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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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

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[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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Can physicians improve health outcomes using new self-tracking tech with their patients? Or is the tech still too inaccurate or impractical? We take a hard look at the reality and potential with a physician testing quantified self practices in his clinic for the last 3 years.

This episode is about quantified medicine or the reality of cooperating with your physician using self-tracking and observation. Working with such feedback aims to bring fourth an integrated approach to health and performance.

Previously, we have looked at the value of a good physician on your team when looking to improve your health in episode 22 with Bob Troia, and at the potential of wearable measuring devices in episode 24 with Troy Angrignon.

Does the Quantified Self approach offer medical benefits? What is the potential of tracking your data and teaming-up with your physician during the healing or performance improving process? What are some simple ways to help yourself optimize yourself?

I think it is hard to take measurable insights and extract it in a medical, steady kind of way. And that’s why I continue to not be afraid of computers taking over my job, because ultimately I think there is a combination of metrics and data, and also presence and attention and experience that work together, and that’s why I think the medical profession has hope.
– Dr. Paul Abramson

Today’s guest is Dr. Paul Abramson who runs an integrative medicine practice in San Francisco. He earned his medical degree at the University of California in San Francisco (UCFS). Importantly, he also holds a degree from the Center for Integrative Medicine at the University of Arizona. As a member of the Clinical Faculty at UCSF, he is doubly board-certified in Family Medicine and Addiction Medicine.

Being a former electrical engineer, Dr. Abramson’s interest in patient self-tracking sprung early in his medical career. In 2007, he founded the My Doctor Medical Group – his medical practice institution offering customized coaching models for individuals. He has adjusted the Quantified Self Approach aiming to gain insight into specifics of patients’ health. He has seen the ups and downs of working with this type of quantifiable feedback. In his practice he cooperates with patients and asks them to be introspective. Given his originality and accumulated experience, Dr. Abramson is an important figure in shifting the paradigm towards personalized medical care and all-important patient involvement.

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. Abramson’s interests in integrative medicine (4:04).
  • How Dr. Abramson defines integrative medicine (4:51).
  • The integrative approach means pivoting through the complexity of conventional therapy and the larger sphere around it (07:10).
  • Early on, Dr. Abramson pivoted towards a novel paradigm of patient self-measurement and observation (10:58).
  • Patient compliance is a problem for those who do not wish to continuously self-observe (14:24).
  • Using biomarker wearable meters provides knowledge important for informed behavior modification (16:39).
  • Dr. Abramson’s team places value on introspection and subjective observation of experience (20:02).
  • Patients are expected to self-explore and support their symptoms with subjective observations (22:53).
  • Determining useful metrics in medical practice requires careful deliberation over their reliability (27:14).
  • Simple subjective data on patient experience can be acted upon in complex medical conditions (29:16).
  • Patients with high intrinsic motivation are better-fit for using metrics in medical care (32:28).
  • Dr. Abramson has successfully applied awareness building exercises in individual coaching models (34:15).
  • Mobile apps can be used to track patient data and integrate it in could-sharing services (37:33).
  • The challenges of self-tracking broadly differ between lack of patient motivation and too-narrow hypotheses about undergoing causes (40:13).
  • Success with self-observation depends on developing optimized coaching matching individual patients (42:23).
  • There is less pressure on doctors’ medical authority positions when collaborating with patients in the context of team-care (49:50).
  • The more responsibility patients take, the more they acquaint themselves and the doctor with their health dynamics (52:16).
  • The biomarkers Dr. Abramson tracks on a routine basis to monitor and improve his health, longevity and performance (54:41).
  • Dr.Abramson’s one biggest recommendation on using body data to improve your health, longevity and performance (58:55).
  • Best ways to connect with Dr. Abramson, who is responsive on social media (60:00).

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

Dr. Paul Abramson, My Doctor Medical Group

Tools & Tactics

Diet & Nutrition

  • Autoimmune Protocol Diet: The Autoimmune Protocol (AIP) diet is an elimination diet that works to reduce inflammation in the intestines caused by autoimmune triggers.

Tracking

Biomarkers

  • Continuous Glucose Monitoring (CGM): Promises greater accuracy than standard one point in time glucose monitoring by capturing the variance of blood glucose over time (Note: in Episode 22 we saw an experiment showing the detriments of just taking one point in time readings). Blood glucose is continuously recorded at frequent intervals such as 1 or 5 minutes depending on the device used. While not a widely established practice, Dr. Abramson claims that continuously tracking blood sugar levels offers insight into fine-tuning medication and behavior adjustments to optimize patient glucose-levels. It’s early stages, but there are a few Continuous glucose meters (CGMs) on the market. Current devices include the Medtroronic MiniMed 530G, the Dexcom G4 PLATINUM System and the Abbott FreeStyle Navigator II (available in UK only).
  • Blood pressure: Blood pressure is expressed in terms of the systolic (maximum) pressure over diastolic (minimum) pressure and its measure is in millimeters of mercury (mm Hg). Normal resting blood pressure in an adult is approximately 120/80 mm Hg. Among numerous indications, blood pressure is used as a biomarker to determine the risk of stroke and coronary heart disease.

Lab Tests, Devices and Apps

  • Zeo Sleep Manager: Zeo was Dr. Abramson’s favorite Sleep Manager (device and app combo) until the company went bankrupt. Zeo tells you how you really sleep, and helps you find ways to improve your sleep. It accurately measures sleep quality and quantity at home. It also discovers factors which harm your sleep cycle.
  • Withings WS-50 Smart Body Analyzer: The Withings company offers devices designed to monitor various aspects of your body. Tracking tools include weight and body composition, pulse, air quality screening, etc.
  • ResMed S-Plus: The company ResMed is focused on healthy sleep. To this end, it offers devices which monitor personal sleep parameters, room air quality, etc.
  • Beddit: The company Beddit offers devices which track sleep using a sensitive force sensor which detect small vibrations caused by your heartbeats, breathing, and movements to provide you with data regarding your sleep.
  • Evernote App: In the context of tracking subjective experiences regarding health, Damien suggests using this app to take notes in a form of a health-diary.

Other People, Books & Resources

People

  • Dr. Andrew Weil: Founder & Program Director of the Center for Integrative Medicine. Dr. Weil is an influential figure for Dr. Abramson’s interests in integrative medicine and his, overall, career.

Organizations

Full Interview Transcript

Click Here to Read Transcript
(04:04)[Paul Abramson]: I’ve been very imbued in the conventional science-based – I put science in quotes – world. I’ve also been very interested in alternative points of view and meditation, and what I would call consciousness and behavior, and the things that are, in essence, insubstantial in a material sense, but I think are often just as relevant to our lives and well-being.

So in that vain, I have individual interests and pursuits in those areas, and then I went to work for Andrew Wylie in Tuscon at the University of Arizona in his integrated medicine program there. I was a residential fellow for a year, and we swapped patients there and had case conferences with some of his…

(04:51) [Damien Blenkinsopp]: To take a step back, what does integrative medicine mean? Because we haven’t really talked about it on this show before.

[Paul Abramson]: Integrative medicine has 100 definitions, and it has been, I would say, used and corrupted by a variety of different people and interests over the years.

As I define it, and I think I’m pretty much in line with Andrew Wylie on this, integrative medicine is a way of looking at all of the available approaches, perspectives, tools, tests, treatments that are out there. And then looking at each individual as an individual, and trying to make a match between what’s going on for them and what is the best combination of approaches.

So in essence it includes all of conventional medicine and science-based, or whatever you want to call it, conventional medicine, and it includes alternative things. And it includes consciousness based things, and it includes mind and body and it can even include spirituality and things that are unknowable as part of the paradigm by which you try to help people both understand what’s going on for them and come up with a plan of what to do next.

So I think it’s completely non-exclusive, and I also apply a very discerning and discriminating kind of eye to it, in that of all the available options out there I’m going to evaluate each one on how useful do I think this is? And there are some things that do not need my sniff test, or my deep investigation that I do not… And once I’ve determined that I’m not really interested in something, or I don’t think it’s going to be fruitful for me as one of my tools, I leave it to the side.

So I do weed things out. It is not an indiscriminate approach of ‘all is good’. It is more like, I’m going to start with an open mind and then apply appropriate skepticism and investigation to choose what tools I think are going to be helpful. And they may vary depending on the individual.

So I do not apply a one-size-fits-all approach to anybody. There’s no one test or one treatment that I think is applicable to everybody. Nor is there one paradigm that I think is applicable to everybody. So, for some people that is dis-concerning.

(07:10) [Damien Blenkinsopp]: So in integrative medicine, is there an actual organization behind that, or is it more a term used for people who are dabbling in functional medicine, the alternative, and the…

[Paul Abramson]: Well, there is now a board certification in integrative medicine for medical doctors. There is a consortium of academic centers in integrative medicine that includes many of the big tertiary care centers in the United States that have integrative medicine centers and research programs.

And I think a lot of that comes into this kind of definition, where it’s consistent with the conventional medical world and a much larger sphere around it.

[Damien Blenkinsopp]: The functional medicine has an organization behind it, so does integrative medicine tend to relate to that more because there’s a big organization behind it? Versus some of the other things you were talking [about], which I imagine don’t have as much structure to them.

[Paul Abramson]: Well integrative medicine ultimately is, I think, integrated, meaning it’s not an either-or proposition. It’s, ‘whatever works’.

Whereas some of the other things out there are more alternative. Where it’s more of an ‘us versus them’ kind of situation, where we have a certain truth and those other people, especially either the conventional people or the alternative people, are biased, wrong, or otherwise not reputable in some way, and therefore you should pay attention to our perspective.

That is not, to me, integrative. But I think the conventional medical world falls into that trap, and I think the functional and alternative medicine world falls into that trap. Equally.

[Damien Blenkinsopp]: It’s kind of like Republicans and Democrats.

[Paul Abramson]: It’s kind of like Republicans and Democrats.

And in reality I would say my flavor of integrative medicine, or what I consider, is it’s not exclusive in that way. It’s like of all the things out there, some of them are valid, some of them are not, some of them work for some people, some of them don’t work for some people.

And you just have to be creative, and you have to be discerning and discriminating enough to not get overwhelmed by the complexity. You have to be able to take this, in essence, if you are not ready for tolerating ambiguity and dealing with massive complexity, then it’s easier to track into something that is simpler, where it’s more clear cut and there is right and wrong.

Whereas if you want to take the big picture, you have to help people weed through all of this complexity to come up with a relatively normal, simple approach that is going to work for them. And then you have to be willing to measure and then accept if it is not working out you’re going to back up and take another set of things and take another approach.

Then in the start-up technology world out here they call it pivoting, where you do something, you go full worth at it, and then you try it to the best of your ability, but you have to be constantly measuring your success. And if it’s not working out, you have to get over your ego and your attachment, and you have to back up and re-think and pivot, and keep moving.

Yeah, that is the [unclear 10:10] approach to medicine that I can think of.

[Damien Blenkinsopp]: That’s a very interesting point because – and you’ll know better than me – people when it comes to health, fitness, these diets, and these types of areas, they get very, very emotional about it. They tend to become fans of a certain approach rather than another.

I guess pivoting is, I understand because I’m an entrepreneur. My first company, I didn’t want to let go of it. I didn’t want to change it at first, until the pain in terms of profit loss got enough that I was like, “Okay, I have to be serious.” And I was taught to be able to pivot and make decisions based on data.

So I guess that probably happens a little bit in the medicine world as well. People eventually get to this point of pain, where they’ve been following some course because of interest, of love, and then they go, “Okay I have to try and get some kind of data.”

(10:58) Now, we first met, albeit kind of briefly because you were doing a talk, at the Quantified Self conference in 2013 – end of 2013 I think it was. And so that’s also one of the things you’ve dabbled in a bit in you integrative medicine. Could you talk a little bit about why you started taking an interest in that and have made that a part of your practice?

[Paul Abramson]: Well I think it does come back to what we were just talking about. You have to gather data about what’s going on for each individual to decide, is this working, is this not working. Or, are there things happening that are not good, that should trigger us, like your losses in your start-up.

The earlier you can detect and decide that things are not going to go down the right path, you should pivot. And yet if you’re not sure, you might continue to go on for a while and take more measurements. But you have to be constantly…

And so I was struggling in medicine with a lack of feedback on my patients. We were meeting and setting a treatment plan in place, and they were going off to do it. And I just was not getting enough feedback to know whether it was working, whether it needed to be adjusted, or whether we needed to completely pivot and try something else.

And so the promise with the Quantified Self approach is that it’s not so much that there is a new sensor or a new test that is interesting to me, but it’s a new paradigm, it’s a new concept that people are going to observe themselves, and then perhaps feed that back into a medical doctor or some other practitioner or some helper that they have, a coach.

But many people just decide to do it for themselves, where they’re moving along with a plan, and they’re measuring, and they’re questioning, and they’re constantly just trying to decide,” Do I keep going, do I add, do I subtract, or do I pivot?”

And I started doing these kinds of experiments with people where you can then take all of human behavior and make it an experimental approach, where, instead of saying, “You have to take this medication for your high blood pressure forever.” People hate that.

What I do is I say, “Wow. You’re blood pressure is really high. We’ve measured it over a whole month and it’s always really high. We know that’s going to wear out your blood vessels, and your kidneys, and your brain, and it ages you faster to have high blood pressure all the time. So, why don’t we lower it? And then, why don’t we start doing some experiments to see if we can find the cause, or reverse the cause, or come up with other approaches that are more agreeable to you, if you’re not really into taking pharmaceuticals every day.”

Which many people aren’t. And at such time as those thing start working, we can think about revisiting. I just say, while we’re doing those experiments, let’s limit the damage. And people respond much better to that. Instead of saying, “Oh, I’m just going to keep the high blood pressure going, and then in six months I will have lost 40 pounds.”

Maybe that happens, maybe it doesn’t happen. Maybe they lost 40 pounds and their blood pressure is still through the roof high. It’s a realistic approach that takes measurement into account, but also addresses what’s going on right now.

And the tools we have from Quantified Self, some of the technology but more the paradigm of self measurement and observation, gives us some hope that the culture could shift into that kind of approach.

(14:24)[Damien Blenkinsopp]: It’s interesting in a kind of work relationship. How does it change the work relationship between you and the patient when you introduce this? Do you work out some specific metrics with them, or is it really very different?

Have you seen this evolve in your practice? Because you’ve been doing this for a few years now, so I’m sure you’ve cut some things that didn’t work, and taken some things that did tend to work, and you’ve kind of got some type of best practice that you’re starting to put in place.

[Paul Abramson]: Well, it’s been humbling. People are very different.

They’re different in their background, they’re different in their medical and psychological situation, they’re different in their social circumstances and their family, and what the support is in their life to do things. And so some people actually just want me to say, “This is what you’ve got, this is what you have to do,” and to prescribe to them. And they go home and they take their drugs.

And we limit the damage, as best we know how with modern medicine, and sometimes that works out, and sometimes that doesn’t. But they don’t have time or interest or, even maybe the perspective, to take a different kind of, more proactive approach.

And for those people, after I challenge it a little bit and determine that it is in fact how they want to be.

[Damien Blenkinsopp]: That’s interesting. Are they not interested enough in their health to, or is it because they’re so busy with other things in life? What is the [reason]?

[Paul Abramson]: For whatever reason, they are not in a position where they want to do something that takes more work. What really sort of takes up more subjective view of reality, like there is a way.

There are many choices out there, it’s not really black and white. Some people really want the black and white. It’s easier for them psychologically, and it’s sometimes they’re just so busy, they’re like, “No way I’m going to have time to do experiments, or even to take my blood pressure twice a week.”

We’re just going to have to go without that. Especially diabetics. A lot of them just can’t check their blood sugar. Type 2 Diabetes, you know, it’s not really medically mandatory in many conventional settings for them to check their blood sugar at all time. You just take the medications and get some blood tests every few months and see how things are going.

That’s very unsatisfying for an engineer like myself. I really would want data and feedback and optimizing. But many people are really not into that. It’s either a cultural thing, or just a logistical thing. They just aren’t going to do that.

(16:39) [Damien Blenkinsopp]: Just out of interest, have you looked at the continuous glucose monitors?

[Paul Abramson]: Oh yes.

[Damien Blenkinsopp]: Have you been using those quite a bit? Or have found them useful?

[Paul Abramson]: Well, I mean they are generally able to be covered by insurance. They’re very expensive.

[Damien Blenkinsopp]: Yeah, about a 1,000-1,500 dollars, something around there.

[Paul Abramson]: The supplies are also very expensive. Each and every week you need a new implanted sensor that could be hundreds of dollars. So, it can really add up in a hurry per month and the initial costs. Such that many people aren’t going to do that.

Now if you’re a Type 1 Diabetic from a young age or even an older age where you have no insulin around, and insulin pumps are in the offing, then often they can be covered. But for Type 2 Diabetics it’s usually a completely out-of-pocket expense. And what I’ve found is that there are often incredibly great insights that one obtains from the continuous glucose model, but only some people get on-going benefit.

[Damien Blenkinsopp]: What kind of [insights]? Does it enable you to take some specific actions when you see some kind of behavior that they’re undertaking which is interfering with your goals, or…?

[Paul Abramson]: I’m not really offering generally to watch their data continuously.

[Damien Blenkinsopp]: Yeah.

[Paul Abramson]: What we are doing is having them get self-feedback, and then take notes in one way – electronic or paper – of their experiences with that data from the glucose monitor. Because you have to calibrate them with a finger stick multiple times per day, and you have to use it properly to try to get valid data. And then you get to see in real time if you eat something, or if you exercise, you get very quick feedback about how it affects your blood sugar, both immediately and later.

And so you can get pretty profound insights about that, and they are sometimes very unexpected. That some things lower your blood sugar and some things raise your blood sugar, and they don’t match what the conventional wisdom says should happen.

And then somethings people just have to get it in their face that, “Wow, if I exercise my blood sugar really is so much better.” It’s motivating enough that it’s going to make them exercise more.

But a lot of people, after they get those insights, if they’re Type 2 Diabetic, they can simply just use those wisdoms to change their behavior, and they don’t have to go through the hassle of calibrating and wearing an implanted monitor that has something go into their skin changed every week and calibrated several times a day. A lot of people don’t really want to do that on-going.

So then when you look at the up-front expense for something that they’re only going to use for a relatively limited period of time in most cases – because most people are not going to want to be doing that level of hassle if it’s not required because they’re not Type 1 Diabetic – a lot of people chose not to do the continuous model.

Maybe when we get the truly non-invasive blood-glucose sensor that is both accurate and possible. When I was an electrical engineering grad student at Stanford in the early 1990s, I was doing consulting for start-ups. Before there was the first technology, the first internet tech.

And I worked for a couple of different start-ups that were trying to get non-invasive blood glucose monitors, where they would shine a light through you, or they would use ultra-sonic. They would use various technologies to try to get, from the outside, your blood sugar. And the problem is glucose is such a small molecule, and so hard to differentiate from other molecules that really a lot of companies went belly-up back then, and they are still failing today.

(20:02)[Damien Blenkinsopp]: I think there’s a couple of watches. I’ve seen them around. I haven’t looked into them. I was concerned about the accuracy. I guess I’m a bit dubious about [them].

Because even the continuous glucose monitor, which you were just saying you have to calibrate it, right? And it’s got something actually implanted in you. So the accuracy of a watch with optical – I think they’re using optical – would seem kind of not achievable at this point.

[Paul Abramson]: This is the exact technology that they were trying to come up with in the start-up in 1992. And it ultimately did not kind of work out. And I think that at some point someone is probably going to do it, but to my knowledge it has not yet been done in a valid enough way that you could actually take action on the results.

But maybe there is something that I don’t know about that came out this year, and I will continuously watch that Weiner Chart. [unclear, 29:48-] at that, somewhere about 15 years ago after watching failure and failure.

So, I would just say that the measurement technology concept is something that you need to be very skeptical about, because if you’re going to take bold action based on the numbers, it better be accurate and reliable and reproducible and usable. So that is an on-going concern for me.

Now, more subjective measures, what we really came to in our self-tracking program here, one, is that we don’t apply a similar methodology to anybody. Everybody kind of gets a custom approach based on where they are in their readiness to do things, and what problem they want to solve.

But we’ve also really heavily weighted it toward, what I would call, subjective measures that require them to actually stop and pay attention to what’s going on in their experience. Because the objective measures that don’t take any [action], the passive tracking approach where I wear a monitor and it spews data out at gigabytes per minute, it does not require awareness and it doesn’t require self-knowledge. The learning is later when you look at the data.

Whereas if you aim to gather the data, if you have to introspect and think and become more aware of what’s going on about your pain level, or whatever your symptoms are, or your emotional state, or in any way something that you have to pay attention to measure – because we don’t have a measurement for headache except by your self-report – the data gathering itself becomes a therapeutic tool.

The act of tracking is part of the treatment in that they become much more aware of what is actually going on for them, so that when we start trying to change things or treat or affect things in a positive way, they actually have more basis on which to do that, and we can identify more potential targets for more interventions.

(22:53)[Damien Blenkinsopp]: So you think basically building their awareness so that you can create that feedback is one of the most important parts of it?

[Paul Abramson]: For us, it is. And I’m a behaviorist at heart. I like to have people try things overtime, and to see whether building new tracks and new behaviors in their brain can affect their body and their experience and their entire reality.

[Damien Blenkinsopp]: So do you then find that patients are able to come to you with insights more so than before? Because all traditional [unclear audio cut, 23:25]. I have some mystery problem. I’m coming to a doctor, and the first thing to do is talk about my symptoms. Go for a questionnaire, try and figure out what’s going on.

Do you find that sometimes that first picture, say compared to a second picture when you’ve had them self-tracking something you thought was relevant, could be quite different? Because it is a subjective experience, and they learn to improve their self-awareness and have a better hold of what’s going on. And maybe, do they sometimes come up with some insights like, “It’s funny. I’ve noticed that every time I do this, then I get these symptoms.”

[Paul Abramson]: Right. Well people often come to their doctor – and that’s my frame of reference, because I’m a medical doctor and people come to me – they come with symptoms, but they also come with conclusions. And they might be already having diagnosed themselves, or they might just have made some assumptions or conclusions about why they’re having the experience that they’re having.

And I think the self-tracking paradigm encourages them to back up to the raw symptoms, and also the circumstances that they find themselves in. You know, looking broadly at what are their circumstances and what are their symptoms in as concrete a fashion as possible. And not making any assumptions. And then we make some hypothesis. But we frame them as hypothesis and not conclusions, and that gets them into an exploratory mode.

Whereas if someone comes to me and says, “I have a urinary tract infection.” And I am a [unclear, 24:50] and I have eight minutes, I will prescribe ciprofloxacin to them for the urinary tract infection, and they will go away. Especially if they say, “Oh I’ve had them many times and I know what they’re like.” That is not my style of medicine.

I’m going to say, “Well what are you actually feeling?” And they’re going to say, “Oh, I have burning when I urinate” or “I have fevers” or “I have back pain” or whatever. It’s very likely in someone coming to the doctor that they are correct, in that circumstance, but sometimes they’re not. Sometimes they have a yeast infection and it’s not a bladder infection, and giving them antibiotics makes it worse.

So I think you should always back up. But then especially if it’s something vexing, they have probably been trying to figure out and fix it on their own for some time. Weeks, months, years, decades sometimes. So if it were something, if their conclusions were correct – not their diagnosis, but their assumptions and conclusions – I believe they would have figured it out, and they never would have met me.

So therefore, the fact that they are coming to me with the time and expense and the hassle of going to a doctor, it’s very intimidating for some people, it means they are probably ready for a pivot. It’s a sign that it is probably time to take a different approach.

So if I can get people to back up and look at the raw data, the raw symptoms, and then we can look at all the possibilities and start to make some hypothesis. And some of the hypothesis might be the conclusions they have drawn, but they have to be willing to have some flexibility about looking at other options. Otherwise, I might be a poor match for them.

If they just want someone to take their conclusions and follow their line of thought, then my view is, okay, they either don’t need me at all, or they only need me because I – in California – can order laboratory tests for them. Or I can order medications for them that they can not legally order on their own. So in essence I am just a proxy for them having gone through the license pathway that I’ve gone through, and I’m not really functioning as a physician as I define it.

And so I try to resist getting involved in just being a tool that they can wield, and I try to work with people who actually want to back up and really take a look at what is going on.

(27:14)[Damien Blenkinsopp]: So what kind of metrics have you typically found to be useful? You said the qualitative. Are these ratings from one to 10 for symptoms? What kind of things have you found that are useful?

[Paul Abramson]: A wide variety of things. With each metric we have a discussion about what is the, what are we going to track?

Let’s say for a headache, are we going to track mild, moderate, severe? Are we going to track zero to four? Actually, the numbers and bins of data collection that you define dramatically affect the results of your tracking. You have to all agree on what each bin means.

What does three stars mean? It can vary widely over many people, and that makes it useless. And then they have to have written down what each metric means so that they can apply it as consistently as possible over time. Because if they drift in what a headache of three means, then their data is going to be very hard to use.

So, we try to apply this sort of N of 1 controls as best we can to define things clearly, to re-visit them, to keep people calibrated. And then try to figure out is it a negative two to two scale, or is it a zero-four scale that’s going to be helpful. And try to make it as simple as possible so that people can actually do it in real life.

Sometimes you have to use subjective narrative data, and that’s why we’ve taken a coaching model rather than a computer analysis model. Because the most interesting things sometimes are the things that they write. Their observations about the process, or about the data. It could be a picture of something, it could just be a description of how they were feeling at the time that they had the high-blood pressure. That’s actually much more interesting.

[Damien Blenkinsopp]: So is that like a journal alongside whatever you’re tracking?

[Paul Abramson]: Yeah. And it could be an electronic journal, or a paper journal. My challenge with technology tools is they have to beat paper. If they do not win over paper, then you have to question why you’re using technology.

(29:16) [Damien Blenkinsopp]: It’s interesting that you’ve brought that up, because I struggle with my own problem, just figuring it out, and what kind of first worked for me was using EverNote as a journal.

[Paul Abramson]: Sure.

[Damien Blenkinsopp]: Just as kind of like a diary every day, one note for every day in a folder which was called ‘Health Diary.’ And then also tracking some metrics. And like, “Oh, that’s interesting. I wrote– “

[Paul Abramson]: Paper apps. It’s almost paper.

[Damien Blenkinsopp]: Right. Yeah. And it’s easy to search. I mean, that’s why it’s nice, because if you have some kind of hypothesis in your head, you can select that folder and you can search for that keyword, and you’re like, “Oh, look. It happened on four days, and maybe it coincides with the metric.”

[Paul Abramson]: Sure. And that’s what I would call primitive technology like paper. And sometimes it is the best approach, because something much more complicated will keep you from gathering the data, because it’s too cumbersome.

It’s very hard to apply machine learning and machine interpretation of data because the raw numbers rarely have the meaningful insights. And our basic model, we’ve gotten more flexible about exactly how we implement it.

Initially, we were doing a weekly coaching model, where people would track, the data would be shared with a coach who would meet with them – in person or virtually – every week to review their data and basically elicit their memories of what happened that week that they had not taken down as part of the data. So they would use the pictures or numbers or whatever they had tracked.

People remember a week. Most people. Whereas if you go back a month, people do not remember the moment to moment experience they were having. Which is probably why psychotherapy is typically a weekly model, because you don’t have to reinvent the wheel every time, you can build on the previous week because you remember.

And so the coaching model would allow people to tell the story around the data, and then the coach would concisely record the story and plug it into the project, or the experiment that we were running, and try to write down the story and the insights that could be taken. And then the insights and the summary of the story could be fed back to me, the physician, where very quickly I could think about it and apply my perhaps greater perspective or set of ideas, and make suggestions.

And so it became very time efficient for me. Rather than me going through the data for an hour every week, I can go through the coach’s notes for a few minutes and be almost as effective. And in some cases much more effective than I could be trying to be the coach myself.

The raw data was almost never the actionable. Now, that’s not always true. If we’re just doing a very simple tracking experiment where your blood pressure is 220 over 120, and we want it to get lower very quickly, and we’re going to track what you’re doing and what medications you’re taking, and how often you’re taking it, and track your blood pressure.

There you actually do have a much more concrete, discrete kind of experiment that you could apply some sort of automation to. But that’s not typically why people are coming to me. Most people are coming with much more complicated and murky problems where subjective data is really the actionable data.

(32:28) [Damien Blenkinsopp]: If we’re talking about the situations where you’ve found this most useful, is it it the more mysterious, people haven’t been able to figure out any[thing], the complex, multi-factorial potentially.

But as you mentioned, is there also something on the very hard side, nearly technical, where you have a blood pressure marker and it’s a very focused metric, that you are like, “We have to get that down.” From doctor’s experience and everything, this is the thing we need to focus on. So you know ahead of time what you want to focus on.

Are those the kind of two situations, or are there other situations where…

[Paul Abramson]: I would say it’s a whole spectrum, but the key factor is that if the tracking based on insights and memory and subjective recall are round objective data that you’re gathering is by it’s nature very labor intensive. Like this process, to really do a meaningful tracking experiment, is labor intensive and costly in various ways.

You have to hire help, you have to spend a lot of time, you have to think about it. You have to be involved in the process, and for that reason, that typically is applied to problems that are either very urgent or long-term vexing for people. They tend to be more complicated because they are at the end of their rope, and they need help, and they are ready to do anything just to figure this out.

[Damien Blenkinsopp]: Right.

[Paul Abramson]: And that’s a wonderful situation to be in.

[Damien Blenkinsopp]: For a doctor, yeah. Compliance.

[Paul Abramson]: Their intrinsic motivation is very high. The outcomes tend to be good in anyone who comes to a doctor with high intrinsic motivation to do whatever it takes. And we do select in our practice for people with that description. So our outcomes are phenomenal, but part of that is selecting some people who are ready to do whatever it takes to figure this out.

(34:15) So the other area other than complex medical mysteries that we’ve applied this to, well there are several areas. One, our awareness building exercises, where about half of our practice is also a complex addiction treatment practice for high-functioning professionals. And some very intelligent people, many of them in the tech industry, who have what I would consider very mundane addiction problem.

[Damien Blenkinsopp]: Is this like caffeine, or are we talking more…

[Paul Abramson]: Alcohol, cocaine, prescription opiates.

[Damien Blenkinsopp]: Okay. Is this quite common now? Because we all hear bout the performance culture, and everyone–

[Paul Abramson]: It is incredibly common now.

It has always been incredibly common, and yet it continues to be incredibly common. And the more fast and stressful and complex society gets, as we’re currently going through a little boom here in San Francisco, I would say it increases. And the number of people who go out of control increases, where it gets beyond the place where they can self manage, and they seek professional help.

So we are often trying to get people to do very basic tracking [endeavors]. Whether it’s their internal mood state, or their discomfort level, or interactions they’re having with other people. Or whatever triggers they encounter that trigger them to want to self-soothe or improve their performance by taking their substance or alcohol of interest. And it’s a very simple tracking model aimed at getting them to be more aware, so that they can then have more decision over their reality.

The other one is, like the blood pressure example. Where we are trying to achieve, or what’s been going on forever, is the diabetes blood sugar tracking model. Physicians have been asking people to track their blood sugars for a long time now, and it’s actually very useful.

The last realm, I would say, is in the performance improvement category. People who are okay but they want to be better, or they want to achieve a certain goal, whether that is in their body composition or it’s in performance at a triathlon, or it is in their work performance and their attention and their ability to accomplish things.

It’s more of a positive desire to improve by tracking and feeding that. That’s very motivating for me, and yet it is hard to find the people who want to do the self-tracking approach to that, because it’s pretty labor intensive and these tend to be busy people.

So if you’re an Olympic athlete and you have a whole team of people geared up at measuring you, at feeding back and changing your performance and changing what you do, and you have all that support around it, I think people can pull it off, if they’re a competitive high-level professional athlete.

For the regular person without that support team, we have had some challenges trying to construct a model that is both affordable and does not require an NFL team support staff to accomplish, and also doable by people who are also leading lives and not full time training. That’s an on-going exploratory area for us, and trying to find what is a model, in a manageable way.

(37:33) [Damien Blenkinsopp]: In terms of any tools you use, just kind of talking practicalities here, are you just asking people to use a little mobile phone app and put down a note in that, or is it sometimes Excel, or is it basically whatever they need, you’re like, “What would you find easiest to track this metric that I want you to look at.”

[Paul Abramson]: We have been using the mobile phone app that we’ve been working with a developer on called MyMe, which I have been on record has having mentioned over the years, which is a very simple way to just set arbitrary buttons up for whatever they want to track. And set whatever ranges of metrics you want to track, take pictures, etc. and then collate it on a central server where they account is owned by the individual, not by me, but then they choose to share their data with the coach or with me during the sessions.

Otherwise they hold they data and own the data, and we just keep in our files our observations of the sessions with them while looking at the data. And so that keeps it simple from a privacy standpoint and from a daily curation standpoint. And it’s worked fairly well.

We also, if they don’t like that tool or if they have different things they want to measure, we will take a whatever-works approach and try to get them to use other tools, most of which are not geared towards this. Most of them are geared towards other applications, most of the existing tools.

Amazingly, there isn’t a good, flexible generic tool that’s consumer available, where you can also involve a team. And maybe there is. Now, when you can share the data but it’s also designed at helping analyze things and helping collate and curate data.

And so MyMe is working on that. It’s not yet available to consumers, it’s just sort of for clinicians and doctors and people who are working with people who are self-tracking.

[Damien Blenkinsopp]: So there are other people like you working with MyMe?

[Paul Abramson]: Yeah.

[Damien Blenkinsopp]: Okay. Alright. All this stuff we put in the show notes.

[Paul Abramson]: Then there’s various companies that have tracking devices, and each one has their own cloud where they track the data from their own devices, and some of them will integrate data from other devices apps. And it’s coming together in some ways that I think might be good, but it’s been so slow to develop that I’m frustrated.

[Damien Blenkinsopp]: Yeah.

I used to be a telecoms consultant, and I worked in the interactive television market in the UK, which was one of the first markets in the world, and they had this walled-garden approach to it. And we were all talking about the open, like you have to open it up. And it took nearly a decade to happen properly.

And it’s always the same, except for the internet, luckily, which was pretty much open to start with.

(40:13) So, that’s great. What are the biggest challenges you’ve come across in trying to make self-tracking work? Have you had any failed, like – I don’t know how to put it – have you had failed self-tracking projects, where you’ve just been like, “Okay, after six months of tracking let’s just ditch this?”

[Paul Abramson]: Basically, they fall into two camps. One is where the self-tracking paradigm is too much work or isn’t intrinsically rewarding enough for the person to keep them going. Where the time and expense and hassle and all that isn’t worth it, and they drop out once they just get frustrated, or don’t continue.

The other is that their hypotheses are too narrow. The hypotheses they are willing to consider are too narrow. And we explore those deeply and broadly and do not find the answer in that narrow set of hypotheses, and they tire of doing the project, because it seems hopeless.

Whereas, I actually believe that there is always a way, but it may not be a way forward that people expect or desire.

[Damien Blenkinsopp]: So it’s basically like a process of elimination with one experiment, another experiment?

[Paul Abramson]: Well if the only hypothesis is that some food is causing my symptoms, and we just need to find what food, combination of foods, or other environmental physical inputs, are causing my symptoms.

And once we really convincingly do out that experiment, either they are willing to do the experiments, one, and the answer is not food – we believe that for a while. Or they are unwilling to do some of the experiments because they are too attached to certain things.

[Damien Blenkinsopp]: I love coffee.

[Paul Abramson]: Or marijuana, or [unclear 41:55]. Unwilling to give up certain things. But we look at everything else, and everybody gets tired. Those are the places where actually there’s a different paradigm that we need to apply. We need to do a pivot, but they don’t want to pivot.

And then you run into a dead-end in the start-up of events, or start-up company ends, ceases to be. And everybody goes off to do other things, and that is sometimes what happens.

(42:23) [Damien Blenkinsopp]: Great. And you referred to earlier that you had a lot of success with this. Could you share some of the success stories you’ve had? Has this improved your practice, would you say immensely, a bit?

[Paul Abramson]: I would say it has improved it measurably, but not immensely.

[Damien Blenkinsopp]: Immensely is a big word.

[Paul Abramson]: We are still working on optimal paradigms, to make the paradigm match the individual, and to try to bring it into a combination of energy and time and price that can match anybody. And we have not yet figured all that out. So that’s why it’s not immeasurably.

If we can apply these kind of concepts to every patient, and successfully because we can custom make it for each individual than it would be game changing. And that’s what we’re aiming for.

So I say this, successes are where either there is a simple answer, or a complex simple answer. It’s too complex for them to have figured out by introspection and their own tracking, but with some professional help we can get to that slightly more complicated insight that allows a dietary change or experiment or supplements or changes in their medications, or some other intervention to suddenly work. And then sometimes the tracking helps them to implement that intervention.

If it’s a food change, sometimes that takes a lot of time to change habits, behaviors, and family food production dynamics, etc. And sometimes the self-tracking is very supportive in that. Or, we exhaust one avenue of exploration and it gets them to the place where they are ready to consider other paradigms, where maybe it’s not food, maybe it’s, I don’t know, my relationship with my husband and son.

Maybe, as one patient found out, there was some very, very stressful, vexing, and long-standing family dynamics going on at home that clearly, once we got to know them, were contributory to the situation and symptoms.

[Damien Blenkinsopp]: What kind of symptoms, just to give people a reading on this?

[Paul Abramson]: The common classes of symptoms that people come to that are hard to diagnose are fatigue, pain of various kinds, neuropathic pain or muscular, skeletal pain, and gastrointestinal symptoms. And when those are accompanied by relatively normal tests and investigations from a conventional paradigm, many times they run into roadblocks with the conventional medical world, where they say, “Well you’re normal.”

So, you are plunked into a wastebasket diagnosis that doesn’t really describe why, it just describes what is going on in a very descriptive, but not very helpful way. Chronic fatigue syndrome doesn’t, in it’s current form, really help people to move forward, except weight and exercise, and similar things that are not typically very satisfying to people. And when they work, it’s great, but for some people that’s not the whole answer.

It could be very inflammatory conditions and rheumatological conditions that do have objective markers that are abnormal that don’t fit into any paradigm. So that I’m tempted to throw heavy drugs at them. And yet they just run into a diagnoses appended by the word NOS, not otherwise specified, meaning it’s not something that the conventional world takes a strong interest in, because they don’t have a discrete category to put it in.

And so that is one common class of people where sometimes it is what they think it is, because they have been reading blogs on the internet that say that food is the cause. If you change your food, you can cure anything. That is a common paradigm that you read about on the internet, especially people promoting a certain food paradigm, that basically all mystery illnesses should be treatable with food. Or are from some food trigger, that if you eliminate it or figure it out.

Hence the autoimmune protocol diet, which is an extreme elimination diet, or is very specific and very hard to implement, and may help some people, but for most is just, it’s not the end all answer. And so many people come very frustrated and wanting to find [some solution], but they’re still on the food path.

And once we kind of figure out that maybe there are other factors involved, even medical or psychological or social or spiritual, we can come up with a more integrative approach that is much more fruitful for them, either to fix their symptoms or to make it so that the symptoms are not as disabling, or that they can do everything they want to do in life because they’re able to mitigate the symptoms and improve their ability to function with those symptoms.

Because it’s of my opinion that getting the symptoms to go away, while it is always the goal, sometimes in this world there are mysteries, and being comfortable that sometimes there is a mystery and you have to work with it is the paradigm shift that has to happen.

Now, you don’t want to start with that, because ultimately people come to a doctor to get cured. And that’s really the cultural paradigm that we operate in, and I like to acknowledge that, and I like to participate in it, but I also like to continue to try to expand the paradigm to include other things.

[Damien Blenkinsopp]: So you’re saying you can improve the situation as well.

[Paul Abramson]: Yeah. And sometimes actually taking a more open-minded approach about what could be contributing and working on function rather than cure. Improving function rather than the functional medicine paradigm/vision that underline all illness, there is some root cause that you can discover, and once you discover the root cause, everything will get better.

And that is wonderful when it happens, and yet sometimes you have to take a more solution focused and practical approach to, “What do I want to accomplish in my life? How can I get there?” Sometimes that actually causes the symptoms to diminish, even though you never really find out what caused them.

So I think it’s helpful to keep an open mind about that, and yet most people in our society come in with a materialist obsession that it must be some biochemical or discoverable, testable thing that is causing my symptoms. And we have to work with that for a while.

And either it’s true and we cure them and we’re heroes – I get to be Dr. House every so often where I discover that mystery root cause, and it’s beautiful. But other times we have to take a more practical approach.

I think in the psychotherapy world, there’s the Freudian analytic perspective, where you find that one insight from your childhood and then your current problems will get better, or there’s the cognitive behavioral approach where, we’ll let’s just deal with what’s going on now and how you’re going to deal with it, and maybe what happened in the past will sort of take care of itself. And so I think that can be applied to human medicine, or physical medicine, as well.

But I always meet people at whatever level of the materialist spectrum their on, and I go there first. Because ultimately, they need to do the experiment for themselves. They cannot take my word for it.

(49:50) [Damien Blenkinsopp]: Right.

It sounds like a very team focused approach to the whole doctoring thing, which isn’t really traditional. It sounds more from the modern world. I mean, we’re seeing team building and team practices in a lot of what we do in the world now, thanks to corporates and so on. Would you say that it’s changed the way you approach the practice, and the way you work with patients?

[Paul Abramson]: I think I’ve always taken this approach to working with patients. It’s not new to me. And yet, I think you’re right, in the conventional paradigm, it is hard to find. There’s a lot more words and verbiage around this team approach in the healthcare world now because of the politics going on, but in practice it’s still really hard to find a collaborator, someone who is more focused on doing the process right than on the outcome.

And we’re going to really focus on improving the process and changing the process dynamically as we go through working with each individual. That comes from my engineering background in systems engineering and out of control system theory and designing things is that you have to constantly change your approach based on what’s going on. And that takes feedback and communication, and it takes two people who are aligned working together.

Now there is a power differential. I have an MD, I wear a stethoscope, there is some value to that role differential. Someone who is looking for help from a professional who, in theory, has maybe some things to offer based on my experience and training and insights. And at the same time I like to also align with whomever I’m working, and work together so that we’re focused on if the process isn’t working. We can talk about that and fix the process.

If we get to the answer and the conclusion, we can celebrate together. And if that is vexing and takes longer, or is more difficult to find, well then we can pivot together. Or they can separate from this, and they can move on to other paradigms or other people to work with, and that’s fine too.

So there’s less pressure, in a certain sense, on, “I’m going to throw this problem at the doctor and the doctor is going to spit an answer back at me,” because that’s an all-or-nothing kind of proposition. Either it works and you’re happy or, much more likely, it’s not exactly right and somehow there’s been a failure.

(52:16) [Damien Blenkinsopp]: Would you say you need the patient to take some responsibility? The example you just gave is basically where they are saying alright, I don’t have responsibilities, just give me the fix.

[Paul Abramson]: Well, the more responsibly the patient takes, the better. An extreme example is the patient who does not consult a doctor and just does the [unclear 52:31] on their own. And those people exist. There are many of them. They achieve great results and I never meet them, except at Quantified Self.

If you are doing it on your own successfully, then you never meet me as a patient. However, in many cases people get frustrated, or they need new ideas, they need new paradigms, they want to explore with someone who can meet them at their level and have a very, very quick and useful conversation, and then help them to implement.

And I have the tools of pharmacology and laboratory testing and other testing, and access to specialists. You know, I have all the medical tools at my disposal, if they are appropriate.

[Damien Blenkinsopp]: And the experience. It’s all good doing an n=1 experiment, but if someone has been overseeing hundreds of experiments they learn things from those experiments in themselves, which could be relevant to you case.

[Paul Abramson]: I think so, except I’m continuously amazed at how individual people are. Even in problems that are relatively, I would say, conserved among individuals, like alcohol and the human brain. It’s really not that, there are only a few different ways that that tends to manifest on an obvious level, how people relate to alcohol, and yet their individual circumstances and details are unique, which makes every approach unique.

And so I say, I have gotten some insights from the self-tracking that apply to others. I think it is hard to take measurable insights and extract it in a medical, steady kind of way. And that’s why I continue to not be afraid of computers taking over my job, because ultimately I think there is a combination of metrics and data, and also presence and attention and experience that work together, and that’s why I think the medical profession has hope.

If you can provide presence, and attention, and experience, and knowledge, and then integrate data into that, you can actually be helpful to someone more frequently. And so that’s why I do what I do.

(54:41) [Damien Blenkinsopp]: Paul, I also just wanted to find out a little bit about you, and what you do with yourself when it comes to the Quantified Self, or any kind of tracking of metrics or biomarkers. Is there anything that you track for yourself on a routine basis, or you’ve explored, potentially?

[Paul Abramson]: Right now I’m tracking sleep, mostly just sleep duration. I think I’ve gotten the insights about sleep quality from various previous tracking endeavors. More as a behavioral thing to try to get myself to lie down more, which is particularly vexing for me.

And I’m tracking weight and body composition as I do different dietary experiments. Partly for my own health, and partly just to experiment with different dietary approaches. And, I’ve done many experiments when I have had problems that I wanted to fix, or wanted to understand better.

And some of them haven’t been fixable, but I understood them better and that helped me to deal with them. Headaches, and other things that I’ve talked about in the past. So I would say I use my baseline as I’m not doing lots, and lots of time intensive of self-tracking, because I don’t have the time involved.

The investment of time and resources is more than my available disposable resources, and the problems aren’t serious enough to warrant giving up other things. But when something important comes up, I start to implement more tracking.

(56:03) [Damien Blenkinsopp]: Right, right. So, in terms of the sleep quality you mentioned, what do you use to track that? Because I know sleep is a bit of a tricky area to track. Are you using MyMe today to track your hours, or what are you doing for that?

[Paul Abramson]: It all started with the Zeo – rest in peace – which allowed you to get some, albeit not 100 percent accurate, EEG data out of your sleep and sleep stage, and it was very nice. I didn’t mind wearing a headband every night, which some people found objectionable.

Now there are better tools, some of which I’ve experimented with, from Withings and ResMed and Beddit, where they’re less invasive tools to track your sleep that don’t require a headband. I think right now I’m using just an app on the phone that lays on the bed and has an alarm built into it and tracks start and end time of sleep.

It also records sounds, so if you snore it will give you all the snippets of snoring through the night. It’s just a simple app on the Iphone. I think I use the simplest tool for whatever I’m actually interested in. So right now I just set my alarm, and when it wakes me up I know how much time I was asleep.

And I have some subjective notes I take about that, like how was my sleep. And I’ve found that those notes correlate pretty well with reality when I’ve used actual medical sleep tracking devices that you use for sleep studies on myself in the past.

I’ve found that Zeo correlated well enough that I could actually use that data. And now I don’t actually need the Zeo even to know what’s going on with my sleep, because I know what it feels like.

[Damien Blenkinsopp]: I actually do the same as you, I just track the number of hours I sleep with a little timer on my Iphone. I just click it when I go to sleep, and I click it when I get back up.

Out of interest, how many hours do you sleep? What do you consider good or bad?

[Paul Abramson]: My personal ideal is 8 hours, almost exactly. 7.9 to 8.1, somewhere in there. And when I get that much…

[Damien Blenkinsopp]: You feel better?

[Paul Abramson]: Everything improves.

[Damien Blenkinsopp]: That’s good.

[Paul Abramson]: Both subjective and objective.

[Damien Blenkinsopp]: And have you got any little tools that have got you there? Because I’m always at seven. I’m always trying to get to eight but it’s hard.

[Paul Abramson]: Right. Well my particular app tracks over the last 14 days what my cumulative sleep deficit is compared to eight hours.

[Damien Blenkinsopp]: That sounds scary.

[Paul Abramson]: It is. And so when I get up above 10 to 15 hours of sleep debt in two weeks, other people don’t behave as well. I mean, that’s my observation. I’ve found that I’m not performing as well, and it manifests as the external world not cooperating.

[Damien Blenkinsopp]: That’s interesting. That’s good, then it goes back to you saying not everything is about food, and sometimes it’s the other psychological or emotional things, which are probably harder to identify.

(58:55) What would be your number one recommendation to someone who is trying to use data to make better decisions to improve their health, performance, or longevity, or any aspect of themselves?

[Paul Abramson]: I would define a relatively simple goal that actually really matters to you. Either it’s something terrible that you want to fix, or it’s something really juicy and rewarding that you want to achieve, and then set up as simple a self-tracking experiment as you can. Most people cannot pull off complex self-tracking unless they have diagnosable obsessive-compulsive disorder, or some spectrum of that.

So you have to just start with simple things that are as easy to track as possible, and some goal that’s really motivating, so you have the best chance of actually doing it, and seeing if this modality, if this type of thing, works for you. Some people find it intolerable, some people find it absolutely fascinating and motivating. And you can always add complexity later.

And then if you try, and it’s a great modality for you but you can’t pull it off, you need more accountability or more insight or more help designing experiments, that’s when you involve a coach all the way up through a medical doctor who’s interested in this kind of thing.

[Damien Blenkinsopp]: Great, great. Thank you for that great recommendation. Totally agree with it.

(60:00) So what would be the best ways for people to connect with you? Is it Facebook or your website, or where do people usually [reach you]? Are you active anywhere, or how else would people try to connect with you?

[Paul Abramson]: I’m variably active on Twitter, at PaulAbramsonMD. We do have a Facebook page and Google+ page. I’m easily findable on the internet. I usually do respond to social media.

If people want to become patients at my documedical group, my practice in downtown San Francisco, they can just call us up and we can describe how it works and how people can come in. I usually don’t work as patients with people that I have not met and examined, for personal and professional reasons.

[Damien Blenkinsopp]: Yeah, isn’t that a legal requirement in California?

[Paul Abramson]: It’s subjective. And yet I find that my intuition and my ability to be helpful to people improves dramatically if I have sat in the room, if I have had sometime in a room with them, and if I have laid my hands on them and examined them. Things work out much better.

I have tried both ways, and so I’ve just decided that I’m going to meet with people who can meet with me here in San Francisco. And that does restrict my ability to work with some people.

Otherwise, I can have theoretical conversations with people. My time is pretty darn limited in terms of how much banter I can do on social media, but I do my best to be available.

(change)[Damien Blenkinsopp]: Excellent. Alright, so we’ll put all of those in the show notes, and your website of course. Is there anywhere else you would suggest people look to learn about Quantified Medicine, for want of a better term. Are there any resources you’ve come across that you found helpful, and might be helpful to people?

[Paul Abramson]: Well the Quantified Self movement – it’s really more of a movement than an enterprise – but it holds meet ups all over the world, in many cities, and it also has an annual conference, or semi-annual I think, in the Bay Area. And frequently there’s the one in Europe.

So that’s a wonderful community to connect to where there’s an inner sanction of people of all different persuasions. And so you can always find someone who wants to do something similar to you in that community, because it’s a very heterogeneous community.

As far as others, there are so many different things going on in medicine around self-tracking. I think the reason Quantified Self appealed to me is that it does not have a strong vested financial motivation or conflicts of interest. And so you can go there and everybody is pretty much there just to be there. There are some people tying to sell things, but they stick out pretty obviously.

And it’s very egalitarian and anybody can speak. So I like that, whereas everything else you have to filter through the business model perspective. If you can do that, especially here in the Bay Area and in Western Europe there’s a lot of enterprise going on around this.

So it’s more about finding things that speak to you. I don’t have any particular points of focus.

[Damien Blenkinsopp]: Great, thanks. Well Paul, thank you so much for your time today. I really appreciate it. It was a great discussion.

[Paul Abramson]: You’re very welcome, it’s been great to be here.

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Is the Fast Mimicking Diet (FMD) an easier way to get the benefits from fasting? In this self experiment I tracked lean muscle mass gains, improved metabolism (ketones, glucose), strong regeneration signaling (IGF-1) and a couple of downsides.

Last month I undertook my first 5 day water fast. It is turned out to be a really helpful tool for my health and productivity, so I committed to make it a monthly ritual for 12 months.

With each month the plan was to push the edge a bit to learn more from the experience – refining the approach to the fast with the different options available and tracking the results to see what could give me the biggest payoff for least effort.

Enter the “Fast Mimicking Diet” – an easier and safer way to get the same benefits as pure water fasting. It created a spark of media coverage around it following the publication of a new research paper on it in June 2015. Two of the articles actually had two journalists become fast mimicking diet guinea pigs for 5 days (Peter Bowes at the BBC, and Victoria Lambert at The Telegraph).

It’s clear to me that most people will never do a water fast because it looks like a psychological feat fit only for diet equivalent of extreme sports fanatics. So the Fast Mimicking Diet was an obvious choice for fasting experiment #2.

If it does make the fast much easier – I just might be able to persuade some more of you to take the jump and grab some of those upside benefits for yourself.

What is the Fast Mimicking Diet?

Prolon l-nutra
Photo: L-Nutra

The exact details of what the Fast Mimicking Diet is in terms of food breakdown aren’t available publicly. Which in part, can be explained by the fact that the main researcher behind the fast mimicking diet, Valter Longo, owns a patent on the FMD (published January 2015) and a company which has designed a comprehensive packaged FMD dietary product ProLon.

For our purposes though there is enough information available to put together our own version of it. The Fast Mimicking Diet I used and the other versions below, are based on some very specific FMD design points found in Longo’s January 2015 patent and the June 2015 study (the macro and micronutrient do’s and don’ts).

The nutrition rules established for the Fast Mimicking Diet are:

  • Each month (3 / 4 cycles in studies): 25 days eat normally, 5 days FMD
  • High micronutrient content (i.e. greater than 50 percent by weight) from natural sources
  • Ketogenic: Restricted protein and a high percentage of calories from fat

In practice this translates to:

  • Day 1: 54% norm caloric intake 1,090 kcal (10% protein, 56% fat, 34% carb)
  • Days 2–5: 34% norm caloric intake 725 kcal (9% protein, 44% fat, 47% carb)

For the nutrition geeks out there I’m sure you’re already thinking up some Fast mimicking diet recipes to play with. For most of us though, this sounds pretty much like techno-babble… Don’t worry though, there’s a much easier way to look at the FMD.

Fast Mimicking Diet Recipes

avocadosIt turns out that days 2 to 5 are pretty much equal in calorie intake and macronutrient ratios to just 2 normal sized avocados (based on NutritionData numbers here).

That’s one avocado for breakfast. One avocado for dinner. Done.

For simplicity sake, you can just run all 5 days that way.

(Note: Sizes of Avocados vary depending on origin. Florida origin avocados are larger, and California origin smaller for example. If you’re using the smaller variety, it will be 3 avocados per day).

Then you need to take care of the micronutrients. For that you take 4 tablespoons of broad spectrum greens powder (a supplement made from dehydrated vegetables).

So your day ends up looking like this.

  • Morning: 1 Avocado + 2 tablespoons of greens powder
  • Evening: 1 Avocado + 2 tablespoons of greens powder

That takes all of the thought out of it.

Note: For those who are more ambitious, Josh Mitteldorf has posted some FMD recipes that you can put together.

itunes quantified body

The Fast Mimicking Diet Experiment

The Specific Fast Mimicking Diet Variation Tested

My personal goal for this experiment was to emphasize regeneration of the immune system – and I’m impatient about it. So I used a reduced FMD this time to ensure that I was giving my body as strong as possible starvation signal, while supporting its processes. For this reasons I cut out the macronutrient intake (the avocados) and only went with the 4 tablespoons per day of greens powder (micronutrient intake).

So the experiment results you’ll see below are from a modified FMD – just the micronutrient intake.

Specifically this is what I consumed during each of the five fast days:

  • 4 tablespoons of greens powder
  • Filtered water with real salt added
  • 2 cups of black coffee
  • Activated charcoal from time to time as a gut toxin binder

Biomarkers Tracked to Understand Benefits/ Risks

For the biomarkers I used Fast Mimicking Diet study as the basis, basically copying their timing and tracking with just one – albeit quite large – difference

In the study they tracked their post intervention results after 3 cycles of FMD. I would only be doing it after 1 cycle. For this reason the results could be expected in my case to be less significant – that would be the assumption, however it’s not what happened.

Biomarkers Tracked by Area

the-tracking-fmd

5 Day Fast Mimicking Diet Results

Metabolic Switch to Ketones a Day Earlier than Fast #1

My metabolism switched from glucose to ketones one day earlier than in my first 5 day fast. Like last time the fast “felt easier” once I’d switched from glucose to ketone metabolism. So by the afternoon of day 2 of the fast the hunger pangs or discomfort had pretty much gone.

At their peak, my ketones were just a little higher than last time at 7.3 mmol/L. This was 29 times my baseline, which is a lot higher than the average 9 times above baseline noted in Longo’s Fast Mimicking Diet study. We have an interview with another guest coming up in the next weeks discussing the importance of this variation in ketones (higher variation = better).

My blood glucose dipped a little lower this time also settling in at a consistent 57.5mg/dL in the fasted state. This is 64% below my baseline vs. an average 40% below baseline from the study.

Metabolism: Blood Glucose and Ketones

Ketones and Glucose Fast Mimicking Diet

I continued to track ketones and glucose after the fast ended at the 120 hour mark (end of 5 days). So it’s interesting to note that it took my body 2 days to really switch back out of ketone to my normal metabolism once the fast was ended.

Looking at Seyfried’s Glucose-Ketone Index (GKI) (from episode 16) the fast was shown to be more effective this time round. In the chart below you see #1 Water Fast compared to #2 Fast Mimicking Diet. In this 2nd fast my body spent 18 hours longer in Seyfried’s therapeutic zone for cancer (lower than an index of 1) than in the first. That extended the therapeutic window to 71 hours – an impressive total of nearly 3 days.

Metabolism: Seyfried’s Glucose Ketone Index

Glucose Ketone Index Fast Mii

My assumption here is that it’s the fact that this is my 2nd fast that my body switched to ketone metabolism quicker this second time. It’s a pretty significant change compared to my first fast, so unlikely to be just variance. It’s possible that my version of the FMD somehow supported this also – but my bet would be that its my body having learned to adapt to the fasted state quicker. Future fasts will provide more insight around this.

Does the Fast Mimicking Diet = Lean Gains?

In my last fast I ended up being concerned that I’d lose weight every fasting cycle and if repeated monthly eventually ending up a skinny strawstick version of myself. More concerning, I was wondering if it was lean muscle mass that I was losing.

This time round I had the BodPod to control whether it was lean mass or body fat I was gaining or losing. In addition, the FMD study shows a slight lean mass gain on average for people doing cycles of FMD. Although mine was a minor version I was hoping to avoid a decline in weight as with last time.

Using my Omron scales there was a 1.7kg (3.7lb) from baseline to day 7 after the end of the fast (day 12).

Weight (Kg) via Omron Home Scales

Weight-gain-fast-mimicking-diet

The BodPod results were even more promising. It turned out that I had gained nearly 3lbs (1.3kg) of lean mass over the 12 days. The body fat change was negligible.

Body Composition (Kg) via BodPod

fast-mimicking-diet-lean-gains

Note: You’ll notice that the Omron scales and weighing scales used with the BodPod did not agree. A reminder of the importance of using the same device to track whenever possible due to inter-device variances. The BodPod is the more accurate.

Regeneration & the Immune System Reset

And we come to the last but in my opinion most important item. Did the biomarkers show an indication that my body and immune system had regenerated as has been shown in Longo’s study?

The IGF-1 results are promising. There was a nice drop of IGF-1 44% below baseline. This compares with an average of 22% reported in the study. The BBC journalist Peter Jones, one of the study’s participants, had a drop of 60%. The hope was to see a significant drop and recovery of IGF-1 like this as it correlates with the gene signaling required for regeneration. Also of note my baseline IGF-1 levels hover between 115 and 120 ng/mL – these are below the typical reference range for my age (132-​333 ng/mL) likely due to my long term ketogenic dieting (~7 years with different variations at this point).

IGF-1 (Insulin-like Growth Factor 1)

igf-1-fast-mimicking-diet

The bigger interest for me was the immune system of course. The results here were a little disappointing – very hard to judge if anything happened. In the study they noted bigger changes in one class of white blood cells: Lymphocytes. This held true in my results with a larger % drop from baseline compared to all white blood cells.

White Blood Cell and Lymphocyte Counts

white-blood-cells-fast-mimicking-diet

Anecdotally, the situation is personally clearer for me. As with my first fast I had a period of a week after the fast where flu-like symptoms and fatigue taxed me. With this 2nd fast it lasted a little longer, extending to between one and a half and two weeks.

Since that time I’ve noticed once again a bump up in my perceived wellness. Less fatigue. More energy. Less symptoms in general from the lyme and babesiosis infections I’ve documented (see the complete story behind these in the last experiment intro).

So, again, the fast has been worth it for me.

But it’s not a black and white story. As we’ll see in the next section…

The Opposition: Adrenal Fatigue

Fasting is known to stress the adrenals, and for me personally this is a particular concern, since I already have documented low adrenal function. To continue my monthly fasting cycles I decided I would have to see improvement in my adrenal function compared to a baseline I established last November 2014.

Having been on treatment since March 2015 to support recovery of the adrenals I would have expected some progress. However, I felt that the fast may counteract that progress potentially. Or exacerbate it.

This may or may not have been the case. However, the results of my adrenal functional profile show continued deficiency compared to the low normal reference range.

Adrenal Functional 4-Point Cortisol Panel (Morning & Total)

adrenal-function-panel-fasting

While the fast has in my opinion lived up to the studies in terms of reseting and regenerating my immune system to some extent – it’s probably also true that it has not helped my adrenal recovery.

It wouldn’t be wise (or responsible) to continue this cyclic fast given this downside.

Potential Confounders for these Results

I’ve discussed what in my opinion are the most likely takeaways from the results so far. However, there are other possible explanations. These are the potential biases that I’ll keep an eye out for or/ and try to eliminate in future fasts.

    Metabolic Switch

  • Positive bias: Long time ketogenic/ high fat diet (5 years) which may mean I’m an outlier compared to the population with respect to switching to ketone metabolism.
  • Negative bias: Documented high inflammation biomarkers last 3 years (this tends to disrupt glucose regulation, and indeed my HbA1c numbers and fasting glucose are not as good as before this inflammation – tropical infection driven)
  • Lean Mass Gain

  • Positive bias: Creatine Monohydrate supplementation ongoing for most of the last 3 years with some breaks here and there. Last 3 months consistently. Could the 5 day break from creatine for the fast, then retaking in post 7 days have an impact? Doubtful that it would be this significant.
  • Positive bias: Currently I have a low lean muscle mass compared to historic norm due to a large amount of muscle mass I lost the last 3 years (again infection driven). This could account for a greater increase for my personal situation as my health normalizes and may not be repeatable in future cycles.
  • [?] bias: Diet change. I’ve increased the amount of resistant starch type 3 in my diet since just after Fast 1 and a few weeks before Fast 2. This means I am eating more carbs in my baseline diet. This did not change between beginning and end of the fast 2 testing period, but it is a longer term change.
  • Adrenals

  • Positive bias: Adrenal Supports. I Have been taking adaptogenic herbs and adrenal complex since March 2015, theoretically this should have led to some improvement.
  • Negative bias: There was a 3 day coffee roadtrip binge between Fast #1 and Fast #2 where I consumed 3 X coffees plus per day. A lot of fun but pretty irresponsible given my adrenal situation. This could be a greater factor in the negative results than the fasts.
  • White Blood Cells

  • [?] bias: Documented suppressed immune system for last 3 years? (consistently bottom 10-15% of normal reference range)

The 5-Day Fast Mimicking Experience

About the experience of the FMD itself – there’s not a lot to say beyond the fact that it felt much easier.

None of the symptoms I experienced last time occurred. There were no headaches like last time. There was less dizzyness when getting up quickly. Also no skins rashes. I’m tempted to attribute this to the micronutrient support provided by the green’s powder the idea being that it provides the nutrients required for detoxification and liver processes amongst others, thus better dealing with a potential increase in toxic load from lipolysis (breaking down body fats which tend to store fat soluble toxins).

Also I did more physically. On day 5, the last day of the fast, I went on a trip to London to a couple of labs to get blood labs and BodPod tests done. This wasn’t a big deal and I didn’t feel weak in doing so. This compared with the first time where on the 5th day the physical weakness was a lot more noticeable.

Potentially on day 4 and day 5 I noticed my stomach a little more than with the water fast. In my first water fast I had pretty much dropped the issue of eating or being hungry. But with this time round, possibly because I was taking the green powder- I was more aware of my stomach, and a little grumble here and there. But it was marginal and not really uncomfortable. Just slightly different.

Personally, I’m not 100% sure that all of these differences I’ve noted are absolutely physiological. Some of it could be put down to feeling a lot more comfortable in the fasted state due to having already done it before. I’d say some of it could be just me expanding my comfort zone and getting along with things while paying less attention to the fasted state.

Next Steps – A Change of Plan

While I would love to continue the fasting cycles, and I would even feel comfortable doing it as a “life routine” given the upside benefits, for now I’m going to give it a break.

The next few months I’m going to focus on adrenal recovery – with additional supports – to try to get that parameter moving in the right direction.

Once they have stabilized or shown progress I’ll come back to the fasting cycles for more…

What I’d Like to Explore Next

I’d like to explore a few of the ideas that have come up this time in future fasts:

  • Metabolic adaptation: Will my time to switch to ketone metabolism get shorter the more fasting cycles I do?
  • Lean Gains: Is it possible to continue to gain lean body mass with repeated FMD cycles?
  • Full FMD: I imagine for my next FMD I’ll take the avocados too. This will help to make the fast safer as a reintroduction after working on my adrenals. Otherwise I’d like to know how the full FMD compares to my micronutrient only FMD.

Have you done some kind of fasting before? What was your experience like? And what other types of fasting are you interested in learning about? Let me know in the comments.

Tracking

Biomarkers

  • Blood Ketones (Beta-Hydroxybutyrate / β-hydroxybutyrate): Blood ketones are the gold standard for measuring your state of ketosis. During the fast, ketones are expected to peak in the range of between 6 and 7 mmol/L based on Seyfried’s work and experience. In episode 7 Jimmy Moore notes that values over 1.0 on your blood ketone monitor give you the benefits of ketosis, and there is no need to go over 2.0. Tim Ferriss also prefers this range, noting that his best mental performance is typically with values between 1.1 and 1.7 mmol/L.
  • Blood Glucose (mg/dl): A measure of the level of glucose in the blood at one point in time. Dr. Seyfried’s therapies target reduction of blood glucose levels to limit cancer cell growth, and according to his theories high blood glucose is a biomarker of increased cancer risk. For the fast he notes values between 50mg/dL to 60mg/dL are standard. Non-fasting values should be below 80mg/dL ideally, and at least 92mg/dL.
  • Glucose-Ketone Index (GKI): The ratio between the concentration of glucose in the blood to ketone bodies in the blood. The calculation is Glucose (mmol)/ Ketone (mmol). Dr. Seyfried created the index as a better way to assess metabolic status. Therapeutic efficacy is considered best with index values approaching 1.0 or below. Patients with chronic disease like cancer have consistent index values of 50 or more.
  • Weight (lbs, Kgs): Standard weighing scales measurement of weight in morning without clothes (to avoid biases).
  • Lean Body Mass (lbs, Kg): Sum of weight of all non-body fat weight in the body. Calculated by combining your weight with a lean body mass % estimate.
  • Body Fat (lbs, Kg): Total bodyfat weight for your body based on a calculation using your weight with a bodyfat % estimate.
  • IGF-1 (Insulin-like Growth Factor 1): In caloric restriction and fasting IGF-1 drops, while consumption of high glycemic carbohydrates and protein spike IGF-1. Measured in ng/ml (or nmol/l in the UK). Normal ranges vary by age and gender (see reference here). More info on IGF-1 and its uses here. (Note: Damien’s baseline levels are 119 ng/ml, just below the “standard reference range” for his age group).
  • WBC (White Blood Count): A count of white blood cells found in the blood, low levels can indicate immunosuppression, while high levels can indicate an existing infection with active immune response.
  • Lymphocyte Count (White Blood Count): A count of white blood cells found in the blood, low levels can indicate immunosuppression, while high levels can indicate an existing infection with active immune response.
  • hs-CRP (hs C-Reactive Protein): A common marker of inflammation. As a general rule, the closer your marker comes back to 0, the better. Consistent values of 1mg/L or over are indicative of cardiovascular risk. Measured in mg/L. We discussed this marker in detail in episode 26

Lab Tests, Devices and Apps

Lab Tests

  • Functional Adrenal Stress Profile (BioHealth 201): Damien uses this adrenal functional panel based on recommendations from practitioners and his physician on its higher sensitivity and accuracy to diagnose status of adrenal function compared to others on the market.
  • Hematological Profile: Also known as Complete Blood Count (CBC). A standard test providing information on your blood cell breakdown including red blood cells, and white blood cells. Can be run with virtually any lab test company and is used routinely as a first screen by physicians and in hospitals for diagnosis.

Devices

  • Blood Ketone/ Glucose Monitors: The Precision Xtra in the U.S. or Freestyle Optium Neo in the UK are the current recommended monitors. You’ll need lancets, ketone strips and glucose strips also.
  • Ketonix: Damien used the “Ketonix Sport” during this experiment to compare the results with those of the blood ketone results. The results from the Ketonix did not correlate very well with the blood ketones measured – so we’ll be sticking to tracking blood ketones directly in future self-experiments.
  • BodPod: An accurate approach to measuring your body composition and separating out your % lean body mass (muscle, organs, bone) vs. your body fat. You find BodPods in some high end gyms, but more often in fitness labs.
  • Omron Body Composition Monitor: Used by Damien for his home weighing scales although he no longer uses the body composition functionality as he finds the bio-impedance technology used too variable. As noted in this experiment the weight metrics turned out to be a fair bit different to the BodPod more accurate standard also.

Tools & Tactics

Diet & Nutrition

  • Fast Mimicking Diet (FMD): Also known as the periodic fast mimicking diet, since studies to date have focused on using 3 to 4 cycles of 5 days on the diet each month. The main summary paper, “A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan” was published in the Journal of Cell Metabolism in June 2015.

Supplements

  • HealthForce Greens Powder: The greens powder Damien used in the experiment. There are many greens powders on the market of varying quality. Another one he’s used in the past is Amazing Grass Greens Powder.
  • Activated Charcoal: A broad spectrum binder used to bind to toxins in the gut and carry them out. There are high cost versions such as Activated Coconut Charcoal (potentially less contaminants) and lower cost versions such as this. If you buy others check the ingredients – they often have added sugar and other undesirables.

Other People, Books & Resources

People

Additional Charts and Data

Click Here for Additional Charts

Inflammation (hs-CRP)

There was no significant change in hs-CRP which was in line with what was expected from the fast mimicking diet study. In the study out of range (over 1 mg/l) values will normalize to under 1mg/l, however in range values like mine see little change.

hs-CRP (C-Reactive Protein)

hs-crp-fast-mimicking-diet

References:

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Oxaloacetate is an important metabolic intermediate in the energy pathway of the mitochondria. Recent case studies support the use of oxaloacetate as a nutritional supplement to help regulate blood glucose levels, potentially support longevity and protect the brain.

Can you get similar beneficial results from a nutritional supplement as you can from a water fast (previously discussed in episode 16 and episode 28)? Oxaloacetate supplements (also discussed in this episode with Bob Troia) are currently being studied for their use in improving blood sugar regulation and potential anti-aging properties.

…through the clinical trial that was done. We know that 100mg [of oxaloacetate] was effective in reducing fasting glucose levels in diabetics.
– Alan Cash

Alan Cash is a physicist who has spent years researching the effects of oxaloacetate. Through his efforts and travels he has seen great success for terminally ill patients and more who use oxaloacetate to supplement their health. Cash helped stabilize the molecule so that it could be used as a nutritional supplement and continues to advocate and study its use so that more research and clinical trials can continue to support its use.

In this interview we get into the nuts and bolts of how oxaloacetate works, the current studies underway, and some different ways you can use it depending on what benefits you are seeking.

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

itunes quantified body

What You’ll Learn

  • The implementation of a calorie restriction diet may work to consistently increase your lifespan and reduce any age related diseases (6:19).
  • Calorie restriction seems to affect the energy pathway of the cell (9:20).
  • We can essentially “bio-hack” our systems by tricking the cells into thinking that the NAD to NADH ratio is high so that fat production is reduced (12:50).
  • Human trials have shown that calorie restriction reduces fasting glucose levels and atherosclerosis (13:46).
  • Reducing age related diseases will increase the average lifespan and increase the maximum lifespan for every cell in the body (14:32).
  • Oxaloacetate is an important metabolite involved in one of the energy pathways in the mitochondria, the power house of a cell (16:20).
  • Oxaloacetate is used in the Kreb’s cycle to oxidize NADH to NAD (17:09).
  • A human clinical trial in the 60’s demonstrated that the use of oxaloacetate as a nutritional supplement reduced Type 2 Diabetes symptoms (20:00).
  • As the dosage increases from the minimum 100 mg other system processes occur, such as the reduction of high glutamate levels, which is one of the damaging factors for closed head injury/stroke victims (22:33).
  • A medical food called CRONaxal contains a large dose of oxaloacetate which, when used in conjunction with chemotherapy, can reduce tumor size and sometimes stop tumor growth completely in patients with brain cancer (26:07).
  • Fasting/a calorie restricted diet is another technique that has been shown to slow brain tumor growth (27:53).
  • Some cancer patients have already seen results with oxaloacetate supplementation and calorie restriction diets, however these are just individual cases and not clinical trials (28:46).
  • Recently, clinical trials have begun to study oxaloacetate as a treatment for different conditions such as mitochondrial dysfunction, Parkinson’s disease, and Alzheimer’s disease (30:13).
  • Oxaloacetate may also work well to reduce inflammation and increase neurogenesis in the brain (32:30).
  • Oxaloacetate may also become an important supplement for athletes who encounter severe head injuries during their sport (34:30).
  • Long term potentiation, the restoration of the ability to learn, may improve for patients after a stroke or closed head injury if oxaloacetate is used in combination with acetyl-l-carnitine (36:18).
  • Alan Cash spent years proving to the FDA that there do not seem to be any negative effects found with taking large doses of oxaloacetate (38:35).
  • So overall, oxaloacetate has an immediate pharmacological effect on the glutamate in the brain and a long term genomic effect on the mitochondria (46:30).
  • When trying your own experiment, take a daily fasting glucose level for a couple weeks to see the normal variability and then follow with oxaloacetate supplementation along with daily reading of your glucose levels (48:06).
  • The biomarkers Alan Cash tracks on a routine basis to monitor and improve his health, longevity and performance (55:29)
  • Alan Cash’s one biggest recommendation on using body data to improve your health, longevity and performance (58:49).

Alan Cash

  • Terra Biological: Alan Cash’s company which produces the stable form of oxaloacetate.
  • Oxaloacetate supplementation increases lifespan of C. elegans: The original study published by Alan Cash on PubMed.
  • : you can contact Alan Cash with questions using this email address.

Tools & Tactics

Supplements & Drugs

Oxaloacetate is available in a few versions in the market today – all of these come from Alan Cash’s company since he developed the proprietary method to thermally stabilize it and as such make it usable. A number of studies on Oxaloacetate were mentioned in this interview – see the complete PubMed list here.

  • benaGene Oxaloacetate: The nutritional supplement (100mg) version of Oxaloacetate to promote longevity and glucose regulation.
  • CRONaxal Oxaloacetate: This version of oxaloacetate is a medical food (containing oxaloacetate) which, when used with other treatments such as chemotherapy, has been shown to significantly improve outcomes and quality of life for cancer patients.
  • Aging Formula Oxaloacetate: Dave Asprey’s supplement is the same as the benaGene version of Oxaloacetate.
  • Acetyl-l-Carnitine: Mentioned with respect to a study where a combination of oxaloacetate and acetyl-l-carnitine reduced long term potentiation impairment in rats.
  • Metformin: A drug which is used to improve blood sugar regulation in diabetes. Researchers are looking at its wider applications as a knock on effect from improving blood sugar regulation to cancer and aging.

Diet & Nutrition

  • Calorie restriction: this dietary regimen involves a significant decrease in daily calorie intake and has been shown to slow the aging process as described in this review article. You can learn more about the potential benefits and the arguments against the anti-aging benefits of calorie restriction in episode 14 with Aubrey De Grey.
  • Fasting: The fasts referred to in this episode were complete water fasts that were also being used in combination with oxaloacetate in order to attempt to “stack” the effects and get better outcomes. The examples given were case studies of cancer patients (no clinical trials have been completed as yet). For more information on fasting as a possible cancer treatment see episode 16, and episode 28 on our water fasting self-experiment.
  • Calorie Restricted Ketogenic Diets: In a similar light to above, the anecdotal cases discussed for cancer were patients use of ketogenic diets (that put you into ketone metabolism, by restricting carbs and protein, and emphasizing fat) which were also calorie restricted. This involves stacking two nutritional strategies: ketogenic diets have been shown to be therapeutic for some conditions like alzheimers and blood sugar regulation related problems as has calorie restriction in general. Then some of these cases were also combining the use of oxaloacetate, again to try to stack the effects from these three tactics to further improve outcomes. See episode 7 for complete details on using ketogenic diets as a tactic to improve health.

Tracking

Biomarkers

  • Blood Glucose Levels (mg/dL): A measure of the level of glucose in the blood at one point in time. Fasting blood glucose levels are specifically taken when you have not eaten for at least 8 hours and optimally would be between 75 and 85 mg/dL. Health concerns with blood sugar regulation such as diabetes risk start to rise over 92 mg/dL. After taking oxaloacetate for many weeks Alan Cash suggests that your fasting blood glucose should vary less when compared with any control levels. These levels can be measured at home using a glucose monitor and glucose testing strips (an explanation for the use of glucose monitors can be found in this episode).

Other People, Books & Resources

People

  • Hans Adolf Krebs: Krebs is best known for his discovery of the citric acid cycle, or Kreb’s cycle, which is the main energy pathway of a cell.
  • Dominic D’Agostino: Well known for his work with ketogenic diets and performance.

Organizations

  • Calorie Restriction Society: This organization is dedicated to the understanding of the calorie restriction diet by researching, advocating, and promoting the diet through regular conferences, research studies, and forums.

Other

  • Kreb’s Cycle: oxaloacetate is one of the components involved in this energy pathway in the mitochondria of a cell.
  • NAD/NADH: the effects of oxaloacetate in the Kreb’s cycle changes the ratio of NAD and NADH in the mitochondria which in turn affects the energy available to the cell.
  • Orphan Drug Act: This law passed in the US in 1983 has provided more opportunities for researchers and physicians to pursue drug development for rare, or “orphan”, disorders.
  • Calorie restriction PubMed results

Full Interview Transcript

Click Here to Read Transcript

[Damien Blenkinsopp]:Alan, thank you so much for joining the show today.

[Alan Cash]: Oh, thanks. It’s always a thrill to talk about oxaloacetate.

[Damien Blenkinsopp]: First of all, I’d just like to get a bit of background story as to why you got interested in this at first. What’s the story, basically, behind how you got interested in oxaloacetate, and started getting involved with it?

[Alan Cash]: That’s a pretty weird story.

It turns out I had a brain condition where nerves sometimes grow very close to arteries. I had an artery that wrapped around my nerve. Every time my heart beat it acted like a little saw and eventually cut in through the myelin sheath that surrounds the nerve and protects the nerve, and went directly into a nerve bundle that was a major nerve bundle in my neck. And the result was instantaneous pain.

I found out that I was very lucky; I was able to get it corrected. They just went into the back of my head and followed the nerve until they could find where it crossed over, and they untangled it and put in a piece of Teflon. So now I don’t stick, but the pain is 100% gone, which is really nice. A miracle of modern science, because it was pretty terrible.

In looking up this condition, I found that it was really a condition of aging. As we grow older, your arteries get about 10 to 15 percent longer, even though we’re not getting 10 to 15 percent longer. So they have to fold over, go someplace, and it was just bad luck that it folded over next to this nerve.

As a physicist I thought I’d look into aging and see, whats the current state of what we can do about aging. And thankfully at that time there was a lot going on with the basic fundamentals of aging and trying to understand this, and looking at all the data that’s out there. That’s what physicists do; we take a huge amount of data and see where the kernels of truth are. We try to think of E=MC2, or F=MA, how much that describes about the universe.

And looking at the aging literature, the thing that stood out the most is almost nothing works, which is disappointing. The one thing we did find that worked consistently throughout the animal kingdom was calorie restriction. That was discovered back in 1934 in Cornell University.

It’s not just the diet. It’s essentially establishing a baseline of what you’d eat if you had all the food available, and then backing off that baseline anywhere from 25 to 40 percent. And when you do that consistently over a long period of time, we see several things. One, we see an increase in lifespan. Not just average lifespan of the group, but the maximal lifespan is also increased.

For small animals that live short times, that could be anywhere from 25 to 50 percent increases. In primates, we’ve seen an increase in lifespan of about 10 to 18 percent, depending upon the test. So we’re thinking in humans, we’ll probably see something in that range if you calorie restrict your whole life.

The other things we see though are a reduction in age related diseases, such as cancer. Our animal models indicate that incidence of cancer is 55 percent less in animals that calorie restrict. And that’s one of the most effective methods we have of preventing cancer, that we know of.

Incidence of neurodegenerative diseases such as Parkinson’s and Alzheimer’s are either reduced or greatly delayed. Incidences of any kind of autoimmune type issue, or inflammation issues. So it’s very, very powerful this concept of calorie restriction, and it wasn’t until just recently that we figured out molecular pathways of why it’s working.

[Damien Blenkinsopp]: So, in terms of the actual mechanisms for what’s going on in the body when we calorie restrict, what happens? What is it that creates these benefits and these changes in our biology, versus disease, and longevity in general?

[Alan Cash]: We’ve been looking at that for a long time as a question, and some of the things that we looked at were does it matter if it’s the calorie restriction with fats, or does it matter if it’s just carbohydrates or proteins. And what we’ve seen is it’s pretty much across the board ‘calories’.

There are various diets out there – there’s a new diet every week it seems like – that looks at restricting one form or another of calories, or fats, or proteins, or even specific components of proteins. But what we’ve seen in general in calorie restriction is it’s the number of calories.

So, based on that it seems like it’s an energy proposition, and looking at the energy pathways there’s been focus on the ratio of two compounds that are pretty much the same. Nicotinamide adenine dinucleotide, or NAD, and it’s reduced version NADH. So that ratio, which is also known as the redox of the cell, is looking at the energy of the cell. And when we have a very high NAD to NADH ratio, we see effects very similar to calorie restriction.

[Damien Blenkinsopp]: So in terms of what that’s actually doing, do we understand why the changes in NADH create this change in our biology?

[Alan Cash]: You know we’ve been able to trace this, and what we see is increasing the NAD to NADH ratio – and you can do that through a variety of ways – but that increase is measured by a protein called AMP protein-activated kinase, or AMPK. What AMPK does is it monitors, essentially, the NAD and NADH ratio, or the redox of the cell.

Think of it as a see-saw, so with AMPK as the fulcrum of the see-saw and NAD on one side and NADH on the other side. When the see-saw is in one position, AMPK will then act with other proteins that translate to the nucleus and turn on genes. When the see-saw is in a different position, AMPK will work with other proteins that translate to the nucleus and turn on different genes.

So let me give you a specific example. If you’ve had a lot to eat, your NAD to NADH ratio will be low. And AMPK will turn on genes that help with fat storage and production, because you’ve got all this extra energy, so hey let’s store some of it. So it will actually start producing proteins that deal with fat storage and synthesis.

On the other hand, if the see-saw is in the different position, if you haven’t had a lot to eat, there’s no point in storing fat. And so your genes will not be making these proteins that assist in making fat production. So how can we use that information?

For instance, when we trick the cells into thinking that the NAD to NADH ratio is high – or that the animal hasn’t had a lot to eat even if it has – we can slow down the rate of fat production, which could be interesting for people on diets. What we see is that you still gain some fat, but you just don’t gain it as fast.

So, biochemically, there are reasons why when you go on a diet and you lose all that weight, and you stop the diet and you rebound back very quickly. We can slow down the rate of rebound if we can keep the NAD to NADH ratio up high, because then the genes that are produced that create and store fat aren’t being produced. So there’s some really neat tricks that we can use to bio-hack into our systems that are existing systems.

[Damien Blenkinsopp]: Yeah, yeah. There are quite a few potential benefits to calorie restriction. We’ve come across some of these before. We’ve spoken with Dr. Thomas Seyfried about purposefully doing fasting for this kind of work as well.

What are kind of list the main big areas which people have seen this impact, like diabetes. What have you seen in your area, areas where people are meaningfully impacting this area with calorific restriction?

[Alan Cash]: We’ve actually done human trials in calorie restriction, and what we see is a reduction in fasting glucose levels. We also see a reduction in atherosclerosis, which, considering heart disease is the number one killer in America, if we can reduce that you’re going to have people living longer. That alone is huge.

[Damien Blenkinsopp]: So that just begs the question, when people are doing these estimates of longevity, is it because you’re reducing the risk of many of the kind of diseases that kill us – like cancer and neurological disorders, and heart disease – that people are living longer, and therefore you’re getting a higher longevity score? Or are they kind of separate topics?

[Alan Cash]: It’s both, actually.

Reducing these diseases is going to bring up the average increase in survival. So that would give you your average increase in lifespan. But there are certain people who don’t get these diseases, and they live a long time. But calorie restriction has been able to increase the maximal amount of lifespan. So that’s making every cell in your body live longer.

And we see that in our animal tests. For instance we started off working with these little worms called C elegans, which are used a lot in research because we understand, somewhat, the genetics of them. And one of the interesting things about these worms is once they go into adulthood, they don’t produce any more cells. That’s it.

They only live for about 30 days, but they live with the cells that they have. So if we can extend their lifespan, it means that we’re allowing each of their cells to live longer, and to be functional for longer. And when we increase the NAD to NADH ratio in C elegens, we see up to a 50 percent increase in lifespan.

So, as I said, it’s both. It’s eliminating a lot of these diseases that are associated with aging. I mean, think of all the diseases that you get when your old that you don’t get when you’re seven years old.

[Damien Blenkinsopp]: So, I’m sure you’re aware of Aubrey de Grey? We had him on the podcast previously talking about his seven areas of aging, which are basically diseases of aging. So he’s looking at it from that perspective. So, in terms of oxaloacetate, which is the mechanism you were using to generate that, where does it actually come from? What is it?

[Alan Cash]: Well, it’s a human metabolite. It’s in something called the Krebs cycle, which is what gives us power in our little mitochondria. So, mitochondria can be thought of like a little power plant. Glucose is the fuel for the power plant.

So the more mitochondria you have, the more power plants you have, but you have to also have the fuel, the glucose, to up-regulate that. So oxaloacetate is one of those critical components within the mitochondria. So it’s in every cell of your body already.

Now, when we give it to animals, the reason we started looking at oxaloacetate is in looking at our energy pathways, oxaloacetate can break down into malate, which is another metabolite. It’s found in excess in apples. And as part of that reaction, it takes NADH and turns it into NAD.

[Damien Blenkinsopp]: So it takes it from reduced into the oxidized form?

[Alan Cash]: Yes, and so in doing that, because you’re taking something from the denominator and putting it in the numerator, it changes the ratio very rapidly. The first person who measured this ratio change was Krebs himself, back in the 60’s. He added oxaloacetate to the cells and he saw a 900 percent increase in the NAD to NADH ratio in two minutes. So, huge changes with this human metabolite oxaloacetate.

Now, oxaloacetate has got some problems. It’s not very stable, it’s highly energetic. Commercially it’s available through chemical suppliers, but you have to store it at -20 degrees Celsius. If you want to make popsicles out of it, you could probably do that. But putting it into a usable supplement has been very difficult, and that’s why you don’t see it very often.

We came up with a method to thermally stabilize it so that it can be stored at room temperature for a period of up to two years without degrading. And that’s how we were able to introduce this into the market.

[Damien Blenkinsopp]: Great. So, in terms of where it comes from, in my understanding it’s also something that is part of foods. So there are foods which have oxaloacetate in it, so it’s basically a nutrient that’s found in the environment?

[Alan Cash]: Yes. Absolutely. Although it’s only found in very, very small amounts. There are some foods that have higher amounts of oxaloacetate, and these are foods that typically have higher amounts of mitochondria.

So, for example, pigeon breast has a lot of oxaloacetate in it because you need tremendous amounts of mitochondria to power flight. That’s what one of the most energy intensive things out there, is flying around. But you need about 18 to 20 pigeons breast to get the amount of oxaloacetate that we see as the minimum for seeing some of the gene expression changes we want to accomplish. So it takes a lot of pigeons.

[Damien Blenkinsopp]: So you’ve determined the minimum effective dose, which is around how much?

[Alan Cash]: So far – and this is from a human clinical trial – one of the side effects of calorie restriction in primates is it eliminates Type 2 diabetes, which is a good thing. And it turns out they, in trying to mimic calorie restriction – which is what we’re trying to do is turn on the same molecular pathways – we looked at oxaloacetate, and there was a clinical trial that was done back in the 60’s in Japan.

This was published, and it showed that oxaloacetate reduced fasting glucose levels in diabetics. So, we knew that this is one of the side effects of the calorie restricted metabolic state, and we could look at, in humans, what is the most effective dose.

And what we found is they did a range in this clinical trial of 100mg to 1000mg. There were no side effects in the 45 day trial. 100 percent of the people saw a reduction in their fasting glucose levels, which was good because they were all diabetics. We couldn’t understand why this wasn’t commercialized back in the 60’s.

So I actually flew to Japan to interview the department that was responsible for this clinical trial. The conversation went something like this, “Hi. I’m Alan Cash, your department produced this paper on oxaloacetate working in diabetics to reduce fasting glucose levels. Where’s the follow-on work?”

They said, “Well there is no follow-on work.” And I said, “Well why not?” They said, “Well because it’s a natural ingredient.” And I said, “Yeah it’s not only natural, it’s a human ingredient. So toxicity is extremely low.” And they said, “Yes, but we can’t get a patent on it.” And that was pretty much the end of the conversation.

So, as far as knowing the dosing and what’s effective, we already have a clinical trial showing where the minimum effect is, which is 100mg, which is where we set our sights to put out a nutritional supplement.

[Damien Blenkinsopp]: Yeah.

So, was there any advantage for the people, if we take the most extreme example, the people taking 1000mg in that study, was there any advantage to it? Did it impact blood sugar regulation differently?

[Alan Cash]: Yeah, well actually, as the dosage increases, we start looking at other reactions that oxaloacetate are involved in. And one of the main other reactions is the combination of oxaloacetate with glutamate. So, oxaloacetate and glutamate link together and that reduces glutamate levels in the brain.

Now that can be important for certain people. For instance, in a closed head injury, 20 percent of the damage to your brain is caused by the actual strike to the head, the damage to the tissue. 80 percent of the damage is caused by the aftereffects. And those after effects are in your brain it releases something called a glutamate storm.

Glutamate is one of those essential brain chemicals that you need to function properly, but if you get too much of it it excites the neurons to the point where they die. So this glutamate storm is responsible for about 80 percent of the damage.

And what they’ve been able to show now with oxaloacetate is primarily in tests over in Europe – the Weizmann institute out of Israel is doing a lot of this work, and there’s also some people in Hungary and Spain that are doing quite a bit of work with oxaloacetate. But they’re able to show that oxaloacetate, if you can get it to a stroke victim or a closed head injury victim within two hours, 80 percent of the damage is eliminated.

[Damien Blenkinsopp]: Wow. What, do they just take a small dose, or what does it have to be?

[Alan Cash]: No, you’ve got to take a lot, because you have to get it into your bloodstream, and if you take, let’s say, two 100mg capsules of oxaloacetate we’ve seen the data in the bloodsteam, only about five percent gets through. The rest of it is used up in the liver and intestines. That’s not a bad thing, because you want to keep those things healthy. But to get it so that it starts reducing glutamate levels in the brain you want to increase it’s supply in the bloodstream, and so you’ve got to take a lot.

[Damien Blenkinsopp]: So, basically after that is it always five percent? If I take 1000mg, is it just going to be 15mg?

[Alan Cash]: We don’t know. There may be a point where you start overloading the liver and more passes through. I can tell you that we have a medical food that is directed towards people with brain cancer, because if we can reduce the glutamate levels in the brain we see better results.

[Damien Blenkinsopp]: Because people, just to get back to it, is it that people with brain cancer tend to die from glutamate toxicity? Is that one of the main mechanism for their death? Or is it acting on other dimensions?

[Alan Cash]: Well, one of the main predictors of survival is the amount of glutamate that’s produced because what the tumor does is it produces tremendous amounts of glutamate, and it kills the surrounding tissues so that the tumor can grow into that area. So, if you can stop that, you don’t kill the tumor, you just stop it growing.

And this is essentially what we’re seeing with the product called CRONaxal, which is a medical food [that] is a high, high dosage oxaloacetate. So you may take the equivalent of 30 to 60 capsules of the nutritional supplement per day, and we’re seeing in animal tests a 237 percent increase in survival.

So FDA gave us an Orphan Drug designation for oxaloacetate for brain cancer. In the actual human work, we’re just doing case studies right now, but in the 17 case studies that we have MRI data on, the oxaloacetate was in conjunction with chemotherapy. So you use them together, it was able to stop tumor growth, or reduce tumor size, in 88 percent of those patients.

[Damien Blenkinsopp]: Wow, so that’s pretty great statistics there.

[Alan Cash]: Yeah, considering some of these people with glioblastoma, their tumors were growing at a rate of 80 percent per month. You can do the math there, it’s not a great equation.

And we were able to bring that growth rate to, in one guy’s case – he was 42 years old, two kids, a nice guy – we were able to bring that growth rate to zero for eight months. That’s very significant when chemotherapy alone only increases survival by a month and a half.

[Damien Blenkinsopp]: Wow, right. So, you were also saying earlier, we were just discussing you looking at combining oxaloacetate with fasting. We spoke to Dr. Thomas Seyfried about this recently, and you may be seeing potentially better results with that? Or it might be–

[Alan Cash]: Well what we’ve seen so far, fasting is one of the techniques used in brain cancer to slow or retard the growth of the tumor. It’s one of the few things that has been shown to work, especially a calorie restricted ketogenic diet, where you eat more fats.

And the thinking behind that is that you reduce glucose levels tremendously with the ketogenic diet, and glucose is one of the things that feed the tumor. Now, the other thing that feeds the tumor, according to Dr. Seyfried, could be glutamate. And so if we can reduce glutamate levels also with oxaloacetate, we may see some impressive results.

And we’re already starting to see that in anecdotal cases in patients. We had one young man who had a slow growing brain tumor that’s been able to stop it’s growth with a combination of calorie restriction and oxaloacetate supplementation with our CRONaxal product for a period of two years now.

[Damien Blenkinsopp]: Wow. And so is he taking around 6000…

[Alan Cash]: No, his tumor is slower growing, so he’s taking about the equivalent of 10 capsules a day.

We’ve also had recently a woman with Stage 4 breast cancer. Her latest report from her PET scan and her MRI data, they can no longer find the tumor, or tumors; she had like four of them. And all she was doing was calorie restriction and about 10 capsules of oxaloacetate.

There’s some real promise here, but it’s very early on. We don’t have the clinical trial data that supports this in a statistically significant manner, we just have individual cases. Although those individual cases are stunning, it would not be prudent to rely upon those cases.

[Damien Blenkinsopp]: Right. Well, have you got any plans to have any clinical trials? Was that something that might be occurring soon in that area?

[Alan Cash]: Yeah, well we’re actually in clinical trial for a variety of conditions. One is mitochondrial dysfunction. There are certain people that are born with genetic defects that affect the mitochondria.

We have one infant that’s been on oxaloacetate now for nine months that is showing normal development, whereas normally with this type of defect we would expect the infant to have passed away six months ago. So that’s pretty interesting.

We’re also in clinical trial for Parkinson’s disease because anecdotally we’ve seen some interesting cases where the oxaloacetate has reduced the symptoms of Parkinson’s disease. And lastly, we’re in clinical trial for Alzheimer’s disease, so we’ll see how those all play out.

We’re getting ready to start some clinical trial work in pediatric brain cancer, because if we can get away from doing chemotherapy, it’s just a whole better quality of life.

[Damien Blenkinsopp]: It sounds like one of the main mechanisms. So if you’re looking at Alzheimer’s disease, they also use ketogenic diets, and so it’s obvious that the glutamate is helping, but do you think it’s also the aspect of improving blood sugar regulation is potentially helping in all these diseases as well? Is that one of the factors?

[Alan Cash]: It certainly could be a factor. We just published a paper in human molecular genetics that showed that oxaloacetate increased the amount of glucose that the cells could uptake in the brain, it increased the number of mitochondria in the brain. So we not only built more power plants, but we’re now having a way to fuel those power plants.

The interesting thing is that oxaloacetate is also a ketone. So you don’t necessarily need glucose to fire off all those neurons in the brain, you can actually use oxaloacetate as a power source. So, the other things we’ve seen with oxaloacetate in the brain in animal models is a reduction in inflammation, and probably most exciting is we’ve seen a doubling of the number of new neurons that are produced.

Ten years ago we used to think that the number of brain cells you have is static, that those brain cells that you lost in college are forever gone by imbibing in too much alcohol, but now what we’re seeing is that there’s an area of the brain called the hippocampus which continues to produce new neurons. And as we age, this function decreases. So our ability to repair our brains decreases.

Well oxaloacetate in animal models doubled that rate of production, and not only did it double the rate of new neurons, but the length of the connections between the neurons was also doubled. So, if you think about, well if a neuron can connect to a neuron that’s further away you get more interesting connections, more interesting abilities to have different variables.

It makes your brain more plastic, is what we say. And oxaloacetate has been able to show both that increase in neurons and the length of the neurons. So it’s pretty exciting work.

[Damien Blenkinsopp]: Yeah, so brain injuries – you were talking about brain injuries before – I guess a lot of us think about brain injuries as a big thing, like maybe a car crash or something, you have a big serious brain injury. But now they are also looking at athletes, for instance in football where they’ve been heading the ball and areas like that, and they’re seeing there’s a lot of damage.

So could this potentially be a tool for sports? If you’re playing in football, would it make sense to be taking this stuff whenever you’re going to a match, or something like that, to reduce the kind of damage you’re getting each time you’re heading the ball, and so on?

[Alan Cash]: I think so. I mean, my daughters play volleyball at a very high level – one’s at Pepperdine, and the other is going to be at Hofstra next year – and occasionally they get hit in the head with a volleyball. They’re middle blockers, they go up, and they just get slammed in the face. So I always have a bottle of oxaloacetate in their gym bag, and if they get hit in the head they’re told to take 10 capsules right away and to continue taking 10 capsules for the next week or so.

I don’t want to suggest that you should use oxaloacetate for any kind of disease. Mostly it’s a nutritional supplement, there is the medical food also that’s specific for brain cancer. And I just want to make that clarification that the work really hasn’t been done in clinical trial.

Now, over in Europe they are working on that. They’ve done a lot of animal studies, and the interesting thing they’ve found is that if they can get oxaloacetate into these animals that have been hit on the head with a hammer within two hours, it reduces the amount of brain damage they experience by 80 percent. They’re looking at a lot of things in Europe, and it’s very, very exciting work.

[Damien Blenkinsopp]: Yeah, it seems like this is a really interesting molecule, because it seems to be having an impact in a lot of different things. Of course, it’s all early stages of research, like you say, but it seems to have quite a lot of potential.

I saw another study where they had combined oxaloacetate with acetyl-l-carnitine and they were looking at that. Could you talk a little bit about that? I believe it was long-term potentiation it was impacting.

[Alan Cash]: Yeah, long-term potentiation is a measure of how plastic your brain is, how well you can still learn. And when they go into the brain of animal models and give them a stroke, an artificial stroke, and then measure long term potentiation, the levels drop significantly.

When they use oxaloacetate or a combination of oxaloacetate and acetyl-l-carnitine, they saw 100 percent restoration of the brain’s ability to learn again, in very short order. And this could be very important for people with stroke, closed head injuries, that type of thing.

But again, this is early work, it’s been done in animals, it’s been very successful in animals. And both oxaloacetate and acetyl-l-carnitine have very low toxicity profiles, so the risks are low there, but we still need to do this in clinical trial and make sure that there are no unexpected results in humans.

[Damien Blenkinsopp]: Right. Yeah, so ALCAR or acetyl-l-carnitine, a lot of people I know have been taking it for a very long time. So in terms of toxicity for oxaloacetate, as you said there was the trials where you had 1000mg per day. Has anything above that been tested? Because it sounds like with some people you’re actually giving 10,000 or more in specific cases.

So, in terms of toxicity, is there any evidence to say that it could be harmful in any way if someone overdoses, or potentially someone in a specific situation?

One thing I was just thinking about while you were talking was in terms of glutamate, you say it helps to deactivate glutamate. In some people who are normal and have normal levels of glutamate, could that impact them in any way in terms of their brain performance, memory, things like that?

[Alan Cash]: That was a multiple question, and let me address them one at a time.

[Damien Blenkinsopp]: I’m sorry.

[Alan Cash]: As far as toxicity, in order to bring the supplement into the United States we had to prove to the FDA safety because this is considered a new dietary ingredient, even though it’s in just about every food we eat but not at the levels that we’re giving it to people at. So we had to prove safety, and we spent quite a bit of money and three years of my life proving safety to the FDA.

One of the things we had to do is feed animals as much oxaloacetate as we could stuff into them to see at what point in time 50 percent of the animals would die. And what we found out is we got up to about 5000mg per kilogram of body weight in animals, and we still couldn’t get any of them to die.

[Damien Blenkinsopp]: Did you get any negative reaction at all?

[Alan Cash]: We couldn’t find one. Now, what we are seeing in humans, especially in some of these people with brain cancer that are taking the equivalent of about 60 capsules a day, we do see an increase in burping.

[Damien Blenkinsopp]: That’s interesting. It’s kind of random.

[Alan Cash]: Yeah, well it relaxes the upper sphincter muscle in the stomach, and we see an increase in burping in some of the people.

[Damien Blenkinsopp]: That’s interesting.

[Alan Cash]: But that’s about all we’ve seen so far. So, from a toxicity standpoint, this appears to be a very safe molecule.

[Damien Blenkinsopp]: Well, that’s great. Do you remember the multi-part question, or shall I repeat it?

[Alan Cash]: Yeah, the second part was what if you take a lot of this and you’re just a normal person, what would you expect to see? Some of the things we’ve seen are really interesting.

We have an R&D project where we’ve developed an oxaloacetate tablet that goes under your tongue. And so we deliver a lot more oxaloacetate to the bloodstream, which preferentially reacts with glutamate. And what we see with that tablet is an increase in the ability to [unclear 40:04] because if you can turn down glutamate levels a little bit in your brain, you don’t have some of that repetitive cycling of questions, you’re able to focus more, you’re able to pay attention better.

It’s kind of like, the way I can explain it, it’s like you’ve been meditating for a half an hour, so you have this incredible focus but it’s not jittery. Like if you have 10 cups of coffee you can also have more attention, but your whole body is shaky. This is more, you’re very relaxed, and you just have that increased ability to focus. It’s pretty cool.

[Damien Blenkinsopp]: It sounds like you’ve been testing it yourself.

[Alan Cash]: Yeah I test it always on myself, because if I’m ever going to give it to somebody else you’ve got to feel confident enough in it’s effects to try it on yourself first.

[Damien Blenkinsopp]: Yeah. You know, it would be nice to hear, how do you use oxaloacetate yourself? Do you have some kind of routine, or what do you do with it?

[Alan Cash]: Yes, I use it primarily for anti-aging, because I’m after that [00:41:11 – 00:41:14:17 audio error repeated “we see an increase in burping in some of the people.”] I take like three caps a day, which is a little bit more than our recommended one cap a day, but I get it for free, so what the heck, right.

I’ve also started working with this sublingual dose whenever I’m tired. Like if I have to drive somewhere and it’s late I take one and immediately I’m awake and my focus is there. Or if I’m in a conference and its 4 o’clock on the third day of the conference I find that it helps quite a bit. So that’s how I use it.

A lot of athletes are using this now because we’ve been able to measure a decrease in fatigue and an increase in endurance. We don’t see an increase in strength, just an increase in endurance. So a lot of endurance sport people take one to two capsules about 15 minutes before competition, with about 100 to 200 calories.

[Damien Blenkinsopp]: So it sounds very quick acting, in terms of you’ve take it in and within a very short period it’s going to have that impact. Are you talking about it feeding the mitochondria, basically?

I mean, you spoke earlier about it basically being like a ketone. Do you think that’s the mechanism there, or is it because it’s stimulating the mitochondria somehow?

[Alan Cash]: Well there’s been some work out of UCSD showing that oxaloacetate activates pyruvate decarboxylase and allows the citric acid cycle to process faster. So you get more ATP production, which would tie with the endurance effect.

We’ve been able to measure the endurance effect almost immediately, and we published that in the Journal of Sports Medicine. We saw about a 10 percent increase in endurance. And you think, you know, 10 percent is not all that much, but in a lot of athletic competitions 10 percent is huge.

So that’s the short term effect, and that actually only lasts about two hours. And then if you want it again, you have to reapply.

[Damien Blenkinsopp]: Yeah. So a marathon runner would be dosing every couple of hours?

[Alan Cash]: Yeah, about every two hours.

The second effect though is longer term. We’ve seen that oxaloacetate supplementation increases the number of mitochondria, or the mitochondrial density in the cell. So it produces more of the power plants so that when you feed it more glucose, you can turn it into fuel faster.

But that takes typically, you know, anywhere from two to six weeks to see the effect on that. And you have to take it daily. What we’re doing is we’re increasing that NAD to NADH ratio, which then activates AMPK, and chronic AMPK activation has been shown to start the process of mitochondrial biogenesis, or producing more mitochondria.

[Damien Blenkinsopp]: Is there any reason we want that activated? Anything you know of like in the research, where it says like chronic activation of AMPK could lead to any downsides?

I have another question, just to kind of give you a bit of context to that. Is it worth cycling oxaloacetate? So having a month on, or a couple of months on, a couple of months off, or anything like that?

[Alan Cash]: Yeah, a lot of supplements that deal with stressing your cells in order to get an effect they work better if you cycle them. For instance, echinacea. Echinacea works because it’s an irritant. So you turn on your stress response and get a response, but if you take it all the time, your body gets used to it.

Oxaloacetate doesn’t work as a stresser, it works to turn on genes and turn on the development of more mitochondria. So no you want to take it all the time.

[Damien Blenkinsopp]: Great, and so we were discussing earlier, I was just asking you about potentially doing a lot of experiments with oxaloacetate, and you were saying that for most of the effects it’s really this aggregated, this cumulative effect.

We want to be using it for between two and six weeks before we see the effects. And then, if we stop it’s probably going to take that amount of time before those effects disappear. But they will disappear, so it’s something that you really kind of have to take on an on-going basis.

[Alan Cash]: Yeah, yeah. Because it’s, well there are two effects. One is a pharmacological effect, like for instance the reduction of glutamate in the brain. That happens almost immediately, so some people when they take this they get that feeling of peace because they’re just reducing their excitatory chemical in their brain.

But the other effect is a genomic effect, and while your genes start producing these proteins right away it takes a while for the proteins to be enough in number that we see measurable effects. We can see those effects in typically four to six weeks.

For instance, blood glucose levels would be one that we’ve been able to trace that down to activating AMPK, which is the same thing that the diabetic drug Metformin does but through a different pathway, and the up-regulation of a gene called FOXO3A, which deals with glucose stability. But that takes time, it takes usually four to six weeks.

[Damien Blenkinsopp]: So, for the people at home, if they were going to design their own little experiment, it would be basically measuring blood glucose stability, is that the main, is it the variant which is reduced, or is it actually lowered in general?

[Alan Cash]: One experiment that they could try is start off with a baseline. Go to the drugstore, get a glucose meter and some little paper strips, and take your fasting glucose levels for maybe a couple of weeks. You see the variability, because even in fasting glucose levels, you’re going to see the levels bounce all over the place.

And then start oxaloacetate supplementation, one or two capsules a day for a month, and take your daily glucose levels. You won’t see much change for about three weeks, and then what we typically see is a slight reduction – in non-diabetics – in fasting glucose levels.

And more importantly, a reduction in the swing. So you don’t see as high a high, and as low a low. And that reduction is typically on the order of 50 to 60 percent, so you have better glucose regulation. And in normal people, that’s not a bad thing.

[Damien Blenkinsopp]: Right. Just if we’re talking in terms of performance, just throughout the day I think people’s performance goes up and down. Some of the reasons people try new diets such as Paleo and Ketogenic and so on is to try and even out their blood sugar a bit more so they don’t have these typical dips people get after lunch when they need another shot of caffeine to get through the afternoon.

So I’m sure probably you can see how that could impact their performance in that way. That would be interesting.

[Alan Cash]: Yeah. Absolutely.

[Damien Blenkinsopp]: So how would you recommend someone takes oxaloacetate? Would it just be 100mg one capsule? Would it be in the morning, once daily?

What would be the recommended way to try this out, for someone who is just normal and healthy, and they’re just more interested in the long term benefits, and so on.

[Alan Cash]: For the long term benefits, we looked at the minimum amount that you could take – I believe in small measures for big effects – the minimum amount over time, and we know that through the clinical trial that was done. We know that 100mg was effective in reducing fasting glucose levels in diabetics. We’re turning on those genes that we want to turn on.

So, one capsule a day. It doesn’t matter if you take it in the morning or the evening, what does matter is that you take it every day, because we’re trying to increase that NAD to NADH ratio and keep it pretty steady, so that we continuously activate AMPK. And that continual activation is what turns on the genes and gives us the gene expression that we want to see to see extended lifespans.

[Damien Blenkinsopp]: Great, great, thank you. Are there any situations where you would recommended people – because you’re taking 300mg yourself, and obviously you don’t have the costs that other people would have – but are there other situations where you would think it would be interesting for people to take a slightly larger dose?

[Alan Cash]: Yeah, but I really can’t recommend that, as I’m not a physician, I’m a physicist.

[Damien Blenkinsopp]: Right, right. We’re getting outside of the nutritional realm again.

[Alan Cash]: Yeah, and that [can] be a dangerous thing for us to do.

[Damien Blenkinsopp]: Absolutely.

[Alan Cash]: Definitely our CRONaxal medical food for [treating] cancer, they would take a lot more oxaloacetate.

[Damien Blenkinsopp]: Great, great. If someone wanted to learn more about the topic of caloric restriction and oxaloacetate, where would you say, are there any books or presentations or is there any other resources people could look up that would help them to learn more about this?

[Alan Cash]: Absolutely. There’s quite a bit in PubMed, so they could go to www.pubmed.com, or .gov, and just type in ‘oxaloacetate’ and ‘calorie restriction’. We’ve got some papers in there that we’ve published.

And they can also look at oxaloacetate and other things like Parkinson’s, Alzheimer’s, cancer, you know, if they’re interested in that, and see what animal data there is out there right now. There’s not a lot of human clinical work done yet.

We’re in the middle of some of that ourselves. They can also email me. My email address is acash@benagene.org. I typically get back to people in a couple of days with questions.

[Damien Blenkinsopp]: Great, and I can attest to that, because we’ve been in contact before and I know you make yourself very much available, and that’s really appreciated.

Are there other ways that people could connect with you? I don’t know if you are on Twitter. You have a website, of course, which is benagene.com?

[Alan Cash]: Yeah, we have a website benagene.com. There’s not a lot of information on that because the FDA discourages that. For instance, we can’t legally put any animal data on our site, even though I consider humans animals. I think it’s relevant, but the FDA does not.

[Damien Blenkinsopp]: Right, right. Of course. So, is there anyone besides yourself that you’d recommend to learn about this topic? I don’t know, calorie restriction, longevity. Is there any interesting stuff you’ve read over the years, or have you referred people’s work?

[Alan Cash]: There’s tremendous amounts of data on calorie restriction. And there’s a society, the Calorie Restriction Society, where these people have been restricting their own calories for years, seeing tremendous results, especially in reducing atherosclerosis. In human clinical trial we’ve seen a major drop in atherosclerosis and blood pressure.

[Damien Blenkinsopp]: Do you know if that’s reflected by the CRP? The C-reactive Protein biomarker? Because you spoke about inflammation earlier, I wasn’t sure if that was that marker or another one.

[Alan Cash]: I’ve seen a decrease in inflammation in our studies really through the M4 pathway. I don’t know if C-reactive protein levels are down. We did have a case where due to a genetic dysfunction an 11 year old girl, she was in critical care, her CRP levels were up around 20,000.

[Damien Blenkinsopp]: Wow.

[Alan Cash]: Yeah, yeah. She was…

[Damien Blenkinsopp]: That’s insane.

[Alan Cash]: Yeah. Yeah. She was eating herself alive, essentially. And she was in critical care. They tried just about everything. And this was work done out of University of California San Diego Mitochondria Dysfunction Department. They’re doing some breakthrough work there.

They ended up giving her some oxaloacetate and in two days her CRP levels dropped to zero, and she was released from the hospital and went home. Once again, that’s a case of one person and specific genetic anomaly.

[Damien Blenkinsopp]: Yeah, yeah. Interesting. That’s pretty impressive.

In terms of your own personal approach to data and body data – because we’re always talking about data on this show in terms of our biologies and so on – do you track any metrics or biomarkers for your own body on a routine basis?

[Alan Cash]: Glucose levels. And for a guy, I’m 57 years old, my blood glucose levels are typically in the low 80s, which is pretty good. That’s about the only thing I track regularly. I mean I track my weight, which is very stable. I don’t count the number of hours I exercise or anything like that. I should.

[Damien Blenkinsopp]: I guess. Have you tracked your blood sugar over time? Before you started taking oxaloacetate, or is it since, so you probably wouldn’t see the effects? I’m just wondering if it would be a cumulative effect from you having taking it, I assume, for years now.

[Alan Cash]: I have been taking it since about 2007, which is when we introduced it into the Canadian market. Basically it just dropped. Initially I was up in the upper 80s to low 90s, and over time I’m just pretty much consistently in the low 80s now.

[Damien Blenkinsopp]: So you have seen some kind of steady decline, or did it decline when the genes turned on and then it stayed there?

[Alan Cash]: It pretty much declined when the genes turned on and stayed there, yeah.

Now there’s ways to lower it even further if I went to a ketogenic diet. I know some people who have been doing this, like Dominic D’Agostino. I think his blood glucose levels are down in the 40s.

[Damien Blenkinsopp]: Wow.

[Alan Cash]: Yeah. But he does a very strict ketogenic diet, and he’s feeding his cells with ketones instead of glucose.

[Damien Blenkinsopp]: Yeah, so I was interested – just before we started the interview – also in just cancer prevention, so we had Thomas Seyfried on here and he recommended a five day water fast twice a year.

So it would be interesting to combine that with the oxaloacetate. It might have a potentially beneficial upside, you know, combining those two rather than doing them separately.

[Alan Cash]: Yeah, we’re seeing that in patients now. Hopefully we’ll be able to get some funding for some clinical trials to combine calorie restriction with oxaloacetate in some of these patients. To take the science from our animal data, which is very promising, but it’s not human data. And so hopefully we can continue our research and help some people here.

[Damien Blenkinsopp]: Yeah. I’m guessing it takes quite a while to get these clinical trials going. Would you expect this to be done over the next 10 years? Is there anything that could help you with that, in terms of getting funders, or what could help to push that along faster?

[Alan Cash]: We’ve taken the unusual step in brain cancer of making oxaloacetate available for a disease through the Orphan Drug Act in the US. So this allows for various medical conditions that have scientific basis to be used for a specific disease. In this case, we’re using it for brain cancer, which is an orphan disease.

So that’s helping get the word out, get some anecdotal cases, which I’ve discussed with you a little bit, and increase the interest in getting a clinical trial out there. We’ll see how that all evolves.

[Damien Blenkinsopp]: Great, great. Thank you. Well, one last question Alan. What would be your number one recommendation to someone trying to use data, in some way, to make better decisions about their health and performance, or their longevity?

[Alan Cash]: I think that’s a great place to start. You know the benefits of calorie restriction, and so just counting calories and reducing calories where you can would be one strategy of using data to improve your health. If you keep track of that information.

Keeping track of blood glucose levels, because having lower glucose levels rather than higher glucose levels is going to positively affect your health. The amount of time you exercise.

One of the ways we’ve seen to increase the NAD to NADH ratio is chronic exercise. So calorie restriction is one way, chronic exercise is another way. A drug such as Metformin can increase your NAD to NADH ratio, or activating AMPK anyway.

And oxaloacetate as a nutritional supplement over the long term. So there are quite a few ways that you can use data and monitor your data to positively affect your health.

[Damien Blenkinsopp]: Alan, thank you so much for your time today. It’s been really amazing having you on the show with all of these interesting stories about these case studies about the work that you’ve been doing.

[Alan Cash]: Yes, and just as, again, as a disclaimer, we don’t want to recommend this nutritional supplement, which we manufacture, called Benagene, which you can get at www.benagene.com, for any disease.

Not to diagnose, treat, prevent, or cure any disease. It’s primarily, we developed this to keep healthy people healthy.

[Damien Blenkinsopp]: Great. And I take it myself too, so I’m kind of following in your footsteps there.

Well Alan thanks again for your time today, and I look forward to talking to you again soon.

[Alan Cash]: Alright, thank you very much.

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A walk-through of the 5-day water fast with the tracked results (ketones, glucose, weight) and the practical do’s and don’ts to make the most of the experience.

I’m not a fan of cancer. The only people I’ve lost in memory – my grandfather and other close family – it was cancer that took them. NOT putting an end to the fun of life because of cancer has been a part of my plan since my early 20s.

So after my discussion with Dr. Thomas Seyfried in episode 16 I was looking forward to put his 5 day water fast “cancer insurance policy” to work.

As I read into the details to start planning my prolonged fast what I found convinced me even more this was something I had to do soon.

Maybe what I discovered would inspire you to try a 5 day fast soon too?

Fasting for Reasons Beyond Cancer

Since getting bitten by a tick in Phuket, Thailand a few years ago I’ve been fighting some chronic health issues.

I discovered that it’s probable that these are at least in some part due to lyme disease and babesiosis infections I only got documented earlier this year (and thus had never been treated for). It bears mentioning, since there’s a fair amount of non-rigorous and dubious material on the internet on the subject of lyme disease in particular, that this was documented via the IgM/ IgG labs, and met CDC criteria.

What does this have to do with fasting?

It comes down to this: Having a stronger immune system gives you a better chance of eliminating lyme. Since in cases like mine where it was not treated in the early stages it seems to be relatively tricky and long-winded to get rid of. I’ve made it a rule to collect and put into practice anything that improves the odds of a quicker recovery.

And… fasting is a potential new tool to speed up recovery.

Valter Longo, Director of the USC Longevity Institute, has published a large number of studies on fasting and caloric restriction and their application to treat disease and enhance aging and longevity. Some of his recent work showed that prolonged fasts (e.g. 3 to 5 days, of a similar format recommended by Seyfried) can regenerate up to 30% of the immune system.

Or in other words, a fast can eliminate old tired (and most probably damaged and dysfunctional) white blood cells and replace them with more effective shining new ones.

I’ll admit this got me excited. It was definitely something I wanted to add into the “war plan” my integrative doctor and I had put in place against lyme and babesiosis.

(Note: Before planning this fast I ran it and Longo’s research papers by my doctor to get it signed off by him. If you have any chronic health issue and are undergoing any treatments you should do the same.)

As you’ll see below, the 5 day water fast (and other prolonged fasting configurations) has many potential upsides.

After having gone through the experience and seeing the quantified results, I can say it’s something I will use as a tool frequently going forward. Most likely once per month, or once per quarter.

The Upside: Reasons to Do a 5 Day Water Fast

Beyond the potential health and longevity upsides there were also a couple of others I was particularly interested in.

    First, the health benefits:

  1. Reduce future cancer risk or as a tool for those with cancer to combat it (details in this episode with Dr. Seyfried)
  2. Promote longevity and slow aging (via similar mechanisms to caloric restriction)
  3. Multi-system regeneration providing potential improvements in the immune system and mental performance (Valter Longo’s work – this 2015 paper has some highlights)
  4. Reduce diabetes risk and cardiovascular disease risk and improve blood sugar regulation
  5. The non-health benefits are perhaps more personal to me:

  6. Building greater mental resilience through the process of overcoming the challenge of a fast? The stoics used hard life experiences to learn to deal with the mental ups and downs of life more easily.

    As an entrepreneur, where ups and downs are pretty much routine, I’ve grown to value this ability immensely. Exposing yourself to more extreme hard challenges numbs you to the emotional pain and you find you become more indifferent to life’s ups and downs (read less reactive). You can read up on this in the book The Obstacle is the Way by Ryan Holiday (which I must have listened to 8+ times), or articles on the philosophy of stoicism on Tim Ferriss’ blog.

    A 5 day fast struck me as exactly the type of “safe but challenging experience” that builds mental resilience more generally. Once the fast is done, you realize it’s absolutely not a big deal. And other life challenges also seem to dim in their intensity and importance.

  7. A new life experience: What would it feel like to fast for 5 days? How would it effect my body? physically? mentally? We should all experience the extremes of the human experience provided they are within the limits of safety and healthy. It’s an important tool to learn about ourselves, our limitations, strengths and weakneesses – self awareness is a skill that can be learned. Going to the extremes to get a real feel for the breadth of life is part of living a life well lived.

itunes quantified body

The 5 Day Water Fast Results

Big Metabolic Changes Kick Start on Day 3

My metabolism switched from glucose to ketones (and fatty acids) by the end of the 3rd day, which fits with what is generally expected based on the standard biochemistry literature.

On typical non-fasting days I’ll hit between 1 and 2 mmol/L ketones (see my baseline data in appendix here) because I eat a reasonably high fat diet. It wasn’t till day 3 till I broke the 2 mmol/L threshold and went beyond, eventually peaking at nearly 7 mmol/L blood ketones. At the same time my blood glucose hit a stable low of just under 60mg/dL.

Overall, I felt less mentally sharp and found the fast hardest between the end of day 1 till around beginning of day 3. Is this ‘harder part’ of the fast a rough period of adaptation to using ketone and fatty acids as the main fuel source? Perhaps. In my case the switch in the blood results follows closely the ease of the experience for me – once blood ketones and glucose inverted the experience was easier.

fast-glucose-ketones

Seyfried recommends the use of a Glucose-Ketone Index for monitoring the therapeutic value of the fast against cancer. The goal is to have your value of this index below 1 which is considered the ‘therapeutic zone’.

67 hours into the fast my index dove below 1, and it bottomed out around 90 hours, from then on hovering between 0.5 to 0.6. So I was in the therapeutic zone for all of days 4 and 5.

fast-gki

Exactly on plan: My blood glucose, ketone and GKIC markers settled into the expected ranges Seyfried outlines in his book for the fast. That’s between 50 to 60mg/dL for blood glucose, and between 6 and 7 mmol/L for ketones.

Lagging Metabolism Adjustment at End of Fast

When I hit the 120 hour (end of 5 day) mark I dug into a couple of big bowls of bone broth. Quickly full and satisfied seemingly as if the fast had never taken place.

The next day I had a higher carb than usual breakfast. We’re not talking crazy, just some blueberries and yacon syrup (for the gut, will talk about this soon in another episode) with bulletproof coffee (ghee, MCT oil and coffee). Despite this my ketones stayed high and actually hit their peak of the whole experiment (6.8 mmol/L) nearly 24 hours after the fast had ended.

This makes sense. It’s normal to see a lag of response of the blood readings the first 3 days of the fast while you adapt to ketones/ fatty acid metabolism. So it follows that there would be a lag in the switch back to primarily glucose metabolism.

Was Weight Loss Permanent? or Just Momentary?

Interested in the fast to lose weight also?

Cycling into 5 day fasts say once per month, could be quite effect based on my data (~loss of 1 lb per day in terms of permanent weight loss, not just momentary during the fast).

If weight loss isn’t desirable, which is my case, you’ll need to compensate to regain lost muscle weight post fast.

Within a few days I had recovered one third (3 lbs) of the 9 lbs I’d lost during the fast. I consciously made an effort to eat as per usual to see if it the weight would naturally come back on. Two weeks later after the end of the fast (day 19) it’s still stabilized at 6 lbs down. Actively compensating for this in between future fasts will require consciously eating to gain weight.

fast-weight

HRV, Muse Calm and Mental Performance

I also tracked my HRV with the ithlete app, my daily meditation sessions with the Muse Calm and my mental performance via reaction tests at Quantifed Mind.

These weren’t my main focus for this fast, so the data isn’t extensive enough to make any big conclusions. However, looking at what I collected, I plan to take a closer look at mental performance and HRV in future fasts.

First thing in the morning HRV dipped at the start of the fast (day 1 and 2) and go back to my normal range from then on. This is a pretty good fit with how I felt during the fast. The first two days were a little rough as I had a headache, but from then on I felt more ‘euphoric’ and productive than usual.

This time round I haven’t seen any noticeable increase in HRV post-fast (potentially a bit more of the opposite) whereas intermittent fasting typically raises HRV. Something to keep an eye on for future fasts especially as I have to deal with my own personal variable – adrenal fatigue.

Adrenal Fatigue Confounder? I have documented adrenal fatigue currently (low cortisol output as a knock on effect of the chronic stress from lyme disease and babesiosis infections). I suspect the adrenal fatigue would be the cause of any negative HRV impact, and would be personal to me (if you’ve tracked HRV during a fast let me know your experience in the comments).

This may have been behind or contributed to my less consistent sleep and shorter duration sleep as noted before.

It is very common (even fashionable) to fast on meditation retreats. The idea the retreats promote is that fasting helps to calm the mind.

Although I got my best Muse Calm score to date on one morning (80% calm), I didn’t notice any real difference between fasting and my normal scores.

The 5-Day Fast Experience

Two of my fellow entrepreneur buddies (Patrick Stiles and Patrick Kelly (@pjkmedia)) recently also did the 5 day water fast so we caught up to share notes on our experiences. Our experiences turned out to be pretty different in some areas. You can listen to our full note swapping discussion in this episode.

Here’s the brief highlights of my experience from the discussion:

  • Day 1 and day 2 were a little challenging in terms of hunger but not that noticeably (I put this down to my previous experience with intermittent fasting and ketogenic diets)
  • A headache from the end of day 1 to the beginning of day 3 (potentially linked to the switch in brain from glucose to ketone use)
  • On day 4 and 5 the physical weakness was a lot more noticeable and there was some slight dizzyness when standing up at times.
  • Undercover bad breath: I wasn’t actually aware of this during the fast. My sister mentioned afterwards that she feared for her 1 year old son’s wellbeing when I was playing up close with him towards the end of the fast. Given the high ketone levels, this would mostly be due to high acetone levels in the breath.
  • Rash of spots on chest: I believe this is very much personal to me and my current situation. Fasting tends to lead to detoxification, and potentially stress your detoxification system, as you break down body fat including accumulated fat-soluble toxins and process them. While dealing with lyme these have occurred from time to time (added lyme biotoxin burden causing overload), so it’s unsurprising that adding broken down fat-soluble toxins would lead to this currently. I took activated charcoal daily to help bind and clear any toxins from my system.
  • After a couple of nights of good sleep at beginning of the fast it got progressively less deep as the fast went on whereby I was sleeping between 4 and 6 hours compared to a normal 6.5 to 7.5.

What’s Next? Fasting as a Routine Tool.

The experience during and after the fast has been so positive that I’m planning to do this on a once per month or once per quarter basis. Which one I go with will depend on how my body responds.

As more research comes out on the specifics of Fast Mimicking Diets (FMDs) I’ll also want to test that out, to see if the same benefits can be achieved (or better) with less discomfort.

Immune System Reboot – Any Evidence?

It’s only 2 weeks since the end of the fast so it’s early to tell just through tracking symptoms of my chronic infections (lyme, babesiosis). Nonetheless it’s looking positive from that anecdotal basis. After a first rough work post-fast, it’s been up and up. Meaning more exercise, more activity and generally feeling better with less symptoms.

I’m cautiously positive because lyme and babesiosis are both cyclical in symptoms presentation. I’ll update this section at a later date. The real solution to understand the immune reboot potential or impact of course is more data…

What I’ll Track Next Time

I’ve already begun contacting labs and working out how to dig deeper into the fast on a few levels:

  • Further validating the immune system reboot side by tracking IGF-1 which is one of the main markers used in Longo’s paper.
  • Is this sustainable for me? Is it beneficial as a monthly routine or would that have some negative blowback? I’m looking into tracking Cortisol vis-a-vis monitoring my adrenal fatigue status, and will track weight with future fasts.
  • What’s the downside in terms of productivity for the 5 days fasted? While I didn’t feel like there was much negative impact this time (it felt more positive) it’s something that I’d like to confirm with some short mental performance tests done during next fasting round.

In Practice: How to Do this at Home

For my tracking I took readings 4 times per day for my blood glucose and ketones.

However, I recommend to reduce cost (ketone strips are expensive) and to make it more convenient, you can simply track your blood ketones and glucose once per day in the morning. This will give you meaningful results, and tell you if you’re hitting the same milestones based on Seyfried’s work like I did.

Tracking this way, for a ten day tracking (5 days as control, 5 days of fast) you’ll be looking at a budget of around $80 to $100 all in (versus the ~$500 I spent).

Step 1: Get Your Tracking Gear

  • Combined glucose/ ketone monitor: Abbott is behind the best value for money units, the Precision Xtra Blood Glucose and Ketone Monitoring System in the U.S. and the Freestyle Optium Neo Glucose & Ketone meter in the UK (the one I used).
  • Glucose strips: the latest format that work with Precision Xtra and Freestyle Optium devices.
  • Ketone strips: Purple colored strips for measuring blood ketones (Beta-hydroxybutyrate). These work with both Precision Xtra and Freestyle Optium (Ketone Strips – Note: These are ~$4.50/ unit, I managed to get these at a lower cost per unit in the UK of $1.97. If you know where to source these cheaper let us know in the comments)
  • Lancets: It’s good practice to use a new lancet each day to prick your finger with. These Lancets are the latest format and work with Precision Xtra and Freestyle Optium devices, but are cheaper.

Note: Make sure to buy adequate strip and lancet supplies. I ran out of ketone strips the day after my fast otherwise I would’ve tracked more post-fast data. You lose some strips unavoidably in my experience through a bad reading on the device where for instance you didn’t provide insufficient blood. Make sure to have a buffer of 10% or so to account for this.

Step 2: Track Some Control Data & Learn to Take Readings

This is one of those situations where a video walkthrough is better than 1000s of words. This walkthrough is with the Freestyle Optium Neo, which is identical in use to the Precision Xtra).

I used my control data week (charts in appendix here) to work through any slip ups in taking readings.

You’ll want to get some control days where you take some baseline data eating your standard diet so that you can compare it to your fast. Blood sugar and ketosis metabolism are very personal aspects of our biology as we learned from Jimmy Moore in episode 7.

So the relative change in your measurements (normal diet, fasted states) could be as insightful as the absolute numbers.

Step 3: Schedule in Your Fast

The experience of a fast is highly variable depending on your personal situation as you’ll have noticed from the discussion in this episode with the two Patricks.

There is a risk that you’ll feel pretty rough and weak, and may be a danger to yourself and others (e.g. no driving or other similar ‘responsible’ activities please).

So I recommend you plan ahead and schedule it in for a time when you can quietly do some mental type work, study or rest at home. If you’re able to do more, so much the better, but plan for not being able to do anything.

Step 4: The Fast

Pretty straightforward. Stop eating at your scheduled time (after an evening meal is when most people do it) and start taking readings as set time intervals.

I used a standard iPhone timer alarm to notify me to take readings every 4 hours while awake. If you’re just taking one reading per day, it’s simple enough to make it part of your first thing in the morning routine.

It’s also useful to keep a diary of anything interesting or unusual you notice during the fast. Items I found useful to note down were hours sleep and sleep quality, physical weakness, any fatigue, mood, and other symptoms like headaches or dizzyness. This way you can relate them back to the data afterwards for more insights.

Step 5: Finishing the Fast Points

Boom, you’re done! You’ll be feeling great if it was anything like my fast. There are a few things you may want to keep in mind at this point.

I was advised by friends, and some long term ‘fasting experimenters’ to reintroduce food slowly. The idea behind this is that your body needs a little time to restart enzyme and stomach acid production. Some people experience gut symptoms or/ and bouts of ‘disaster pants’ if they jump straight back into their usual diet (or a ravenous version of this).

In my case, I prepared a bone broth ahead of time so that my first meal was mostly liquid and ate as normal from the next meal onwards. No discomfort or adverse gut symptoms. Straight back to business as usual as if the fast had never happened.

In future I’ll be tracking data for a few days post-fast since this experiment showed that my metabolism took a while to return to normal despite refeeding with a vengence!

Tracking

Biomarkers

  • Blood Ketones (Beta-Hydroxybutyrate / β-hydroxybutyrate): Blood ketones are the gold standard for measuring your state of ketosis. During the fast, ketones are expected to peak in the range of between 6 and 7 mmol/L based on Seyfried’s work and experience. In episode 7 Jimmy Moore notes that values over 1.0 on your blood ketone monitor give you the benefits of ketosis, and there is no need to go over 2.0. Tim Ferriss also prefers this range, noting that his best mental performance is typically with values between 1.1 and 1.7 mmol/L.
  • Blood Glucose (mg/dl): A measure of the level of glucose in the blood at one point in time. Dr. Seyfried’s therapies target reduction of blood glucose levels to limit cancer cell growth, and according to his theories high blood glucose is a biomarker of increased cancer risk. For the fast he notes values between 50mg/dL to 60mg/dL are standard. Non-fasting values should be below 80mg/dL ideally, and at least 92mg/dL.
  • Glucose-Ketone Index (GKI): The ratio between the concentration of glucose in the blood to ketone bodies in the blood. The calculation is Glucose (mmol)/ Ketone (mmol). Dr. Seyfried created the index as a better way to assess metabolic status. Therapeutic efficacy is considered best with index values approaching 1.0 or below. Patients with chronic disease like cancer have consistent index values of 50 or more.
  • Weight (lbs): Standard scales measurement of weight in morning without clothes (to avoid biases).

Lab Tests, Devices and Apps

  • Blood Ketone/ Glucose Monitors: The Precision Xtra in the U.S. or Freestyle Optium Neo in the UK are the current recommended monitors. You’ll need lancets, ketone strips and glucose strips also.
  • Damien’s Routine Tracking Devices : Some of Damien’s daily use apps featured in this experiment including the Muse Calm for meditation, the iThlete Pro app for HRV, and Quantified Mind for mental performance.
  • Healbe GoBe: Damien mentioned that he’s been testing this device, and that the tracking of hours slept works quite well – but that other functions of the device make it hard to use consistently.
  • uBiome: Damien mentioned as a side note on another experiment he’s working on to shift his whole biome to a more positive balance of bacteria.
  • Functional Adrenal Stress Profile (BioHealth): Mentioned by Damien in relation to testing for adrenal fatigue.

Tools & Tactics

Interventions

  • 3 to 5 day Water Fast: The fast featured in this episode. Recommended by Dr. Seyfried as a potential tactic against cancer (reduce risk, or fight cancer disease). More details in Seyfried’s interview. Also used to promote stem cell regeneration of the immune system as per Valter Longo’s work. These fasts are often referred to as Prolonged Fasts in the literature.
  • Ketogenic Diet: The term given to low carb-high fat diets that put your metabolism into a state of ketosis (using ketones for fuel). Damien’s day to day diet shown in the baseline results is at times ketogenic.
  • Fast Mimicking Diet (FMD): FMDs have been covered increasingly in the research and there are two papers covering human clinical trials expected to be published on them in 2015 by Valter Longo’s group. With the FMD you fast 5 days each month by restricting certain proteins and keeping calories below a specific range each day. The goal is to reduce fasting discomfort and downsides while accessing the same upsides as the fast.
  • Intermittent Fasting: A form of fasting where you fast for part of or full days. The most popular formats are using eating windows of 4 to 8 hours each day. Bob Troia discussed his results from intermittent fasting in episode 22.
  • Slow Carb Diet: Patrick 1 mentioned that he’s primarily on this diet from Ferriss’ The 4-Hour Body.

Supplements

  • Activated Charcoal: The only thing I did beyond restricting myself to filtered water and black coffee (total of 3 cups in whole fast), was to take activated charcoal once a day to aid in clearing toxins from my system. I took a handful, around 8 to 10 capsules per day.
  • Brain Octane: Damien takes brain octane every morning in coffee to help raise his ketones.

Other People, Books & Resources

People

Books

  • The 4-Hour Body: Contains a once per week intermittent fasting format that got Damien started with fasting in 2010.

Additional Charts and Data

Click Here for Additional Charts

Pre-Fast Control Data Eating My Standard Diet

Blood Glucose & Ketone Levels at Different Times of Day

control-glucose-ketones

Glucose-Ketone Index at Different Times of Day

Control-GKI

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How well are you aging? We look at an attempt to make an aging biomarker index accessible to consumers that tracks their true biological age and provides feedback recommendations to improve how they age.

In this episode we take another look at longevity through the lens of aging biomarkers. This time taking a look at some of the most well research-supported biomarkers to predict how well we are aging. Or more to the point, how badly we may be aging, and get some early warning indicators, about having to intervene to assure we avoid shortening our lifespan.

Specifically we look at InnerAge, a new panel of aging biomarkers developed by the consumer blood testing service InsideTracker.

The panel provides an index estimating longevity based on a combination of biomarkers, and based on the results, makes recommendations to improve your longevity (AKA put the biomarkers back in the optimum zone, reducing the associated risks of shortened lifespan).


“…for each of those biomarkers, we have an intervention that you can take in order to optimize your InnerAge, and it’s very important for us to take markers that you can [have an impact on]. For example, we are not taking a marker of a disease like BRCA1 or other markers that show whether you have cancer or not, as you cannot do an intervention for that.”

– Gil Blander, PhD

Today’s guest is Gil Blander, the founder, president and chief scientific officer of InsideTracker. Gil has 18 years of experience in systems biology, computational biology, aging, metabolism and caloric restriction research.

During his career he has worked at MIT, the Weizmann Institute, and several systems-biology and computational biology companies. In this interview he walks us through the new aging panel, InnerAge, and the research and thinking behind why the company chose each of the biomarkers in the panel.

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

  • Gil’s interest in biomarkers arose at the age of 12 when the death of a close family member made him think about age and longevity. (5:12).
  • Gil founded InsideTracker, with the aim of having a way of doing a monthly health check-up with optimal values for various biomarkers that are tailored to each individual (8:06).
  • When we look at biomarkers in the blood, they can show us where we are in terms of health and based on that, we can find optimal zones for each biomarker. (9:30).
  • The team of scientists and two year research process it took to cut down the aging biomarkers from hundreds to the top five (12:55).
  • How InnerAge uses an algorithm to estimate your chronological age, and recommend interventions based on your biomarker results (17:06).
  • Examples of some of the interventions including food supplements, exercise and lifestyle changes used to push biomarker values back into their optimum zones and reduce risk of shortened lifespan. (18:58).
  • Other biomarkers included in InnerAge are vitamin D, testosterone for males, CRP (22:35).
  • Why testosterone was included for men in the panel and why they have used different optimum ranges according to age and fitness activity (23:03).
  • InsideTracker is building its own database with information from athletic populations that do primarily strength or primarily endurance training. They are mining the database to determine optimal biomarker levels for each population. The benchmarking tool can be used to tell you how you compare with the rest of the population For example, a large percentage of the population has low vitamin D levels, but InsideTracker can tell you what percentage of the population shares those levels (25:47).
  • For benchmark levels of the biomarkers, InsideTracker shows the optimal range, which is their range, the normal range, which is what is used by the diagnostic companies and out of normal. For some biomarkers, even more ranges are shown (28:55).
  • An interesting biomarker not included in the panel is cholesterol. There are no scientific papers that have shown the correlation between cholesterol, or LDL and longevity. New guidelines by the American Heart association state that cholesterol is not as important as was once thought (30:00).
  • Cholesterol is a building block of testosterone, so if cholesterol is low it will be harder to make testosterone. If you have good metabolism, you can metabolize cholesterol (31:50).
  • CRP is another biomarker included in the InnerAge panel to capture the inflammation dimension of aging. (32:38).
  • InsideTracker should be used repeatedly so that you can see the trends in your values. Samples should be taken at least a couple of times a year for average users (35:09).
  • Other scientists working on aging is Nir Barzilai from New York City and Cynthia Kenyon from UCSF (37:29).
  • Currently, InsideTracker is developing an app that will help you maintain weight, biomarkers and activity (41:46).
  • InsideTracker uses LabCorp request to send samples, but it also uses home kits. They hope that in the future, home kits will improve. (42:18).
  • Theranos’ innovation in finger prick blood samples for a wide range of blood tests. (44:20).
  • Gil Blander’s own personal routines for tracking his own biometrics with InsideTracker and other tools, and the current devices and other services he uses.

Thank Gil Blander, PhD on Twitter for this interview.
Click Here to let him know you enjoyed the show!

Gil Blander, PhD

The Tracking

Biomarkers

  • Fasting Glucose: One of the most commonly used biomarkers. It is used as an indicator of blood sugar regulation and can be indicative of longevity as blood sugar disregulation lies behind many common health issues such as diabetes and obesity. Gil mentions that while blood glucose should be between 65 and 99 for everybody, his aim was to find optimal levels for different populations.
  • Total Testosterone: Low testosterone has also been linked to depression and decreased cognitive ability. Since testosterone levels decline with age, it can be used as a biomarker of aging. Gil Blander included testosterone as one of the biomarkers in the InnerAge panel.
  • Vitamin D (25 Hydroxy Vitamin D): Also referred to as Vitamin D 25-OH. InnerAge panel includes vitamin D as a marker of longevity. This is measured in ng/mL and InnerAge uses ranges of between 40 and 50 ng/ml depending on your profile.
  • Total Cholesterol: Has long been thought to contribute to cardiovascular disease. However, re-evaluation of scientific evidence has shown that cholesterol is not harmful for most people. Cholesterol is a building block for steroid hormones, such as testosterone and estrogen and is an integral part of cell membranes. Since recent scientific data do not support the idea that high cholesterol causes heart disease, Gil Blander has decided not to include it in the InnerAge panel.
  • High Sensitivity C-Reactive Protein (hs-CRP): We’ve discussed this common biomarker of inflammation often on the show. As a general rule, the closer your marker comes back to 0, the better. InnerAge includes CRP in its panel because they implicate higher inflammation as a dimension of aging. Gil Blander notes that because exercise increases inflammation, the test should not be taken for approximately one week after vigorous exercise.
  • Alanine Amino Transferase (ALT): This biomarker of liver function is also included in the InnerAge panel. Normally, levels of ALT in blood are low, but increase if there is liver damage, which may be chronic and ongoing. The Liver is looked at for longevity in this case as its role in detoxification is considered an important predictor of health and longevity.

Lab Tests, Devices and Apps

  • HRV from ithlete: This is an app for iPhone and Android that tracks HRV. It can be used to maximize athletic performance and maintain good health. Gil Blander uses this to track his HRV, as does Damien.
  • MyFitnessPal: This is an app that is used to track nutritional intake. It can be used to track intake of calories, macronutrients and micronutrients as well as energy expenditure. Gil Blander uses MyFitnessPal to track his food intake
  • Nutrino: Nutrino is a “virtual nutritionist” app that connects to wearable devices like Whitings and Fitbit and makes personal meal recommendations. It includes information on what to eat and when to eat it. Gil Blander uses it to track his nutrition.
  • Withings WS-50 Smart Body Analyzer: Gil Blander uses this scale to track his weight and store the data daily.
  • Fit Bit Charge: FitBit is a wearable tracker used by Gil Blander. It monitors physical activity and sleep quality.

Other People, Books & Resources

People

  • Simon Wegerif: was mentioned in the context of his interview on QBP and his app and HRV platform ithlete.
  • Lenny Guarente, PhD: One of the leading researchers on aging and is considered to be the father of the new aging research.
  • David Sinclair, PhD: David Sinclair is a professor of genetics at Harvard Medical School is one of the leaders of aging research. He is also involved in the biotech community and has started several companies.
  • Bob Troia: Bob Troia is known for his n=1 experiments in self-tracking and biohacking. He was a guest on episode 22 of QBP and is a user of InsideTracker.
  • Nir Barzilai: Nir is one of the scientists involved in developing the InnerAge. He is the director of the Institute of Aging Research at the Albert Einstein College of Medicine. He is studying the effects of the environment, especially nutrition, on extending the lifespan.
  • Cynthia Kenyon: Cynthia Kenyon is a professor of biochemistry and biophysics at UCSF and is one of the scientists who has helped develop InnerAge. She is one of the pioneers of research in genetics of aging.

Organizations

  • LabCorp: Laboratory Corporation of America provides lab testing and services. InsideTracker currently uses LabCorp for its lab processing.
  • Theranos: A lab testing service that tests on very small amounts of blood, taken from the fingertip. Their tests promise to be a lot more affordable, convenient and faster than tests from traditional labs.

Full Interview Transcript

Click Here to Read Transcript

[Damien Blenkinsopp]: Hi Gil, thank you so much for joining us today on the Quantified podcast.

[Gil Blander]: Thank you so much for inviting me. It’s a great pleasure
and I already listened to a few of your guests and I really appreciate it because the
quality is very good.

[Damien Blenkinsopp]: Thank you, that’s a great compliment coming from
you. As we’re going to see, you’ve been pretty busy yourself doing some good stuff.
So, could you share first why you got involved with your interest area—what is the
story about why you do what you do at InsideTracker today?

[Gil Blander]: It’s a great question. Apparently everyone is asking me this
question. My scientific journey started at the age of 12 when one of my closest relatives
passed away, triggering my quest and a thirst for knowledge in our body age. Basically,
at that time I decided that instead of being a physician or physicist, what I wanted to do,
I decided to become a biologist. The reason for that is that one of my relatives passed
away and I started to realize that I’m not immortal anymore, and I realized that one day I will be gone. I wanted to live forever; I wanted to stop the clock; I wanted to try to delay the aging-related diseases. So that basically pushed me to become a scientist and to focus and to have my lifetime goal in aging research.

So I’ll fast-forward a few years: I decided to study biology, graduated from Tel Aviv
University with an undergraduate in biology, PhD from the Weizmann Institute of
Science studying aging, and then I came here to MIT in Cambridge, Massachusetts,
and I joined the best lab that studied aging in the world. I studied aging there for five
years, published a lot of interesting papers, did very cool research, but very early when I arrived here to Cambridge, I started to be exposed to what we call “the Kendall square
environment.” There are hundreds of start-ups in biotech, pharmaceutical, and high-tech. I started to be exposed to them and I started to talk with a lot of founders. I started to do some partnerships with them and I very soon realized that I will contribute much more to humanity if I would start my own company than to be a professor in the academia that publishes a paper once a year and maybe five people will read the paper. I realized that that should be my next step.

Even having realized that, it took me some time because I really like the work in the lab
and I did a very cool experiment. So after five years at the MIT, I left MIT and I joined a
couple of biotech companies and worked there just in order to learn and understand the
industry. Also, I really wanted to learn more about systems biology. So I spent a couple
of years there and then, during that time, I was exposed to two other PhD scientists that were really intrigued by the aging process as well, but also were trying to change the equation between healthcare—basically that the healthcare is taking care of the sick and not of the healthy.

We came at that time with the basic of InsideTracker. The basic is very simple. First of
all, all of us are a machine and like a machine, we need to take care of ourselves.
Today, we are not taking care of ourselves. If you look at that, you go to the physician
mainly when the machine or “us” is broken down. When we are breaking down then we
go to the physician. So we decided to find a way to have once a month to have a
check-up that we can basically check ourselves, find what is not completely optimized
with ourselves, then intervene, and then have our body good for a few more months.
I really like the analogy of the car: so every 5000 miles, you take the car to the
technician. The technician plugs a computer into the car, the computer tells the
technician exactly what should be done in order to make the car good for another 5000
miles, should he replace oil or the oil filter and so on. The technician does that and then
the car is good for another 5000 miles. There is a lot of research that shows that since
the time that this routine schedule of maintenance for the car was introduced, in the
80s, the lifespan of the car increased from around 100,000 miles on average to around
200,000 miles on average.

So we said let’s do something similar. We cannot obviously plug a computer into our
body, but we can plug a needle into our vein and extract the liquid gold that we have in
our veins, called blood. Then when we extract the blood, we can look at the biomarkers
that show where you are staying and based on that, you can find optimal zones for each biomarker. I can give you an example; let’s look at the most boring, maybe, biomarker that you know, which is glucose. For all of us, the optimal zone is between 65 to 99. It doesn’t matter if you’re male or female, young or old, Olympian or couch potato, someone that is obese or someone that has a BMI of less than 15; all of us should be between 65 to 99.

We said that that’s wrong; let’s find an optimal zone for each of us based on age,
gender, ethnicity, and athletic activity, and other criteria. Let’s find an optimal zone that
is matched, and then find whether you are within your optimal zone, above or below. If
you are not in your optimal zone, we can subscribe you an intervention that includes
food, supplements, exercise, and lifestyle changes, that basically will help you to bring
yourself to the optimal zone, and when you bring yourself to the optimal zone there is a
good chance that you will optimize your health, your performance, and hopefully, your
longevity.

So that’s basically the background of InsideTracker. I just want to say that all of our
recommendations, the zones, everything, is extracted from peer-reviewed scientific
literature. We have a team of scientists that do that, so we are looking at it very
seriously and taking it very seriously.

[Damien Blenkinsopp]: What are the most common use cases you have
today? You mentioned a few different things like athletes. What are your clients today?
What are they mostly using it for?

[Gil Blander]: We have three main segments of clients: we call them the
train, the gain, and the pain. The train is, as you said, is an athlete: someone that wants
to shave two minutes off his marathon time; someone that wants to play at the fourth
quarter; someone that wants, basically, to approve his athletic performance. The gain is
an interesting segment. People—that are more like me—that are trying to reach to their
forties, trying to stay in their peak performance, trying to reach the afternoon and have
enough energy and enough patience to play with their kids; people that are trying to
perform better in their work, so a lot of executives; those are the gain population. The
pain are people that are sick.

Currently we are mainly trying to serve the train and the gain, because we feel like the
pain, which are sick, have already someone taking care of them—that’s the physician,
and wishing that the physician is doing a good job. We also don’t want to get into all the
regulation—when you are sick, there is more regulation. We are trying to have a proof
of concept or to show to the train and the gain that we can help them a lot, and maybe
in the future, we’ll go also for the pain, but currently, the main customer segment that
we are trying to approach are the train and the gain.

[Damien Blenkinsopp]: Thank you very much for that. You have just
created this new panel, which is called InnerAge, and it’s specifically targeted at aging,
whereas the rest of your platform, as I understand, is a bit more general. When you
were looking at the criteria for selecting biomarkers, how did you go about that? What
kind of criteria were you looking for in order to select the biomarkers that you’ve put
into that panel?

[Gil Blander]: First of all, we built a team of scientists, and actually we
recruited new scientists and we work with our scientific advisory board. I want to
mention that two of those scientific advisors that we have, one of them is Professor
Lenny Guarente from MIT, who is considered to be the father of new aging research
era and is by far considered to be the initiator of the aging research in the world and
considered to be one of the five top researchers of aging in the world.

Another scientist is Professor David Sinclair from Harvard Medical School. He actually did his postdoc at the lab of Lenny Guarente. Now he’s also considered to be one of the leaders of aging research. He’s also extremely involved in the biotech community; he’s started a lot of companies, and one of them called Sirtris—which use what they call resveratol (which I assume that you’ve heard of), a small molecule that is in high concentrations in red wine and has been shown in a lot of studies to increase longevity—was sold to a big pharmaceutical company a few years ago for $720 million. So both David Sinclair and Lenny Guarente help us to do that.

As to your question, we basically spent almost two years looking at hundreds of
biomarkers and trying to see what is the effect of those biomarkers on aging or
longevity. Basically, we were trying to pinpoint, looking at the scientific publications,
which are the five that are the most related to longevity.

[Damien Blenkinsopp]: So, just to take a step back—when you’re talking
about longevity and aging, are we referring to mortality here? Some people when they
think about aging, they’re thinking about their skin and how they look and things like
that. Are we talking about longevity in terms of how long we’re going to live, or is it
other aspects also?

[Gil Blander]: It’s a good question, and the answer is yes. I can give you
again the example of glucose, which is one of the markers that we have in the
InnerAge. We looked at the data and we found a lot of data that showed, not surprisingly, that when your glucose is high, you might compromise your longevity. But
we were looking for better data and we found it in the scientific publication that was
published based on the Framingham Heart Study. I don’t know if you’ve heard about it?

[Damien Blenkinsopp]: Of course, yeah.

[Gil Blander]: It’s basically a study that was done here in Massachusetts,
in a small lake town next to Boston. They followed up the population of this town for
tens of years and measured some biomarkers. What they found is that there is a strong
correlation for the level of glucose at a certain age and your final longevity. Let me give
you an example: if you are 40-years-old or 35-years-old and your fasting blood glucose
today is 70, you have a good chance to reach your 90s; if your glucose is a bit higher,
let’s say 80, you have a better chance to live to your 80s; and if your glucose is in the
90s, you have a better chance to live to your 70s; but if it’s 100 plus, you have a better
chance to live only to your 60s. So based on that, we took the data, we compiled it, and
then you can basically take a person and say, this person’s age is 40, his glucose is X,
so basically based on the glucose, the predicted longevity will be 80. He’s now only 40
so he has, just by the glucose, 40 more years to live.

Now we’re looking at a few other markers, so each of them show us what the effect is,
then we compile it all together using an algorithm and that’s what we show you as the
InnerAge. We show it to you in comparison to your chronological age, meaning what is
your age today.

[Damien Blenkinsopp]: So it’s an estimate of your longevity based on an
average person? The trendline I guess you’re showing is chronological age against this
biological age, and it’s showing it against, say an average 80-year-old or if you’re doing
better than the average, maybe you’re going to live to 100?

[Gil Blander]: Yes, so it uses the average but also, I want to say that it
shows what is happening with you today. It doesn’t say, and we’re not trying to say that
if you’re a 40-year-old male and your InnerAge is 30, we’re not trying to claim that you
will live 10 more years than what you’re supposed to or than the average. What we are
saying is that if you continue to stay like that, you have a chance to live ten years less
or ten years more. So that’s a very important point.

What is also very important is that for each of those biomarkers, we have an intervention that you can take in order to optimize your InnerAge, and it’s very important for us to take markers that you can intervene. For example, we are not taking a marker of a disease like BRCA1 or other markers that show whether you have cancer or not, and you cannot do an intervention for that.

[Damien Blenkinsopp]: Right. We don’t have any ideas about what exact
tool we could use to change the fact that, apart from having surgery and having your
breast removed in that case, but there’s no specific intervention that you have linked to
those. So you stick to things that are actionable, which is great; that’s what we like to
hear on this show.

[Gil Blander]: They are actionable and more than that, they are simple
interventions. So it’s a food supplement, exercise, lifestyle changes, so similar to Inside
Tracker but a bit more simple. And the simplicity comes with the next feature that we
have in InnerAge, which we called “focus foods.” So focus foods are basically nutrient-
heavy foods that will help you to optimize all the biomarkers that are related to InnerAge that are not optimized for you. So basically, focus foods are foods that are personalized just for you based on the level of the biomarkers that you have and they will help you to optimize all the biomarkers that are not optimized just for you.

For those foods, you don’t need to change completely your routine. What you need to
do is pick a couple of them and start to integrate them into your diet. So for example, if
you need to consume more oatmeal, eat it every day; that’s it. You don’t need to
change completely your behavior. Or if you need to eat strawberries, just try to integrate strawberries. Don’t change all your diet. So what we’re trying to do here is very simple because, as you know, it’s very hard for us to change our diet completely. You have a lot of influence on your diet, you are at home or at the office, you are commuting, you are travelling—it’s not easy. But when you have only a few food items that you need to incorporate all the time, it’s much easier to do that.

[Damien Blenkinsopp]: Could you give us an example—you gave us a
blood glucose example—as to what kind of recommendations the tool would make: I’m
40-years-old and my blood sugar is currently at 95. My fasting blood sugar I guess
we’re talking about.

[Gil Blander]: First of all is nutrition. To optimize your blood glucose, it’s
very important to consume foods that are rich in fiber because the fiber helps our body
to absorb the glucose and then the level of the fasting blood glucose decreases, and
that has been shown to increase your longevity. So one thing that it’s very important to
do is to try and consume more food that is high in fiber. Another thing that it’s good to do is to exercise more. Again, depending on the person; if you are a professional athlete, don’t exercise more. But if you are not, exercise more. Also maintain a healthy weight. There is a lot of data that shows in the literature that if you are overweight, you tend to have higher blood glucose. So there are a lot of interventions like that.

Each of our users receives the intervention based on this information. So if you have a
high BMI or you are heavy, you will receive the intervention of lose weight. But if you
are not, you won’t receive it. Or if you are exercising five times a day, you won’t receive
a recommendation to exercise more. But if you are not exercising at all, you will receive
it. So there are a lot of interventions that are personalized and coming to you based on
your profile and based on what will help you to optimize yourself.

I just want to add that we are also taking into consideration your dietary preferences. So you can tell us that you are on the Paleo Diet; you can tell us that you are a bachelor, live in town and don’t know how to cook; you can tell us that you are gluten-free; so we have a list of a few kinds of dietary requirements that you just need to click and then the algorithm will provide to you the food that is good for you and will help you to optimize yourself.

[Damien Blenkinsopp]: Which other biomarkers have you looked at for the
InnerAge panel? Which other ones have you included today?

[Gil Blander]: We discussed the glucose, we also added vitamin D, we
added testosterone for males, we added CRP, which is a marker of inflammation, and
ALT, which is a marker of liver function.

[Damien Blenkinsopp]: Vitamin D, a lot of people talk about that today, so
that’s common about the benefits to the immune system and so on. Testosterone, I
think, is not so obvious for a lot of people—what’s the issue with testosterone? Why’s
that important when it comes to aging for men?

[Gil Blander]: That’s a great question. What we have seen, and I assume
that you’ve heard about it, that the level of testosterone is decreased by 1-2% every
year when we are getting old. Testosterone is important for our muscle tone, it’s
important for our sex drive, it’s important for our mood. So it’s very important to maintain a healthy testosterone in order to maintain the health and longevity.

What you eluded in your question is, is testosterone as important as glucose? and my answer is definitely not. So each of the biomarkers that we included has its own value or its own weight. So, if you ask me if you have low testosterone and have a high glucose, what is more important to take care of? I would say definitely start with your glucose, and then move to the testosterone. But the testosterone is also very important and there is a lot of data in the scientific literature that shows that.

[Damien Blenkinsopp]: I believe there’s a lot of research on strength and
muscle: the higher the levels of muscle you have going on older in life, the better your
longevity chances. So that correlates also with the testosterone.

In terms of testosterone, what kind of ranges are you looking at? Because there are
obviously the lab ranges we often talk about here—you have the LabCorp range for
example—which isn’t necessarily, and I imagine is probably, not the same as the range
you’re looking at, so what kind of reference range are you looking to get people into?

[Gil Blander]: As I mentioned before, we have what we call the optimal
range or optimal zone, and that’s calculated exactly based on the papers, like I told you
before, looking at the population of thousands or hundreds of people and seeing what is the level of testosterone at specific ages. Then we can from that come with an optimal zone based on your age, based on your gender—obviously, because males and females are completed different—also based on your athletic activity. Those ranges come in based on all the demographic information and then we subscribe to you the optimal zone that is good for you. Your optimal zone might be completely different for a person completely similar to you but in a different age or ethnicity or so on.

[Damien Blenkinsopp]: That’s interesting. Do you look at the difference
between someone who’s doing endurance training versus heavy-weight training, the
different approaches?

[Gil Blander]: Yes, we are extracting the information that we can from
the peer-reviewed scientific literature. For some of them we have data, so we are doing
that; for some others, we don’t. Basically, we are trying to extract the most that we can,
but I want to admit that we don’t have everything because not everything is published in
the scientific literature. In order to try to fill the holes of that, we are building our own
database and we are mining the database. We have a lot of athletic active population
who are doing either strength or endurance, so we are starting to extract information
from there and then help our customers to compare themselves more to their peers
than compared to a couch potato doing nothing.

[Damien Blenkinsopp]: Great, I understand. So I’m guessing it’s early stages
in terms of mining the information from the client base. When do you expect to bring in
the first bits of information from that and analysis to help improve the tool?

[Gil Blander]: We are actually doing that already. We have what we call
a benchmarking tool that shows how you stand compared to InsideTracker
community. So for example, we can see that a high percentage of our community have
a low vitamin D. But you want to know whether it’s 5% or 20% or 40%, so we are
showing and sharing it with our community. They like it a lot because sometimes people say, “Oh, I have low D but it’s 50% of the population. It’s not so bad.” So some people like to see, “Oh, everyone’s having this issue so I’m not…”

[Damien Blenkinsopp]: Right, yeah, it’s not so bad.

[Gil Blander]: “… I’m not going to die tomorrow.”

[Damien Blenkinsopp]: Are you able to tunnel down and say, it’s athletes
like me, say I’ve put into your system that I’m an athlete and I’m eating Paleo, would it
be able to position me compared to that population, or is it early stages for that still?

[Gil Blander]: We are doing it currently just for specific customers; we
are basically tailoring it for them. We have what we call an InsideTracker Pro, which
we’re working with some professional athletes, teams, some gym chains, and others.
For them, we are doing what we call a tailoring solution for them. But we don’t supply
that yet for the person that comes to our website. We are working on that and we hope
to have it soon.

[Damien Blenkinsopp]: In terms of the number of users you need to make
this really useful, how many users do you have today and how many would you think
would be important to have to really make lots of statistical analysis? I guess you have
ideas about doing data mining and a lot more exciting and intricate things.

[Gil Blander]: We have many thousands of users. Obviously I cannot
expose the number. I have a statistician on the staff that helps us to analyze and to
evaluate each of them, so basically we are doing rigorous scientific work and statistic
work, and based on that we decide whether we have enough power to share it with our
users.

[Damien Blenkinsopp]: In terms of the benchmarks you’re using, we’ve
already discussed that they’re different to the lab reference ranges, so when I go into
the system would it also show me for instance the normal reference ranges and how
yours are different? Or will people just get your reference ranges? So that they can
compare—say they’ve had tests outside of your system in other places before, when
they’ve been given other numbers.

[Gil Blander]: Yes, it’s a good question. We are showing base, what we
call the normal and out-of-normal, and then we are showing the optimal. For some
biomarkers, we are showing even more ranges. I can give you an example of
cholesterol. There is an optimal, then you have a normal, then you have a near-normal,
you have high, and you have very high. So, sometimes it’s more complex than just
optimal, normal, and the out-of-normal. But in most of the biomarkers, you see the
optimal, which is our range, you see the normal, which is the range of the diagnostic
companies, and then you see the out-of-normal, which is out of the diagnostic
companies. Most of the time, our optimal range is consumed by the normal so it’s a
subset of the normal.

[Damien Blenkinsopp]: Right, I understand. So out-of-normal range means
the standard labs like LabCorp or based on the research and so on; thank you. Which
other biomarkers did you look at that you decided not to include in your panel?

[Gil Blander]: In the InnerAge panel?

[Damien Blenkinsopp]: In the InnerAge one, yes.

[Gil Blander]: One interesting biomarker is cholesterol, which when we
started to work on that I was sure that cholesterol would be part of the panel. I asked the
scientist that worked on this marker after a couple of weeks that he was working on
that, “Okay, show me the papers.” He said, “Gil, I cannot find any papers.” So I told him,
“Are you kidding me?” Well, you have cholesterol, you have statins, and you have
lipidol, and a business of, I don’t know, ten billion dollars. So I told him, “You know what,
I will spend.” I spent four weeks on that and I couldn’t find anything. You could find old
papers but old and new papers haven’t shown a strong correlation between cholesterol,
or LDL, and longevity.

Very interestingly, exactly a year ago, the new guidelines of the American Heart
Association came out, and basically said that cholesterol is not as important as it used to
be. It is important if you are overweight, if you have high inflammation, if you are not
athletically active, if you have a family history of high cholesterol, or if you have blood
pressure, but someone that doesn’t have most of those, it’s not as important as it used
to be. That was a big surprise for me, but apparently we came to the same conclusion
that other agencies or all the scientific community came to, so that was a very big
surprise.

[Damien Blenkinsopp]: There is definitely a lot of movement going on
around the cholesterol markers. One interesting thing with that in relation to your
testosterone is I found it’s easier to get my testosterone raised when I have higher
cholesterol. So I think if you’re on a lower cholesterol diet, it can be more difficult to
raise your testosterone, which you’ve included in your panel.

[Gil Blander]: Yeah, it makes a lot of sense because if you look at that,
testosterone is a derivative of cholesterol. So basically, cholesterol is one of the building
blocks of testosterone. So when you have low building blocks, it’s harder to build the
building. Actually, a couple of weeks ago, another news about cholesterol came out,
and what they’re saying now is that cholesterol is not evil. You can eat cholesterol as
much as you want if you have a good metabolism and your body can metabolize the
cholesterol. It’s not like everyone needs to run away from cholesterol. Again, don’t eat it
like crazy, don’t eat 50 eggs a day, but if you eat one or two eggs a day, you should be
all set, other than someone that has all the risk factors that we discussed.

[Damien Blenkinsopp]: You’ve included CRP. The reason everyone was
focused on cholesterol was for heart disease, but it turns out that hs-CRP is a better
marker, correct? Is that why you’ve included it?

[Gil Blander]: Yes, but CRP is not only for that. CRP is basically a
marker of inflammation and it’s related to cardiovascular diseases, but it’s also related to
a lot of other diseases, including cancer, and even diabetes. So, CRP is a marker of
inflammation, and inflammation is more and more considered to be a big, big problem,
not only for after athletic activity that your inflammation is increased but also for the
average population. Definitely inflammation is very important.

[Damien Blenkinsopp]: As you just mentioned, with athletic activity the
marker would go up, so I guess your tool comes in pretty useful in this situation because
you’re looking at those different populations and saying what’s normal for them.

[Gil Blander]: Exactly. It’s normal that your inflammation will go up after
athletic activity. For example, after a marathon run, I would suspect that your CRP
would be high. But it’s not normal that it would stay high for a week after that. So what
we are doing is we are asking our users to test themselves at a certain time when they
haven’t been running a marathon the day before, or maybe haven’t been highly
athletically active for a week before, and do it also after a day of rest. Then, if your
inflammation is high, that means you have some issue. It could be that you over-
exercise, could be that you have some injury, and it helps us and it helps our users to
pinpoint what the issues are that they have.

[Damien Blenkinsopp]: Great. It sounds like you’ve put a lot of controls in
there. Have you done the same thing with blood glucose? I’m just curious because we
had someone else on the show before, Bob Troia, “Quantified Bob,” and he’d been
tracking his fasting blood glucose daily and I was quite surprised to see how much it
went up and down most days. He was doing football practice some evenings, so he had
some correlation differences between the mornings after the night he’d been in football
practice and exercising versus a normal day when he hadn’t been exercising the day
before.

[Gil Blander]: Yes. First of all, I know Bob very well; he’s a user of
InsiderTracker and he’s a very interesting person. I completely agree with you. A blood
glucose, even fasting blood glucose, can change based on what you have done the
night before. What we are reaching or trying to do with our user or trying to explain to
everyone, it’s not only one time point and InsideTracker is not a tool that you should use
once. You should use it and use it again and again and again, and then when you start
to use it again and again, you see where is your field—Is it running between 80 to 90? Is
it running between 90 to 110? Or is it jumping all over? And usually it should be more or
less flat. And you can also start to see the trend if during the aging process or when you
are becoming older and older, you’re starting to see a trend of increasing it. So I
completely agree with what Bob has showed, but what we are trying to do here is not
looking at one point, not even two points, in order to see a trend you need to have at
least a few points.

[Damien Blenkinsopp]: How often do you recommend people take the
blood samples for the tool?

[Gil Blander]: We recommend that you do it at least a couple of times a
year. We have some users that are doing it four times a year; we have some athletes
that are doing it even once a month in order to really keep them in top performance, but
the average users that we have are doing it around twice a year.

[Damien Blenkinsopp]: Okay. That sounds about similar to me, actually—
what I do—so I’m glad to hear that I’m average in terms of how often I do these panels.
To learn more about InnerAge and any resources of our aging that you’ve come across,
first of all, where can we get information on InnerAge itself?

[Gil Blander]: Everyone can come to our website, it’s insidetracker.com,
and there we have a link to a page that we developed that shows what is InnerAge, an
explanation about focus foods, an explanation about the science, why those
biomarkers, and about the scientists who developed it. We developed a lot of
information for that because we know that it’s the cutting-edge and people need a lot of
information to understand what we are doing, so we devoted a page with a lot of
downloads that you can read PDF after PDF and spend maybe a full afternoon learning
about InnerAge.

[Damien Blenkinsopp]: So you’ve mentioned the scientists you’re working
with on this tool. Is there anyone else you would recommend to get more information
about aging, or are there any references like books or particular presentations that you
found useful in your research?

[Gil Blander]: Yeah, there are a lot of good scientists that are studying
aging. I mentioned Lenny Guarente and David Sinclair. There are a few other leading
scientists that are studying aging. One of them, which is a very interesting person, his
name is Nir Barzilai, located in New York City, and he’s studying mainly long-lived
humans and trying to see what are the changes in their genome and their proteome
compared to the average human, so that’s an interesting person to look at.

Another very interesting scientist is Cynthia Kenyon, who is from UCSF in San Francisco. She’s
focused mainly on the insulin pathway, which is very related to glucose—insulin and
glucose. She started with the model organism slow worms, and now she’s also working
on other model organisms. So I think that if you are looking at, or your audience will
look at those four, you can find a lot of very interesting information.

[Damien Blenkinsopp]: Great, thank you very much for that. What would
be the best ways to connect with you personally? And you on Twitter, Facebook?
Where do people connect to you? Where are you most active?

[Gil Blander]: I actually like Twitter a lot so I’m on Twitter. They can find
me, it’s GBlander1 and they can find me there. If someone has any questions, they can
contact us via our website. On our website there is contactus@insidetracker.com and I
would be more than happy to talk with them.

[Damien Blenkinsopp]: Great, thank you, Gil. I just wanted to learn a little
bit about you before you go, are you using your tool every month? What are you doing
in terms of tracking your biology at the moment?

[Gil Blander]: It’s a great question. I’m using the tool at least four times a
year. There are some months that I’m maybe testing every day. There was one day
that I was testing myself like four times because I’m all the time trying to find new tools.
So we are using home kits and different labs, and often my arm is completely dotted
with blood stains.

On top of that I used to use other Quantified Self tools. I used in the past the HRV from
Ithlete, which you interviewed Simon, and I think that it’s a great tool for the athletically
active population. Currently what I’m testing every day, or all the time, is my activity,
and my weight. I’m trying to use some other tools, so we’re trying to develop now a new
nutrition tool for our users, so obviously I’m using some nutrition applications,
MyFitnessPal, Nutrino, and others. So I’m using a lot of different tools but in the day-to-
day and in the last year, I measure my weight every day by Withings, which is a
European company, which have a great wireless scale. And I’m measuring my activity
using Fitbit, but I did test it from the 23andme to measure my genome, so I’m trying,
because I’m working on that, I’m trying a lot of different tools.

[Damien Blenkinsopp]: It sounds like you’ve got involved in a lot of them. Is
there any key insight; what have you learnt about yourself so far? Is there one important
thing that you’ve learnt from these activities?

[Gil Blander]: Yeah, I leant about myself that data is the key for me. For
example, when I’m measuring my weight, every day I’m measuring it here in the office,
after that I make a decision, should I eat that or should I eat that? Because it’s showing
me every day whether my weight went up or went down. So I succeed to maintain my
weight more or less stable. When I’ve seen that my weight is too high, I use some tools
to see if it’s helped me to decrease it. For example, I did an experiment when my weight
went up after the holidays. I started to log my food in MyFitnessPal and I lost like eight
pounds in a week and a half. The issue is that you cannot continue with it forever
because it’s very time consuming and annoying to add what you ate every day. So it’s a
good intervention but it’s for the short-term.

What we are trying to develop here in InsideTracker currently is find a tool that will
help you to maintain your weight, maintain your biomarkers, maintain your activity,
which is more seamless, and it’s not easy. We have a team of scientists, exercise
physiologists, coaches, and nutritionists who are trying to do that. But it’s definitely not
easy.

[Damien Blenkinsopp]: Yeah, great. Well keep me updated if you’re
coming out with something interesting; that would be great. So one thing you did
mention right there, which I forgot to mention, is I think that InsideTracker, currently
you use LabCorp request to get people’s samples. So you give them some requisition
forms and the person runs down to LabCorp and it gets sent to you, but you said you’re
also using home kits. Is that something that’s going to change in the future or is that just
for you in experimentation?

[Gil Blander]: No we have home kits. So if someone wants to use the
home kits, we have them; we are using home kits. The problem with the home kits is
that we tested a lot of vendors and most of them haven’t had the precision of the
measuring of the biomarkers to be good enough for us. Because we are giving you an
optimal zone, you should have the precision. So we came with two vendors that are
precise enough, but the number of biomarkers is limited. So for one of them we have
only five biomarkers; the other we have seven. But we are still using it because some
people are too lazy to go to the lab, some others don’t live in the U.S., and currently the
lab availability is only in the U.S., so they can use our advanced home kit and we are
sending it all over the world. So because of those reasons we are still using the home
kits.

We also hope that in the future, the quality, the precision of those home kits will be
better, then we could use more and more biomarkers. I really hope, and I think that it
will happen that in the next five years, we won’t need to go to the lab at all, we can use
our iPhone. Basically we are saying that you can bleed on your iPhone, spit on your
iPhone, pee on your iPhone, and then receive a lot of information, so that’s our goal. I
think that it will happen and what is nice about InsideTracker is that we are a
technology diagnostic. We don’t care where the information comes from; what we care
about is the quality of the information because we are running it via our analytic and
then providing to you the ranges and the recommendations. So as soon as the
technology will be good enough, we will integrate it.

[Damien Blenkinsopp]: I’m sure you are aware of Theranos and what
they’re doing. I don’t know if you know, but would you think that their services would be
accurate enough for you when they get to market? Or do you think they’re still focused
on being in or out of normal range and it’s not necessarily sharp enough for you?

[Gil Blander]: Theranos is very interesting. What is interesting is that
instead of taking the blood from the vein, you take it from the finger like the home kits
that we’re using. What is also interesting is the volume: because you’re taking it from the
tip of your finger, you cannot extract a milliliter; you are talking about microliters. What
is also interesting, that they promise, is that you can do it on time. So you receive the
information immediately, while when you do it at the lab it takes a couple of days, and
when you do it with the home kit it might take a couple of weeks. What is happening
with this—at least today, and I don’t know, I hope it will improve—is that even though
that they have a machine that can do it in place, they are sending it to a central lab. So
basically you go to one of the clinics of Walgreens. Currently only in…

[Damien Blenkinsopp]: I think it’s Arizona.

[Gil Blander]: Only in Arizona.

[Damien Blenkinsopp]: There’s one in San Francisco I think, as well.

[Gil Blander]: There should be one in Palo Alto, yeah. So you prick your
finger, they fill a small vial, and then they courier it to the lab. The lab do their analysis
and then you receive the result, I assume a day later, I’m not sure I haven’t tested it. So
you lose the value of the immediate response, that we don’t have, but it sounds like (at
least what they claim is) it’s accurate, which is great. Also, another advantage that they
have is the price: their price, at least the sticker price—what they show on their
website—is much lower than the price that a biophysician would do it, which is great
value. But again, it’s only available in Arizona; it’s not immediate. I think that it’s still an
intermediate solution. So it’s nice progress but it’s not the end product. The end product
will be the…

[Damien Blenkinsopp]: The iPhone.

[Gil Blander]: … your iPhone, yeah.

[Damien Blenkinsopp]: Thanks for the commentary on that because it’s
hard to know actually what’s going on and how far the progress. So it’s still in a trial
stage, Theranos.

[Gil Blander]: I assume so but my knowledge is the same as your
knowledge. I don’t have any internal knowledge about that.

[Damien Blenkinsopp]: Great, thank you. Well Gil, thank you so much for
answering all our questions today. You’ve given us some great insights into how you’ve
constructed your aging panel there.

[Gil Blander]: Thank you so much and I’m looking forward to really cool
entrepreneurs in your future podcast.

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If that’s true then tools that we have today such as ketogenic diets, fasting, lipid replacement therapy and other approaches to mitochondrial repair may help reduce or eliminate the risk of cancer, and even treat it when we have it.

We’ve already seen how important our mitochondria, and keeping them healthy, is in previous episodes, looking at longevity and aging with Aubrey de Grey, and autoimmune diseases with Terry Wahls. Today we add to that list the role they may be playing in the cancer diseases process.

“All cancers can be linked to impaired mitochondrial function and energy metabolism. It’s not a nuclear genetic disease. It’s a mitochondrial metabolic disease… therapeutic ketosis can enhance mitochondrial function for some conditions, and can kill tumor cells.”
– Dr. Thomas Seyfried

Today’s guest, Dr. Thomas Seyfried, is Professor of Biology at Boston College, where he leads a research program focused on the mechanisms by which metabolic therapies such as ketogenic diets and fasting can manage chronic disease and cancer. He sits on the editorial boards of four research journals, and has over 60 published papers on cancer and metabolism.

He is the author of the review paper Cancer as a Metabolic Disease, appearing in the Journal of Nutrition and Metabolism in 2010, and of the textbook in 2012 entitled Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer.

He’s a frequent lecturer and speaker at conferences on the topic of cancer, impaired mitochondrial function, and using ketogenic diets and fasting tactics as therapy to treat and avoid cancer.

This was personally an important episode for me. I hope you feel more in control of your cancer risk after listening to it, as I do having followed Dr. Seyfried’s work.

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

itunes quantified body

Show Notes

  • How the idea that a change in mitochondrial function is behind cancer started in the 1920s (4:10).
  • The ancient energy mechanism through which cancer cells can bypass the mitochondria through fermentation instead of normal mitochondrial respiration (7:20).
  • The part of mitochondrial function that seems to be compromised in cancer – oxidative phosphorylation (8:15).
  • Different types of cancer cells and tumors have varying damage to their mitochondria. The worst and most aggressive cancers have the least mitochondrial function (9:00).
  • The oncogenic paradox (9:00).
  • Lipids such as Cardiolipins in the inner membrane of mitochondria are the part responsible for respiration (15:10).
  • How Dr. Seyfried pooled research from over 50 years together to develop his conclusions on cancer and the mitochondria (18:00).
  • Therapeutic ketosis and fasting can enhance mitochondria (23:00).
  • Ketone bodies produce cleaner energy, with less oxidative stress (ROS) than glucose molecules, when used for fuel in the mitochondria (27:00).
  • Nuclear genetic mutations prevent cancer cells from adapting to use ketone bodies as their energy source (29:30).
  • Which biomarkers could be indicative of cancer risk? (33:10).
  • Using therapeutic fasting of several days to improve your metabolism (36:00).
  • Using combined blood glucose – ketone meters to take readings and using Dr. Seyfried’s calculator to calculate Glucose – Ketone Indices (38:00).
  • It requires 3 to 4 days of fasting to get into the therapeutic glucose – ketone index zone (42:00).
  • “Autolytic cannibalism” to improve overall mitochondrial function – the mitochondria can either be rescued, enhanced or consumed (47:30).
  • The difficulties with directly measuring mitochondrial respiration vs. anaerobic fermentation and lactic acid to assess cancer status (49:50).
  • Weight loss can come in two types, pathological and therapeutic. The weight loss via fasting is therapeutic and healthy (52:00).
  • Cancer patients do better with chemotherapy, with less symptoms, when they are in a fasted state (52:00).
  • Cancer centers currently do not offer mitochondrial based therapies, only chemo or immuno therapies (57:40).
  • The biomarkers Dr. Thomas Seyfried tracks on a routine basis and his use of the ‘fasting’ tool (101:40).
  • What Dr. Seyfried would do if he had cancer (102:30)
  • Should you remove organs if you discover you have a high genetic risk for cancer? (E.g. BRCA1 as with Angelina Jolie) (103:30)

Dr. Thomas Seyfried

The Tracking

Biomarkers

  • Blood Glucose: A measure of the level of glucose in the blood at one point in time. Dr. Seyfried’s therapies target reduction of blood glucose levels to limit cancer cell growth, and according to his theories high blood glucose is a biomarker of increased cancer risk.
  • Glucose – Ketone Index (GKI): The ratio between the concentration of glucose in the blood to ketone bodies in the blood. The calculation is Glucose (mmol)/ Ketone (mmol). Dr. Seyfried created the index as a better way to assess metabolic status. Therapeutic efficacy is considered best with index values approaching 1.0 or below. Patients with chronic disease like cancer have index values of 50 or more. Thomas’ paper on the use of GKI for cancer patients has just been accepted for publishing: The Glucose Ketone Index Calculator: A Simple Tool to Monitor Therapeutic Efficacy for Metabolic Management of Brain Cancer. It is on Nutrition & Metabolism journal here and you can download an excel sheet to calculate the Glucose Ketone index here.
    Glucose Ketone Index - Thomas Seyfried

    Glucose Ketone Index Tracking of a Water Fast as Therapy for Brain Tumors Trial – Thomas Seyfried

Lab Tests, Devices and Apps

The Tactics

Treatments

  • 3 – 5 Day Water Only Fasts: A water-only fast of at least 3 days and preferably 5 days is recommended by Dr. Seyfried as a tool to reduce cancer risk and to lower your glucose – ketone index to 1.0. He recommends doing this twice yearly. For cancer patients he recommends much more intensive use of the water fast.
  • Ketogenic Diets: The ketogenic diet is a low carb diet which also raises the level of ketone bodies in the blood. We discussed this in depth, as well as the Ketone biomarkers and devices in episode 7 with Jimmy Moore on Ketosis.
  • Intermittent Fasting: An approach to fasting where you fast for part of the day or certain days per week. There are many approaches to this, however in Dr. Seyfried’s research he has found this doesn’t have a significant enough impact on raising ketone bodies to be therapeutic. He has only seen this via the water-fast.
  • Hyperbaric Oxygen Therapy (HBOT): Another therapy Dr. Seyfried believes may be beneficial to fight cancer but is relatively non-toxic in comparison to current treatment modalities (chemo and immunotherapies), and would like to trial in conjunction with fasting protocols.

Supplements

  • Oxaloacetate: A support for the mitochondria, also dubbed as an anti-aging supplement as it has caloric restriction mimicking effects. It is sold by Dave Asprey in his “Upgraded Aging” formula.
  • 3-Bromopyruvate (3BP): Dr. Seyfried would like to incorporate this non-toxic molecule in combination with fasting therapies to treat cancer patients.
  • PQQ (Pyrroloquinoline Quinone): Mentioned by Damien as a potential tool for mitochondrial biogenesis.

Other People, Resources and Books

People

  • Otto Warburg: A well known scientist who worked on cancer in the 1920s and 30s and discovered that cancer cells have different metabolism to normal cells.
  • Albert Szent-Györgyi: The oncogenic paradox was first coined by this nobel prize winner for his work with vitamin C and energy metabolism.
  • Valter Longo PhD.: Dr. Seyfried referred to Valter Longo’s work at the University of Southern California on the impacts of fasting on patients undergoing chemotherapy.
  • Angelina Jolie: The actress recently had her breast’s removed when she discovered she has the BRCA1 genetic mutation, that predisposes women to breast cancer.

Organizations

Books

Full Interview Transcript

Transcript - Click Here to Read

[Damien Blenkinsopp]: Thomas, thank you so much for joining us today.

[Dr. Thomas Seyfried]: Thank you.

[Damien Blenkinsopp]: I’d like to start off with basically kind of an overview, because you are putting for a different theory of cancer compared to that that’s been the reigning theory for a very, very long time now. Could you describe the differences between the two theories, and what is the basis for your new theory?

[Dr. Thomas Seyfried]: Well, it’s not that my theory is new. The theory was initiated in the early part of the last century, in the 1920’s through the 30s and 40s, by Otto Warburg, the distinguished German scientists and biochemist. It was Warburg who found that all tumor cells continue to ferment glucose in the presence of oxygen. Put it this way, lactic acid fermentation.

This is a very unusual condition that usually happens only when oxygen is not present. But to ferment in the presence of oxygen is a very, very unusual biochemical condition. Warburg said, with his extensive amounts of data, that the reason why tumor cells do this is because their respiration is defective. So, in our normal bodies, most of our cells generate energy through respiration, which is oxidative phosphorylation. And we generate ATP this way.

But cancer cells, of all types of tumors and all cells within tumors, generally have a much higher level of fermentation than the normal cells. And this then became the signature biochemical defect in tumor cells. And Warburg wrote extensively on this phenomenon, and presented massive amounts of data – he and a number of other investigators.

But what happened after Watson and Crick’s discovery of the structure of DNA, and the findings that genetic mutations and DNA damage were in tumor cells, and the enormous implications of understanding DNA as the genetic material, this just sent the whole field off into a quest to understand the genetic damage in tumor cells. And it gradually became clear to many people that cancer was a genetic disease, rather than a mitochondrial metabolic disease as Warburg had originally showed.

[Damien Blenkinsopp]: Right, so when you were talking about the energy and respiration of the cells, just a minute ago, that was actually in fact the mitochondrial respiration, and energy generation from mitochondria within cells.

[Dr. Thomas Seyfried]: That’s correct. That’s correct, it’s mitochondrial. It’s an organelle within all of our cells, the majority of our cells – erythrocytes have no mitochondria, so they ferment. But the mitochondria are the organelle that dictates cellular homeostasis and functionality, and provides health and vitality to cells in our organisms, and ultimately our entire body.

And when these organelles become damaged, defective, or insufficient in some way, cells will normally die. But if the damage or insufficiency is a gradual chronic problem, the cells will resort to a primitive form of energy metabolism, which is fermentation. Which is the type of energy that all cells had, all organisms had before oxygen came onto the planet, which was like a billion years ago.

So what these cells are doing then is essentially going back to a very primitive state of energy metabolism, which was linked to rapid proliferation. Cells would divide rapidly and grow widely before oxygen came onto the planet. So what these cancer cells are doing is just falling back on the type of energy metabolism that existed for all organisms before oxygen came on the planet.

[Damien Blenkinsopp]: Does that type of fermentation type of respiration, metabolic activity, is that originating from the mitochondria, or from the cell itself?

[Dr. Thomas Seyfried]: No, there was no mitochondria before oxygen came on the planet. So this was purely a reductive activity within cells. It doesn’t require mitochondria, it’s a purely cytoplasmic form of energy. Glucose is taken in, and rapidly metabolized to pyruvate through cytoplasmic in the cytoplasm, and then the pyruvate is reduced to lactic acid or lactide, which is called lactic acid fermentation.

And this then could drive energy metabolism, and the processes that can emerge from this type of energy metabolism. But it’s a very inefficient form of energy generation, and it’s often associated with rapid proliferation.

[Damien Blenkinsopp]: Right, thank you very much. So, in very simple terms it seems like, basically what you’re saying is, as the mitochondria get damaged they stop functioning, and then the cell goes back to the original form of energy generation, and it’s as if the mitochondria weren’t there any more.

[Dr. Thomas Seyfried]: Well it’s not that they’re not there. They are there, and they can also participate in certain kinds of amino acid fermentations. They still play a role in generating energy and nutrients for the cell, but it’s not through the sophisticated aspect of energy generation through oxidative phosphoryation. That part of their function seems to be compromised, but other parts of their function can take place. But they’re not generating energy through what most cells would generate energy through, which is respiration or oxidative phosphorylation.

And I also want to point out, it’s not a complete shut down of oxidative phosphorylation. Tumor cells, depending on the grade, and how fast they grow, and how aggressive the tumor is. It is true that some very, very aggressive tumors have very few, if any, mitochondria. So these cells are primarily massive fermenters.

But some tumor cells still have some residual function of their respiration, and they grow much more slowly than those tumor cells that have no function, or very little function, of their respiration. So it’s a graded effect, but the bottom line is the cells continue to grow, but they’re dysregulated. Because the mitochondria do more than just provide efficient energy. They are the regulators of the differentiated state of the cell. They control the entire fiber network in the cell. They control the homeostatic state of that cell.

So these organelles play such an important role in maintaining energy efficiency. And when they become defective, the nuclear genome turns on these oncogenes, that are basically transcription factors that drive fermentation pathways. So the cells are able to survive, but they’re dysregulated.

[Damien Blenkinsopp]: Right, which becomes cancer.

So, in what ways are the mitochondria getting damaged. What is the context for this kind of damage that takes place today? Is this a modern phenomenon, because, obviously cancer has become a bigger and bigger target of medicine over the years, and, potentially, it’s been growing. I’d like to hear your view on that.

Is cancer something that’s always been around, or is it something that affects us more today, and how is it that the mitochondria are getting damaged?

[Dr. Thomas Seyfried]: Yeah, what you said there is referred to as the Oncogenic Paradox, which has been discussed by Albert Szent-Gyorgyi, who received a Novel Prize for his work on Vitamin C and energy metabolism and these things, and John Cohn from England. These people had referred to this phenomenon as the called the Onogenic Paradox. How is it possible that so many disparate events in the environment could cause cancer through a common mechanism?

And when we think of what causes cancer, we think of carcinogens. And these are chemical compounds in the environment that are known to be linked to the formation of cancer. So there’s a whole array of these kinds of chemicals that we call carcinogens. Then there’s radiation can cause cancer. Hypoxia, the blocking of oxygen into cells, can be linked to the formation of cancer.

A common phenomenon and finding is inflammation. Chronic inflammation that leads to wounds that don’t heal. This is another provocative agent for the initiation of cancer. Rare germline mutations, such as the mutations in the BRCA1 gene that a lot of people hear about because of Angelina Jolie bringing attention to that area. Viruses, Hepatitis virus, papillomaviruses. And there’s a variety of viruses that can be linked to cancer. Age. The older people get, the greater the risk of cancer.

All these provocative agents all damage respiration. Their common link to the origin of cancer is damage to the mitochondria, and damage to the respiratory capacity of the cell. So the paradox is solved once people realize that these disparate, provocative agents work all through a common mechanism, which is basically damage to the cellular respiration.

Now, but people say, “Well what about all the genome mutations? What about all these mutations?” Which is a major focus in the field right now, is that cancer is a nuclear genetic disease. Now what happens is the integrity of the nucleus and the genetic stability of the nucleus becomes unstable once energy from respiration becomes defective.

Now it’s very interesting. All of the so-called provocative agents that are known to cause cancer through damage to respiration release these toxic reactive oxygen species, which then cause nuclear genetic mutations. And this is what most people are focusing on. The nuclear genetic mutations in the tumor cells are the targets and focal point of the majority of the cancer industry. Now, when you look at the disease as a mitochondrial metabolic disease, the nuclear genetic mutations arise as secondary downstream epiphenomena of damage to the respiration. So what most people are focusing on is the downstream effect, rather than the cause of the disease.

[Damien Blenkinsopp]: You’re saying that because mitochondria are damaged and energy output is damaged, that causes the cell to lose it’s integrity?

[Dr. Thomas Seyfried]: Lose the genomic integrity.

[Damien Blenkinsopp]: Ah, genomic integrity.

[Dr. Thomas Seyfried]: Yeah. Most people you talk to about this, they say “Oh, cancer’s a genetic disease. We’re trying to talk all these genetic mutations. Every kind of tumor has all kinds of mutations. We need personalized therapies because the mutations are different in all the different cells, and the different types of cancer.” And that’s true, but all of that is a downstream effect of the damage to the respiration.

So, people are focusing on red-herrings. They’re not focusing on the core issue of the problem, which is stabilized energy metabolism. And this underlies the reason for why we’re making so little progress in managing the disease.

[Damien Blenkinsopp]: So, I don’t know if you can break it down into a bit more detail. The mitochondria are made up of several parts: the outer membrane, the inner membrane, and so on. Is it certain parts, or is it any part of the mitochondria that’s getting damaged?

[Dr. Thomas Seyfried]: Yeah, it’s very interesting. It seems to be we’ve defined the lipid abnormalities, the lipid components of the inner membrane of the mitochondria. So there’s certain types of lipids that are enriched primarily in the inner membrane of the mitochondria. This lipid called cardiolipin. It’s an ancient lipid that’s present in bacteria and in mitochondria, but it plays a very important role in maintaining the integrity of the inner membrane, which is ultimately the origin of our respiratory energy, which is that inner membrane.

And many of the proteins that participate in the electron transport chain depend, or are dependent under interaction in the lipid environment in which they sit. So, lipids can be changed dramatically from the environment, which then alter the function of the proteins of the electron transport chain, effecting the ability of that organelle now to generate energy.

This is a real issue, and that inner membrane can be effected by all these carcinogens, radiation, hypoxia, viruses. The viruses themselves, or the products of the virus, will enter into the mitochondria and take up residence, thereby altering the energy efficiency of the infected cell.

And most of the cells die. When you interfere with respiration, most cells die. But in some cells of our body that have the capacity to up-regulate fermentation, these primitive energy pathways, they survive, and they go on to become the cells of the tumor.

[Damien Blenkinsopp]: Great, thank you for that. So, this is a very different theory to that which most people have come across, which, of course, you just outlined with the DNA mutations. Which bits of research have you pulled together in your book, and in your presentations, that you feel like present this view of the world the most strongly. Are there key research elements, researchers that have gone on, and maybe it comes down to four pieces that you feel strongly support this versus the other argument?

[Dr. Thomas Seyfried]: I think that’s an extremely important point. What is the strongest evidence to support what I’ve just said? And what I did in my book in evaluating the therapeutic benefits that we’ve seen in managing cancer by targeting fermentation energy. How is it possible that we overlooked this information? It’s very interesting.

Over the last 50 years, various sporadic reports had been published in the literature showing that if the nucleus of the tumor cell is placed in a new cytoplasm, a cytoplasm that has normal mitochondria – and this is cytoplasm either from a newly fertilized egg, or an embryonic stem cell. Because now we have this technology where we can do these kinds of nuclear transplantations. And this ultimately was what lead to the cloning of Dolly the sheep, and these kinds of experiments. These had been done many, many years earlier in frogs, and in mice, before we moved on to the larger mammals and things like this.

But it became clear that when the nucleus of the tumor cell was placed into the normal cytoplasm, sometimes normal cells would form, and sometimes you could clone a frog, or a mouse, from the nucleus of the tumor cell. Now this was quite astonishing. Because people were thinking you would get cancer cells, because the mutations in the nucleus, if the hypothesis is correct that this is a nuclear genetic disease and the gene drivers are in the nucleus, then how is it possible that you could generate normal tissues without abnormal proliferation. In other words, normal, differentiated tissues from the nucleus of a tumor cell.

I was able to pull together a variety of these reports that had been sporadic in the literature over 50 years. And when these reports came out, it was considered kind of an oddball report that didn’t support the gene theory, but most people discounted it, because it was one singular report. But every four or five years, another report. Eight years would go by, another kind of report. And some of these studies were done by the leaders of the field, the key developmental biologists, the best there were. These people were heavy-weights in the field.

And they were coming to the same conclusions. That we were not getting tumors from transplanting the cancer nucleus into a normal cytoplasm. We were cloning mice, we were cloning frogs. We were seeing normal regulated cell grow. Now how can this happen, if the nucleus is supposed to be driving the disease?

So what I did was, I put all these reports together in a singular group. And I distilled it down to what the ultimate results showed. And then when you look at the whole group of papers, together for the first time, and the conclusions are consistent from one study to the other, using totally different organisms, totally different experimental systems, the results are all the same. The nuclear mutations are not driving the cancer disease.

And then if you take the normal nucleus and put it into a tumor cytoplasm, you either get tumor cells or dead cells. You never get normal cells. So this was clear. It became very clear to me, and when people look at these kinds of observations in their group and their totality, it’s a devastating statement on the nature of the disease. It’s not a nuclear genetic disease, it’s a mitochondrial metabolic disease. And the field has not yet come to grips with this new reality.

[Damien Blenkinsopp]: Just on that point, quickly, if you were to predict the future, do you think that this view of cancer metabolism is going to get traction in the near future? Say the next five years, next ten years, and what will it take to make that happen?

[Dr. Thomas Seyfried]: Well, it’s already gaining a lot of traction. People are now coming to realize that metabolism is a major aspect of cancer. But, unfortunately, what the field has done, there’s still links to the gene theory. So, the top papers come out and they say, “Oh, the abnormal metabolism in cancer cells is due to the nuclear gene mutations. Therefore, we still must be on the quest to find out what these mutations do.”

They have not evaluated in the depth of the information that I’ve presented. It becomes clear that this is not a nuclear genetic disease. So the mutations are not driving the disease, they’re the effects of the abnormal metabolism.

Now, there’s a groundswell of new interests in this. Now this opens up a totally different way to approach cancer. Once you realize it’s not a nuclear genetic disease, but it’s a mitochondrial metabolic disease, you have to then target those fuels that the tumor cell is using to stay alive. These amino acids and glucose, which can be fermented. Those molecules that can be fermented through these primitive pathways now become the focal point of stopping the disease.

So it becomes a much, much more manageable and approachable disease once you realize that if you take the fuel away from these tumor cells, they don’t survive. They become very indolent, they stop growing, they die. And now this gives you an opportunity to come in and target and destroy these cells, using more natural, non-toxic approaches.

[Damien Blenkinsopp]: Right. If you could reinforce that a little bit, because as I understand it, the current approach, which is pushed the most, is to target all of the different nuclear genetic mutations – and there’s many, many thousands of them, you can’t really count how many there are, because it’s constantly developing – versus, with mitochondria, as I understand it, mitochondria are all the same. So it’s a completely different problem when you look at it from that respective. Am I summarizing it correctly?

[Dr. Thomas Seyfried]: Yes, I think you’re absolutely right. I mean, it’s a completely different problem. It now becomes a problem of energy metabolism. And the nucleus becomes a secondary peripheral issue.

[Damien Blenkinsopp]: Right. And the fact becomes much simpler, because you’re targeting the same problem versus thousands of different problems.

[Dr. Thomas Seyfried]: Absolutely.

[Damien Blenkinsopp]: And then therapy is… Today we’re developing thousands of hundreds of different drugs to target different types of cancer.

[Dr. Thomas Seyfried]: Yeah, it makes no sense. And the issue is every single cell in the tumor suffers from the same metabolic problem. But every single cell in the tumor has a totally different genetic entity. And we’re focusing on the very different aspects of every cell, rather than the common aspects of every cell.

The problem becomes a much more solvable problem once you target the commonality. The common defect expressed in all cells, rather than the defects that are expressed in only a few of the cells. You would not do that until you came to the realization, and saw the data, that this is a disease of energy metabolism, not nuclear genetic defects. It’s a totally different way of viewing the disease.

[Damien Blenkinsopp]: Right. Thank you.

This may be kind of off subject for you, let me know if it is. But, I understand it, there’s also, more and more people are starting to link other types of diseases – say multiple sclerosis, Parkinson’s, and some of the other chronic diseases that we have and are not very solvable today – to mitochondrial disease. So I’m wondering if in any way you link that to the same origin of cancer, here. That we’re discussing.

[Dr. Thomas Seyfried]: Well, those diseases, that’s true. There are mitochondrial abnormalities in Parkinson’s disease, Alzheimer’s disease, epilepsy, and Type 2 diabetes. I mean, you can go right down the list and find a mitochondrial connection to a lot of these different diseases. But the mitochondria can be damaged, and insufficient, and influenced in many different kinds of ways. So, only cells that can up-regulate, significantly up-regulate fermentation, can go on to form tumor cells.

But many of our cells are not killed outright, and they struggle. For example, the brain. We rarely get tumors of the neurons in the brain, because if you damage the respiration of the neuron, the neuron will die.

Many of the tumors in the brain come from the glial cells. These are supportive cells of the brain, they play an extremely important role in the homeostasis of brain function. But those cells have a greater capacity to ferment than do the neurons. So when mitochondria are damaged in neurons, the neurons usually die. You can never get a tumor cell from a dead cell.

Now Parkinson’s disease and Alzheimer’s disease, these are situations where populations of neurons die from reactive oxygen species. So these reactive oxygen species, which are produced by inefficient mitochondria, kill the cell. And the cells never form tumors, they just die. So you have populations of cells in the Substantia nigra in Parkinson’s disease, or in the hippocampus in Alzheimer’s disease, where the neurons are dying. And they’re dying from mitochondrial energy inefficiencies.

And the idea then, is can we enhance neuronal function by using therapies that will strengthen mitochondrial function. And the answer is, yes. And this is why these ketogenic diets are showing therapeutic benefit for a variety of different ailments, a very broad range of ailments. But the diets and these approaches – what we can therapeutic ketosis – can enhance mitochondrial function for some conditions, and can kill tumor cells in other conditions.

So one now has to appreciate a new approach to managing a variety of diseases that may have a linkage through inefficient mitochondrial metabolism.

[Damien Blenkinsopp]: Could you talk about – we’re coming into treatment here a little bit now, based on your theory. There’s the difference between ketone, or like, fat versus glucose metabolism in the mitochondria. And you were just talking about efficiencies. Could you go over that? What is the difference there? Why is it that glucose metabolism is different that of fats and the production of ketones?

[Dr. Thomas Seyfried]: Yeah, well the body is very flexible. It can burn energy from carbohydrates, which is glucose, or it can burn energy from fatty acids. Or it can burn energy from ketones. And we evolved as a species to survive for considerable periods of time without food. It’s amazing how people don’t understand this. They think if they don’t eat food in a week or less, they’re going to drop dead. This is nonsense.

We evolved as a species to function for long periods of time. As long as we have adequate fluids, water, the human body can sustain functionality for extended periods of time without eating. Now, you say to yourself, well where are we getting our energy. We evolved to store energy in the form of triglycerides, which are fat. And many of our organs store fats to various degree, and we have fat cells that store fat.

Now, when we stop eating, the fats are mobilized out of these storage vacuoles in the cells. And the fats go to the liver, and our liver breaks these fats down, like a wood chipper, to these small little ketone bodies, which now circulate through the bloodstream, and they can serve as an alternative fuel to glucose. So we can sustain, because the brain has a huge demand for glucose, but the human brain can transition to these fat breakdown products called ketone bodies.

So this all comes from storage fat, and our brains can get tremendous energy from these ketones. The energy in food comes from hydrogen carbon bonds that were produced during the production of the food. Ultimately from planets and the sunlight. But the energy in the bonds is ultimately derived from the energy of the sun. Now, our bodies break down these bonds, and recapture that energy. What we’re doing then is just recapturing this energy.

Now ketone bodies, when they’re burned in cells, they have a higher number of carbon oxygen bonds. They produce more intrinsic energy than does a glucose molecule, which is broken down to pyruvate, which is a glucose breakdown product. And when ketones are metabolized, they produce fewer of these reactive oxygen species. They work on the coenzyme Q couple within the mitochondria to produce clean energy, energy without breakdown products. It’s a very efficient form of energy.

[Damien Blenkinsopp]: I like that analogy there, because people could relate to how we had lead gas before, and we cleaned it up a bit, and now we’ve got less waste products in the environment.

[Dr. Thomas Seyfried]: Yeah!

[Damien Blenkinsopp]: It’s a little bit similar.

[Dr. Thomas Seyfried]: It’s the same thing. I mean, our bodies are so super energy efficient when we begin to force them into a situation. In the past, this was done all the time, because in the past the humans almost were extinct a number of geological epochs, for the ice ages, lacks of food and all. And I mean, we have a very energy efficient machine in our bodies that can generate this energy from within. Clean, powerful, efficient energy that allows us to sustain our mental and physiological functions for extended periods of time.

And this comes from the genome. Our genome has a remembrance and a knowledge to do this. It evolved over millions of years to do this. The problem today is that this capability is suppressed by the large amounts of high energy foods that are in our environment. And what happens, this then creates inflammation and the kinds of conditions that allow inefficiencies, and eventually inflammation and the onset of cancer.

So, returning to the more primitive states allows our bodies to reheal themselves. And, as I said, here’s the issue. The nuclear genetic mutations that collect in these cancer cells prevent those cells from making the adaptations to these food restrictive conditions. So, because the mutations are there, the cells are no longer flexible. They can’t move from one energy state to the other, like the normal cells can, which have integrated genomes.

So, the mutations can be used to kill these tumor cells, but by forcing the body into these different energy states in a non-toxic way. It’s not necessary to have to poison people, nuke people, surgically mutilate people to make them healthy. There’s natural ways we can do this, if we understand the differences in metabolism between normal cells and cancer cells.

[Damien Blenkinsopp]: So, from your perspective, anything that would help to repair mitochondria, would that be helpful against cancer?

[Dr. Thomas Seyfried]: Oh, absolutely. Absolutely. You’re not going to get cancer in cells that have very healthy mitochondria. If mitochondrial damage is the origin of cancer, and the cells have very high efficient mitochondria, it’s very unlikely. The risk of developing cancer in those situations is remarkably low.

There are groups of people that we have in the United States, the Calorie Restriction Society of America. It exists in other areas throughout the world. These people have a very low incidence of cancer. They’re in a constant state of ketosis, and the incidence of cancer in these people is very, very low.

Now, I have to admit. This is not an easy lifestyle. People don’t want to be restricting themselves all the time, and doing this stuff. This is the issue. We live in an industrialized society that has come a long way to create an environment that is free of the massive kinds of starvations, and these things that existed in the past. So it’s hard to take your body and go back into these primitive states to do this kind of thing.

[Damien Blenkinsopp]: Right. So, there’s [unclear 31:58] a really big focus on what you’ve been saying on reactive oxygen species, which is kind of like the mini explosion that takes place inside a car when it’s running. And I think people can relate to the fact that all engines are causing damage while they’re running, because they’re producing heat, and so on.

So, with the mitochondria, it’s basically the same. And you’re saying that when we’re on a ketogenic diet, or where we’re fasting and we’re producing this more efficient type of fuel, it reduces our assets [unclear 32:23] causing less damage. And it’s an important type of the damage that is caused to mitochondria.

And this is why eventually it helps with the status of the mitochondria, to heal them and repair them, or to limit the additional damage that goes on which would help to promote the cancer. Is that a good summary, or have I got some things wrong?

[Dr. Thomas Seyfried]: It’s a very close analogy. I would say this is exactly what it is. We damage our body by the kinds of foods we eat, the kinds of environments we’re exposed to. And the mitochondria in certain cells just get damaged, and these cells then revert back to a more primitive form of energy, which is fermentation, which then leads to a total dysregulation of the growth of the cell. Collects these mutations that come as a secondary downstream epiphenomena of this.

And the thing of it is is, how do you target and eliminate those kinds of cells. And cancer, people must realize, this is systemic disease, rather than a focal disease. People say, “Oh, what does he study? He’s a liver cancer, breast cancer.”

These cancers are all the same. They’re metabolically all the same. You need to treat cancer in a singular global systemic way, and this then will marginalize and reduce the growth of these cells. And you have to be able to do it non-toxically.

And these ketogenic diets, or therapeutic ketosis, is just one way to enhance the overall health and well-being of the body while targeting and eliminating these inefficient cells. And this can be done if people do it the right away.

[Damien Blenkinsopp]: Great, great. Thank you very much.

So, based on this theory, what kind of biomarkers would give us insights into someone’s potential to develop cancer? Because today we look at 23andMe data, for example, genetics to kind of asses our risks of future cancer. For instance, on mine it says my highest potential cancer is lung cancer. And that’s pretty much the only markers that we’re given. Are there markers related to mitochondrial function, or damage, that you would feel that would be relevant to estimating a future potential risk of cancer?

[Dr. Thomas Seyfried]: Yeah, well I think one of the risks of cancer is high blood sugar, blood glucose levels. I mean this creates systemic inflammation, which underlies a lot of the so-called chronic diseases that we have, including heart disease, and Type 2 diabetes, and Alzheimer’s disease, and cancer. These are just the predominant number of chronic diseases that we’re confronted with.

So, if we know that high blood sugar is a provocative agent that increases the risk for cancer, then making sure your blood sugar levels are low. And the other thing too is elevation of ketones. So we developed what they call a glucose-keton index that can be used for people to prevent cancer, as well as managing the disease.

So if the glucose-ketone index, which we have defined as the ratio between the concentration of glucose in the blood to the concentration of ketone bodies in the blood. If this index can be maintained as close to 1.0 or below, the body is in a very high state of therapeutic energy efficiency. Which is then going to reduce the risk for all of these different kinds of chronic diseases. So, and if you look at most people with chronic disease, their index is about 50 or 100, rather than 1 or below 1.

We’ve just developed this, and we’re working on a paper. It’s called the Glucose-Ketone Index. It was designed basically for managing cancer, because patients who have cancer, if they want to know what these therapies are doing, how they’re working, you look at your index.

Now, people who don’t have cancer, who would like to do something to reduce their risk, they would do the same thing. And people would say, “What’s your index today?” “My index is 1.2.” You’re in a very good state of health.

And if most people – I can guarantee – people who eat regular foods, their indexes are about 60 or 70, not 1.2 below. Because what you do is when you have a lot of carbohydrate in your bloodstream, the ketones are very, very low. They’re like 0.2, 0.1. And you’re blood sugar is like 4 or 5 millimolar, and your blood ketones are 0.1 millimolar. Well what do you think your index is going to be? It’s going to be huge.

But then if you increase your ketones, if you can bring the ketones bodies up to the same level as glucose, then I have a 1.0.

[Damien Blenkinsopp]: Is this sensitive enough to manage potential? You made a very clear scenario of 60, where that’s a very dangerous situation to be in.

[Dr. Thomas Seyfried]: Oh no, no. I don’t want to say it’s dangerous. I want to say it’s the norm.

[Damien Blenkinsopp]: Oh, okay. Great.

[Dr. Thomas Seyfried]: It’s not dangerous. When you take somebody who has Type 2 diabetes, and his blood sugar is like 300 milligrams per deciliter – and you have to divide that by the number 18 to bring it down to millimolar – and his ketones, you can’t even measure them. I mean, these guys are inflamed. Their bodies are in an inflamed state. And inflammation will cause all kinds of effects.

So, you want to bring people down. How do you get these low numbers? Well, you can either go on these calorie restrictive ketogenic diets, or you can do therapeutic fasting, which is water only fasting, for several days. You’ll bring those numbers right down. You’ll get into an extremely healthy state. Because the ketones go up naturally when you don’t eat, and blood sugar goes down naturally when you don’t eat.

So then you enter into these states, it’s called therapeutic ketosis. The problem is it’s very, very difficult for most people in our society to do this, because our brains are addicted to glucose. If you take somebody who stopped eating for 24, 36 hours, this guy thinks he’s going to go crazy. It’s almost like trying to break the addictions to cigarettes, alcohol, drugs. It’s not easy. It’s very, very difficult to break the glucose addiction.

[Damien Blenkinsopp]: Absolutely. It takes a little bit of time to change your metabolism.

[Dr. Thomas Seyfried]: Yeah.

[Damien Blenkinsopp]: So we spoke to Jimmy Moore before. I don’t know if you connected with him before, and his book…

[Dr. Thomas Seyfried]: Yeah, I know Jimmy.

[Damien Blenkinsopp]: Right, right. So we spoke about some of the different ways to measure ketones. We had the blood test, the blood-prick test with the precision, which is a little bit expensive today. And you have the breath test, the Ketonics, which has just come out. With that index, are you using the blood-prick test, or are you using maybe blood labs, or something a bit more complicated?

[Dr. Thomas Seyfried]: There’s a couple of companies that use the blood test, the most accurate. It’s more accurate than the breath, blowing into a ketosis meter. Or you do urine sticks. So the most important measure, of course, is blood. So you have to take a blood stick. There’s only a few meters that can do both ketones and glucose, using the same meter.

You have to use different sticks. There’s a ketone stick, and a glucose stick. So from the same drop of blood, you can get your blood sugar, and then you can put a new stick into the machine, which is a ketone stick, and then you can take the same drop of blood and get your ketones.

Now what we did was we developed a calculator so that all the person would have to do is to push the button on the meter, and it would calculate already your glucose-ketone index. This would give you a singular number from a drop of blood.

[Damien Blenkinsopp]: So you’ve developed your own device, you’re saying, which does that calculation?

[Dr. Thomas Seyfried]: We developed the calculation. It’s called the Ketone Index Calculator. And because you have to convert everything back to millimolar. Because many of the ketone meters give you blood sugar in milligrams per deciliter, and ketones in millimolar. So we have to convert. You can do all this by hand, you just have to do the divisions and all of this stuff.

[Damien Blenkinsopp]: So you’ve got an online calculator where people can put their values in and it will give them the index?

[Dr. Thomas Seyfried]: Well, we don’t have that yet. What we did was develop the calculator that could be incorporated into these meters.

[Damien Blenkinsopp]: I see.

[Dr. Thomas Seyfried]: This is the thing. So people, regardless of whether you’re a cancer patient and you want to manage your disease, or you’re a person who wants to prevent cancer, or you’re an athlete who wants to know what his physiological status is, or you’re someone who wants to lose weight. All of these issues, you can get a sense, a good solid biomarker sense, by looking at your glucose-ketone index.

And everybody can do that from these meters that are capable. But the meters right now are not designed to give you glucose-ketone indexes. And this is what we’re saying; it’s the index that will tell you your overall status, your health status.

[Damien Blenkinsopp]: Right. So I imagine, right now, you’re approaching the providers of these tools to see if they can incorporate this calculation into their devices?

[Dr. Thomas Seyfried]: Yes. Exactly. They don’t have it yet. They’re not even aware yet of the potential market, or interests, among the general population. Not only for people that are afflicted with various diseases, but people who are healthy and don’t want to get those diseases.

So this is a very simple tool. The only drawback from it is you have to stick your finger with a little prick to get a little bit of a drop of blood. The people with Type 1 diabetes do this regularly. This is not an issue. But for those people who are into this, and they want to do it the right way, and they want to get accurate biomarker measurements, then they would do this. For those people who are interested in this.

This is invasive in the sense that you have to prick your finger to get a drop of blood, but it’s not invasive in the sense that you have to take tissue samples, or any of this kind of thing.

[Damien Blenkinsopp]: And so this is something that people could do on an on-going basis? So I’m guessing for someone with cancer – I don’t know if this would be something you would say – they’d probably want to look at daily, or every few days, or something like that. And someone else, maybe it’s just something they need to do a lot less intensive routine, in terms to just monitor the levels of their general ketogenesis.

[Dr. Thomas Seyfried]: Yes. You’re absolutely right about this. People who are trying to manage their diseases thoroughly might want to do this maybe once or twice a day. Just like someone who might have Type 1 diabetes. They measure their blood sugar several times a day.

The issue right now is the glucose strips are relatively cheap – they’re like 50 cents a piece – but the ketone strips are much more expensive. They can range from anywhere from $2 to $5 a stick.

[Damien Blenkinsopp]: Do you know if that’s due to economies of scale? Or if it’s simply because not enough people are using them yet?

[Dr. Thomas Seyfried]: Yes, it’s an economy of scale, absolutely. Because very few people measure their ketone levels. But now, linking those ketones to your overall general health, a lot of people would be interested in this.

And people in general like numbers. They want to know, and especially a singular number that would dictate your state of health. If you can say to somebody, “Listen. My index is between 1.1 and 0.9,” people would automatically know this guy is in a tremendous state of health.

People like to know that. You say, “Where is your number?” And people like to keep log books. They like to record these numbers. And they also link this to a greater sense of well-being. People who have their numbers down in these ranges, they tell me – and I’ve done it. Some people get into a state of euphoria. It’s like unbelievable.

When your body starts burning these ketones, it’s like you enter a new physiological state. And athletes are doing this sometimes. So it’s a whole new realm of how to monitor your own health with accurate biomarkers that give you an indication of your health status.

[Damien Blenkinsopp]: So do you follow a similar prescription to Jimmy Moore? I believe you understand his approach, where he’s eating a high fat diet, or sometimes he’s fasting. Kind of like intermittent fasting, which has become pretty popular these days.

[Dr. Thomas Seyfried]: Well intermittent fasting is, from what we’ve seen in our work, you don’t get the health benefits, the power of the health benefit, until you’ve gone three to four days without any food. Just drinking water. And then those who can go a week, like a seven day period, this is really when you start to see your blood sugars going down and your ketones going up.

But once you can get into this zone – we call it the zone of therapeutic management – where now you know your in the zone, this is where the health really comes in. And when you say periodic fasting, now there’s a lot of people that I know – numbers of people – who have a rather restrictive diet for the week, and then one day a week they’ll not eat anything. So, it’s one day off on food, like a 24 hour period where they’ll just have maybe a green tea, no calories, or just pure water.

[Damien Blenkinsopp]: Some of the intermittent fasting regimes propose that approach, a 24 hour fast every two days.

[Dr. Thomas Seyfried]: Yeah, but then you’ve got to know, okay what did that do to my index? How effective was the 24 hour fast on my index? And you look down, you say, “Well, I didn’t get my ketones up very far. They went from 0.1 to say, 0.5.” Okay, but if I go four or five days, it goes from 0.1 to 3.0. Oh wow, this is the magnitude difference.

[Damien Blenkinsopp]: Yeah. So have you looked at different people, because when we were talking to Jimmy, he was saying that different people have different responses. It’s based on their current state of metabolism. They’ll have to be more extreme in their approach to get the same level of ketones, and the same impact on an index, depending on, potentially, how damaged their mitochondria are. I don’t know how you look at it.

[Dr. Thomas Seyfried]: Yeah, no, that’s a really important point. It’s certain people. It’s also certain sexes. Women can get into these ketone states much easier than men. And young people can get into these zones much, much easier than can older people.

So it’s an age issue, it’s a gender issue. We’ve seen some of our students get down their blood sugars down into the low 30s, which people would say would be a crisis situation, you’d have to go to the hospital. But their ketones are elevated, and when the ketones are elevated, you have no crisis situation. It’s only when you lower blood sugar and don’t elevate ketones that you have this situation.

Males have a lot more muscle, they tend to burn protein, which can be converted to glucose. So their blood glucose doesn’t go down as sharply as women, the blood glucose of females goes down. Females can get their blood sugars down and their ketones elevated – from all the data that we’ve seen for several years on different gender – and this is what we see.

And older people are simply locked into a much longer lifestyle of high glucose. And for them to get their blood sugar down, it’s a real struggle. And also their muscle mass over the age. They have a lot of other issues that play into this whole thing.

And you’re absolutely right, it’s an individual thing. Some people can’t tolerate this. They get really sick, they get light-headed. Where other people make the adaptations much more quickly. So again, people have to know their own physiology.

But they have to have the biomarkers that let them know. They need to see these numbers, and once they see these numbers they’ll know that they’re on the right path, and they probably can do this if they persist a little bit longer. Rather than throwing their hands up, not knowing what’s going on, being very frustrated. And as I said, once you have this information and knowledge, that these kinds of things become much easier.

[Damien Blenkinsopp]: Yeah. It definitely helps with your confidence in something if you can see that, maybe you don’t feel better, or you don’t feel a difference yet, but if you see the numbers starting to move then it gives you that sense of accountability, and motivation also. I think that’s one of the very helpful aspects of these kind of indexes that you’re talking about.

[Dr. Thomas Seyfried]: Absolutely. This is a very important point, you’re absolutely right about this. Because when you see that you’re killing yourself, and nothing’s happening, or you don’t feel anything, but when you see numbers starting to change in the direction you know your hard work is starting to pay off. And then you get motivated, and you want to see then how far you can push these numbers.

Now this is not going to hurt anybody. You’re just lowering blood sugar and elevating ketones, and your body gets into a new state of health. And people feel it, believe me. You can feel this stuff happening. But there’s a rocky road going from the high glucose state to the high ketone state. And that rocky road can be more rocky for some than others.

[Damien Blenkinsopp]: Absolutely. So there are other aspects to mitochondrial health that certain people are looking at at the moment. I don’t know if you’ve come across any of these, but I thought I’d just throw them out in case you had some comments on them.

Some people are talking about mitochondrial repair, in terms of repairing the membranes with specific lipids, by providing those lipids to help reinforce the mitochondria. Other people talk about things like PQQ to help stimulate biogenesis of new mitochondria. I don’t know if you’ve heard about these things, or have any ideas or opinions on them.

[Dr. Thomas Seyfried]: Well, in my book I called it autolytic cannibalism. And this is basically, the mitochondria can either be rescued, enhanced, or consumed through an autophagy mechanism. And when you stop eating, now every cell in the body must operate at its maximal energy efficiency. That means that the mitochondria in those cells must be operational at their highest level of energetic efficiency. Otherwise the cell will die, and the molecules of that cell will be consumed, and redistributed to the rest of the body.

Now, in cells that have some mitochondria effective, or more efficient than other mitochondria within the same cell, the inefficient mitochondria can be incorporated into the lysosome. The parts of that mitochondria can then be redistributed to the healthy mitochondria within the cell. And this way you eliminate internal energy inefficiencies, but without having to kill the cell, because the cell is able to repair itself.

Whereas those cells that can’t repair themselves die, and their molecules are then consumed by macrophages, excreted back into the blood stream, and the nutrients now are used to support the health and vitality of those cells in the body that have this higher energy efficiency. It’s a remarkable state of efficiency. So it works both with individual cells, and throughout the whole entire physiological system.

[Damien Blenkinsopp]: Great, great. Thank you. I’m just thinking, you’ve spoken about fermentation versus respiration. Is there any way to measure that, that you know of? Is that being done in studies? So are the studies coming out are comparing the state of fermentation versus respiration taking place in people’s bodies, and correlating that to cancers, or anything like that?

[Dr. Thomas Seyfried]: Yeah, that’s kind of hard to do, because we all have lactate in our bloodstream, and the lactate comes from erythrocytes, our blood cells. The blood cells have a shorter half-life than many of the other cells in our body, and those cells have no mitochondria. They have no nucleus. So they’re little cytoplasms that primarily ferment.

But they don’t use a lot of energy, because the role of that cell is simply to exchange gases. So it floats around in our tissues, it deposits it’s oxygen and picks up CO2, as more or less a little mailman running around, picking up this and dropping that off. And they have a shorter half-life. But they have lactate.

Now if you have a tumor, or if you’re under hypoxic stress, lactic acid will go up in your bloodstream. But it’s hard to know if a tumor will do that. Sometimes what tumors will do, they have a phenomena called cachexia. This is where the tumor cells will send out molecules that will digest proteins, or dissolve proteins in our muscles and other proteins. And these proteins then go to the liver, and are broken down into amino acids, and the amino acids are conjugated into glucose.

So the glucose goes now into the tumor cell, and some of the proteins and the amino acids go to the tumor cell after being broken down. So the tumor is essentially causing our body to starve to death. We might be eating, but it looks like we’re not gaining any weight, and we’re becoming moribund and looking like we’re starving to death. This is an effect of the tumor,.

Sometimes you don’t see that. Sometimes lactic acid will go up, and sometimes it won’t. So there’s a lot of ambiguity of looking at a good biomarker to assess the state of what level of tumor growth you might have, other than the fact that you’re losing weight even though you’re eating. Which is the cachexic state; you’re kind of wasting from within. This is the whole thing.

And this is one of the fears that the medical profession has with cancer patients, because they say these poor people are losing weight through this cachexic mechanism, and then you come along with a metabolic therapy, and they say, “Oh, this can’t work.” But the issue, of course, is that there’s two types of weight loss. One is a pathological weight loss, and the other is therapeutic weight loss.

Pathological weight loss is cachexia, and of course if you treat it with toxic chemicals and radiation, you get so sick with fatigue, nausea, diarrhea, vomiting. I mean, this is pathological weight loss. Therapeutic weight loss is you’re losing weight, but your body is getting extremely healthy, and killing cancer cells at the same time.

So weight loss can come in two different varieties: pathological and therapeutic. And people have a tremendous difficulty in understanding the differences between these kinds of weight loss.

[Damien Blenkinsopp]: I think we’ve mentioned on a podcast before that when people are fasting in this state, they actually feel better, even if they have, for instance, chemotherapy. They tend to do better in chemotherapy when they have been fasting.

[Dr. Thomas Seyfried]: Yes, because it reduces inflammation. We published a number of papers showing how therapeutic fasting reduces systemic inflammation. Systemic inflammation contributes to a pathological state, and facilitates tumor growth.

So therapeutic fasting, while at the same time you’re taking a toxic drug, it’s like what are you doing here. But it does take the sting out of that toxic drug. People feel better when they’re therapeutically fasting. I think Longo’s group down at University of Southern California has clearly shown that some of these cancer patients can do a lot better, and feel better, when they’re fasting while they’re taking chemotherapy.

But you’re absolutely right about that.

[Damien Blenkinsopp]: Thank you so much for this interview[unclear 53:08] Thomas. I want to ask you just a few more questions to round off now.

What do you think will happen in the next five or 10 years, or hope? What are your visions for this area, in terms of biomarkers, like testing devices, or change in the way we approach this? Do you think there’s specific opportunities ahead, are there specific questions you’re looking at at the moment to resolve, in research, or so on?

[Dr. Thomas Seyfried]: Yeah, well I think the people themselves are demanding a change. The issue is that they haven’t been shown other alternatives, other than the standards of care, which are conducted by the major medical schools: Dana Farber Cancer Center, MD Anderson, John Hopkins, Yale Cancer Centers, Sloan Kettering, UCSF. The major industries of cancer and academics are closely aligned in how to do this.

And it’s not working. We’re having about 1,600 people a day are dying from cancer in this country. And the statistics in other countries in Europe, and China, and Japan, are not far off of this. And if we had Ebola outbreak in this country, where 1,600 people were dying a day, this would be of the greatest catastrophe that people can imagine.

But for cancer, it seems to be okay. This is the norm. Well it doesn’t have to be this way. It doesn’t have to be this way. And the issue here is that the people see that we have more, and more survivors, and people doing pretty well on these metabolic therapies. Why are we not doing this as more of a general treatment as opposed to these toxic approaches to manage the disease?

So I think the change will come from the grassroots. I don’t see it coming from the top medical schools, because these people are not trained. They’re medical education doesn’t give them the training to identify these approaches to therapy. It’s not part of the medical training.

There are a number of physicians that are recognizing this now, and they want to become part of this new approach to cancer management. Now, you have to realize that we’re just beginning. This is just a new field, it’s a beginning field. Even though the science is well, well established, the implementation of this science for patient health is just at the beginning. It can be refined, it can be modified.

A lot of this now we’re talking about, the potential for managing cancer in a non-toxic way with greater therapeutic efficacy, is just beginning. So, I think that we need more trained people. We have to have people that understand this. Eventually, these kinds of approaches will be more and more recognized, and more and more implemented in the overall society.

The problem is people have not yet found a way to make a large profit on this kind of an approach as you can with certain drugs, and immunotherapies, and these kinds of things. But that will probably come in time, once people understand what the best approaches and techniques are.

[Damien Blenkinsopp]: Another aspect I wanted is there’s more research being undertaken on mitochondria over time. Do you think that will help, in any way?

[Dr. Thomas Seyfried]: Yeah, I think it will help a lot, like you said, with the lipids. And we’re looking into this ourselves. I think there’s ways that we can enhance mitochondrial energy efficiency through various diets and supplements, and things like this.

And there will be a real quantitative measures that can assess this, for people to recognize what works and what doesn’t. So I think it’s just that it’s an area that has been not well appreciated, and not well recognized.

And as long as people think that cancer is a nuclear genetic disease, the focus on the mitochondria hasn’t been there. People have known the importance of mitochondria, and it’s been a very major area of scientific research. But it’s not recognized as the solution to the problem. It’s kind of a side effect.

What we’re looking at is understanding mitochondrial functions, and it’s interaction with the nucleus and other parts of the cell to maintain a healthy cell – a healthy society of cells – and a healthy overall physiology. All linked to the mitochondrial energy metabolism. This is going to be a very exciting new development.

[Damien Blenkinsopp]: Yeah, I agree. There’s not a day that goes past that I don’t think about mitochondria these days. And hear someone talk about it. It happens a lot on this show, also.

If someone wants to learn more about your work, and this theory of cancer, and the index you were talking about, where should they go?

[Dr. Thomas Seyfried]: Well, I wrote the book On Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of the Disease. That’s published by John Wiley Press. Unfortunately, it’s a science book and it’s not cheap, like you’d find most of the Amazon books, but it gives you the literature, it gives you the science. It gives you the hard evidence to support everything that I’ve said.

Another book that’s just appeared is Tripping Over the Truth: The Metabolic Theory of Cancer, by Travis Christofferson, who’s written a book for the layperson, where he actually read my book and went back to test all the things that I was saying, and actually talking and visiting and interviewing those scientists who work in the gene theory, and work in the metabolic theory, and get the word directly from them. It reads like a novel, and it’s much less scientifically intimidating than what I wrote.

I wrote this book to convince my peers, and people in the cancer and scientific field, the evidence that supports what I’m saying. This sometimes can be intimidating to the layperson. Whereas Travis went out and actually interviewed those scientists, and asked them the specific questions. And now it becomes a very intriguing story; I mean, how did this cancer thing get so far out of whack with what we know about it. People like to see this, and read it.

So that is another book that’s generating… If you go on Amazon, you’ll see the reviews. They’re all quite outstanding for Travis’ book. And I’ve been privy to a number of other books that will be coming out over the next year, which are harping on the same general theme, that cancer is a metabolic disease, and it can be beaten by metabolic solutions. Totally different than what’s been going on in the main focus.

And this is kind of shocking, because you go to the top cancer centers, and they don’t speak anything about this. They’re still talking about the standards of care as they have been done, or they’re talking about immunotherapies, which is the new buzzword for the cancer field, where you’re going to identify all the mutations, and then make anti-bodies to the defective proteins, and then treat people. And they show a few survivors on the cover of the Wall Street Journal saying how wonderful this works. But they don’t show you the other evidence showing how many people are dying from this.

All this will change, because the people in this society, the public, is going to be fed up with the lack of progress, and what we have is a new way to approach this problem based on solid scientific fact. It’s just that these facts are not well understood or recognized at this point.

[Damien Blenkinsopp]: Great. Thank you very much, and we’ll put all of this in the show notes, so people will find these links easy. Also the index you spoke about, I’m guessing there’s nothing really published about that. If people go to your website in the future, will you have something on there which will talk about that in more detail?

[Dr. Thomas Seyfried]: Yeah. We have a paper that’s under review right now, where we’ve submitted a paper for the index, and we’re in the process of making some revisions on the index. And the index was, in this paper, was mostly focused on managing brain cancer, but we also noted that this index could have a broad applicability to a whole range of different diseases.

And in the Journal of Lipid Research, which is the top journal in the field of lipid biochemistry, I edited one of the issues that was entitled Ketone Strong: Emerging Evidence for the Role of Ketones and Calorie Restriction for the Management of a Broad Range of Diseases. So, more and more scientists are getting involved in this, and more and more information will be coming out. Both in the professional scientific journals as well as in the public interests articles in journals, and magazines, and radio shows.

More and more people will be coming to know this, and I think the field is going to have to deal with it. And I think in the long run, we’ll emerge into a new way to manage these chronic diseases with a lot less toxicity, and greater efficacy.

[Damien Blenkinsopp]: Great, great. Thank you. Now, just two more questions, personal questions for you.

What data metrics do you track for your own body on a routine basis, if any?

[Dr. Thomas Seyfried]: Well, basically I try to get on a scale and see how much I weigh. Obviously, if you can keep your body weight at a stable level for a period of time, this is certainly one way to maintain homeostasis.

I’ve done the three day fast, but as I said, when you’re older like myself, it’s very uncomfortable, but it’s certainly doable. It’s like training exercise. You’d have to do it probably a couple of times a year to get into the state. I think every time you do this, you become more confident in your ability to do it again.

There is a state of uncertainty and discomfort, like, “Oh my god, I’m not eating any food. How can I go, and I feel uncomfortable, and a little light-headed.” And you try to drink water to say, “Maybe I can fill my stomach up with water and I won’t feel as hungry.” And then you start getting water intoxication. And eventually you realize that you really don’t need to drink a lot of water, and you just have to bite the bullet.

But as I said, as we begin to do this, we realize that it’s not so life-threatening as everybody would think it would be. So I think I try to do that. But as I said to a lot of people, they said, “Oh, you must do this all the time.” No, I don’t do it all the time. But if I had cancer, I’d know exactly what I would do.

[Damien Blenkinsopp]: What would you do? Just to speak it out clearly.

[Dr. Thomas Seyfried]: I would stop eating.

[Damien Blenkinsopp]: Completely?

[Dr. Thomas Seyfried]: I’d get my index down below 1, that’s for sure. And then I would transition off to these high-fat, nutritious kinds of diets, ketogenic diets, and maintain my index. And then of course, we’re investigating – it’s very hard to get funds to do this kind of stuff too, because it’s not considered sexy science – what is the best combinatorial therapy that would work with therapeutic fasting and ketogenic diets, that would put the greatest amount of pressure.

And most of it has to do with what kind of non-toxic drugs would you dovetail in with therapeutic fasting and ketogenic diets? And like hypobaric oxygen therapy, 2-deoxyglucose, 3-bromopyruvate, oxaloacetate. I mean, we can go down these lists. Most of these are non-patentable drugs, but they have tremendous power when used together with these other therapies. And most of this stuff is just trying to figure out the dosages, the timing.

These kinds of issues, it’s just like perfecting the engine. How did the car engine become so efficient today from the way it was in 1900?

[Damien Blenkinsopp]: Right. So the things you just mentioned either stress the cancer cells specifically, like hypobaric oxygen, or they support the mitochondria, oxaloacetate, right?

[Dr. Thomas Seyfried]: Yes! Exactly. What you’re doing is you’re enhancing mitochondrial function in normal cells, and you’re putting maximal metabolic stress on the tumor cells. For the first time, we’re using our normal cells to directly combat and battle the cancer cells, while enhancing their health and efficiency.

[Damien Blenkinsopp]: So for someone who has, say we do a 23andMe test – like a lot of people on this podcast do their 23andMe test – and it comes out with some DNA, and it says, maybe you have a pretty high chance of cancer in your lifetime – and it could be lung cancer or whatever. Lung cancer’s not a good one, because often it’s smoking. So, one of the other more general ones, like breast cancer.

What would you basically say that they should be fasting once per month for three days, or twice per year for seven days, and maybe looking at those therapies you just outlined.

[Dr. Thomas Seyfried]: Yeah. People who have Li-Fraumeni syndrome, which is an inherited germline mutation in the gene for P53 which encodes a protein in the electron transport train, or BRCA1. Product of the BRCA1 gene has been found in mitochondria. We look at a number of these so-called inherited genes that increase your risk for cancer. But as I told you, everything passes through the mitochondria The mitochondria are the origin of the disease.

So, the inherited mutations simply make that organelle slightly less efficient in certain cells of our body. Not all cells, but only certain cells, like the breast, the uterine, or these kinds of things. And we know that there are people, like if you inherit the BRCA1 mutation, your risk of cancer goes up significantly. But not everybody who has BRCA1 mutation develops cancer.

So clearly the environment can play a huge role in determining whether that gene will be expressed or not. You can do prophylactic removal of organs, and things like this, to reduce your risk. But it would be just as effective in my mind to transition the body to a metabolic state that would minimize the problem of that gene influencing the mitochondrial function. It seems a lot less draconian than doing these massive surgical mutilations.

Or you can do both. The idea is some of these inherited mutations, they might have a preferred organ – like a breast, or a uterus, or ovary – but you’re not going to remove all your organs. You’re not going to remove brain. You’re at a higher risk, so what can you do to lower your risk? As I said, if you keep your mitochondria healthy, the risk is going to be significantly reduced.

People need to know this so they can make choices that would be best suitable for them.

[Damien Blenkinsopp]: Thank you so much for the information today. This is really an information packed episode. It’s got this great new take on cancer, which I think is very positive, because it’s talking about something which people can have more control about. So it’s not just that this is a new approach, and the older approach has been struggling for quite a while, it’s become very expensive, and so on, with not so much success, but also that this is an approach which is within people’s own manners, sphere of management.

A lot easier to start having an impact on their own lives. So it’s very positive from that perspective also.

[Dr. Thomas Seyfried]: Yeah, I agree. Absolutely.

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