really went into the benefits of intermittent fasting and he’s at the National Institute of Health.

If you get a chance, he gave a brilliant lecture, presentation. If you go to IHMC lectures and look up Mark Mattson, he gave a great talk on this. He talks about all the health benefits.

If you do embark — if your listeners embark on [an] intermittent fasting experiment it would be interesting for them to track their blood glucose levels, their ketone levels, their triglycerides and their c-reactive protein. I think in each one of those biomarkers, if you want to call them that, will improve with intermittent fasting. I’ve seen it.

(1:46:51)[Damien Blenkinsopp]: You’re saying the 16-hour window or one day? Because you said short-fast, do you mean like a one day, 16, or 20 hours?

[Dominic D’Agostino]: Yeah. You could do every other day eating. But I think the easiest thing to do for most people would be, what I’d do if I do intermittent fasting maybe once or twice a week now. I eat two meals a day but like once or twice a week I’ll eat one meal a day, and it varies depending on what I’m doing and testing.

But it will be 18 hours of fasting and 6 hours of eating. Actually I get home late, so it ends being about 20 hours of fasting and four hours of eating. So, it will be 7pm – 11pm. I’ve done it [with] water and abstained from putting fat into my coffee.

I’ve also done what I would call ‘fat fast’, so I would put in some MCTs in my coffee and maybe get a ketone supplement during the day. I would still call that a fast because it’s basically non-glycemic.

[Damien Blenkinsopp]: Yeah, probably has very similar ketone and glucose effects.

[Dominic D’Agostino]: Yeah, I actually find that it’s optimal. So, I would call that a modified intermittent fasting protocol, where you would get in some fats and exogenous ketones during that fasting period. I’m a little less hungry once I go into that eating window.

I think that’s good too, so I tend to not over eat that much. My body is still strongly in a state of ketosis that has probably enhanced a bit with the supplementation. It tends to dampen my appetite a little bit so I’m not as ravenous.

But I don’t generally don’t get that ravenous anyway when I eat. But, I would experiment with that the intermittent fasting. I think it’s so easy to do. I mean intermittent fasting is easier to do than the ketogenic diet that’s what I find with people.

So, do some experiment, get some initial blood work, read up about it, listen to Mark Mattson’s talk on [the] IHMC website and you’ll find it there. I’m sure there’s a lot of blogs on the subject and do blood work before and three to four weeks after.

You’ll see pretty big effects, especially six and eight weeks after. You’ll see even bigger effects on your lipid profile and metabolic biomarkers.

(1:49:04)[Damien Blenkinsopp]: Excellent thank you so much for that, that’s a great one. Where would someone look to learn more about your topic? Are there any good books or presentations on the subject you’d recommend if they want to learn more about the whole subject of ketones and ketosis?

[Dominic D’Agostino]: One of the go to book that I would recommend is Jeff Volek’s ‘Art and Science of Low Carbohydrate Performance’. It’s a mandatory reading for students entering the lab just to get a hand on what the ketogenic diet is. The Ketogenic Diet Resource is a website maintained by a friend of mine, Ellen Davis, and I think has a lot of good information on it.

But I maintain a website to throw up links, compile links in there called ketonutrition.org. If you click on resources from the homepage, it will take you to dietary consultants, books, publications, list of podcasts, and lectures on there on a variety of subjects that hit on pretty much all the topics we’ve discussed. I probably need to get on there, but it’s relatively updated. I’ll probably update that in the next month or two.

Metabolic Optimization too, that’s a website that I started with Travis Christofferson who wrote the book ‘Tripping Over the Truth’ which is an excellent book that covers the metabolic theory of cancer. Travis and I maintain the website Metabolic Optimization, and we have Thomas Seyfried on.

We’ve had Adrienne Scheck, we’ve had Bruce Ames actually was our first guy. We’re going to line up a bunch of other speakers on metabolism so that’s another area where they can look up information on these topics.

[Damien Blenkinsopp]: Great, thanks for that. Are you active on Twitter? Where could people also connect with you and keep updated of what you’re at?

[Dominic D’Agostino]: I tried to post at Twitter maybe once or twice a week, not like super active. But on Facebook I post a little bit more. My page is maxed out, I got 500 or 5,000 people following me.

So I’ll probably create a more public page. But you could still follow me because I post things open to the public. I will post usually one or two studies per day, or podcasts or lectures per day on my Facebook page which should be very easy to find.

It’s always sort of topics relevant to the interests or the topics that we covered today. Sometimes I dual post on Twitter and Facebook, important things that pop up as far as studies and lectures and things like that.

(1:51:39)[Damien Blenkinsopp]: Excellent. Of course, we’ll put links to everything you’ve mentioned here in the short notes. Is there anyone besides yourself? You’ve already mentioned a few people, but was there any you would pull out and you would recommend if people wanted to learn more about the subject? Are there are some other people that you would recommend also?

[Dominic D’Agostino]: Yeah. My colleagues, there’s so many of them. I try to stay very active in collaboration. It’s really good for scientists to collaborate to help get their work out there. Also, to get other people to validate the findings that you did in the lab.

So, I know you’ve had Thomas Seyfried. He’s a great friend and colleague of mine. Adrienne Scheck is a fantastic scientist and a pioneer in ketogenic diets and moving the ketogenic diet into clinical trials at Barrow Neurological Institute.

There’s some of the mentors that even got me into this field — would be Dr. Eric Kossoff. He’s a neurologist at Johns Hopkins. He’s been a pioneer in using a ketogenic diet for kids with epilepsy, so look him up.

John Roe who’s a neuroscientist and pediatrician. He was originally at Barrow Neurological Institute and he was the first scientist I ever connected with to discuss this. The use of the ketogenic nutrition for oxygen toxicity.

Dr. Richard Veech he had a profound influence on me when I first got into this area of ketogenic diet and discovered exogenous ketones. It was his reviews on the subject. So if you look up on some of his reviews on ketones and the therapeutic effects of ketones, they’re really good.

Susan Masino has been really supportive of our work and she’s doing some really innovative work looking at the effects of the ketogenic diet on adenosine. Adenosine is a neuroprotective substance that’s elevated, has anti seizure, anti-convulsant, neuroprotective effects.

So, we actually have a lot of these speakers [who] will be coming to our Metabolic Therapeutics’s Conference which will be held either the last week in January or the first week in February. We had a number of speakers, we had Eugene Fine, Colin Champ, David Ludwig, David Diamond, he was a colleague of mine here at USF and [we] talked about cholesterol and statins.

We had Eric Kossoff, Adam Hartman, and a bunch of scientists. So, I would tell your listeners to go to the Metabolic Therapeutic’s website. We’re in the process now of sending out the invitation for speakers.

And pretty soon, I think we might have a preliminary site set up for that, but we’ll be updating that soon with all the different speakers and the topics that are going to be talked about. We really try to emphasize basic science, so you’re going to find lectures on neurophysiology, cancer biology, proteomics, tracer based metabolomics.

Performance — Jeff Volek will be there talking about performance. It will be a mix of things related to not just the ketogenic diet but metabolism in general.

[Damien Blenkinsopp]: Sounds fantastic so anyone can attend that?

[Dominic D’Agostino]: Anyone can attend that, yeah. We should have the registration going up soon. The problem that we had is that last year the venue was small. We wanted originally to keep it small, to cap it at about 250, but we had to turn so many people away.

So, this year we’re going to blow it up a little bit and probably have about maybe 600 – 700 people, hopefully in the same venue. But we’re going to get the whole hotel. You’re going to find a lot of great companies there that are producing these exogenous ketones.

So, Pruvit is going to be there, probably Forever Green, the company Kegenix – they make a great product that I’ve been testing recently during my travels. KetoSports hopefully will be there, and Quest Nutrition has a big footprint in our conference and they have been incredibly supportive of our work.

Scivation, who’s really the leader in branch chain amino acid supplements, will be there. Let me see, we have a lot of good sponsorship supporting this area of research. It’s really exciting to me that it’s becoming so popular it’s easy to find companies that are now emerging that are interested in developing products that can enhance nutritional ketosis.

So it’s fun to see a market for this evolving. They’re are creating products that I think will be very beneficial to patients even that are following nutritional ketosis for managing a disease process.

I do get Emails every single day from patients that are using these products that made a world of a difference. They couldn’t get into ketosis and once they did or their trial did, they started getting all these benefits from the ketones.

[Damien Blenkinsopp]: It’s a super exciting area, you’re very lucky to be right in the center of it.

[Dominic D’Agostino]: Yeah. I do feel lucky.

(1:56:48)[Damien Blenkinsopp]: Just as a quick anecdote, I gave some MCT powders and C8 to my mother because she has tremors. They have been getting worse over time, and they are so much better it seems. She was really surprised by that.

But it is an exciting area, they have so many crazy benefits, so broad compared to the other things we looked at. Which is one of the reasons I’ve covered it several times in different episodes, fasting, ketosis, all of these.

Whereas most topics I don’t cover in many episodes but this one has just so many applications, it’s just interesting. I think it’s worthwhile for people to learn more and more about it.

[Dominic D’Agostino]: Absolutely.

[Damien Blenkinsopp]: Dom, thank you so much for your time. I really appreciate it, we’ve covered such a wealth of topics. I know there’s so much more you could talk about. So, thanks very much for your time.

It’s been great talking to you.

[Dominic D’Agostino]: Thanks for having me Damien. I appreciate it.

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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!

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

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

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

Video Recorded on Day 10 of Fast Just Before Refeed

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

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

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

This led me to ask:

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

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

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

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

itunes quantified body

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

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

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

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

Why Do a 10 Day Fast?

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

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

The 10 Day Water Fast Results

Metabolism on 10 Day Fast Looks Similar to 5 Day Fast

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

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

10 day waterfast ketones glucose
A few interesting points:

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

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

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

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

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

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

Weight Loss 10 Day Water Fast

Testosterone on a Fast: Big Drop & Libido Changes

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

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

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

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

Testosterone: 10 day fast

Is it OK to Fast with Adrenal Fatigue?

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

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

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

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

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

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

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

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

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

Metabolized Cortisol Levels (Baseline and Fasted)

10 Day Fast Total Cortisol (Metabolized Cortisol)

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

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

That’s good news.

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

24 Hour Free Cortisol Levels (Baseline and Fasted)

10 day fast 24hr free cortisol

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

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

Did Mental Performance Keep Up During the Fast?

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

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

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

10 Day Fast Mental Performance

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

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

The 10-Day Fast Experience

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

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

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

Nonetheless there are things to note…

Physical Weakness

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

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

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

Sleep – My Next Challenge

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

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

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

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

The Mind Retreat

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

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

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

The Post-Fast Rookie Mistake

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

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

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

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

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

I resorted to drinking exclusively blended green vegetable smoothies.

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

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

Symptoms – The Back Rash

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

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

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

The Takeaways

So coming back to the questions we want to answer:

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

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

Tracking

Biomarkers

  • Blood Ketones (Beta-Hydroxybutyrate / β-hydroxybutyrate): Blood ketones are the gold standard for measuring your state of ketosis. During the fast, ketones are expected to peak in the range of between 6 and 8 mmol/L. Dominic D’Agostino mentions that metabolic acidosis with values over 5 mmol/L place an additional burden of processing on your body, so in non fasting states keeping values between 1 and 5 mmol/L may be optimum.
  • Blood Glucose (mg/dl): A measure of the level of glucose in the blood at one point in time. Values of between 50mg/dL and 60mg/dL are standard for fasts. Non-fasting values should be below 80mg/dL ideally, and at least 92mg/dL.
  • Glucose-Ketone Index (GKI): The ratio between the concentration of glucose in the blood to ketone bodies in the blood. The calculation is Glucose (mmol)/ Ketone (mmol). Dr. Seyfried created the index as a better way to assess metabolic status. Therapeutic efficacy is considered best with index values approaching 1.0 or below. Patients with chronic disease like cancer have consistent index values of 50 or more.
  • Weight (lbs): Standard scales measurement of weight in morning without clothes (to avoid biases).

Lab Tests, Devices and Apps

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

Tools & Tactics

Fasting Protocols

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

Supplements

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

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

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

Personal Note: Background on Using Minerals in Fast

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

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

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

Other People, Books & Resources

People

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

References:

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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.

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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

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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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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