Heart disease affects 50% of the U.S. population in their lifetime. Learn how to accurately quantify your personal heart disease status and risk, and if necessary, take clear actions to reduce that risk by eliminating plaque in the arteries.

This episode presents an in depth look at heart disease because this is one of the most likely things to shorten our lifespan. We focus on the key topic of quantifying your real heart disease risk.

One in three deaths in the United States are caused by cardiovascular disease. Even worse, one of out two Americans will suffer some form of heart issues, meaning that one half of the population is at risk. The total costs for dealing with heart disease are larger than any other disease by far, estimated at 650 billion dollars in the US.

While heart disease is a big risk which is worthwhile taking a look at, it is not a big risk for everyone. For some people there are other health risks they should look at and assess. Thus it is important to know if heart disease is something you personally need to act on – in a proactive way which reduces the risk for it. Are there specific factors you need to be concerned about?

The way to approach this issue is by quantifying our risk for cardiovascular disease. Naturally, understanding of risk goes beyond the typical cholesterol numbers. We discussed some of the problems with cholesterol biomarkers in Episode Seven with Jimmy Moore which is a useful preamble to this episode. In this show we go deeper into details, looking at metrics which give you a real accurate view of your heart disease status and risk.

There is a way to be very accurate, both [by] blood work and by imaging. To really nail down your personal risk of experiencing the number one killer in the Western world, heart disease.

– Dr. Joel Kahn


DrJoelKahnNew
Dr. Joel Kahn
University Professor & Heart Prevention Doctor

Joel Kahn has focused his career on preempting cardiovascular and heart disease. His goal is to reduce risks as well as to avoid surgery and cholesterol – lowering drugs. He takes a proactive approach by using information and interventions to ensure that heart disease does not become a problem in patients.

He is a clinical professor of medicine at Wayne State University School of Medicine, and Director of Cardiac Wellness, Michigan Healthcare Professionals P.C. He is a Summa Cum Laude graduate of the University of Michigan School of Medicine and author of two books, The Whole Heart Solution and Dead Execs Don’t Get Bonuses: The Ultimate Guide to Survive Your Career With a Healthy Heart.

Joel has also recently set up the Kahn Center for Cardiac Longevity. In their institution they emphasize early imaging of arteries and extensive laboratory evaluation for the correctable root causes of heart disease. So Joel and his clinic have a very quantified and longevity focused approach to this whole area, which is great to see.

I think this is an episode everyone should listen to, because absolutely everyone is going to have to deal with these issues in their life. Inevitably everyone comes into contact with heart disease, whether it be through themselves, their family, or their friends.


The episode highlights, biomarkers, and links to the apps, devices and labs and everything else mentioned are below. I’d love to hear what you think of the episode – and if it has helped you – let me know in the comments!

itunes quantified body

What You’ll Learn

  • What led Dr. Kahn to choose a career in cardiology (4:30) .
  • A holistic view of the true causes behind developing heart disease (6:17) .
  • The causes behind heart attacks and strokes are tightly related and how both conditions are preventable (9:05).
  • How the condition of the endothelium (inner wall of blood vessels) and mitochondria affect cardiac health (10:26).
  • The biomarkers Dr. Kahn uses in his practice and ways to personalize medical and lifestyle advice (15:08).
  • Infrared Sauna treatment is proven to have positive effects on cardiovascular disease treatment (23:27).
  • Using chelation in treating disease to lower toxins levels – including heavy metals (26:03).
  • Early detection of coronary artery plaque using a CAT-scan for coronary artery calcium (30:47).
  • Because CAT scans are radioactive an ultrasound-based carotid IMT test is used for following disease progression (37:09).
  • How to get informed and decide whether to get a coronary calcium test (39:24).
  • Understanding genetic testing results in conjunction with imaging of arteries (41:04).
  • The Liposcience NMR technology platform offers the most accurate measurement of LDL cholesterol particle density (43:35).
  • Familial genetics and lifestyle when tracking lipoprotein levels as a biomarker for cardiovascular disease risk (44:07).
  • Using C- Reactive Protein (CRP) as a biomarker for cardiovascular disease risk (46:36).
  • Measuring blood vessels inflammation as part of a comprehensive heart health assessment (48:04).
  • Diet recommendations for preventing heart disease and examples of successful programs (50:00).
  • Replacing dairy products with healthy hydration is beneficial but strict ketogenic diets exhibit negative health effects by causing adrenal stress (54:19).
  • Why dark coffee is generally a health drink and the caveats to consider when consuming coffee (59:00).
  • Scientific and medical practice sources for discovering topics in this episode (1:01:32).
  • The biomarkers Dr. Joel Kahn tracks on a routine basis to monitor and improve his health, longevity and performance (1:03:50).

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

 Dr. Joel Kahn & The Kahn Center for Cardiac Longevity

Books by Dr. Kahn

Tools & Tactics

Interventions

  • Far Infrared Sauna: Sauna treatment improves heart health, especially in patients who have suffered heart attacks or have blocked arteries. As Dr. Kahn claims, repeated treatment consisting of 15 minutes infra-red sauna followed by 30 min rest helps the body sweat-out toxins and improves cardiovascular system function (See study looking at use of infrared sauna therapy for heart patients).
  • Chelation: Chelation therapy has been scientifically proven to rid the body of excess of toxic metals and is approved by the FDA for this purpose. This published study summarizes the findings of the US National Institute of Health clinical trial – specifically on using intravenous EDTA chelation therapy for coronary heart disease. We covered chelation and removing metals in greater depth in past episodes: episode 13 with Chris Shade (Mercury) and episode 19 with Garry Gordon.

Supplementation

  • EDTA: EthyleneDiamineTetraacetic Acid is the main chelating supplement discussed in this episode, and which is supported by the studies, in particular to chelate lead.
  • Niacin: Also known as vitamin B3 – is an essential human micronutrient. Supplemental niacin is primarily used to treat high cholesterol. Dr. Kahn claims that niacin is particularly good at lowering lipoprotein(a) levels – a proven risk factor for cardiovascular disease.
  • Proline / Lysine: Dr. Kahn claims that intake of these amino acids may prevent the damage that lipoprotein(a) otherwise imposes on the cardiovascular system.
  • Coenzyme Q10 (CoQ10): Helps support healthy mitochondria in cells. In turn, this maintains a robust cardiovascular system. Dr. Kahn encourages most of his patients to take this supplement.
  • Vitamin CLiposomal Vitamin C: Proponents of the Pauling Therapy from Linus Pauling argue that heart disease can be treated, and even cured, by substantially increasing Vitamin C intake.

Diet & Nutrition

  • Nitric Oxide (NO) Supporting Foods (Watermelon, Hemp Seeds, Pine Nuts etc.): Nitric Oxide (NO) is synthesized by the inner walls of blood vessels – known as the endothelium. It prevents arteries from constricting or spasming. NO prevents heart attacks in both an immediate and a long term time frame. Dr. Kahn suggests foods which support NO synthesis including watermelon, hemp seeds and pine nuts.
  • Coffee: As a drink, coffee is a rich source of beneficial antioxidants. However, it’s positive effects may depend in part on what type of caffeine metabolizer you are. If you metabolize caffeine slowly then you have a tendency to feel jittery or racing heart and there is some evidence that it may be less heart healthy than for fast metabolizers of caffeine. However, overall caffeine is considered a health food in most studies, and Dr. Kahn recommends 1 cup of black coffee per day to his heart patients.
  • Tea: The intake of tea is also an advisable health practice including green tea, herbal tea, hibiscus tea, or chamomile tea before bed – which is a source of sleep support.
  • Vegetarian / Vegan Diets: A vegetarian diet excludes meat by focusing on plants for food, but may include animal products such as milk and eggs. In addition to excluding all meat products, a vegan diet also excludes all animal products. Dr. Kahn argues that in world areas where people live the longest, and with the greatest freedom from heart disease, the populations are not completely vegan.
  • Paleo: This diet is based on the foods that paleolithic humans might likely have eaten. It includes meat, nuts, and berries, and excludes relatively – recently developed food products including animal products such as milk. Dr. Kahn described his view that there is a lack of scientific evidence to support this diet for cardiac health.
  • Ketogenic: A ketogenic diet is a diet that induces a state of ketosis in the body where the body uses ketones instead of glucose for fuel. Typically this involves a diet with low carb and low to moderate protein intake with high fat intake. Previously, we discussed measuring ketones and ketogenic dieting in Episode 7 with Jimmy Moore.

Tracking

Biomarkers

Cholesterol Based

  • High – Density Lipoprotein (HDL): The traditional measure of ‘good cholesterol’ used by doctors and healthcare. Levels above 60 mg/dL are considered protective of cardiovascular disease. Dr. Kahn stresses the importance of checking your cholesterol, even at around the age 18 or 20.
  • Low Density Lipoprotein (LDL): The traditional measure of ‘bad cholesterol’ – the type which causes heart disease. Less than 100 mg/dL is considered an optimal level, while levels between 160-189 mg/dL increase the risk for cardiovascular disease. Research has shown that LDL alone is not the best predictor for cardiovascular risk. Actually, LDL particles with the smallest sizes are most damaging to the cardiovascular system. Dr. Kahn puts more emphasis on using the LDL particle number and LDL particle size metrics.
  • Lipoprotein(a): Lipoprotein molecules carry cholesterol and similar substances through the blood. A test can be done to measure a specific type of lipoprotein called lipoprotein-a. Higher levels of this marker are associated with risk of artery damage. Dr. Kahn states that in most labs normal reference ranges for lipoprotein(a) should be under 30 mg/dL.

Blood Sugar Regulation Markers

  • Fasting Glucose Levels: A biomarker used to understand blood sugar regulation. Optimum levels are between 70 and 90 mg/dL. Higher levels indicate some level of blood sugar dysregulation, which increases risk for diabetes II.
  • Hemoglobin A1C: A form of hemoglobin which is measured to identify the average plasma glucose concentration over prolonged periods. Higher levels of hemoglobin (A1C) indicate poorer control of blood glucose levels. In turn, these are associated with diabetes and cardiovascular disease risk. Normal levels are less than 5.7%, pre-diabetes levels range between 5.7 to 6.4%, while higher than 6.4% is indicative of diabetes.

Inflammation Markers

  • High Sensitivity C-Reactive Protein (hs-CRP): Elevated hs-CRP levels indicate inflammation which is damaging to inner artery walls. If your level is below 1 mg/L then you do not have a cardiovascular disease risk. Because of the proven clinical use of this biomarker, Dr. Kahn claims it is high time for cardiovascular patients to start measuring hs-CRP.
  • Homocysteine: Elevated homocysteine blood levels indicate blood vessel inflammation and higher risk for coronary artery disease. This marker has previously been discussed in episode 5 with Ben Lynch and in episode 29 with Dr. Nicolson.
  • Lipoprotein-associated phospholipase A2 (Lp-PLA2): This biomarker gives insight into inflammation of blood vessel walls and is useful as part of a comprehensive assessment. The PLAC test measures the activity of ALp-PLA2 (an enzyme) in a patient’s blood. Individuals with test results showing Lp-PLA2 activity greater than 225 nmol/min/mL are at increased risk for cardiovascular disease.

Other

  • Ferritin: Serum ferritin acts as a buffer against iron deficiency and iron overload. Levels are measured in medical laboratories as part of the workup for detecting iron-deficiency anemia. The ferritin levels measured usually have a direct correlation with the total amount of iron stored in the body. Female normal reference range is 12-150 ng/mL and for males it is 12-300 ng/mL.
  • Myeloperoxidase: A very sensitive biomarker for predicting myocardial infarction in patients with chest pain. It shows added predictive value compared to measuring hs-CRP alone.
  • Vitamin D: A vitamin which is essential for bone development and maturation and prevents osteoporosis. The Vitamin D Council suggests an optimum level of 50 ng/mL. The 25-hydroxy Vitamin D Blood Test is the most accurate way to measure how much vitamin D is bioavailable to be used by your body.
  • Free Testosterone: A steroid sex hormone. Physiological effects include muscle growth, increased bone density, and development of male sex characteristics. Free Testosterone is a small portion of this hormone which is bioavailable, because it remains unbound by carrier proteins in the bloodstream. Free testosterone reference ranges for females are 1.0-8.5 pg/mL and 50 – 210.3 pg/mL for males.
  • Estradiol: This is the primary female sex hormone. For females, the levels of this hormone vary greatly because of its key role in regulating menstrual cycles. In the normal reproductive cycle, estradiol levels measure typically <50 pg/ml at menstruation, rise with follicular development (peak: 200 pg/ml), drop briefly at ovulation, and rise again during the luteal phase for a second peak. At the end of the luteal phase, estradiol levels drop to menstrual levels unless there is a pregnancy. The reference range for healthy adult males is 14-55 pg/mL.

Lab Tests, Devices and Apps

  • Coronary Artery Calcium Score (CASC) Test: This test is a type of CAT scan which determines whether your arteries contain clotting plagues by quantifying calcium presence. By measuring calcium scores, the extent of blocking can be determined. This test lasts very short (under a minute), does not require injections, and is not claustrophobic. CASC tests have been shown to predict mortality.
  • Carotid Intima-Media Thickness (IMT) TestThis test measures the thickness of the walls of your arteries and helps determine whether you have a higher risk for cardiovascular disease. Individuals with unwanted CASC Test scores should undergo IMT ultrasound as a follow up for disease progression or risk. This is because the CASC test is based on a x-ray CAT scan, as opposed to the harmless ultrasound waves used in the IMT test.
  • WellnessFX Cardio Lipoprotein Profile: This test panel includes a number of lab tests, including the comprehensive analysis of lipoprotein particle numbers and sizes. It uses the accurate direct-measurement laboratory method (NMR (Nuclear Magentic Resonance) lipoprofile). Individuals with patterns of higher counts of smaller particles have a more concerning lipoprotein profile than those with less particles with greater size.
  • Life Extension Company Blood Testing: Joel mentioned LEF as one of the organizations that provides direct to consumer blood testing that he trusts.
  • Caffeine Metabolism Genetics: Whether you metabolize caffeine more rapidly or slowly depends on the presence of a Single Nucleotide Polymorphism (SNP) genetic variation in the liver enzyme responsible for metabolizing caffeine. The company 23andMe offers a genetic test for identifying slow metabolizes who may be at increased risk for cardiac attack due to coffee consumption.
  • Toxin Concentrations: These can be measured using blood or urine tests available in specialized labs. We’ve covered this subject extensively in previous episodes – see episode 13 with Chris Shade (Mercury), episode 19 with Garry Gordon (Lead) and episode 23 with Kara Fitzgerald (other metals and chemicals).

Other People, Books & Resources

People

  • Dr. David Katz: Founding director of Yale University’s Yale-Griffin Prevention Research Center and current President of the American College of Lifestyle Medicine.
  • Tim Russert and James Gandolfini: Both men were prominent individuals in American culture, whose lives were shortened by sudden unexpected cardiac attacks.
  • Linus Pauling: An American biochemist, author, and educator as well as one of only four individuals to have won the Nobel Prize twice. During the 1990s Pauling put forward a plan for the treatment of heart disease using vitamin C.
  • Stormie Jones: Was the world’s first recipient of a successful simultaneous heart and liver organ transplant at the age of sixShe suffered from an inherited genetic condition named Heterozygous Familial Hyperlipidemia which made her liver unable to remove cholesterol from her bloodstream. In turn, this was also causing her serious heart problems.
  • Nathan Pritikin: An American inventor, nutritionist and longevity researcher. His program features the Pritikin Diet which is focused on a variety of whole (unprocessed) or minimally processed foods.
  • Dr. Dean Ornish:  A cardiologist and the founder of the non-profit Preventive Medicine Research Institute. He coaches patients towards a vegetarian diet but not a strict vegan diet. His program is defined in four specific elements of lifestyle. It is the first scientifically proven program to “undo” (reverse) heart disease by optimizing stress, diet, physical activity, and social support.
  • Dr. Caldwell Esselstyn: His proposed diet for cardiac health is strictly vegan with under 10 percent of calories coming from fats. His program for patients includes walking, meditation, stress management, yoga, and other lifestyle choices to decrease cardiovascular disease burden.
  • Dr. Neal Barnard An associate professor of medicine at the George Washington University School of Medicine. He has led numerous research studies investigating the effects of diet on diabetes, body weight, and chronic pain.
  • Dr. Garth Davis: Among the leading researchers in the field of bariatric medicine – a branch which deals with the causes, prevention, and treatment of obesity.
  • Dr. William Davis: A cardiologist and author of the Wheat Belly blog.
  • Dr. David Perlmutter: A Board-Certified Neurologist and Fellow of the American College of Nutrition.
  • Dr. Alessio Fasano: An Italian researcher who sees pediatric and adult patients in the Center for Celiac Research and Treatment at the Massachusetts General Hospital. He is carrying out important research on the health impact of eating grains.

Organizations

Books and Video

Full Interview Transcript

Click Here to Read Transcript

[04:30][Damien Blenkinsopp]: Joel, thank you so much for coming on the show.

[Joel Kahn]: My complete pleasure.

[Damien Blenkinsopp]: So, I’d like to start with a quick story about how you became a cardiologist; why did you get into, specifically, holistic cardiology?

[Joel Kahn]: Sure.

I knew really from a very young age that I wanted to be a cardiologist. I actually had a very small issue as a young child with a tiny hole in my heart. It healed, but I had the pleasure of seeing a very fine heart doctor until I was about 18 years old.

It had a very good impression on me; [there were] a few scary moments being in a big hospital as a little kid, but overall it was actually very positive. And kind of pursued a fast tract to making this my career. I’ve been doing it now for almost 26 years after training.

Holistic? I just always felt people are more than a pill. Doctors are wonderful people, nurses are wonderful people; I don’t have a chip on any shoulder. But I was exposed to some really good people. I got very involved in nutrition, nutrition lead to Mind Body, nutrition lead to Standard and Alternative Fitness, nutrition lead to supplements, Yoga, meditations.

So I just poured my heart and soul into studying and learning, and expanding my tool box for patients. And then I said, I’m going to start writing about it, because I don’t know if [they] are practicing it. So it’s all been a wonderful journey that’s far from over.

[Damien Blenkinsopp]: I didn’t realize you’d had that heart issue. Is it completely resolved now?

[Joel Kahn]: Yeah. Yeah. It’s very common, a little worrisome to the parents — god bless my mother and father. But it’s another example of if you don’t get in the way of things, the body can often heal itself. And this was a relatively minor thing, so good for that.

[Damien Blenkinsopp]: Great to hear. And it gave you the motivation to get started in all of this. It’s kind of funny who life always does that; it kind of steers us in the direction we end up going.

[06:17] I was wondering, because you’ve been looking at this holistically — and a lot of people focus on the heart, cholesterol, and things like this — could you explain what a formula to get heart disease would be, in terms of a holistic view? Because when you read through your book, it gives you a much more global view of how heart disease comes about than we’re typically used to.

[Joel Kahn]: Yes. And you know, we don’t want to throw away the basics. In essence, there’s two ways to approach this.

Our government, the United States government, has been publishing for a while, every 10 years, major causes of death. And unfortunately heart disease is at the top of that list, every list, every 10 years. But that’s not really the true causes, and starting in 1993 some very open-minded researchers said, “Let’s talk about the true causes.”

And the true causes for 80 to 85 percent of premature deaths were three activities: smoking, poor fitness, and poor diet. And those true causes dwarfed everything else. And it always dwarfed genetics. It’s a lifestyle world, baby, in terms of developing or preventing heart disease.

So, heart disease develops because we smoke too much; fortunately, under 20 percent of the population, and it used to be 40 to 50, so major inroads, it’s falling. Heart disease develops because we don’t move enough, and we’ve gone from farming and active community 150 years ago to everything being tech based, and we’re blessed with all of that. But we are paying a price.

And we now have to use, I have an app on my phone that reminds me to stand 5 minutes every hour. So we’ve come full circle, where technology was the problem and now technology will provide solutions. And desks that go up and down so you can stand at work and such.

And then heart disease develops because of the change in our diet since the Golden Arches hit California in the 50s, and all that’s followed with giant companies and processed food, and our crazy lifestyle where we don’t have time to make meals from whole foods anymore. Those are the big three by far.

A good friend at Yale, head of Preventative Medicine Dr. David Katz says, “Forks, fingers, feet.” Fork, what you do with it will determine your life; fingers what you do in terms of smoking, and feet whether you move and exercise that body. And really that accounts for the majority of it.

Sleep, stress, and love would be the other three. Adequate sleep, managing stress, and including yourself in a community to be surrounded by loving, like-minded people would round out the top six. And that’s a pretty holistic view, but it’s not very difficult, and it’s not very sophisticated.

[Damien Blenkinsopp]: Yeah, great, thank you very much for that.

[09:05] And I think when we think about heart diseases we often think about heart attacks, but is stroke related to heart disease as well? Is that one of the outcomes from the same kind of mechanism?

[Joel Kahn]: Yes. Stroke is a little bit more diffuse or widespread in terms of trying to nail down the cause. The number one listed cause of death in the United States is heart disease, such as heart attack. And number three is stroke, with cancer between the two. Therefore, if you lump heart disease and stroke, cardiovascular disease is the number one cause of death in every segment of the population over age 30, men and women.

But stroke has a shared cause to heart attacks; that is you can get clogged arteries from the lifestyle measures, and in part genetics that I just ran through. But there are other causes of stroke: bleeding disorders, heart rhythm disorders.

So the data is you can prevent about 80-90 percent of heart attacks through adopting a healthy lifestyle that’s neither expensive nor difficult, just rarely done. And you probably can prevent about 60 percent of strokes. It’s not as high because the cause is more commonly something other than atherosclerosis, or hardening of the arteries.

[Damien Blenkinsopp]: Great, thank you for that. Yeah, because I wasn’t really aware that they were so tightly related and preventable as well.

[10:26] In terms of stressors and some of the other mechanisms, could you talk a bit about the actual mechanisms behind heart disease? How this takes place? Without getting, obviously, into crazy detail, because it can get pretty detailed.

But in your book you talk about a variety of factors that we don’t often think about, such as mitochondria, and the gut, and other areas. And we don’t think about those leading to heart disease. So could you give us some kind of overview to show us how these mechanics are working to create a condition.

[Joel Kahn]: Well certainly, and one term that readers and listeners may not be familiar with but is important to grasp is something called your endothelium. And that is, essentially, inside every artery in your body — miles and miles of arteries carrying blood to your brain, your pelvis, your heart, your organs, your toes — is a one cell layer thin lining, like wallpaper on a wall.

And until about the 1980s we thought it was simply just a cell barrier between blood on the inside and the structure of the wall on the outside. But now we know that the endothelium makes many chemicals, the most important of which, or perhaps the most crucial, is nitric oxide, a little simple gas that in a healthy artery is created in abundance.

Arteries making nitric oxide because of a health endothelium will resist the clotting of blood; you want the clotting of blood when you cut your finger, you don’t want the clotting of blood when you’re on the verge of a heart attack. The nitric oxide will prevent; arteries from constricting, or spasming, which again can trigger a heart attack; the Raynaud’s blue-white-red fingers some people struggle with in the cold; leg pain on walking; and also the actual plaque, the actual build up of debris in arteries is resisted by a healthy endothelium with healthy production of nitric oxide.

So, that’s one physiology, and the good news is things that we would associate with a healthy lifestyle –eating a lot of produce, fresh fruits and vegetables, exercising your body, adequate sleep, good blood pressure, good blood sugar, good cholesterol numbers from a healthy lifestyle — are all associated with a healthy endothelium. And if you have a sick endothelium, you can make it healthier though a healthy lifestyle.

All of these things resoundingly shown scientifically. For example, eating watermelon, [it’s] very rich in chemicals that support nitric oxide. Hemp seed [is] very rich in chemicals that support nitric oxide. Other seeds and nuts similarly: pine nuts.

The other one [is] as you mentioned; inside every cell are little organelles, or little structures inside our cells. We have trillions of cells —- brain, heart, muscle, everywhere — and their powerhouse to generate function is called your mitochondria. We don’t think about them, we don’t give our mitochondria a kind of shout-out, we don’t wake up in the morning and say, “Thank you mitochondria for taking care of me while I slept seven and a half hours.”

But indeed, aging is a stress on our mitochondria where they won’t function to make energy so well. And unfortunately we now know not only bad lifestyle, which is way too common — sedentary lifestyle, food-based poor lifestyle, smoking poor lifestyle — but environmental toxins clearly affect our mitochondria: pesticides, herbicides. There’s data that genetically modified products and the herbicide roundup affects our mitochondria. Nutritional deficiency like low magnesium from not eating enough produce affects your mitochondria.

And our cells will age quicker and won’t function as well, and may produce fatigue, may produce congestive heart failure, shortness of breath. But again [it is] an area of science that is very hopeful, because lifestyle can cause our mitochondria to be much more efficient, and, probably most strongly, exercise. The actual number and health of your mitochondria in your muscles goes up when you exercise. You actually, you can be in your 40s and 50s and you can create more mitochondria by regularly exercising to a fairly vigorous degree for a while.

So yeah, those are concepts that I think are important to share. And there’s ways to boost the function of both our endothelium and our mitochondria, both by lifestyle, and not — I’m a fan of selected supplements. The supplement Co-enzymeQ10, CoQ10, which is more commonly used in Europe than the United States, helps support healthy mitochondria and [it’s] something I encourage most of my patients to be on.

[15:08][Damien Blenkinsopp]: Great. So, on this show we talk about a lot of biomarkers, and I know you have preferences for different biomarkers from the standard.

Could you, first of all, walk us through some of the very typical. I mean, when most people go to their doctor they are given the standard cholesterol markers. So could you talk through the LDL, the HDL, the total cholesterol, and if you use those, and how useful you find them.

[Joel Kahn]: First step, and I always like basics, is get your cholesterol checked, even at around age 18 or 20. Because one out of every 400 people may have an inherited disorder called Heterozygous Familial Hyperlipidemia, or FH, and you may be 18 years old with a cholesterol 450.

One out of every 400 is not all that rare. In a typical high school in this state that might be six kids. And it’s better to know it at age 18 or 17 than to find out in an emergency room at age 45 with a heart problem.

But in my practice, I do advanced cholesterol lab values. There’s a variety of different ways. For example I can see two people with a cholesterol of 220 and the LDL cholesterol of 120, and they may be at very different risk for artery damage because we can break down the size of their LDL, the number of particles in their LDL. Usually it’s a technology called NMR spectroscopy, but it’s become a very low cost lab that’s much more accurate.

So I can have two people and I can speak to them differently; that’s called personalized medicine. And say, “Nancy, your LDL is actually very favorable. You don’t have much. They’re large particles, and I think we can leave you alone and continue your good lifestyle. And Joe, your LDL of 120 is constructed largely of small, dense particles, and you’ve got way too many of them. And we’ve got to really kick that lifestyle in gear, and your nutrition in gear, and we’ve got to get that belly a little thinner.”

You know, it can help me define a more guided approach. But when we’re talking population, a standard finger prick or church-based or work-based cholesterol is a good starting point.

[Damien Blenkinsopp]: Right. It’s just a screen to see if it’s worth digging further. So basically, if LDL comes up high, you’d be like, okay I’ll look at the particle number and size to see if this is a problem.

[Joel Kahn]: It can. Yes, that’s one of the things we can do to refine if, everybody needs encouragement about lifestyle, but if they need beyond that consideration of medication or more intense lifestyle.

[Damien Blenkinsopp]: Great. So is it possible for someone to have a high LDL number, which is over the standard reference range, and it not be a problem because the size of their particles is large and small number of particles, basically?

[Joel Kahn]: Yeah. We broke up a little, but cholesterol is associated with developing heart disease. And it is causative, there’s no doubt. I mean, I reflect back when I was in cardiology training in Dallas, Texas.

I took care of a little girl, 11 years old, who was known around the world, Stormie Jones was her name, sweet girl. And she was born with a genetic disorder where she had both genes defective, that was called Homozygous FH. It’s very rare, it’s about one person in a million. But that little girl had had a heart attack, a bypass, a balloon, by the age of 12. And to argue that cholesterol doesn’t have a direct role in damaging arteries has many pieces of science behind it, animal and human, but I always reflect back on Stormie Jones.

So cholesterol is important, but there’s so much variability in human physiology. So when I’m dealing with one person, I try to find if their arteries are healthy or not. There are ways to determine if there’s any early plaque, if there’s any early endothelial damage.

And if I see somebody with a fairly high cholesterol at age 60, for example, but they have no evidence of plaque, no evidence of endothelial damage I’d have a very hard case to put them on a prescription drug, in my mind, because there must be other factors that are protecting them. And yes, they may have an additional 30 or 40 years to worry about, but I’m really going to stress to that person lifestyle — healthy diet, exercise, weight management, blood pressure management — and not necessarily write a prescription drug.

And, you know, there’s always the opposite too. There are people that have had a heart attack, or a bypass, and relatively moderate risk factors, and then we really have to go on a search. We have to go on a search for other biomarkers, like something called Homocystine, lipoprotien(a), Ferritin.

There’s a lot of people that are prediabetic that fall through the cracks, and are suffering artery damage from their prediabetes, but it’s really not been offered as a diagnosis, and that’s kind of a very common one, for example.

[Damien Blenkinsopp]: Right. With the Homocystine, for example, are you looking for the causes? Or are you trying to look a bit further back?

So if you get some high cholesterol numbers and some particle numbers that are indicative, is homocystine more indicative of a cause, so you can refine your prescription, the treatment you recommend? Or is that just a basic filter for your assessment?

[Joel Kahn]: No, I think the ultimate joy is trying to get back to the root cause. And the root cause, certainly the majority of it, is lifestyle. And we’ve talked about that, food choices, which I’ll go over carefully with patients: processed versus unprocessed, high in saturated fat versus low, high in added sugar versus low. [And also] body movement, body fitness, body exercise, adequate sleep, methods of managing stress.

For example, it’s been shown that meditation can have a significant effect on lowering your cholesterol. Kind of pieces of scientific data that are published that aren’t talked about much. When you’re stressed out your cortisol level goes up, your blood sugar goes up, your blood cholesterol goes up, your blood pressure goes up. And a practice of breathing or yoga or meditation can fairly dramatically lower blood cholesterol.

So then getting at the root cause, now the question is after those basics, which need to be addressed every visit, over and over — sleep, stress, nutrition, fitness — do we go further? We do know that there are environmental toxins, and we do know that heavy metals we’re exposed to through cosmetics, through industrial exposure, through dental fillings. We often carry a burden of mercury and lead and cadmium.

Smokers not only are ingesting all kinds of toxic carcinogens, but the ground in Virginia is said to be quite rich in cadmium, which is fine if you have it in the battery that’s powering your radio but you don’t really want cadmium in your blood stream in your body. So you can use blood analysis, hair analysis — take a little snip of hair — or urine analysis and determine if a person has greatly elevated levels of some of the pesticides, herbicides, pollutants like heavy metals.

And sometimes the course directed at identifying and removing those can really restore a person’s health to a much higher level. It’s a slow process because you accumulate those things slowly, and any plan to exit them by avoiding; if it’s an industrial exposure taking more care or changing jobs, don’t walk on your lawn the day that they spray the pesticides or look for more natural organic way to treat your lawn. Consider whether your mercury in your mouth might be a problem or not, you can get tested for that, for example. All those things.

But then there are strategies to remove some of these toxins. And of course considering eating organic versus non-organic to lower our input of pesticides. These are all strategies; and then there are more advanced strategies.

I’m a big fan based on some very fascinating and rich scientific data of the health benefits of sauna on our overall health, and specifically our heart health. And the amount of data that supports it is surprisingly rich, but very rarely taught in the annuls of medicine, of course.

[23:37][Damien Blenkinsopp]: Is that any type of sauna, or is that the infra-red version?

[Joel Kahn]: Well the infra-red is the hottest and most widely mentioned, because in Japan, starting about 20 years ago, heart patients have been treated, heart patients who’ve had a heart attack, heart patients who’ve had blocked arteries or even the very serious problem called congestive heart failure, have been treated with 15 minutes of infra-red sauna followed by 30 minutes of rest and it has been shown that they can enjoy dramatic improvements in health.

And these are all actually published studies; scientific journals, some of them involving up to about 200 patients, which is getting to be respectable size for a research project at all. So that’s infra-red sauna, which is a special kind of deeply penetrating heated dry sauna; not that common in this country at this point. People can consider buying one for their home for under $1000 up to a few thousand, or finding a spa that might have an infra-red sauna, which is growing interest in this country.

But recently, as you may be aware, out of thin [24:50 unclear] came a large research study with 2000 people that were asked how often do you get in a sauna, how long do you sit in a sauna, and all that tracked with actually survival and heart health. And the number of days a week that people used sauna, and the number of minutes per sessions were kind of linearly related to overall health, which was large, and shocking, and made the news. And that’s a slightly different form of sauna. It was dry sauna but not infra-red.

So I think there’s much hope in perusing that. And the theory is that it may have something to do with detoxification. There’s no doubt that the sweat that is generated in such a thing as infra-red sauna is rich in heavy metals, richer than your urine or richer than your blood. You’re actually exiting these toxins from your body in your sweat.

So I’m a big fan of that. Then you can get into other approaches, so called oral chelation, juicing, using green vegetables like broccoli, sprouts, oregano, parsley and other greens to accelerate the exit of some of these toxins from your body in a fairly easy and natural way.

[26:03][Damien Blenkinsopp]: So it sounds like heavy metals in particular sound like something that you think they are quite relevant and important to heart risk issues.

Did you see, I believe there’s some studies with EDTA and heart disease more specifically and the impacts on it with some of the plaque and things on it. Am I correct in that, have you seen those studies?

[Joel Kahn]: Yeah. I was not a fan of recommending chelation. And so let me just take a step back, because not everybody is going to be familiar with chelation.

But because of industrial exposures to heavy metals in the 40s and the 50s — for example a worker exposed to arsenic in an explosion, or lead — there was an interest in trying to treat those acute toxicities. And various medicines like EDTA have been shown in those kinds of exposures to be quite helpful. And they’re, in fact, approved by the FDA for use in these industrial exposures to heavy metals: heavy lead, cadmium, mercury and such.

But in the process of some of those treatments, there were reports that people with heart disease were describing that they were having less symptoms. And some sharp clinicians were observing this and started to specifically treat some people with clogged arteries of their heart and their legs with chelation. And that, to this day in the United States, is not an FDA approved treatment; you won’t get paid for it, and in your charting you could be subject to some exposure for saying that’s why you’re treating them. Using i.v. EDTA for the reversal of atherosclerosis as opposed to heavy metal toxicity.

So, all of that was kind of subject to derision from the standard medical community, including myself. If you would have asked me four years ago, can we talk about the science behind chelation — I know there’s people that say they feel better, but do we have much science? You would have been very hard put.

So again, very forward thinking people about 10 years ago approached the National Institute of Health and said we need to resolve this; is this witchcraft, is this good care, and let’s do a study. And surprisingly the United States government came up with about 30 million dollars and designed a trial using kind of standard i.v. chelation protocols in, ultimately, 700 people that had survived a heart attack — that’s what was required to be entered in — and they were supposed to show up for about 40 weeks.

Some of them got EDTA based intravenous infusions, some of them got some vitamins, but there was no EDTA in there. And at the end of that study, which took a little longer to complete than hoped, was a little bit more difficult to recruit patients, but the overall trend of the study favored an improvement in outcome, like the combination of being alive, freedom from a heart attack, freedom from needing a bypass and hospitalization in those that got the active chelation.

And specifically two groups, if any of those 1700 people were diabetic or any of those 1700 people had actually experienced a fairly large heart attack in the background in their history, they had a dramatic improvement. It was a 40 percent reduced chance of having a bad outcome. And if you had a pill that within about four to five years reduced those bad events by 40 percent, you’d have a blockbuster new pill.

So chelation looked good, actually, and the combination of i.v. chelation plus potent multivitamins — because that was another aspect of the trial, it’s called the TACT trial, Trial to Assess Chelation Therapy — that the combination of i.v. chelation once a week and potent twice a day multivitamins had the biggest impact. But that was announced, I think it was around November 2012, so more than two years ago.

And there’s really been no movement since to seek out reimbursement, or FDA approval. Most doctors clearly are not set about to offer intravenous therapy. There’s a very small chance of harm. You can lower blood calcium levels because it’s going to chelate minerals, and calcium is one of those so very often the mixture has to have some nutrients and mineral support in it. But I have referred patients to colleagues of mine in the area that are experienced and certified in chelation.

[Damien Blenkinsopp]: Great, great, thank you for that, because the connection is appreciated by a lot of us.

[30:47] So I wanted to look at some of the, because I know you recommend some more accurate tests. For someone who really wants to know for sure their heart disease risk and where it’s at, if the status of their plaques, what do you use to accurately and directly see what the picture is looking like?

[Joel Kahn]: Yeah, well thank you for asking that question, because that’s really my passion. My passion is to teach people that there is a way to be very accurate, both by their blood work — and we talked about that — and by imaging, which we’re going to talk about right now. To really nail down your personal risk of experiencing the number one killer in the Western world, heart disease which can come on suddenly, without warning, and the next day there’s a funeral tragically leaving spouses and children and parents wondering how did nobody pick up that there was a burden of disease.

I’ll just give you a quick example. Sadly a friend of mine lost her husband, who was a prominent businessman in my town, who was a very fit person [who] ate healthy, looked good, wasn’t overweight, enjoyed athletics, and a little over two years ago went out for a bike ride on vacation and never came back. And was found at the side of the road and shown by autopsy to have a 99 percent blocked Widow-maker artery. And that shouldn’t happen.

My passion is to say, that’s tragic and we need to circle around that family with a lot of love, but let’s not let the next family and the next family and the next family, you know the Tim Russerts and James Gandolfini from Sopranos and such. We just had a bank president in my town, about three or four weeks ago, who experienced the same tragic end to his life, a man I’m sure was getting good medical care, absolutely.

So, there is the most accurate way right now to [if] you’re 45, 50, 55 years old, you’re concerned that this this number one killer in America could be creeping up inside silently; And you should be concerned, particularly if you’re overweight or sedentary, or [have] blood pressure, cholesterol, blood sugar issues, smoked in the past, [have a] brother, sister, mom, dad with heart disease.

There’s a CAT scan that takes 10 seconds, 20 seconds. You lie down, you’re pushed into a tube, a CAT scanner. It’s not around your head, it’s not claustrophobic. No i.v., no injection of medication. The CAT scan is done, you go home, you get a report. It’s called a coronary artery calcium scan, or coronary artery calcium score, CACS.

You can see the three heart arteries on the CAT scan without any injection of contrast material. Your arteries should contain no calcium; calcium should be in your bones and your teeth. If your heart arteries have calcium, your heart arteries have plaque. And you’re going to have that way before you ever need to have your bypass, your stint, or your heart attack therapy. So you can find out.

And there’s a number associated with it. If your score comes back zero, you have youthful arteries that are free of calcium, and your 10 to 15 year risk of a heart event are extremely low. Keep living healthy, but you can take a sigh of relief.

And if your arteries are prematurely calcified, you’ve got plaque. You may not be 80 percent blocked, you’re probably not going to need a stint or a bypass, but you need to see somebody about it. So that number could be 20, or 100, or 200.

I get people that show up, I saw one yesterday, totally good looking guy 61 years decent lifestyle, his calcium score was 1,100, mainly in the one artery we call the widow-maker. That’s a ton of burden of abnormal artery that we need to deal with by identifying why, and we’ve talked about some of that search.

He had already had a stress test that was normal, so he doesn’t need an angiogram, stint, or bypass, but now he needs a cardiologist who cares about lifestyle and all of the things we’ve talked about. We talked about yesterday about sauna, and heavy metal assessment, and advanced lipid blood work, and a daily aspirin. He’s a heart patient now, so I plead with people now.

[Damien Blenkinsopp]: Right. Yeah, I guess in that situation you would kind of throw everything at it, because it does sound like you were pointing out the worst case scenario, the worst score you’re likely to see.

Would you kind of throw everything at that case? Should he be really worried, and say, “Whoa, I’ve got to really change my lifestyle. Heavy metal chelation, everything I can.”

[Joel Kahn]: Yeah, that person needs to become a good student of the disease, reading my book, reading a book by Dr. Dean Ornish, a book by Dr. Caldwell Esselstyn. Many many good resources: Dr. Neal Barnard, Dr. David Katz. There’s plenty of good resources online for free, or books, or watch the DVD Forks Over Knives. I mean, many good resources, and I encourage my patients to do all of that.

But we ordered up a pretty in-depth analysis, and we’ll sit down in a few weeks and design a personalized plan. Now on the other hand, I see people all the time, they’re carrying extra weight, their cholesterol is 250, their diet isn’t exactly what I’d called in-line with nutritional goals, and their calcium score is zero at age 65. They’ve gone through six decades of life and are identifying no calcified plaque in their arteries, and their risk is very low.

And I don’t want them going to fast food places and eating their french fries, but I can cut back a bit on their medical treatment and focus on lifestyle with a great sense of joy and relief. And I see that a lot; a brother died at age 44 and the sister is zero and is going to smile for the next few years that she isn’t also carrying a burden of life-threatening plaque.

The oddity about the test is in the United States it’s not covered by insurance in about 48 states; 10 years ago places were charging 700 or 800 dollars. It’s very easy now to find that test under 150 dollars, sometimes under 100 dollars, which makes it very reachable for most people.

[Damien Blenkinsopp]: Is it quite widely available, like a lot of hospitals have these machines?

[Joel Kahn]: It’s just a standard CAT scanner, you do have to have special software to calculate that score, but it’d be very surprising if [in] most medium or large towns at least one of the hospital systems, or all of them, don’t offer it.

[37:09][Damien Blenkinsopp]: Okay. As it’s a CAT scan, is this something you shouldn’t do to often because of the radiation? With your patients, if someone’s got a score of 1000 or above, I guess you’re tracking progress over time to make sure it’s not increasing and you’re reversing some of that damage. But are you concerned at all about radiation, and do you do anything about it?

[Joel Kahn]: Well it’s an excellent question. I am a bit hesitant to repeat the CAT scan to follow their disease for two reasons: every time you do it it is some additional radiation, and number two there is not much data that you can drive that calcium out of the artery.

For example, the TACT trial, the chelation trial didn’t, unfortunately, assess calcium score. It would have been nice if we actually knew. So I don’t know the natural history. I know the natural history tends to go up if you do nothing; there are some studies that your calcium score may go up 30 percent a year. So if your score is 100 this year, it may be 130 next year. That’s just an average; it’ll be less for some, more for some. But I’m not so sure what I’d do with a repeat calcium score, because I fear they all go up.

There is an alternative test, called a Carotid IMT, intima-media thickness. This is an ultrasound. So ultrasound, of course, is no radiation; ultrasound can be repeated. And there’s about 700 medical studies on the value of having a special ultrasound machine with special software, that measures the thickness of the wall of your carotid artery.

And that is something you can track every year, every six months, compared to databases that have thousands of people age matched and sex matched, to make sure your arteries aren’t rapidly getting thicker and more plaque ridden. And hopefully actually seeing some improvement. So, if I have somebody with a bad calcium score, I’m probably going to use an ultrasound technique to follow them so I don’t need to keep exposing them to radiation.

That’s kind of a high level approach, but we’ve got the disease that’s the number one killer in America. So we’re throwing all kinds of high pollutant, expensive technology at other issues, it’s about time and way overdue that we try and prevent a million heart attacks in the next couple of years in this country so families don’t get ripped apart.

[39:24][Damien Blenkinsopp]: Who would you recommend takes the calcium scoring test?

[Joel Kahn]: Thank you for asking that. Not people who know they have heart disease. So if you’ve had a stint, a bypass, if you’ve had a previous angiogram that showed you’ve got 40 percent blockages, you already know you have a problem and you need to be working on it with somebody that can direct you.

However, it would be somebody aged 40 to 45 and up who has risk factors; brother, sister, mom, dad with early heart disease; high blood sugar; high blood pressure; smoker. Or maybe around age 50 to 55 just because you’re halfway through life and you’ve got the number one killer in America lurking around.

The American College of Cardiology, a fairly conservative group, gave very high endorsement of this coronary artery calcium score for people with risk factors. So if you’re 50 years old and you’ve got high blood pressure, boom: American College of Cardiology endorsed, and unfortunately not covered by insurance. They would leave it in a gray zone.

If you’re perfectly healthy 50 year old, do you need it? Well, I think that’s a personal decision between you and your doctor. I tend to favor getting one because it’s a very low dose of radiation and we still are dealing with the biggest silent killer in America.

There’s a very interesting documentary that came out two months ago called The Widowmaker. And it’s available online, about 90 minutes. I’d encourage anybody to watch it. It’s all about this topic of coronary artery calcium scoring and why is it not more available to make inroads into the health of Americans and identify those at risk.

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

[41:04]There are actually a lot of other blood markers. If you look at WellnessFX — I don’t know if you know the WellnessFX lab for consumers?

[Joel Kahn]: Which blood test is that, sir?

[Damien Blenkinsopp]: It’s not a specific blood test, it’s a lab which is directed at consumers. So it’s a company called WellnessFX, and some people are using those for blood panels.

[Joel Kahn]: Right.

[Damien Blenkinsopp]: So they have a large array. There’s a few companies like this, but WellnessFX is the best known at the moment. So it’s direct to consumer. They have a cardiovascular panel, which is why I bring it up. And there’s quite a few things on it.

So I wonder if you could just comment on some of the values that they include in their panel, if you find them useful. Because it seems like to me that there are so many markers linking to cardiovascular disease it makes it more complicated.

Because we have all these markers, and I’m sure someone like you could maybe get more data and get a better picture, but for the majority of us, it builds up this kind of complex mass of data. And maybe some of them would be out of range, some of them aren’t out of range, and we’re like, “Okay, so where does this put me? I’m not really sure.”

[Joel Kahn]: Yeah, I agree. I am familiar with WellnessFX. There are some others — I have no financial ties to any of these. There’s an organization that I very much like called LifeExtension.org. They’ve been in Fort Lauderdale for 35 plus years, and you can directly get a kit and blood work — a male panel, a female panel — and they’ve got hundreds of thousands of data points built up over the decades.

So you’re right, I think it is worth [it]. I have not seen the advanced lab test we talk about, the particle number, particle size. I have not seen that available in a direct consumer way; I’m not absolutely certain if that’s at WellnessFX. But you’re going to get a good screen, and you can learn quite a bit.

But I do go back to the idea that imaging arteries remains the kind of litmus test. You can have a lot of abnormalities in your blood stream, but you really need to know if you’ve either got thickened carotid arteries by the ultrasound, or if you have calcified, hard arteries by the CAT scan. You need to know that at least once to make sense of the blood work.

These biomarkers are all associations, where the imaging studies are direct imaging. So I favor the coronary artery calcium scan. In some places [it] requires a prescription, but since it doesn’t involve insurance, not everywhere, you can often arrange it on your own.

I encourage people to pursue these direct blood tests, like you said.

[Damien Blenkinsopp]: Yeah.

[43:35] I just wanted to go through a couple of them. You mentioned the NMR, which is, as I understand it, the most advanced blood test if you really want to understand your heart disease risk. Is that kind of the best one you find, in terms of accuracy and getting the closest to the same bar as the calcium score, if you’re just looking at blood?

[Joel Kahn]: Yes, in terms of blood, that LDL particle number which is most commonly obtained through the Liposcience NMR technology, is at the present, I believe, still the most accurate particle in the blood you can measure.

[Damien Blenkinsopp]: Yeah, Great.

[44:07] So WellnessFX, they have something called LPa, or lipoprotein(a). Are you up to speed on that one? Do you find that one useful? Because it’s a little bit similar in that it’s looking specifically at low density lipoprotein, I understand.

[Joel Kahn]: Yeah. Lipoprotein(a) is a cholesterol particle that a smaller number of the public has heard about. A very large amount of science saying it’s a blood test, the higher your level, the higher your risk of artery damage. It seems to be a highly inherited abnormality.

So I get it basically in pretty much everybody once, but I’m particularly aggressive in people that have a family history of early heart disease in their relatives, because that may be the factor. Usually in most labs lipoprotein(a) should be under 30, and in some patients of mine it’s over 200; it’s seven, eight, or nine times elevated above normal.

What is still lacking a bit is an absolutely clear cut trial that shows that lowering it — we can talk about lowering it in a minute — but lowering it makes a long term difference, just because there hasn’t been such a trial designed and carried out long term. Lifestyle can lower lipoprotein(a), hormonal balance of female and male hormones can lower lipoprotein(a), Niacin is particularly good at lowering lipoprotein(a).

And there’s some work going back all the way to Linus Pauling that you can minimize the effects of an elevated lipoprotein(a) by taking Vitamin C, strengthening the wall of your artery, taking some amino acids called Lysine and Proline, and that they may prevent the damage that lipoprotein(a) may do otherwise.

So there is, finally, there actually is a very strange therapy where, much like dialysis, you can get your blood cleansed through a filter. And this is an FDA approved treatment of people like that little girl I mentioned, Stormie Jones, if she were still alive today. That’s a therapy that would be used for somebody with a familial super high cholesterol.

But that filter also takes out lipoprotein(a), so if somebody has a very high level and vascular disease, that’s an option. So, it’s important, I believe, for people to measure their lipoprotein(a). And again it’s genetic, but I mentioned some things you can do.

[Damien Blenkinsopp]: Great, great.

[46:36] So one that I’ve been using for a long time is high sensitive TCRP. Is that something you find useful?

[Joel Kahn]: I do. We’ve been measuring C-reactive protein for decades, because we were measuring it to assess rheumatic fever, so it has a history going back literally decades and decades. But then along came a patented test, the high sensitivity test, and that seems to be more reflective of artery wall inflammation.

And inflamed arteries are more prone to suffer heart attack, stroke, clot and the rest. So you do not want an elevated high sensitivity C-reactive protein. And you want to measure it. And it is highly correlated with increased risk.

So then I’d get on a search for why it might be elevated, and most common would be abdominal obesity, poor nutrition, a lack of exercise, poor sleep or sleep apnea. But you can also look for occult causes like gum disease, periodontal disease and such, unsuspected prostate disease, prostatitis, and probably a diseased gut. Our Western processed foods, high in salt, sugar, and fat causing gut disorders. Lack of adequate microbiome health probably causes inflammation.

So you’ve got to work on the entire patient in a holistic way.

[48:04][Damien Blenkinsopp]: And so I don’t think we’ve really covered this properly, but inflammation is directly related to heart disease as well? Or is it a bit more of a wavy line?

[Joel Kahn]: Yeah no it’s prime time to measure inflammation and high sensitivity C-reactive protein. There’s also a number of other markers out now, like myeloperoxidase, and a test called the plaque test that give insight into inflammation in vessel walls and can be quite useful in a comprehensive assessment.

[Damien Blenkinsopp]: Great, great.

So in terms of some of these indicators, like CRP, the lipoprotein(a) , they’ve got others like alpolic protein, the HDL, the LDL, none of these are binary, as I understand them.

So if someone has a high CRP score, say it’s four or something like that, is that a sure thing that they have some kind of heart disease risk as well? Or could it just be related to some inflammation, or something like that.

You’re really using these as indirect indicators and you can’t trust the picture from that, but it’s just kind of a notice [that] I should go see a physician and investigate maybe if it’s calcium score.

[Joel Kahn]: Yeah. If it’s elevated, it should prompt a search into lifestyle, it should prompt a search into, as I say, gut health, gum health, prostate health, any other. Even though it’s felt to be largely a vascular marker, it’s a marker of the disease and it participates in, actually, vessel damage. But sometimes it can be very frustrating and unclear. I’ve had people with very high C-reative proteins: 40, 50, 60, 70, 80.

There’s a very limited experience with using a shotgun approach, after searching for every possible cause, an antibiotics like minocycline in the tetracycline family. I have been taught that, and I’ve had rare experience to do that with patients after a very thorough evaluation for every other kind of cause of elevated C-reactive protein. And it came down dramatically and stayed down.

[Damien Blenkinsopp]: Great, great.

[50:00] I wanted to tackle one thing. Could you go over the diet you recommend? As background, I’m Paleo and we’ve often talked about ketogenic diets and high-fat diets on here with people like Jimmy Moore and so on.

So could you give your perspective, where you come from with respect to heart disease; what kind of diet and lifestyle are you recommending?

[Joel Kahn]: I like to stay, in every aspect where I can, grounded in the science that’s available. And in terms of artery health, heart disease, survival and heart disease, the weight of the data is not in the ketogenic or Paleo world, the weight of the data like by 100 to 1 in terms of science at least, is in the world of nearly or completely plant based diet.

[Damien Blenkinsopp]: Okay, so is that a vegan diet?

[Joel Kahn]: Yeah. Well vegan, I’ll distinguish those very briefly.

But you can look at epidemiological studies like the Blue Zones, five areas in the world where people live the longest with the greatest freedom from heart disease, none of them are completely vegan. Except actually Loma Linda, California is one of those five Blue Zones, the longest lived community in American, and ten percent of that community is strictly vegan, the other 40 percent are vegetarian, and the remainder are omnivores. They are the longest lived people in the United States and they have the highest percentage of vegans in the United States of any community, because of the Seventh-day Adventist Church there.

So you can look at epidemiological studies like that, or you can look at the data on heart disease reversal, which is a concept that is scientifically sound. Two centers started studying [that], actually three, Nathan Pritikin in what’s called the Pritikin Longevity Center in Florida. He was an engineer, not a physician.

But Dr. Dean Ornish, a cardiologist, began in the early 1980s a lifestyle that is a largely vegan diet. If you really read between the lines its a very low oil, no added oil diet; so less than 10 percent of calories are from fat. He does allow his patients to have some non-dairy fats and some egg whites. So by strict definition it’s vegetarian not vegan.

And he has now pursued that dietary research for more than 30 years. It’s actually approved by Medicare, because the data is so strong that for heart patients it can halt and reverse their symptoms and disease, and minimize their need for medical care.

Dr. Caldwell Esselstyn began the same research project at the Cleveland Clinic in the 1980s, and has similarly shown [with] follow up catheterizations [and] follow up on patients’ health, dramatic reversal of heart disease without stint, without bypass. And his diet is strictly vegan and again under 10 percent of calories are from fats. Kind of the opposite approach to many ketogenic diets.

And, very compelling, Dr. Ornish has taken his program, which is more than diet —- Dr. Ornish emphasizes 30 to 60 minutes of walking, an hour of stress management by meditation or yoga, and group support — and has shown that in prostate cancer you can halt and reverse prostate cancer with his program. And he’s embarking now on a program in breast cancer, which I suspect, but we’ll have to wait, the results will be positive.

So it’s dramatic research, it’s not out of date. I hear some of my colleagues say, “Oh, Dr. Ornish’s data is aged, it’s old.” Well, he’s working with Nobel Prize winning scientists and continuing to put out some of the most cutting edge data on nutrigenomics and epigenetics. And his diet is one that if all of America were to follow to a large part we’d have a tremendous drop in the burden of chronic diseases like dementia, diabetes, cancer and heart disease. Without question; it’s been scientifically proven.

So my recommendation, I lead in Detroit a patient’s support group for people striving to stick to Dr. Ornish, Dr. Esselstyn, the Pritikin program, the Dr. Neal Barnard, you know, reversing diabetes program. And we have about 1000 volunteer people in the area that get together for meetings and group sessions, and it’s been profoundly effective in improving their health at very low costs, very grass roots.

[54:19][Damien Blenkinsopp]: Yeah. So what do you think of the Paleo principles of dairy and grain avoidance? Would you include those in your recommendations, or are those not relevant?

[Joel Kahn]: Sorry, the question was about grains?

[Damien Blenkinsopp]: Yeah, grains and dairy, in general.

[Joel Kahn]: I’d love everybody to stop eating dairy. I don’t view it as a health food in any setting, and it’s a tremendous burden on animals and the environment. And if somebody is not willing to eliminate animal products from their diet but would be willing to eliminate dairy, it’s one of the most frequent food allergens that people react to. It may be involved in the pathogenesis of Type 1 diabetes in children and young adults.

I wish we could legislate a dairy free world. Even the Harvard School of Public Health has advised greatly minimizing your dairy intake and replacing it with healthy hydration, like water, teas, and coffee, unsweetened; even alcoholic drinks, to a limited degree.

But grains, I know it’s contentious. I have had the pleasure of spending time with Dr. Bill Davis of Wheat Belly, Dr. David Perlmutter of Grain Brain, and I think also a name that’s not as well known, Dr. Alessio Fasano, who’s an Italian scientist now at Harvard who’s really doing amazing research on what grains do to Celiac patients and what’s the actual molecular pathways.

And I tend to favor Dr. Fasano, who I think I’m fairly quoting that one percent of the population is showing signs of Celiac disease, six to seven percent of the population if tested shows signs of gluten sensitivity. And that leaves over 90 percent of the population that neither has Celiac nor documented gluten insensitivity and if they’re reacting to grains, they’re reacting very briefly in a way that’s not a big deal.

And they should be part of a healthy diet. If you look at the scientific data, which I just reviewed and published a blog on in the past six weeks, even just in the last two years the data on whole grains and health is an amazingly strong body of data for survival, for freedom from heart disease, freedom from diabetes, freedom from cancer.

And it’s always a question, what’s it substituting? If you’re eating whole wheat pasta, whole wheat bread or wheat germ you’re probably not eating donuts and fried food and vending machine food because you’re exhibiting an intelligence in a selection on the healthier part of the spectrum.

So, I always encourage my patients that are having problems, take a four week elimination diet from gluten. If you’re having runny noses, rashes, if you’re having unexplained headaches, maybe even for an unexplained cholesterol elevation it could be that it’s inflaming your gut, and four weeks would give us some input on how you’d feel and biological markers.

But I eat whole grains consistently and recommend to my patients they do the same if they’re not in that small percentage.

[Damien Blenkinsopp]: Great, thank you for that clarification.

So if someone is on a Paleo diet or ketogenic high-fat diet, is there a test they could take? Would it be the calcium score, would you recommend that they take that if they want to assess if it’s having some impacts?

[Joel Kahn]: Yeah, well my comment and advice for those that are following a ketogenic diet is if you’re doing it for 10 days to fit into a tuxedo for a wedding, it probably will work and you’re probably not going to do yourself any harm. Long term, again I have to go to science, which there were at least two or three major studies saying long term low-carb ketogenic diets are associated with increased risk of death.

These are studies involving tens, and tens, and tens of thousands of people; yes, they’re databases, yes they’re association studies, but they are strong because there is no data that you live longer with a ketogenic diet. And in the last nine months there’s been specifically a study that ketogenic diets after heart attack are associated with the increased risk of dying.

So I strongly advise my patients not to follow ketogenic diets, and if they choose to, yes I think they should have all the biomarkers. If they don’t know of atherosclerosis then they should be having calcium scoring and possibly the carotid ultrasound testing. But I would advise them against it.

I know it’s all the rage, but it is a stress on the body, it’s a stress on the adrenals. And the healthy carbs found in vegetables, even starchy vegetables and whole grains, are adrenal pleasing sources of nutrition.

[Damien Blenkinsopp]: Great, great. Thanks for the clarification.

[59:00] Winding up, this is kind of a thing that affected a lot of my friends in their 20s. People were working very hard and were taking a lot of caffeine and generally very stressed, [and] we were getting a lot of pains around the heart area.

One of my friends went to a doctor and he said it was just stress and caffeine. I don’t know if you’ve come across this before; is this an issue, or is it just a symptom which isn’t really that important? Maybe too much caffeine or something.

[Joel Kahn]: Yeah. Caffeine in general, I mean it’s interesting. There is some genetic variation, and there is even a blood test you can get that’s a SNP, single nucleotide polymorphism, it tells you if you metabolize caffeine rapidly or slowly. If you metabolize it slowly, it’s going to hang around longer and give you more tendency to feel jittery or racing heart. And if you metabolize it rapidly, otherwise.

But with that aside, if it doesn’t bother you, caffeine is, in most studies, a health food. Now of course, like everything, you dump in some manufactured whitener and sugars, and you don’t have coffee anymore you have some modified, processed, anti-health drink. And certainly a frappuccino isn’t a cup of coffee.

But black coffee, dark roasted coffee two or three cups a day is generally a good boost in the morning, a good brain support. I always would cut it off about two in the afternoon so it doesn’t interfere with sleep. It’s a rich source of antioxidants.

There’s a little concern that your readers may know about that some coffees may be contaminated with mycotoxins, fungal toxins. You don’t really know it because it’s not measured and reported on American coffee sources; it is in Europe, and in fact there’s limits in Europe where they can’t be sold. Coffee beans sit outside and they can get moldy, and the mold can get into the coffee beans.

So you can ask around where you buy your coffee; it’s not a topic that a lot of people know about, and it may be a source of some illness for some people that are sensitive or are drinking lower quality coffees that may have mycotoxins.

With those couple of comments aside, I am pro-coffee. My heart patients ask me, I tell them enjoy a cup of black coffee. I certainly also urge them to enjoy green tea, or any of the teas actually; herbal teas, hibiscus tea, chamomile tea before bed [is a] wonderful source of soothing and sleep support.

[Damien Blenkinsopp]: Right. So it doesn’t sound like there’s any specific mechanism there which would be giving people heart pain from just coffee. Maybe something more like stress?

[Joel Kahn]: Right. There should be no heart pain.

[Damien Blenkinsopp]: Okay, great.

[1:01:32] So, where should someone look first to learn more about your topic? Are there any good books, your books, or presentations on some of the subjects you referenced?

[Joel Kahn]: Sure. I [1:01:41 unclear] appreciated that, and I probably do need to get back to some hospital rounds here. But I do have an active website at www.drjoelkahn.com. And all the blogs and TV interviews and podcasts and things I’ve done over the last few years are there. I encourage anybody to take a peek.

I do have two books out. Last year The Whole Heart Solution, published by Reader’s Digest. And this year a self-published book — but they’re both on Amazon — it’s got the title, Dead Execs Don’t Get Bonuses: How to Survive Your Career With a Healthy Heart, which I think is an important topic and the title has caught a lot of people’s attentions. It’s a real plea to not be one of those dead execs, or dead anybodys, for as long as you can.

I would encourage anybody to read anything by Dr. Dean Ornish, Dr. Caldwell Esselstyn, Dr. Neal Barnard, Dr. Garth Davis in Houston. All active scientists, researchers, clinicians that I think are speaking from the heart about overall health and sort of bucking the trend that all fats are good and animal products are benign.

We just don’t speak about the environment enough. We just don’t speak about animal rights enough, and we have to have a holistic approach to our plate; our plate represents an impact on forests and impact on our waterways and impact on our grandchildren’s world. And our plates represent a process that is very often extremely cruel, extremely unfair to beings that feel and sense pain and terror. And it’s as if we can’t talk about that.

We have labels — Paleo, Mediterranean, Ketogenic — but that’s only partial descriptions. I like to eat a kind diet and my plate is filled with kindness. So I hope that spills into my life as much as possible.

[Damien Blenkinsopp]: Thanks so much for all of those references. That’s a lot of material for people to get through. We’ll put all this stuff up on the show notes, of course.

[1:03:50] One last question. In your own personal life, are there biomarkers that you track on a routine basis? What do you do in terms of collecting data for yourself, for optimizing health and performance, or whatever?

[Joel Kahn]: Yes. I mean, I’ll do inflammatory markers like C-reactive protein, advanced lipid tests like LDL particle number and size. I’ll look at my Vitamin D levels. I’ll look at my male sex hormone, estradiol, total and free testosterone; I try and keep those optimal through natural ways, exercise, weight loss, weight lifting and such, healthy diets, toxin free diets that don’t interfere with the process. Blood sugar and insulin sensitivity, fasting glucose, hemoglobin A1C, important markers. So those would round out the majority that I’m doing: homocysteine level

[Damien Blenkinsopp]: Great, thank you very much for that.

Well Joel, it’s been really great to have you on the show. You know, we’ve covered a lot of ground today and a lot of markers, and I’m sure it’s going to clarify a lot for the audience.

[Joel Kahn]: Well there’s so much people can do. They’re in control of their health. And it starts with realizing that, and realizing the power of food, the power of fitness, the power of abstaining from smoking, the power of sleep, the power of friendship, and then getting credible information. And your podcast has done a wonderful job [with that], and I’m very honored to be able to share with your audience.

[Damien Blenkinsopp]: Thank you.

[Joel Kahn]: Have a great day, sir.

[Damien Blenkinsopp]: You too.

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What is genetic testing able to do and not do with current services? We talk with one of the top genetic lab services to understand how technologies differ in accuracy and where it is working, where it is not yet ready and why.

In this episode we look at the impact that genetics has on our health and wellness. With rapid discoveries in epigenetics, the picture isn’t as clear as when we thought genetics was everything. Epigenetic factors regulate which parts of our genetic blueprints are actually active and working for us at a given time.

As previously covered throughout this show, the typical “cookie cutter” approach to genetic testing often doesn’t lead to results. We look at the potential for genetics to give us precision medicine and precision health, where people get targeted advice and care fit for individual needs. You are an individual; you are an n=1 experiment.

In which areas does modern day genetic testing give actionable information? For instance, what drugs should you use? What diet may best fit you? Which health complications are you most at risk for in the long term – so that you can strategically manage these and put the effort in where it’s really going to count for you?

We put a team together to really go after genetics as a solution for patients, and using genetics and genomics as a solution for patients, and also physicians, for risk assessment or to give them insight into personal issues and to try and take some action against it.
– Michael Nova

Today’s guest is Dr. Michael Nova. He is Chief Innovation Officer and Founding Executive at Pathway Genomics. The company is an accredited clinical laboratory that offers genetic testing services from screening for cancer and other disease predispositions – to precision health and medicine advice. These services differ and are broader than those of 23andMe, which you probably know about as you listen to this show – that’s the genetic testing company that most people have heard of and used.

Pathway Genomics is the first company to bridge artificial intelligence and genetics-based precision medicine or a health mobile app to consumers. It does this in partnership with IBM, and notably IBM Watson which is IBM’s artificial intelligence machine learning platform.

Dr. Nova is the inventor of many of Pathway Genomics’ solutions. He has over 30 patents and many studies published in peer-reviewed journals. He is also a winner of the World Economic Forum Technology Pioneer Award. Finally, he’s a serial entrepreneur and is on the board of advisors for IBM, which is a pretty big deal.

I hope you enjoy this interview with Dr. Michael Nova and it helps you to understand how genetics can be valuable to you personally.

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

itunes quantified body

What You’ll Learn

  • Dr. Nova’s roots in genetics and how Pathway Genomics differs from 23andMe in structure, technology, staff, and interpreting testing results (06:12).
  • Why reporting on genetic tests varies between companies; why testing does not produce ‘black and white’ interpretations of tested parameters (15:22).
  • The meaning of personalized / precision medicine; current applicability and future prospects, as numerous testing technologies become cheaper (17:46).
  • How genetic test panels are researched and converted into actionable information for physicians and individuals (20:40).
  • The complexity of genetic and epigenetic tests and why professional guidance is required when making health decisions based on results (29:30).
  • Why epigenetics is more complex than genetics and how genes are switched on / off by interactions with the environment or due to behavior (33:50).
  • Pathway Genomics and IBM’s Watson collaboration – integrating extremely diverse and data-dense medical information into meaningful outputs (36:11).
  • How genetic testing improves pharmacological prescription decisions and why increasingly complex data is even more useful (39:20).
  • Optimizing exercise for individuals using genetic information (46:04).
  • How to access information about personalized medicine and genetic testing (47:33).
  • What information Dr. Nova tracks on himself and why it is crucial to be aware of your genetics (49:46).

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

Michael Nova, Pathway Genomics

Tools & Tactics

Diet & Nutrition

  • Mediterranean Diet: All diet recommendations at Pathway Genomics are generated based on a Mediterranean diet. Based on personal genetic information, diets can be modified towards a low-carbohydrate or low-fat diet.

Tracking

Biomarkers

  • BRCA genes: There are two BRCA genes, BRCA 1 and 2. Certain mutations in these genes are associated with a high risk for developing breast and/or ovarian cancer. Full gene sequencing and results interpretation is offered by the Pathway Genomics BRCATRUE test. Angelina Jolie underwent preventative breast surgery because of her positive BRCA 1&2 status and her family history with breast cancer.
  • Maximal Oxygen Consumption (VO2 max): The maximum rate of oxygen consumption as measured during exercise, usually on a motorized treadmill. VO2 max reflects the aerobic physical fitness of an individual. The Pathway Genomics PathwayFit test includes sequencing of genes which are relevant to VO2 max in individuals.

Lab Tests, Devices and Apps

  • Pathway Panorama (Not Yet Available): This will be a genetics-oriented mobile health application. It is intended to integrate personal genetics with publicly available scientific medical information from trusted sources. Using the IBM Watson engine, the app will compare this information to the standard of care and provide personalized feedback on health and well-being.
  • Fitbit Charge: Fitness watch with automatic monitoring.
  • Pathway Genomics: Genetic Testing Panels

  • BRCATrue: A genetic test that searches for mutations in BRCA1 and BRCA2 genes.
  • PathwayFit: Analyzes over 75 genetic markers known to impact metabolism, exercise, and energy use within the human body. Provides insight into how your body may process sugars, fats, nutrients, and vitamins. This is the most popular test of Pathway Genomics.
  • Healthy Weight DNA Insight: One of the most comprehensive weight-related genetic tests available. Unique combination of nutrigenetic, medication, and general health information.
  • Mental Health DNA Insight: Identifies genetic variants that affect the metabolism and efficacy of psychiatric medications. More than 30 common antidepressants, mood stabilizers and antipsychotic medications included.
  • Pain Medication DNA Insight: Identifies genetic variants that affect how an individual will respond to the analgesic effects of certain types of commonly prescribed pain medications.
  • Cardiac DNA Insight: Tests for the genetic risk of a variety of heart-related health conditions. Examines eight classes of drugs that affect the cardiovascular system.
  • Genetic Testing Technology Platforms

  • Fluidigm Assays: Pathway Genomics uses Fluidigm assays with high precision and whole gene sequencing to detect ALL Single Nucleotide Polymorphisms (SNPs). These are variations in DNA code which are usually associated with predispositions towards health-related conditions. In comparison, the company 23andMe does not use Fluidigm technology.
  • Illumina Chip Seq Assays: In addition to Fluidigm technology, Pathway Genomics uses this technological platform for genetic testing. The company 23andMe also uses this type of genetic testing technology.

Other People, Books & Resources

People

  • Prof. Roger Guillemin: Dr. Nova started his career in genetic at the laboratory of Prof. Guillemin – who was awarded the 1977 Nobel Prize for Physiology or Medicine for his work with hypothalamic hormones.
  • Jim Plante: Founder of Pathway Genomics.
  • Eric Topol: An American cardiologist, geneticist, and digital medicine researcher. Mr. Topol is a leading voice in the field of personalized medicine and putting the consumer in charge of his/her own healthcare.

Organizations

  • IBM Watson Health: Overview of healthcare applicability of the IBM Watson’ artificial intelligence platform.
  • 23andMe genetic testing A popular and accessible genetics testing service company. The 23andMe model is focused on testing for subsets of SNPs (Single Nucleotide Polymorphisms) across various genes.
  • GeneMed: The company provides cancer and infectious disease diagnostic reagents for different instruments and technology platforms. This company also provides development and commercialization services to partners for improving In Vitro Diagnostic (IVD) products.
  • Lab Corp: Laboratory Corporation of America provides lab testing and services, with expertise in esoteric testing, genomics, and clinical and anatomic pathology.

Other

Full Interview Transcript

Click Here to Read Transcript

(06:12)[DAMIEN BLENKINSOPP]: Michael, great to have you on the show.

[MICHAEL NOVA]: Thank you, it’s my pleasure.

[DAMIEN BLENKINSOPP]: How did you first get into the area of genomics, and now it’s personalized medicine, but was there an evolution towards that? When did this first start for you?

[MICHAEL NOVA]: I was a research associate at the Salk institute a while back in a Nobel Prize winner’s laboratory – his name was Roger Guillemin. It was a very large laboratory; it had a lot of different technologies and scientists that were involved with it, as you can imagine.

The overall function of the laboratory was to study growth factors, and so we were studying everything about growth factors. We were studying how the proteins worked, tissue culture, how they interacted with each other, the DNA and RNA genetics of these growth factors, everything you could think of.

[DAMIEN BLENKINSOPP]: When you say growth factors, what exactly would that be for?

[MICHAEL NOVA]: Things like human growth hormone and thyroid releasing hormone and corticotropin-releasing factor, every kind of growth factor.

[DAMIEN BLENKINSOPP]: Okay. Things that stimulate growth in the human body?

[MICHAEL NOVA]: Yeah, in one way or another. He got the Nobel Prize for the first person to isolate TRF, which was a growth factor that was released in the hypothalamus. A signal that is released in the hypothalamus goes to the pituitary and then turns on all these thyroid hormones. That’s what he got it for, and so we were just peeling back the onion on a lot of different growth factors using different technologies.

I got into genetics there and then I started a couple of companies and took one public in the biotech area. We’ve almost used genetics as part of the technology, but it’s only been recently when we started (with Jim Plante, the founder of Pathway Genomics), we put a team together to really go after genetics as a solution for patients, and using genetics and genomics, I guess, as a solution for patients, and also physicians, for risk assessment or to give them insight into personal issues and to try and take some action against it.

I think it’s really been within the last ten years that the technology has been inexpensive enough that we could even try to use it directly for patients.

[DAMIEN BLENKINSOPP]: Great. First of all, I think a lot of people have heard of 23andMe, but they haven’t necessarily heard of Pathway Genomics, so could you give us a comparison of how the technologies compare and how the service is different? I know Pathway Genomics kind of evolved over time, so potentially a bit of that back story would be helpful too.

[MICHAEL NOVA]: Sure. First of all, the major difference is we have our own laboratory; 23andMe doesn’t. We have a big laboratory staff and scientific staff and curators and all that. All the tests come back to our laboratory and we do the DNA isolation and we do the reading of the mutations on different types of machines and then develop a report that goes back to the physician, which is the second difference: we’re only a physician’s ordered test; we’re not direct to consumer. So there has to be a physician in the loop or some kind of health provider in the loop, certainly on the ordering side, but also on the interpretation of the test.

All our tests are covered by insurance in the United States – that’s a third differentiator. We sell our tests in 44 different countries…

[DAMIEN BLENKINSOPP]: So just on the insurance angle; I understand it that you’re targeting a much smaller range of genetics, and basically you’re targeting specific arrays of things that you want to look at, like pharmacogenetics and other areas of the human body, whereas 23andMe is very, very broad in terms of what they look for?

[MICHAEL NOVA]: Yeah that was going to be my fourth!

[DAMIEN BLENKINSOPP]: Oh sorry.

[MICHAEL NOVA]: You took the wind out of my sails with that one, that was going to be the fourth big differentiator. We offer, like you said, panels of genes. We have a test for fit, nutrition and exercise, which only covers those two elements and then some eating behaviors and some metabolism.

Then we have another test for pharmacogenetics, like you mentioned. And one which is specifically for psychiatric, and another one that’s specifically for pain medications. Then we have a cardiovascular test, a cardiovascular risk, which also has some diet and exercise components in it.

So we have about 12 different product lines, 12 different types of tests, including BRCA. We do whole genome sequencing or next generation sequencing for the entire BRCA gene, if you know that gene. It’s the one that is prominent in certain ethnic groups for hereditary breast cancer. It’s the same gene that Angelina Jolie had. So we test for that as well.

We’re the only comprehensive genetic testing company that has health and wellness products all the way to hardcore next generation sequencing products for risk assessment for things like breast cancer.

A new thing that’s coming is we have an alliance with IBM, who’s an equity partner, and we’re building a mobile application that will basically put an artificial intelligence super computer in a handset to help with managing patient information and giving recommendations back directly to the user. That will be a direct to consumer type of product, but at this point we don’t sell any of our genetic tests direct to consumer.

[DAMIEN BLENKINSOPP]: I’d like to take a little step back because 23andMe and you are really very different propositions. There’s also the technology and the accuracy of the tests, and you have a different price point as well. Whereas I think for 23andMe for the whole thing right now, it’s $99; per array, yours is roughly $199 per different panel. So why is that, what’s the difference in the technology and what you’re delivering?

[MICHAEL NOVA]: It depends on the genetic tests. We do Fluidigm assays for our smaller arrays of up to about 80 different genes; 23andMe doesn’t do that. They basically take an Illumina chip that’s got a certain number of markers on it and run that chip for their $99 test. We also have that chip-based technology and then we also have the sequencing technology, which 23andMe doesn’t have.

So we have, the sequencing technology is basically more expensive than the Fluidigm or TaqMan assays, which are probably the least expensive.

We run every different type of genetic testing in here, but some of our reports require more than one platform. Some of them require the Fluidigm platform plus either maybe a sequencing or plus an Illumina chip, so the cost varies on a particular report based number one, on the technology that we’re using – it could be more expensive to run that particular report.

Then the way we do the reports is also different. We have a physician that reviews the results, we have a dietician that reviews the results, we have all those people that are on staff that are patient and can access at any time, so there’s a little bit more cost that’s embedded into the test or tests, depending on which one the clinician orders from us.

[DAMIEN BLENKINSOPP]: Right. Are your tests 100% accurate, so we could run them one time and we’d know for sure which gene SNPs we have?

[MICHAEL NOVA]: Sure. We have our own laboratory and it’s CLIA certified, CAP certified, it’s New York State certified. We’re the only comprehensive genetic testing company that has a health and wellness panel that’s been certified by New York State, which is very difficult to get.

23andMe can’t sell in New York State; they can’t sell in certain countries because direct to consumers is illegal. It’s illegal in places like Brazil and Singapore.

Our accuracy, since we’re licensed by three or four different licensing bodies, they come in here and inspect us all the time, at least once a year on all of them. So, we have to be extremely accurate.

[DAMIEN BLENKINSOPP]: I guess what I’m getting at also is the chip set that 23andMe is using is pretty reliable but it’s not 100% accurate, as I understand it. So in the past when I’ve done tests – I’ve done the 23andMe and I’ve done some other more specific genetics tests – and the answers weren’t the same. As I understood it, it was related to the technology that 23andMe uses, which is very economical to get a lot of data – which is interesting, so look at a variety of risks – but if you want to actually get clinical based information where you’re going to make decisions, you should run with the sequencing technology that you’re using with your panels to be 100% certain. Or am I looking at the wrong things there?

[MICHAEL NOVA]: No, I think you’re right on one aspect or a couple of aspects of what you said. I think that for things like the BRCA test, which is a very serious type of genetic test, 23andMe only reports on a couple of variants on the BRCA mutations, whereas we run the entire sequence. So the doctors come to us for that particular test; they would not necessarily go to 23andMe, even though the mutations that they provide and the way they do it are probably accurate, but they, just by definition, miss stuff.

It doesn’t mean that their technology is bad, which it isn’t; it doesn’t mean that the way they run the Illumina chip is not sufficient. That’s not correct. For what they’re reporting on, it’s perfectly adequate.

[DAMIEN BLENKINSOPP]: So everything you get reported should be correct with their technology as well – the Illumina chip?

[MICHAEL NOVA]: Yeah and I think it’s a good company. 23andMe is a good company. There are good companies like us and 23andMe and some of the other ones – we’ve been at this for eight years or seven years; we know what we’re doing. We just happen to have our own laboratory and so we’re under a lot of different kinds of governance that 23andMe isn’t under.

(15:22)[DAMIEN BLENKINSOPP]: Do you use blood samples as well, or is it saliva samples?

[MICHAEL NOVA]: Sure, we can use blood, saliva…

[DAMIEN BLENKINSOPP]: Is there a difference in the quality, or is it exactly the same, it doesn’t really matter which one you use?

[MICHAEL NOVA]: Both samples have different pluses and minuses, but trying to get to the same endpoint you still have to conform to what the governing bodies and what the licensing groups want us to report on. So we don’t have any choice but to make them equal in the end – if you gave us a blood sample or a saliva sample. But the way we do each one… in some respects it’s harder to do saliva because there are more contaminants in it and whatever, but then it’s a much easier test. People don’t necessarily want to get needle stick all the time.

[DAMIEN BLENKINSOPP]: I guess I’m trying to understand like I had a blood test run through DNA sequencing and a couple of the SNPs were different compared to my 23andMe. What would be the cause of that or is it a mystery?

[MICHAEL NOVA]: We can’t do that necessarily. We would certainly have to report on the same SNPs in the report in the same way so I don’t know. It could be a number of different things.

23andMe, again, has been around for a long time and so I think the accuracy of their reports and what they’re reporting on is really good. It’s hard for me to make a kind of black or white decision on something like that.

[DAMIEN BLENKINSOPP]: No, no, I’m not talking black or white, I’m just curious if there was a technological basis or something like that.

[MICHAEL NOVA]: There might be.

[DAMIEN BLENKINSOPP]: Yeah, I just figured it was the slightly different configuration of the technology.

[MICHAEL NOVA]: I’ll give you a really good example here and I think people don’t realize it: If you went and got a SMAT panel or a CAM panel from one company, like LabCorp, or you went and got one and put in the same sample to Quest, there’s no question that there will be a little bit of difference in what each one of these things reported on, but just a tiny bit of difference. That doesn’t mean that they’re wrong – either of them.

People think that genetics is black and white and the laboratory results are exactly 100% supposed to be the same all the time; that’s not necessarily true. And then we don’t know a lot more about the genetics either: There are 25,000 different genes, and we probably know what about 10,000 of them actually really do, but then they have to work with each other and all this kind of stuff.

I think getting the information on the particular SNPs is not necessarily the hard part; the hard part is interpreting what it means and giving that information back to the patient.

[DAMIEN BLENKINSOPP]: So it may be just a different reporting basis, that’s what it sounds like.

[MICHAEL NOVA]: Yeah, it could be.

(17:46)[DAMIEN BLENKINSOPP]: Taking a little step back, because I know this is basically your area, what does a shift to personalized or precision medicine and health mean versus where we are currently in the world?

[MICHAEL NOVA]: As a physician, we’ve always kind of practiced personalized medicine. When somebody comes in and they’ve got some condition they’re worried about, we give them their medications or help based on them as a person. But now, we’ve got a lot more tools. There’s a lot more granularity in what we can actually see that might be affecting this individual or even preventing things from happening.

Genetics is just one of those tools. So there’s genetics, there’s epigenetics, there’s transcriptomics, there’s all these different types of technologies now that are becoming less and less expensive. They’re kind of getting weaved into the management, if you will, of patients, and that’s what doctors are doing, basically, with our reports.

Precision medicine is just another name for personalized medicine, but I think one of the reasons there’s a much bigger push for it now is that we’re really seeing some major advances in cancer-targeted therapies using genetics, we know cancer is a genetic disease, a molecular disease. We’re now starting to target individual mutations in these cancers to give better results.

We’re now getting a clearer understanding of things like obesity – there are 97 genes that are related to obesity – they’re all different metabolites. It’s not necessarily going to be one size fits all and now we just have technologies that are getting less and less expensive to weave in information for the physicians to make decisions on. That’s where it’s at right now.

This is going to be an ongoing process forever; there’s going to be some sort of genetics or -omics or precision medicine technology that we’ll be able to use to really personalize individual therapies or prevention regimes or whatever you want to call it.

b>[DAMIEN BLENKINSOPP]: I guess one of the things about personalized is, if we take a comparison: If you have a cough today, you’re given the same drug no matter who you are; but in the future – and you have a panel which is pharmacokinetics – you could look at the impact of the drug on you – depending on your genes, drugs have a different impact. So it’s taking it up to a much more personalized level than what is possible today by just looking at someone.

In some cases, maybe you’ll see they’re different and maybe have got some blood test that is slightly different, but the genetics adds another layer of personalization.

[MICHAEL NOVA]: This is standard knowledge in the industry that anywhere between 40 and 50% of all drugs that are prescribed fail for the user, and especially the first time around. That’s a huge number.
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If we can add some way of tailoring those drugs – maybe you take this antidepressant instead of that antidepressant or you take this cough drug versus some other cough drug because your liver is metabolizing it different based on your genetics – you’re more likely to get a much better result.

Again, that is certainly where everything is headed in this whole precision medicine area.

(20:40)[DAMIEN BLENKINSOPP]: Great. So I also just wanted to talk to you – your tests are insured compared to the other ones, so I guess that the extent of research done on the specific panels is quite deep to get to that level where now tests can be insured.

[MICHAEL NOVA]: Yeah it depends. I’ll just take Medicare as an example because they’re kind of the gatekeeper for insurance coverage and our tests are covered by Medicare. The way that Medicare does it now in the United States, it looks at a panel on a gene by gene basis, and some genes have more clearly defined outcomes and predictability than others. So, on a panel of 80 genes, they might only cover three or four of them, but that’s enough to cover the entire cost of the panel.

There are three big levels of gene coverage in America. There’s a) genes that are covered automatically, like methylenetetrahydrofolate and some of the genes for warfarin metabolism. These are covered automatically, it’s an automatic payment, and since the technology on the panel is cheap enough, at least for us, to get over the cost of doing just that one gene, whatever Medicare decides to pay us, we make enough money to cover the panel. That goes for all the other insurance companies too, whether it’s United Healthcare pays on certain things, Aetna pays on certain things. Some insurance companies don’t pay at all on genetics, one way or another, so it really is not just based on whether the data is good enough, but it’s also based on whether a certain insurance company thinks it’s relevant enough to pay for it.

[DAMIEN BLENKINSOPP]: Right, right. As you’re saying, only part of your panel will necessarily be covered by that, and then there’s other things you’ve added, which you feel are relevant too. How’d you make those decisions? What kind of level of research has to be done?

[MICHAEL NOVA]: Yeah. We have a very strong curation. We have, I think, 15 PhD level geneticists and genetic counselors, and myself and a number of MDs, and we basically go and we grind through the literature. We look for human clinical studies and see if the data is relevant enough or there’s enough human clinical studies to put the gene into the panel and then report on it. We can only report on what the human clinical studies tell us.

There are plenty of genes and plenty of studies out there that we never would report on because we don’t think it’s relative; we don’t think that the data is strong enough. So to give you an example, in our healthy weight and fit test – which is our most popular test by far – we rate the science level in the test.

A really good clinical scientific study, let’s say on thousands of patients, and it has to be replicated in the same ethnic group, showed the same results and hopefully over multiple times, then that gets four stars.

Then there are other studies that aren’t quite as well validated but we think that there’s relevance because it might only have been done in two or three clinical studies of 500 patients each, which isn’t necessary a thousand patients but it’s 500 and it does show the same phenotype or it does show the same direction for what the genetics is reporting on. That’s a pretty good study so that gets put in the test too.

[DAMIEN BLENKINSOPP]: Great. I was going to actually ask you which was your most popular test but you’ve already brought it up.

So in terms of what that test gives people, who’s asking for the test and in what conditions are physicians looking for this kind of test? Is it someone who’s had a recurrent obesity problem for a very long time? What are the kinds of conditions and what’s actionable about that information for the physician once he gets it?

[MICHAEL NOVA]: For that particular test, we have a lot of different types of physicians that order it. Some are obviously looking for weight management, weight control in their population. But we also have people that are diabetics that are trying to use it to control their sugar levels or hemoglobin A1c levels, so we have a whole group of anti-diabetic groups that are using the test.

We have cardiovascular groups: many cardiologists think that most cardiovascular disease can be prevented by diet and exercise changing, so we have a lot of cardiologists that order the test and try to put people on more balanced types of diets, more personalized types of diets. Not necessarily to lose weight but to cut down lipid levels and other things that cardiologists worry about.

Then we have performance groups: we have performance athletes, we have gyms like Equinox health clubs that order our tests for a lot of their gym members to either increase performance or put on muscle mass, depending on what exercise.

So basically we have a lot of different types of groups, not just one type of clinician or group that orders the test.

[DAMIEN BLENKINSOPP]: Great. Is there an example you could walk us through of one of the most actionable genes in that area which people look at?

[MICHAEL NOVA]: Well, on that particular test… or do you mean all our tests?

[DAMIEN BLENKINSOPP]: The most popular one, because you said this was the most popular, if there’s one specific gene that people watch out for more than others.

[MICHAEL NOVA]: I don’t think it’s one particular gene. There are about 80 genes that we report on and we chop up the test into basically seven different sections. One section has to do with what is the best diet for you if you’re trying to lose weight and we have four different diets. That’s based on 50 different genes and how they interact with each other. Then we give you a diet recommendation, whether it’s low-carb, low-fat, standard Mediterranean or balanced diet. All of our diets are based on Mediterranean, but some have lower carbohydrates than others; some have lower fats.

Then we also give diet plans along with. So that’s a very popular part of the test, that section.

Another popular part of the test is we have a behavioral section, which looks at things like eating disinhibition – “I can’t stop eating.” Those genes around “When I start eating, I can’t stop eating.” Those genes in your dopamine pathway. We look at sugars – “Do I have a sweet tooth? Do I tend to like sugars more?” So this whole behavioral section is a very popular chunk of the test as well.

Then we have a standard metabolism section – we look at things like do you have a tendency to have increased insulin? Do you have a tendency to have increased lipid levels? Those types of genes, and there are multiple genes in that section – 20 or 30 genes in that section, so that’s also a popular part of the test.

[DAMIEN BLENKINSOPP]: Right. One of the interesting scenarios I think is the diet, the high fat versus the low-carb and the low-fat. Because a lot of the dietary recommendations today, it’s basically which crowd do you want to go with? I’m with the low-carb crowd; I’m with the high fat crowd, high protein…

Some of the genes can be pretty significant in that area, like the APOE gene. Could you talk a little bit about that and how that influences your diet and whether fats are going to be good for you or are basically going to be problematic.

[MICHAEL NOVA]: Let’s go back and look at diets in general. Most people, if they got on a diet and it was less calories than they usually intake and they stayed on that diet for years, they would probably lose weight. But it’s very difficult to get people to do that for a number of reasons.

So what we try to do is we try to look at particular genetics around fat metabolism – and APOE is one of them, and PPARgamma, and even FTO and some of these other genes – and not only how you process fats but also how you taste things. You have bitter taste receptors that we look at.

People don’t eat things that they don’t like, so we try to tailor the diet based on a number of these big subsets, whether it’s how you metabolize lipids – and people that have two copies of the FTO gene, there’s no question that they have trouble metabolizing fat in a low carbohydrate diet than somebody that doesn’t have those. That gene has been very well characterized and is a known obesogenic gene along with MCR4. If you put those two genes together, people that have those two genes tend to be about ten pounds overweight than people that don’t have them.

So we take that information, then we go back and we design a diet that’s based around not only what your metabolism is but also what you potentially would like to eat and make it a diet that isn’t too rigorous, that you’ll never stay on, and then try to give you direct diet plans – basically what to eat, literally, on a daily basis: Breakfast, lunch and dinner, this is what you should eat.

Then we have diet specialists and nutritionists and exercise physiologists and all that stuff, that if you really need help with that kind of stuff, we have ways to get you that as well.

I guess what I’m getting at is we don’t like to look at genetics in a vacuum. It’s one part of a big puzzle, and the more pieces of the puzzle we can put together, the more success we have for personalizing things for the user. That seems to really work.

We have other 20,000 physicians in the US that are ordering our tests and they keep ordering it over and over again, along with our diet plans and whatever information we give them, and the results speak for themselves – they’ve shown that what they get out for their patients is really working.

(29:30)[DAMIEN BLENKINSOPP]: Can we just go back to a distinction that you made was that you’re not doing genetics, you’re more doing genomics, right – the interaction of all of the genes together? Is that what you mean by you were saying?

[MICHAEL NOVA]: That’s a little bit of a slicing that onion really thin.

[DAMIEN BLENKINSOPP]: So what is the approach? You’re saying that it’s not a good idea to look at just one specific gene on its own?

[MICHAEL NOVA]: Yeah, very few things are one gene and then you have something bad happen. Even then, even for things like BRCA, it’s still only a relative statistic. Even if you have BRCA and you’re Ashkenazi Jewish and have the mutations that are relevant, there is still only a 80% probability that you’ll end up having breast cancer. So that means there’s 20% that you wouldn’t have breast cancer.

So very few things are one gene, one bad outcome, fortunately. It’s usually multiple genes. Again, we talked about obesity – there’s at least 80 or 90 different genes that have something to do with making somebody obese. And how they all work together? That’s the gold nugget in all this business is how to figure out how they all work together.

[DAMIEN BLENKINSOPP]: The BRCA gene is interesting because they’re pretty extreme decisions, or as you say, very rational decisions, but a lot of people see it as an extreme decision that Angelina Jolie has taken and it’s been in the press and everything.

One factor into that is that there’s genetics versus epigenetics and how we approach genetics in practice when there’s potential for some epigenetic influence and where the gene’s not actually turned on or off, right? You don’t know which one it is – is it turned on or is it turned off? Were Angelina Jolie’s BRCA genes – were they turned on and, therefore, they did represent the risk?

So, just based on what you said there, you said there was an 80% chance – I don’t know if that was a real statistic with a certain BRCA gene, but would it be in that kind of order that they were looking at BRCA?

If you took your BRCA panel, even not looking at the epigenetic influence, is there an 80% chance that that risk really exists, without taking into account the epigenetic influences?

[MICHAEL NOVA]: Correct. And remember, BRCA was first isolated in the Ashkenazi Jewish population – that’s where it’s most relevant. Angelina Jolie had family members who had breast cancer. So her decision to have surgery was based not only that she was BRCA1 and BRCA2 positive but also the fact that her mother, I think, died of breast cancer, and she’s half Ashkenazi Jewish.

So there were a number of factors that went into her decision to have surgery, not only to have her mammaries resected but also to have her ovaries taken out. I think she went down that path as well because there’s an increased risk, potentially, for ovarian cancer, which is still a very serious disease.

So you have to take all the information in total. If there was no breast cancer in her family and she wasn’t part Ashkenazi Jewish, then there might be a reason to not potentially go down that path. But that’s up to her and her clinician to work that out.

That’s why we don’t think a test like that, which is a very serious test, should ever be direct to consumer. That, for us, is something that really needs some guidance along with trying to make decisions about that.

[DAMIEN BLENKINSOPP]: Right. Excellent. I think the epigenetics area – how do you approach working with your physicians and advising them?

Do you ask them to look at factors like you were just talking about hereditary? – what’s the situation with your parents, your grandparents; other things you can look at in conjunction with some of your tests in order to capture the epigenetics? – whether something’s actually taking place or not: Do you say, “You should run these blood tests if you get these genes, and thus you could make a better decision based on that,” or do you tend to keep it to the genetics themselves?

[MICHAEL NOVA]: We tend to keep it to the genetics at this point because epigenetics is fairly new. There’s not enough data – although I do totally believe in it – in a lot of respects for us to weave that in to the process of, “You’ve got this gene but it’s not turned off.” We can do that from a technology stand point, but there’s not enough clinical data to make really informed decisions around that.

[DAMIEN BLENKINSOPP]: Right. I was talking more, at this point, as you say, epigenetics is relatively new and it’s probably quite expensive at this point for you to be integrating that type of service.

[MICHAEL NOVA]: Those kinds of expression assays – although Illumina has a methylone chip, but I don’t think it’s a clinical grade thing – it’s definitely more expensive than the genetics.

(33:50)[DAMIEN BLENKINSOPP]: I was thinking more about metabolites and lipids and things like that. So for example, we were talking about the APOE, so if your cholesterol markers are off, that would be an indicator that that gene is switched on – correct?

[MICHAEL NOVA]: Yeah, something is definitely not working correctly or you’ve got something in your diet, also, that’s not the correct diet. Maybe you’re eating too much of X, you should be eating more of Y. So there’s, again, a number of different factors – genetics, epigenetics, proteomics, metabolomics.

The metabolomics and the proteomics and looking at lipid panels, those give you a snapshot, an immediate time of day, this is what your lipid level showed. What genetics does is give you a tendency towards where potentially the lipid levels in the long run will go if you don’t take certain actions doing certain things.

[DAMIEN BLENKINSOPP]: Yeah it does. I think the area of epigenetics is potentially very confusing to people because there is this aspect of genes potentially staying switched off. Say, for instance, exercise is an important mechanism for turning off – I’m not saying this is true – but the APOE gene, right?

[MICHAEL NOVA]: There’s been data that’s shown that FTO gene for obesity can be mitigated with certain exercise and diet regimes; those are known facts. There are starting to be really hardcore data around using the environment, and epigenetics is all around using the environment – what you do in your environment to turn genes on and off – and there is data around that.

That would be one example of something that in the near future we might end up reporting on. You can change how genes are expressed by something in the environment.

[DAMIEN BLENKINSOPP]: I’m sure at this stage it’s just at a discussion level with you and colleagues and other people that you know, but how far out do you think these kinds of things are, like being able to take the next step and understanding the epigenetic aspect of it and making decisions based on that as well as just the genetics?

[MICHAEL NOVA]: Epigenetics in some respects is even more complicated than the genetics because there are so many different things that can turn genes on and off: there are methylation patterns, there are acetylation patterns, there are phosphorylation patterns, which means molecules that actually bind the DNA, or histones or whatever, and modify things and turn genes on and off.

And then there are all the microRNAs. There’s thousands of different microRNAs, the junk matter in DNA that will turn genes on and off if they’re expressed or not. So it’s extraordinarily complicated!

(36:11)[DAMIEN BLENKINSOPP]: IBM is an equity partner in Pathway Genomics?

[MICHAEL NOVA]: Yes.

[DAMIEN BLENKINSOPP]: Right. I wanted to talk about Pathway [unclear 36:16] but I think it’s also relevant to what we’re discussing right now, it being so complex and everything. Are you looking at bioinformatics and things like that potentially in the future?

[MICHAEL NOVA]: See that’s what computers are really good at. They’re good at taking noise, basically. Whereas we would look at it and not come up with any pattern; a computer’s really good at making patterns out of things. They’re not necessarily sentient, but they’re really good at taking databases and huge amounts of information and then telling you that these two things are linked together – that’s what the information is. That’s basically what we’re starting to build with IBM.

We have a very strong bioinformatics group and engineering group, and this is an artificial intelligence. Basically, it’s the Watson artificial intelligence that can play chess and was on “Jeopardy!” the show in the United States. So we have to train it.

We like to say it’s a little bit like a dog: you train the dog by lobbing it a question and seeing what answer you get back and seeing if it’s relevant. 99% of the time to start with it’s not relevant, then you have to tell it why it’s no, and go back “It should be this instead of that.”

It’s a huge process to train, especially around health care, because there’s nothing that’s more data dense than health care data. It’s not just genetic data we’re interested in; we’re interested in your electronic health record, your lab results, your wearables – your Fitbit data and all that other stuff. We want to take all that information and then compare it to the standard of care that’s what’s going to be in the Watson engine, and then give you back a recommendation that’s really personalized.

If you asked a question like, “I’ve got a nose bleed” – if you have our mobile app Panorama – “I’ve got a nose bleed, what should I do?” you would get a different answer potentially than what I would because I’ve scanned all this different information about you and compared it to what is the standard of care, and since you’re a little bit different in this gene and your latest lab result is a little bit different over there and maybe you went for a run and fell on your face, all of those bits of information are really important in order to give you a decision or some sort of recommendation about what to do.

[DAMIEN BLENKINSOPP]: Right. That sounds incredibly ambitious.

[MICHAEL NOVA]: Sure.

[DAMIEN BLENKINSOPP]: But you are going to release something relatively soon, aren’t you, so what will that be when it comes out?

[MICHAEL NOVA]: We will have public beta, sometime September to October time frame this year. We’re going through trials right now with the alpha version.

Like you said, it’s a very complicated problem because it deals with a lot of different types of data, and then getting that data so Watson can understand it, which is a whole engineering task on its own, and then getting the right information into Watson – or IBM, the super computer, the artificial intelligence – and then getting the right and curated information in there so it has the state of art in what people are thinking in terms of health care.

So you’re right, it’s extremely ambitious, and we’re really, really excited about it.

[DAMIEN BLENKINSOPP]: Yeah I can imagine. It will be fun to use it when it comes out. Is it going to be sold through iTunes or something, how’s it going to work?

[MICHAEL NOVA]: Yeah, we’ll go through the iStore and all that, and whatever Android is.

(39:20) [DAMIEN BLENKINSOPP]: Okay great. One of the other things we touched on that I wanted to get a bit deeper into because I think a lot of people don’t realize how varied this is, is pharmacogenomics.

You have several panels; it’s quite extensive the number of panels, it seems, under that area, because you have mental health areas and other areas. Is it extremely varied the impact a drug can have on each and every person? Is this very common that drugs have very different impacts per person?

[MICHAEL NOVA]: I’ll start with the panel. We have two or three different panels for pharmacogenomics. One is what you mentioned, it’s a mental health panel that has things like anti-depressants, antipsychotics, mood elevators, 30 or 40 different drugs and they each are metabolized in your liver a little bit differently.

One drug is metabolized differently to another drug, and we look at those mutations in your liver enzymes – they’re called cytochromes.

Then there are also transport proteins that have variance in how the drug is transported from the blood into the cells. There are a couple of drugs in there that have different transport kinetics. Then there are some of them also that get excreted by your kidneys, and they have a little bit different kinetics.

So we put that whole panel together on mental health based on a lot of this genetic information, or the best that we could find. Doctors use it to try and start somebody out on a drug rather than guessing what this person should have, or they’ll change a drug based on the genetics because they’ll understand why this potential drug isn’t necessarily working.

Then we have other panels. We have a pain panel, which does the same kind of thing but around pain medications – the codeines, oxycodone, morphine, tramadol, things like that – they get metabolized differently.

[DAMIEN BLENKINSOPP]: When you say metabolized, it means processed by the liver?

[MICHAEL NOVA]: Yeah, processed by the liver. There’s also transporters and uptake and excretion that are a little bit different for some of these drugs. Again, we use that information on a broad panel of different genes to tailor what potentially would be better for somebody than something else.

That kind of data is getting better. The good thing about genetics in general is that the data just gets better and better; it doesn’t get worse. It’s not like cold fusion – it’s not going to go away. It’s just going to be integrated more and more into the practice and pharmacogenetics and, obviously, drug metabolism is a huge deal.

To give you a good example: in the Asian population, there’s a drug called carbamazepine and it’s used as an anticonvulsant. There are genes involved around the metabolism of carbamazepine that if you have these particular genes, you will probably have a very high likelihood of going into Stevens-Johnson Syndrome if you take carbamazepine, and that’s a very serious disease.

[DAMIEN BLENKINSOPP]: Stevens-Johnson Syndrome; could you just describe the effects of that because I don’t think it’s very common but it’s pretty horrific, right?

[MICHAEL NOVA]: Yeah, it’s an allergic reaction basically, an immune reaction against this particular drug and you can basically end up dying from it – you go into anaphylactic shock and your skin starts to slough off. It’s a really nasty way to go if you want to call it that way. But again, it’s not very common.

But it is common more in Asians, and so screening for carbamazepine is 100% done in South-East Asia, Taiwan, places like that that are still using the drug as part of an anticonvulsant regime. They won’t put anybody on it if that person comes up with that particular variant.

That’s a really good example of how using a genetic test will really literally dial out a lot of drugs or dial in a drug based on your genetics.

[DAMIEN BLENKINSOPP]: Right. Currently though today, it’s a little bit of a trial and error process if you see a physician. Even with antibiotics sometimes, unless you’ve had tests done, it’s trial and error. We’re working hopefully towards a place where there won’t be any of that trial and error, it will be eliminated over time by these kinds of tests.

With the caveat that epigenetics sometimes will have some influence, so it’s not 100% fallible. In terms of the pharmacogenomics, there’s still some potential that basically says “This drugs better than this one for you”. It’s not 100% fallible, correct?

[MICHAEL NOVA]: No. Again, what we try to do in the genetics business is report on what the literature tells us – period; that’s the bottom line – and is that result valid.

We know, in pharmacogenetics, that across all drugs, 40 to 50% of them fail when they’re first given, so that’s a huge problem. So, dialing in the right drug, even though it might not be 100% correct… although the Stevens-Johnson issue, with this particular gene and carbamazepine, is almost 100%, so there’s nobody in their right mind if they knew that that patient had those particular genes would put somebody on carbamazepine because that’s one of those issues that is almost really one gene, one effect – you just don’t do it!

[DAMIEN BLENKINSOPP]: Yeah, right, when the risk is so high. What other high risk ones are there? Is warfarin a big one?

[MICHAEL NOVA]: Yeah warfarin potentially could be a big one for a couple of reasons. A dosing of warfarin to begin with is a little bit difficult, you have to have really strong expertise in doing that. The way it’s done is it’s done over a period of time to figure out what your INR is and how you’re metabolizing it and then getting the right dose.

Warfarin is a serious compound; you don’t want to mess around with it. It’s basically rat poison and it’s a very serious anticoagulant, as are some of the other ones like Plavix. But if you can figure out initially which dose of warfarin is better for that individual based on its genetics, that’s a good thing.

Warfarin tends to be used when a problem arises, like potentially a stent or you’ve got some sort of other issue that needs anticoagulation so you need to put them on warfarin immediately. I think that having a point of care warfarin test for pharmacogenetics is probably the way that that is going to go. Nobody wants to sit around and wait for a day for some sort of genetic test to come back before they put them on a drug like warfarin if they need it immediately, if they’ve got an embolic stroke or something like that; you’re just going to do it anyway.

[DAMIEN BLENKINSOPP]: Right. That kind of information is helpful to have it already pre-done. That is why – it’s pre-empting the need for genetic data on you. In some cases it’s worthwhile doing, right? Cancer…

[MICHAEL NOVA]: Yeah, and then the holy grail in a certain period of time it will be 500 dollars or a thousand dollars to get a whole genome sequence of all your genes, all your DNA. Then everybody gets it done, insurance will probably pay for it, and it just gets put in your record at birth. That’s probably where it’s going.

If you look at the long-term goal of getting everybody genetically tested, that’s probably where it’s going to end up. Then you’ll just pull down the information when you need it – it’s already in your file, it’s in your electronic health record. Does this patient respond to carbamazepine? Does he respond badly to warfarin? You’ll just know that because you’ll just drop down the information electronically.

(46:04)[DAMIEN BLENKINSOPP]: Great, thanks for that. One other thing you mentioned, which I’m sure is going to be interesting to some people, is the athletics aspect and the performance there. Have you got any specific examples of genes you’re looking at and reporting that are useful for training or changing/optimizing there?

[MICHAEL NOVA]: Yeah, there’s a lot of genetics on VO2 max. Some people tend to have a tendency to have a higher VO2 max than other people based on their genetics. How do you use that information in order to tailor your workouts? Maybe you’re one of these people that has a low VO2 max, maybe you need to do more X exercise than somebody that has a tendency to have a higher VO2 max. So there are genes around that.

There are genes around power and endurance: some people tend to be more power people, which means that they respond better to power athletics or power sports than people that are endurance runners. There are some pretty famous genes in that power area – actin is one of them and ACE and some other genes.

Then there are genes around exercise and insulin response, exercise and sugar response. Our panel covers a lot of these and gives you a broad snapshot of what potentially would be a better type of exercise for you than somebody else.

[DAMIEN BLENKINSOPP]: Right. so the type suggestions would be resistance training versus endurance aerobics, cardiovascular kind of work – these kinds of recommendations?

[MICHAEL NOVA]: Yeah, and then a sophisticated personal coach – we use an Equinox personal coach – uses that information to tailor what types of exercise regimes, along with their diet, potentially would be better, you’d get more response around than something else.

(47:43)[DAMIEN BLENKINSOPP]: Great, thank you. Where would you recommend someone look to learn more about personalized genomics? Are there specific books or presentations of the subject that you know are good resources to learn more about this?

[MICHAEL NOVA]: I think we have a couple of them on our website, pathway.com. There’s a lot of them out there. The University of Utah has a very comprehensive genetics database.

If you really want to get down to hardcore genetics, all the genes are listed in certain databases such as GeneMed and NIH has a database of all the genetics and all the genes, all the variants and what they mean.

You can Google in “Genetics textbook” and there’ll be 50 of them that come up. Hospital groups like the Mayo Clinic has a really good genetics site, Harvard’s got a good one, Stanford and UCSF, they’ve all got really good information on those websites about genetics.

[DAMIEN BLENKINSOPP]: Great, great, great, thanks. How could people best connect with you and learn more about you and your work? Are you on Twitter or are you active anywhere else?

[MICHAEL NOVA]: Yeah, people lob in stuff to me all the time. I figure my email is usually the best way to get hold of me, or Twitter – we have a Twitter account from Pathway Genomics. A lot of information gets disseminated through the usual media outlets.

[DAMIEN BLENKINSOPP]: Alright, great. Is there anyone besides yourself you would recommend to learn more about this, for personalized approaches, whether it be pharmacogenomics or anything else?

[MICHAEL NOVA]: There’s a lot of academic groups, every major university has somebody that’s doing it. I could certainly give you a list of…

[DAMIEN BLENKINSOPP]: It sounds pretty broad. I don’t know if there’s anyone more in the populous base, potentially working with big companies like IBM or doing some similar work, potentially different in some areas to you that would be of interest?

[MICHAEL NOVA]: One person that’s been pounding the genetics drum bag for a long time has been Eric Topol, you’re probably familiar with him. He’s one of the leaders in personalized and putting the consumer in charge of his own health care. That’s basically what we’re trying to do here from a number of different angles.

(49:46)[DAMIEN BLENKINSOPP]: Great, excellent. A couple of questions now just on your own personal approach and view of body data; what kind of things have you had tracked for yourself, whether it’s genes or other biomarkers or fitness activity trackers? What kind of things do you track on your own biology?

[MICHAEL NOVA]: I’ve had my genome completely sequenced, so I know as much about my own genome as probably is available. So in that respect, I know what’s good for me. Then I’ve certainly changed around my diet a little bit and the types of exercise that I do based on what my genetics have shown me.

I do wear one of these Fitbit tracking gadgets, and there’s a lot of them; there’s a lot of different types. Then I’m going to for sure use Panorama, this health care app that we’re going to come out with, because it will be integrated into your cell phone. You type in “What shall I do for my exercise today?” and it will tell you, “Based on your genetics or lab results X, Y, Z, you should do this. You’ve already done a thousand steps, you should do this now. You can eat this. There’s a store around the corner, you can buy it there.”

There’s a whole bunch of different parameters that I think will be very, very useful in terms of tracking where you won’t know what’s really happening. I think that’s another thing that users will like about Panorama is there’s not going to be a lot of input; you don’t have to do a food log.

Users don’t want to do that kind of thing. We live in 140 character world!

[DAMIEN BLENKINSOPP]: Yeah, there’s a burden to collecting information.

[MICHAEL NOVA]: There’s a total burden. That’s a very good word to use. There’s a total burden and we’re trying to make it very easy for it to be done automatically, so you feel as though you almost have a guardian angel on your shoulder, in some respects.

[DAMIEN BLENKINSOPP]: Are you integrating it with existing sources of information or are you just making the app very easy to integrate? A bit like Evernote, which you can upload all sorts of things into it.

[MICHAEL NOVA]: Yeah, it will be both. You’ll be able to take what you want, or we’ll go out and find it. We’ll go get your Fitbit data, we’ll go get your electronic health record, we’ll go get whatever lab result, provided we get permission from you to do it, obviously. There’s consent that’s going to be involved in this whole thing.

We’ll try and make that, as you said, that burden or that bar really low. We’ll make it very easy for you to get a very inexpensive genetic test through the application.

[DAMIEN BLENKINSOPP]: So you’ll be able to buy a Pathway genetic test through the app and it will get integrated automatically?

[MICHAEL NOVA]: Yeah, or anybody else’s genetic test. Whether you’ve got 23andMe’s; we’ll integrate that information in there.

[DAMIEN BLENKINSOPP]: Great, great. Okay last question – I always ask this of everyone – what would be your recommendation to someone trying to use some data, any kind of data, to make better decisions about their health?

[MICHAEL NOVA]: Knowledge when it comes to preventing things from happening and to changing your behavior when it’s based on real science is a very powerful thing. We hear that all the time – “Oh, that’s why I didn’t like X or Y. Now I know it’s not all my fault. Now I can change it and stick to some potential diet regime with a lot more confidence and I’m going to get a better outcome.”

So for us, knowledge is power in order to change behavior, and that’s the name of the game for a lot of us is trying to change your behavior. Because you have a lot of power to be able to do that. Giving the consumer more information about themselves is a very powerful thing.

[DAMIEN BLENKINSOPP]: Right. It’s like once someone understands something more clearly, it gives them more clarity, it gives them more confidence; it makes it a lot easier to keep that behavior on board.

[MICHAEL NOVA]: Right.

[DAMIEN BLENKINSOPP]: Well Michael, thank you so much for your time today. I really enjoyed the chat.

[MICHAEL NOVA]: My pleasure.

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

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

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

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

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

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

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

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

itunes quantified body

What You’ll Learn

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

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

Dr. Rob Knight

Tools & Tactics

Interventions

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

Supplementation

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

Diet & Nutrition

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

Tracking

Biomarkers

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

Lab Tests, Devices and Apps

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

  • uBiome: This test can be ordered and used by anyone in their home. The test allows collection of microbes from your gut, mouth, ears, nose, or genitals.
  • Electroencephalogram (EEG): EEGs record electrical activity in the brain. The frequency of waves can indicate whether brain function is normal or disturbed. Alpha (8-13 waves per second) and beta (more than 13 waves per second) waves are the most common in healthy, awake adults.
  • Magnetic Resonance Imaging (MRI): MRI scans are use pulses of magnetic energy to visualize internal organs and structures. It can be used on almost any area of the body and provides information on tumors, bleeding, injuries, blood vessels, or infection.

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

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

Other People, Books & Resources

People

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

Organizations

Other

Full Interview Transcript

Click Here to Read Transcript

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

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

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

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

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

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

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

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

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

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

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

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

[Rob Knight]: Yeah, sure.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Very, very interesting.

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

[Rob Knight]: Correct, yeah.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Rob Knight]: Yes.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Great.

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Yes, absolutely.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Right, so again, in that case we’re kind of hoping that no one tries to do clinical trials with the probiotics in products. It’s kind of no-win situation in that respect.

[Rob Knight]: Well it is a bit of an issue. It’s sort of like the issue with dietary supplements for athletic performance. So any time one tends to actually be effective, like say steroids, for example, it gets banned immediately. So you can draw your own conclusions about the effectiveness of the ones that are still on the market.

[Damien Blenkinsopp]: I guess one of the nicer things about that is currently when we take antibiotics it’s not really acknowledged that it causes any specific disease, although people may have gut upsets and any issues like that.

So I guess if these supplements continued to be marketed, and perhaps trials are just done on the basis of changing microbiome, that wouldn’t interfere because it’s not a disease endpoint. A specific disease endpoint, as I understand it, would be a specific classified disease, which is currently basically regulated today. So as long as they stay out of those disease areas, is it not a problem?

[Rob Knight]: Yeah, that’s exactly right. And that’s in part why as a consumer, it’s often very frustrating to see what claims are being made because those claims are now typically very carefully worded and very carefully negotiated.

[41:05][Damien Blenkinsopp]: So I know that you’re also involved in the Ancestral Microbiome Project.

[Rob Knight]: Uh-huh

[Damien Blenkinsopp]: Could you give us a quick update on how far you’ve got with that, and also what it is for the people at home.

[Rob Knight]: Sure, absolutely.

So the goal of this project is essentially to compare the microbiomes of different people living relatively isolated lifestyles and seeing whether they contain microbes that we as Westerners have lost with the hygiene or antibiotics. Or diets perhaps, that cause us to lose some of those kinds of microbes that could be beneficial.

There was a paper that just came out two weeks ago led by Cecil Lewis at the University of Oklahoma on the Matses who are a group of hunter-gatherers in Peru. There’s another one coming out soon that I can’t tell you about because it’s embargoed. But there’s some ongoing work that we’re doing with the Hadza in Tanzania, and the project that’s led by Jeff Leach.

So the Hadza are the last hunter-gatherers in East Africa in the Rift Valley where, of course, humanity evolved. So they’re the last group that’s still exposed to the microbes and to the mammals and to the plants that we would have evolved with during our early evolution. And so they’re very exciting to look at from that standpoint.

But basically the idea is to compare different groups and to understand first there’s still anything that they have in common that we might have lost more recently. And then the second thing is that try to understand similarities and differences in different human populations in terms of their microbiomes and how those microbes relate to different lifestyle features, to human genetics and to other factors.

It’s going to be incredibly fascinating from a science point of view. And from the point of view trying to figure out how our microbiomes should be shaped to optimize health.

[Damien Blenkinsopp]: Yeah, this is great.

I understand that Jeff — have you spent time with the Hadza as well, or has it just been Jeff that’s spent the time with the tribe?

[Rob Knight]: I went there for a week last year. It was just a spectacular experience.

[Damien Blenkinsopp]: I understand that Jeff, at least just spending time there, his microbiome changed. And he also used a fecal transplant from the Hadza to see a more extreme change.

But what I thought was interesting was just living amongst them and spending time with them, he saw some changes in his microbiome also. But I guess you haven’t had your sequenced yet, but potentially over that week you would have seen the same changes.

[Rob Knight]: Possibly. We don’t have the sequence data for that, although that would certainly be interesting to look at.

I should note that’s also true if you start living with a new partner, for example. You’ll converge on their microbiomes relatively rapidly. And one thing of interest at the moment is trying to figure out how much your microbiome records about the people you’ve lived with and the places that you’ve lived.

We don’t really know the answer to that at this point, but it’s certainly interesting to think about.

[Damien Blenkinsopp]: Well it is, just from a health perspective as well. Especially as it’s getting quite common to have IBS and things like that these days. It kind of makes you question these kind of things. How communicable is it, or not? I guess there’s a lot.

[Rob Knight]: Yeah, that’s a great question. I don’t [think] there’s been done a lot on communicability of IBS, but there are some probiotics that have done pretty well in clinical trials for IBS.

[Damien Blenkinsopp]: Yeah. So we’ve got a solution anyway.

[Rob Knight]: Yeah, and it has been linked to the microbiome by a number of different studies including some work we did with [unclear 44:25]. So yeah, it’s definitely a fascinating area. And the potential that some of these conditions could have microbial cures as well as microbial causes is very interesting.

[Damien Blenkinsopp]: Great, thank you very much Rob.

[44:40] So what are the best ways for people to connect with you, and learn more about you and your work?

[Rob Dunn]: Well, my TED Talk is a really good starting point. There’s a book associated with that Talk called Follow Your Gut, which is going on sale tomorrow actually.

[Damien Blenkinsopp]: Is that on Amazon?

[Rob Knight]: Through Amazon, and also I think it’s available as an iBook through the Apple Store. That’s a good way to find out more. It’s a relatively short book. The idea is to make it a friendly general introduction rather than going into a lot of technical detail about a whole lot of names that you’ve never heard about.

And also it’s got an Appendix that gives you a good overview of how you should interpret your American Gut results, and what things you can and can’t learn at this stage, and what we hope to be able to find out from us in the future.

[Damien Blenkinsopp]: Great, we’ll put links to all those in the show notes.

[45:22] Are there any other good books or presentations for people interested in the microbiome in general, and learning more about it? Are there any references that you commonly give out to people, which are good resources to check out?

[Rob Knight]: Yeah, Marty Blaser’s book. So Marty Blaser’s book Missing Microbes is fantastic, and really gets into a lot of detail about how hygiene and antibiotics may have led to the rise of a lot of autoimmune diseases, and other chronic diseases that are a problem today. And also one specifically about the dangers of over prescription of antibiotics. So I definitely recommend that one.

Ed Yong’s blog, Not Exactly Rocket Science, routinely covers microbiome topics. As do Carl Zimmer’s columns. Michael Pollan wrote a very nice piece in the New York Times in 2012 called “Some of My Best Friends are Germs,” and he’s continued to cover the microbiome on and off since then. Those pieces are all very good.

Jonathan Eisen and Jessica Green both have talks that are available through TED. Jonathan’s talk gives a very good introduction to what microbes are and what they do out there in the world. And Jessica’s features, it’s focused more on the built environment. And it’s talking about the relationship between the microbes in our bodies, and in the spaces we inhabit, and how we might want to design buildings that are green not just in terms of the plants, but also in terms of the microbes. So not just energy, but also microbial use.

So those would be some really good places to start. There’s definitely a lot of more technical resources out there, but you can probably get to those from the ones that I mentioned. And especially the references in Marty’s book and in my book are a good place to get started with more technical material.

[Damien Blenkinsopp]: Great, thank you so much for that. That’s very extensive, clearly.

[47:11] So I’m also interested what your personal approach is to body data, whether it’s for your health, your longevity, or your performance. Do you track and metrics or biomarkers for your own body on a routine basis?

You’ve already said that you take stool samples every single day. Is there anything else you do? And those stool samples, just by the way, for instance if you go to the toilet twice per day, do you take two stool samples, or are you taking one per day?

[Rob Knight]: Initially I was taking one per day, and I’m trying to capture all of them to the extent possible.

So in terms of auxiliary data I must admit that I’m not nearly as diligent as some other people who are interested in this sort of thing have been at tracking every single thing they’re doing every day. In part that’s informed by some of the studies where people have tracked a tremendous number of measures and not seen a lot. So that’s been relatively difficult to justify that level of additional time commitment.

Mostly what I’m tracking are things like, so periodically I’ll do a food and dietary inventory. Tracking things like travel is important. I would track medications except I essentially haven’t had any during that interval. But it’s the sort of thing that I would keep track of if it became relevant. That kind of thing.

[Damien Blenkinsopp]: Great, great. I’m guessing that most of these things are something that you’re doing in the realm of science, because you’re exploring the specific subject.

Do you think you would control for any of these if you weren’t involved in the science itself, out of a personal interest? How would you kind of modify that, if you weren’t currently studying you as an n=1 experiment to further the science? On a personal level, what kind of things do you think you would be doing?

[Rob Knight]: All kinds of things are interesting, it’s just a matter of how much time you’re willing to put into it, and how much money. So it would be very interesting to do blood and urine metabolites frequently, perhaps even daily.

It would be very interesting to get finer grade resolution on fitness, like with an activity tracker, that kind of thing. Given what we’re now starting to find out about brain microbe links it might be really interesting to, for example, track EEG readings over time and draw those microbial data.

You could even imagine doing like an MRI of yourself every day to see whether that complex multifarious specs tracks what the multifarious specs to find biomarker biome. Although that’s definitely a level of efforts and expense that it’s just not worth it at this point.

But what I think this is one of these things where the more data you have, the more potential you have to find out something really interesting that you wouldn’t have expected.

[Damien Blenkinsopp]: Great, thank you so much.

[49:44] The last question, what would be your number one recommendation to someone who is trying to use data in their life for better decisions about their health, their performance, or longevity? Something about their body. What would be your number one recommendation on how to use data effectively?

[Rob Knight]: There are a lot of different ways that could answer that question, but I guess my number one recommendation would be that what’s in the literature, like randomized controlled trials about what works and what doesn’t, are probably a really good guide as to what you should do initially.

Now, you might want to modify that based on observations of your own body, because anything that’s in the literature has got to be based on population averages. And one thing we know about people is that there are tremendous amounts of variability. So what works on average in the clinical trial is not necessarily going to be what works for you individually.

So, start with solid evidence from clinical trials, especially randomized placebo controlled trials, and then modify that based on your own observations about your own health whether it’s meticulously recorded, and you have over a long enough period of time that you have reproducible observations, not just off one anecdote.

[Damien Blenkinsopp]: Thank you there for some great insights into randomized controlled studies, and the averages also, which comes up sometimes on this show. Averages don’t necessarily mean you. So thank you for reinforcing that point.

Rob, thank you also for making time available today. I really enjoyed this show. You’ve obviously got a very, very deep background in this stuff, and we covered a lot of material. Looking forward to read your book also.

[Rob Knight]: Okay, great. Well thanks Damien, and thanks again for your interest in this, and this is only going to get more exciting as we find out more and more about the microbiome.

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Water fasting or ketogenic therapies may be effective with some cancers, and not with others. Learn about the PET scan and how it can provide insights into whether a cancer is likely to be responsive or not to the water fast tactic we’ve covered in previous episodes.

In this episode, we return to look at ketosis and water fasts as a tool to help treat cancer. This builds on the previous episodes looking at Ketosis with Jimmy Moore and the impact of water fasts on cancer with Dr. Thomas Seyfried.

In this episode, we dig deeper into the cancer topic looking at how ketogenic or low-carb diets may contribute via mechanisms related to insulin and ketones to inhibit cancer growth. We look at why only some types of cancers may benefit from these types of ketogenic treatments, and the data behind it. The data backing up this episode, is that of the PET scan — Positron Emission Tomography. PET Scans can be used to understand what type of cancer a person is dealing with and more importantly, whether it is likely to respond to ketogenic therapies or not.

For cancers that are dependent on glutamine more than glucose… They can be aggressive… and they may not show up on a PET scan, and they also may not be responsive to a low carbohydrate diet.
– Dr. Eugene Fine

Our guest is Dr. Eugene Fine. He’s currently a professor of Clinical Nuclear Medicine at the Albert Einstein College of Medicine. Most recently, in 2012, he published a study in the scientific journal of Nutrition on 10 cancer patients treated with a low-carb diet. He’s currently expanding his research by working on the use of low-carbohydrate diets combined with chemotherapy in animals.

This is all linked through his area of specialism, which is PET scans — positron emission tomography — where he has been identifying and monitoring cancers for the use of this type of scan. We’ll also touch on some of his studies looking at the impact of ketones, in vivo, on normal cells and malignant cells, and how that differs compared to glucose.

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

itunes quantified body

What You’ll Learn

  • Reducing carbohydrates in diet and reducing insulin secretion in the body may inhibit cancer growth (4:06).
  • How ketones inhibit cancer cells (10:06).
  • Why are cancer cells over-expressing uncoupling protein 2 and reactive oxygen species (12:35)?
  • Dr. Fine explains how he uses PET scans to identify many different types of cancerous cells and severity by using fluorodeoxyglucose, or FDG (17:32).
  • If the cancer does not show up on the PET scan (as is the case with prostate cancer and glutamine dependent cancers) it may not respond to a low carbohydrate diet (23:57).
  • Dr. Fine discusses quantitating the PET scans (30:50).
  • Any inflamed area might also show up on the PET scan associated with the FDG (32:36).
  • This research is in the beginning phase and needs to be studied on a larger scale as the next step (34:11).
  • Dr. Fine describes his “recharge trial” where cancer patients were put on a low carbohydrate diet to observe the effects of the diet (35:00).
  • During the trial the patient’s blood levels were measured to determine whether they were ketotic (37:42).
  • Dr. Fine discusses the results of this recharge trial by identifying that inhibiting insulin may have effects on cancer progression/remission (40:31).
  • Cancer may adapt to the environment where it “grew up”. So if you develop cancer already on an low carb diet, will not be affected by a low carb diet as an intervention (45:05).
  • Damien and Dr. Fine discuss other ways to change ketone/insulin levels (49:44).
  • High calorie versus low calorie diets are discussed (53:13).
  • The biomarkers Gene Fine tracks on a routine basis to monitor and improve his health, longevity and performance (1:03:29).
  • Gene Fine’s one biggest recommendation on using body data to improve your health, longevity and performance (1:09:14).

Eugene J. Fine, MD

Tools & Tactics

Drugs & Supplements

  • Metformin: A drug which is used to improve blood sugar regulation in diabetes. Researchers are looking at its wider applications with cancer treatment as it has been found to inhibit insulin secretion.
  • Ketone esters and salts: A new range of supplements making ketone bodies directly available to the body and thus inducing ketosis. There are various forms including Beta Hydroxybutyrate Monoesters (BHB monoesters), and Beta Hydroxybutyrate mineral salts (BHB combined with Na+, K+, and Ca2+). One available for purchase is Ketosports KetoForce and Ketosports KetoCaNa.

Diet & Nutrition

  • Low-carbohydrate diet: this programme limits carbohydrate consumption to increase ketosis. This was the main discussion point for this episode.
  • Ketogenic diet: The ketogenic diet is a low carb diet which also raises the level of ketone bodies in the blood.

Tracking

Biomarkers

  • Beta-Hydroxybutyrate/β-hydroxybutyrate (Blood ketones): Ketone bodies can be used as a source of energy, similarly to glucose, for most cells in the body. However, now it is recognized that ketone bodies might inhibit the growth of cancer cells instead of fueling them. Some information about testing ketone levels can be found here. Normally, there should be little to no ketone bodies in the blood or urine. However, ketone bodies increase during a low-carb diet. The most accurate way to measure ketone bodies is through a blood draw but urine tests are also available. More information on ketones and ketogenic diets can be found in episode 7.
  • Insulin: Insulin is a hormone produced in the pancreas and released in response to blood sugar levels and metabolism of carbohydrates and fats. This hormone controls the glucose blood levels to attempt to maintain normal levels. Fasting insulin levels are normally less than 25 mlU/L. After a spike of glucose in the system (after eating) insulin levels will rise but should normally not reach levels higher than 275 mlU/L. Glucose production in the body is inhibited when more insulin is released. Hyperinsulinemia occurs when there is too much insulin circulating in the body.
  • Hemoglobin A1c (HbA1c): Measure of glycated hemoglobin, or hemoglobin to which glucose has become attached – a process that occurs when blood sugar levels become excessively elevated. A proxy measure used to assess your average blood sugar over time. Since hemoglobin is part of the red blood cells it is exposed to blood sugar over the lifetime of the red blood cell, thus giving a measure of exposure over the cells average lifetime (approx. 3 months). As such this measure is used to identify blood sugar control issues. Standard lab reference ranges show anything below 6% as fine, however this already represents blood sugar dysregulation. Optimum HbA1c levels are below 5%. HbA1c has been well researched.
  • Blood Glucose Levels (mg/dL): A measure of the level of glucose in the blood at one point in time. Fasting blood glucose levels are specifically taken when you have not eaten for at least 8 hours and optimally would be between 75 and 85 mg/dL. Health concerns with blood sugar regulation such as diabetes risk start to rise over 92 mg/dL. Levels can be measured at home using a glucose monitor and glucose testing strips (an explanation for the use of glucose monitors can be found in this episode).
  • Cholesterol-HDL and LDL: The cholesterol biomarkers include lipoproteins and triglycerides which are found in the blood. There are standard markers that all doctors and labs will run, and some newer specialist labs that are more specific and accurate. There are two main types of lipoproteins, HDL and LDL. We covered these markers extensively in episode 7.

Lab Tests, Devices and Apps

  • Positron Emission Tomogrophy (PET) scan: A PET scan is a functional imaging technique used to image body processes. As described in this podcast, a PET scan can be used to identify cancer presence and severity. A radioactive tracer, fluorodeoxyglucose, is used to tag these cancerous cells. As discussed by Dr. Fine, the cancerous cells identified in this way may be treated using a low-carb diet as a supplement.

Other People, Books & Resources

People

  • Steve Phinney, MD, PhD: Dr. Phinney has completed research regarding low carb diets.
  • Jeff Volek, PhD: Dr. Volek has also participated in research about low carb lifestyles. Together, Dr. Phinney and Dr. Volek wrote a book called The Art and Science of Low Carbohydrate Living.
  • Douglas Spitz, PhD: Dr. Spitz is a radiation oncologist who has studied the ketogenic diet as an additional treatment for cancer. His research can be read here.
  • The Caveman Doctor: Colin Champ, MD is a radiation oncologist who has researched the role diet plays as a supplemental treatment for cancer.
  • Otto Warburg: Warburg hypothesized in the early 1900’s that aggressive cancer growth is due to energy generated by the breakdown of glucose.
  • Thomas Seyfried, PhD: Dr. Seyfried is interested in fasting and diets used to treat cancer. More information can be found in The Quantified Body podcast.
  • Valter Longo, PhD: Dr. Longo has published many articles regarding fasting benefits for cancer patients.
  • Dominic D’Agostino, PhD: Dr. D’Agostino is well known for his research with ketogenic diets and performance. More information can be found here.
  • Richard Feinman, PhD: Dr. Feinman is a professor at the State University of New York. He has collaborated multiple times with Dr. Fine. Dr. Fine wrote two blog posts on Dr. Feinman’s site: Part 1 and Part 2.

Full Interview Transcript

Click Here to Read Transcript

[Damien Blenkinsopp]: Gene, thanks so much for joining us on a call today.

[Gene Fine]: Oh sure. Good to be here.

[Damien Blenkinsopp]: To give a better background, we spoke to Dr. Seyfried about his ideas and his work on ketogenic diets, fasting, and cancer. And what I found interesting about your work is you’ve dug into different areas, and you’ve differentiated cancers and I wanted to get up to speed about what you’ve been up to. And potentially, also, you’ve got some slightly different views on the whole thing.

So, first of all I wanted to talk about what do you see as the mechanisms of effect behind, if we’re inducing ketosis to inhibit the cell growth of some cancers. How is that working from your perspective?

[Gene Fine]: There really are three linked mechanisms, I believe, that have the potential to inhibit cancer growth. And two of them — well actually all three of them — one is that by reducing carbohydrates in a diet. And we have to realize that most of the carbohydrates we consume are sugars and starches, which digest the sugars — about 90 percent of them.

[And] that if we strictly limit carbohydrate to very low values, we’re inhibiting insulin secretion. And insulin alone is a stimulus to cancer growth. So, if you inhibit insulin you’re reducing one of the important stimuli to cancer growth through that alone. The insulin receptors on cancer cells will be inhibited, and so the growth signals will be inhibited.

[Damien Blenkinsopp]: Is that differentiated? Normal cells have uptake of insulin and they respond to insulin also. Is it that the cancer cells respond to a greater degree? Or what’s the difference there, if there’s any?

[Gene Fine]: No, not at all. In fact, I think the concern would be that the cancer cells may respond to a lesser degree. However, the important thing is that as adults we need some insulin. Without any insulin, we’re Type One Diabetics, but we don’t need much insulin at all.

We need insulin when we’re kids, because kids grow up when they have carbohydrates and protein and insulin helps them grow. When you’re an adult and you eat too much carbohydrates it tends to make you grow sideways. So excess insulin in an adult is not such a good thing; it contributes to obesity and to diabetes.

[Damien Blenkinsopp]: I guess we would throw in body builders in there as well, because they’re always trying to stimulate insulin to stimulate greater muscle growth.

[Gene Fine]: Yeah, well I mean if you’re extremely physically active, you probably can eat whatever you want. I’m not talking about recommendations for body builders; I haven’t studied that. I know that others have. Jeff Volek and Steve Phinney have looked at athletes, and they recommend low-carb diets for them as well.

But the main group that I’m really talking about is the average person who is, unfortunately, a little bit more sedentary than they used to be. And in this group we really don’t need very much insulin to go about our normal activities. And so carbohydrate restriction is probably safe.

[Damien Blenkinsopp]: Right. So would you put protein in there as well? Because protein also can stimulate insulin.

[Gene Fine]: Yeah, that I think is an interesting and maybe more controversial area.

Protein certainly can stimulate insulin. And the question about how much protein to consume in a diet is really an important one, but an independent question which I think has not been answered. I mean, if you look in the literature recommendations for protein in the diet are all over the page; they vary from 20 grams a day to 150 grams a day.

So I don’t know that I’m really in a good position to comment on that because it hasn’t really been adequately studied by anyone, including us. In our own study we didn’t limit protein, so we might have done better than we did if we had.

But nonetheless, our human study did show that the patients that had the highest level of ketosis were the ones who did the best in terms of stable disease or partial remission of their cancers. And those who had the lowest levels of ketosis had progressive disease.

[Damien Blenkinsopp]: So you’re talking about how insulin inhibition mechanism, are they basically opposite correlates? So when insulin goes down [it is] in response to ketosis going up? Is that basically the rough mechanism, so that you could map those to each other? That’s why with a low carbohydrate diet, ketosis goes up and insulin goes down.

[Gene Fine]: Yes. I didn’t actually clarify that. I was saying, yes, that’s the general idea.

I didn’t quite complete the thought that really there are three mechanisms by which a very low carbohydrate diet could inhibit cancer growth, and one of them is, as I say, by reducing carbohydrates in the diet and reducing insulin secretion.

Insulin by itself is a stimulus to cancer growth, but very low insulin will at least have the potential to slow that. So insulin by itself would slow the cancer growth. And there are two cellular mechanisms, so I could insulin twice.

But in addition, there are systemic effects in the whole body, and very low insulin causes mobilization from fat cells — in fact, that’s how you end up losing weight — and the fat gets broken down in the liver. And increased breakdown of fat in the liver leads to production of ketone bodies and ketosis. And ketosis independently, we’ve shown at least in metabolic studies in cell culture, that ketosis itself can cause inhibition of cancer cells. So it can inhibit cancer cells; it leaves normal cells alone. And as I say, we also showed that in our human study.

[Damien Blenkinsopp]: Yes. Yes, thank you. So there’s three mechanisms.

[Gene Fine]: Yeah. Well two of them I consider to be insulin, because there are two different insulin pathways that could be inhibited. And the third mechanism is the systemic effect of low insulin causing ketosis in the liver.

Increased fat mobilization causes ketosis in the liver, and the ketone bodies circulate in the body. Normal tissues tolerate it very well and can use ketone bodies as a fuel, but the cancer cells — at least that we’ve shown in vitro — can be inhibited by them.

[Damien Blenkinsopp]: Great. It’s interesting to look at the mechanisms, just in case later on people discover different tactics for modifying insulin, for example. I mean, like there’s drugs and stuff. Or, for introducing additional ketones or something.

So, we were talking just before the call about the study where you were actually looking at how ketones inhibit some of the cancer cells. Could you talk a bit about that? Because I know there was some glucose and ketones involved, and it was interesting how it’s done.

[Gene Fine]: Yeah. In cell culture studies, when we started this a few years ago, we studied three different normal tissue lines that were fibroblasts, which are normal connective tissue that we have in our body. And we also studied seven different cancer lines. Five colorectal cancer line variants and two breast cancer lines.

And what we found was that all seven of the cancer lines — well we grew all of the tissues for four days in a cell culture in glucose medium. And we saw how much they grew. But in parallel with that, we also grew the same cells in glucose medium but with added ketone bodies.

And, as I mentioned before, ketone bodies are a nutrient for normal cells, so we didn’t expect there to be any problems in the fibroblasts, and in fact the fibroblasts continued to grow normally when we added another nutrient.

However, all seven cancer lines showed growth inhibition. And they had differing degrees of growth inhibition when we added the ketone bodies. And we found that the degree of inhibition of the cancer lines was proportional to how much they over-expressed a particular protein called uncoupling protein 2, which actually reduces the efficiency of the cell in producing ATP.

So it turns out that the cancer cells were producing less ATP than they ordinarily would when we added ketone bodies. So the ketone bodies were metabolically inhibiting ATP production, and in proportion to their over expression of this interesting protein.

And the degree of ATP inhibition was exactly proportional to the degree of growth inhibition, which makes a lot of sense. That it requires ATP to grow. So that seemed to be pretty good evidence that we had at that point that it could be metabolic inhibition of cancer cells by these ketone bodies.

[Damien Blenkinsopp]:Yeah, that’s interesting, because, like you said, you’re actually adding something, you didn’t change [anything else]. You’ve got the same amount of glucose, so theoretically, even if cancers couldn’t process the ketone bodies very efficiently, they have the same amount of glucose there. So, in theory they could have been okay. But you’ve actually shown that somehow the ketone bodies are inhibiting that.

Would it be fair to say that the cancer cells are trying? It’s like they’re taking in the glucose and the ketone, and that they’re trying to process that. But because of the inefficiency, they’re not able to. Because it’s kind of interesting that it’s got this inhibitory mechanism there. It’s like they’re trying to, but they’re not very successful at it.

[Gene Fine]: Right, and one of the big questions is, of course, why are the cancer cells expressing uncoupling protein 2. And this has been observed that cancer cells were expressing uncoupling protein 2, for at least 10 or 15 years. There were studies in the early 2000s that I first saw that got me clued into the fact that they were doing this. And I thought well what could uncoupling protein 2 do to a cancer cell, and why would they do that?

The general explanation that I’ve adopted is that cancer cells also overproduce, what are called reactive oxygen species. And reactive oxygen species are chemically active molecules that are produced in all tissues, normal cells as well. But they’re higher in cancer cells than they are in normal cells.

And the thing about reactive oxygen species is that they actually act as sort of a two edged sword. They’re required for normal cell signaling. They’re a signaling molecule that helps cells grow, and develop, and proliferate, and so forth. However, they also are very chemically active and can cause mutations.

And mutations are also somehow the life-blood of cancer cells. Cancer cells become cancerous on the basis of mutations, and in fact they’re sort of evolutionary masterpieces in that they continue to evolve because of mutations. If a particular cancer mutation kills a singular cancer cell, well that’s fine, that cancer cell dies. But if another mutation that happens to be caused in another cancer cell makes that cancer cell even more aggressive, well then the cancer becomes more aggressive.

So, reactive oxygen species when over-expressed in cancer cells actually provide a mechanism for continued growth and continued development as an aggressive cancer. The problem, of course, is much too high reactive oxygen species will kill a cancer cell, as they will kill any cell. In fact, it’s very high levels of reactive oxygen species that are caused by chemotherapy, and are caused by radiation therapy.

So there has to be a limit on how much reactive oxygen species a cancer cell can actually produce. And what I believe, and I can’t say that I’ve proven this at all, is that the increased expression of uncoupling protein 2 — uncoupling protein is in fact, or believed, to limit reactive oxygen species. So it makes sense to me, but without proof, that the reason — quote unquote reason — for the increased production of uncoupling protein 2 is to provide a natural limit. A higher limit than a normal cell, but a limit on the amount of reactive oxygen species that the cancer cells produce.

So that’s my my overall belief. UCP2 is there for a reason. But it happens, it just happens, that that reason, which is important for the cancer cell, may actually be exploitable in terms of diet, because it also reduces the efficiency of production of ATP. I don’t know if that exactly adds up, but that’s what I believe.

[Damien Blenkinsopp]: Yeah, my understanding is — I’m just trying to re-summarize from what I understand and how it fits in — mitochondria create reactive oxygen species, and they tend to do that more with glucose fuel than with ketone fuel at a higher rate. And also when they get damaged they tend to create more reactive oxygen species, so they’re not as efficient. Does that fit in with what you just said?

[Gene Fine]: Yes.

[Damien Blenkinsopp]: Okay, great. So, somehow it seems like when the ketone bodies are being used though, in this scenario it’s potentially creating more reactive oxygen species via ketones, because of the protein change there?

[Gene Fine]: I think that’s not really clear. I don’t believe the ketone bodies… Other people who have looked into this a little bit, I think, are somewhat ambiguous about it as well.

I don’t believe that ketone bodies cause increased reactive oxygen species, but I can’t say that I know that for certain. I do believe, from at least the mechanisms that we’ve explored, that ketone bodies provide a complementary way of inhibiting cancer growth metabolically. If they also produce increased reactive oxygen species, and therefore contribute to higher levels of reactive oxygen species that are cell killing, that would be interesting.

But I don’t have direct proof of that. I believe that’s been suggested by others. Possibly Doug Spitz who’s a radiation oncologist, and I don’t know but Colin Champ, who is also a radiation oncologist. He’s written about this, but I’m not sure he’s described increased reactive oxygen species production through ketone bodies. It’s possible.

[Damien Blenkinsopp]:Alright, so great. There are some mechanisms you’ve been looking at there.

And another that’s been interesting about your work is that you’ve been looking at the differences between the different cancers in your studies with PET scans, which is of course your background and your area. Could you talk a little bit about the PET scan and how you use it to assess the cancer?

[Gene Fine]: Yeah, sure.

Most cancers — most aggressive cancers I should say — end up becoming, well first of all they begin to outstrip their blood supply. Their blood supply becomes erratic, and instead of having blood vessels well supplying nutrients to the cancer cells, the cancer cells become relatively hypoxic; they don’t usually have enough oxygen. And hypoxia will interfere with the ability of a cell to use the Krebs cycle as a means of developing energy.

So most cancer cells actually depend on glycolysis, which is anaerobic glucose metabolism, in order to develop their ATP. Now, because they’re using so much glucose and they over express glucose transporters and glycolytic enzymes, because they’re using so much glucose, if you inject a glucose like tracer — a radio tracer — whether it’s carbon-11 glucose, or another one that we liked to use in general nuclear medicine, fluorine 18, fluorodeoxyglucose.

This is a glucose analog, and it gets taken up very avidly by cancer cells that are aggressive. These aggressive hypoxic cancer cells take up FDG very avidly. There’s also something called the Warburg effect, which Otto Warburg, famous biochemist, demonstrated 100 years ago that aggressive cancers, in fact, they may be hypoxic but that even if you expose them to normal oxygen conditions, they still retain this glucose and glycolytic dependence.

In any event, the result is the same that aggressive cancers light up on a PET scan if you inject a patient with FDG, with fluorodeoxyglucose. And a PET scan is basically a nuclear medicine study. These radioactive tracers give off emissions, which allow you to see where the radio tracer goes.

So FDG distributes through the body. Glucose is used by a lot of tissues, so you can also see the heart, you can see the brain because these are often glucose utilizing structures. However, you don’t expect to see FDG in locations where it shouldn’t be. But if you have metastatic disease, which these kinds of hypoxic glucose dependent cancers, FDG will go to those sites as well.

And in fact this one image can be used, or a total body PET scan using FDG can be thought of as a one step metastatic workup, because you can actually see the full distribution of cancer cells throughout the body.

[Damien Blenkinsopp]: So is this the gold standard for assessing the severity of cancer? Could you give us an idea of when you would use this kind of scan?

[Gene Fine]: Yeah, everything in medicine really is very empiric. So if it works, it works. And certain cancers are particularly avid for this kind of tracer, where they do become hypoxic glycolytic cancers. And it’s turned out to be useful in management of cancers in one way or another.

For example, in a solitary pulmonary nodule, you’re trying to determine if this is likely to be a cancer or not or if it’s a benign module. Benign nodules don’t tend to take up glucose that avidly, but the malignant ones do. So an FDG scan can be very useful in just a diagnosis of whether a lung nodule is in fact cancerous.

But PET scans are useful in the management and decision making processes of breast cancers, of uterine cancers, actually a variety of lymphomas, in particular, are usually quite avid and PET scans can be quite helpful. Esophageal cancers, gallbladder cancer, colorectal cancers, PET scans can be quite useful because they light up, and they show you not only where the tumor is, but where the metastases are.

[Damien Blenkinsopp]: And the other thing, I guess it would simply appear bigger if it’s getting worse? So on your PET scan, if you did one every three months with a cancer patient and it was getting worse, you’d see it getting bigger and potentially spreading to other areas of the body. Is that how it comes back?

[Gene Fine]: Yes, you can definitely see how it spreads.

And nowadays I should actually say that most PET scan devices are actually two devices in one. They’re PET and CT, CAT scans. So you actually can get even better information, because the CT scan is really a computerized three-dimensional x-ray. So you’re actually able to see exactly where in the body.

The PET scan doesn’t have a road map of the anatomy, it’s just where the fluorodeoxyglucose goes. But on the CT scan, it gives you the underlying anatomy, so you get the anatomy as well as the functional arrangement at the same time and in the same locations. So you can identify exactly where you’re seeing it. And that’s very helpful.

I should actually mention that there are certain cancers that PET scans are not useful for. For example, pretty notoriously, prostate cancer is an unusual cancer. It’s unusual in a lot of ways.

Actually 80 percent of prostate cancers are rather slow growing and indolent. And probably for at least that reason, that may be one expression of the reason why they don’t actually take up glucose that avidly. It’s usually the aggressive [cancers] that take up FDG.

But also some other cancers, such as mucinous cancers that are filled with so much mucin that you lose out the effect of what you see on a PET scan. So mucinous cancers of the colon and the of the lung often don’t take up much fluorodeoxyglucose.

Squamous cell carcinomas of the lungs of course are very avid, but these mucinous ones are not. And endocrine tumors, very functional, they’re often not as glycolytic. They often operate on oxygen and they can have a normal Krebs cycle and normal metabolism. So thyroid cancers, unless they’re extremely aggressive, are not this slow growing, and they take up much less FDG. So PET scans with FDG are not as useful for certain kinds of cancers, such as these.

[Damien Blenkinsopp]: That’s important because — tell me if this is over simplifying — anything that doesn’t show up in a PET scan, would it be less likely that any type of low carbohydrate diet or inhibition of insulin and up-regulation of ketone is going to have an impact on it, as we’ve been talking before?

[Gene Fine]: Yes, true.

In fact that’s very interesting because — I was mentioning prostate cancer before — prostate cancer actually, it’s not even approved for PET scan use, I should mention. Because they say 80 percent of prostate cancers don’t take up FDG. But in fact prostate cancer is also not associated with obesity. It’s not associated with hyperinsulinemia. It’s not associated with high glucose levels in the blood.

In fact, interestingly, there’s an inverse association of diabetes with prostate cancer. Patients with diabetes — it’s a little bit odd to use the word, because I’m not sure that it’s accurate, it may not be cause and effect, but it’s at least an association — are so called protected with diabetes against prostate cancer.

Now I don’t want to recommend getting Type 2 Diabetes to protect yourself against prostate cancer, but the point is that not all cancers would respond to a low-carb diet either. It doesn’t seem to have anything to do with the mechanism of that particular kind of cancer.

[Damien Blenkinsopp]: Right. The mechanism you described earlier was higher insulin would lead to more aggressive cancers, but in this case you’ve described, Diabetes 2 you’d have higher insulin, but it’s actually reducing the likeliness of getting prostate cancer. Is that correct?

[Gene Fine]: Yeah, it appears to be. As I say, at least epidemiologically, it fits the mechanism of the — I should also mention that 20 percent of prostate cancers are actually very aggressive.

So this is a distinct minority of prostate cancers. I don’t know that anyone has done much study of whether these aggressive prostate cancers, this subvariant, which grow much more rapidly, actually are glucose dependent. They may well be, but I don’t know that they’ve been studied this way. So I can’t comment on those. But they might be FDG avid.

The other thing though is that actually aggressive cancers, very aggressive ones, not uncommonly develop a taste for, not glucose, or not just glucose, but also an abundant amino acid that circulates in the blood called glutamine.

For cancers that are dependent on glutamine more than glucose, they might have even bypassed. They can be aggressive, and they may be glutamine dependent, so they may not show up on a PET scan, and they also may not be responsive to a low carbohydrate diet. So there are other subtleties here that have to be explored before knowing exactly what to do in these kinds of situations.

[Damien Blenkinsopp]: Well I’m guessing potentially restricting glutamine might have a kind of impact there. I guess there’s no studies that have been done on that.

[Gene Fine]: That’s hard. It’s hard to do that, because glutamine is synthesized by the body, and it just comes out of ordinary metabolism.

Glutamine and Glutamate are products of protein metabolism. Glutamine can actually be synthesized, glutamate can be synthesized from alpha ketoglutarate, which is a product of ordinary metabolism. So it can actually be synthesized, and is, and then circulates in the blood steam in high concentrations. And you can’t really restrict glutamine in a diet and expect glutamine to go away; it won’t happen.

I think there are approaches that are trying to figure out how to limit glutamine in the blood, but I’m not sure how successful they are. It seems to be an important metabolite and substrate for a lot of different mechanisms. It’s actually used by the brain, indirectly at least. And so, there really are glutamine restrictions, I think, is something still for the future.

[Damien Blenkinsopp]: In summary out of everything you’ve been saying, that the fasting approach or the low carbohydrate approach is, in your view, only applicable to some types of cancers, and typically the most aggressive ones.

[Gene Fine]: Yes, I would agree with that.

The other thing I should mention is that the fact that there are plausible mechanisms where cancers could be inhibited by a low carbohydrate diet, cancers of the types that we’ve been discussing, doesn’t guarantee that it would be inhibited.

And I should also mention about the PET scan, that a PET scan in the way we used it in our clinical pilot study in 2012 with 10 patients was that the PET scan indicates that we can at least identify a cancer that is glucose dependent. We can do that on a PET scan. So those, from the perspective of our hypothesis are carbohydrate, or at least have the potential to be carbohydrate restriction sensitive.

It doesn’t guarantee it, because we don’t actually know which cancers will have the appropriate characteristics and qualities. Maybe not all cancers will express uncoupling protein 2, or whatever other mechanism we were describing earlier. So we can’t guarantee it.

And in fact, if I would describe the hypothesis that I believe, it’s that — I actually have this on a slide in front of me because I like getting the wording exactly right — that large cohorts of individuals with cancer in the developed world do not experience sustained ketosis, or other features common to the insulin inhibited very low prone state. We’d expect many cancers to express a range of plausible vulnerabilities, and accidental adaptations to this unfamiliar metabolic microenvironment.

So, I think that’s the broadest statement that I feel comfortable making, that we can’t guarantee that an individual cancer is going to be responsive to this, even if it has a positive PET scan, because we don’t yet know all of the characteristics that are required. But we do believe that those kinds of cancers are at least eligible for that possibility.

[Damien Blenkinsopp]: Right. Well so it sounds like at the moment there’s nothing really concrete on this, but we think there’s a higher probability of some types of cancers, so that the most likely cancers to respond to this would be ones which tend to be more glucose dependent.

[Gene Fine]: The ones that show up on PET scans would be the ones that would have eligibility. So, we actually treated in our 10 patient study a range of patients, and there were several with lung cancers, there were several with breast, several with colorectal. There were a couple with esophageal [cancer]. So those were the ones that we actually treated.

This was a very small study, so it’s a little hard to generalize from them. But in addition, as I say, the ones that are associated with hyperinsulinemia and hyperglycemia could also be eligible, I would say; endometrial, uterine cancers, perhaps pancreatic cancers, and others have actually begun studying that as well. Possibly kidney cancers, and maybe gallbladder cancers as well.

So these are the ones that I would consider to be at least potentially eligible for this, depending on what else we learn.

[Damien Blenkinsopp]: Great, great.

Particularly in those cases, if I have cancer I’d probably want to get a PET scan to see if it lights up.

I don’t know if you have an index there or if it’s just something visual you use. Do you have any kind of index you use with PET scans to understand the severity, like how much is lit up?

[Gene Fine]: Yeah, there are ways of quantitating PET scans, and you can eyeball the uptake, which is often done for purposes of saying whether the cancer has spread to a location or not. If you have a primary.

But if you have a, I like using the solitary pulmonary nodule because so many of them are benign and others are also malignant. And so people have attempted to develop quantitation, and there are a variety of different ways. One of the common ones is called the standardized uptake value.

And you compare the uptake there, essentially, to the average uptake in the whole body. And a value has been assigned by a number of investigators as a cut off that can be useful, and that’s an SUV of 2.5. That’s two and a half times the average value in the body is assigned as being a cutoff for cancers.

Now all these cutoff values have overlaps, and some of them turn out to be benign, but the frequency tends to be much higher. And the higher the SUV the higher the likelihood for cancer.

The reason that there can be uncertainty in this is that the uptake of fluorodeoxyglucose can also be seen in inflammatory tissues, and inflammatory situations, for example even in pneumonia. You can see pneumonias take up FDG. You can see benign granulomas take up FDG, although they usually take up less. But in fact you can get false positives.

[Damien Blenkinsopp]: Oh, so could this be any type of inflammation in the body? Basically where white blood cells are active?

[Gene Fine]: Yes.

[Damien Blenkinsopp]: And there’s a lot of inflammatory conditions in the gut these days. Is that something that would potentially influence it?

[Gene Fine]: Yes. You do in fact. With the colon there are also patterns of uptakes, so the thing is inflammatory conditions in the intestines and the colons, for example, usually there are patterns of uptake, and you actually see an outline of the colon with FDG distributing itself throughout the colon and basically showing the shape of the colon.

Whereas cancers usually have a site of origin and they can be somewhat irregular. But they generally have a round or a spherical type of initiation and shape. And come in clumps. So there is usually quite a big difference between what you see intestines and that as well.

But these are non-invasive diagnostic tests, which are absolutely marvelous because things used to be much more invasive. But they do have false positives. Your goal in a non-invasive test is to be able to screen well, and therefore identify those patients who may have this condition.

And if it’s negative it can be extremely helpful because then the patient doesn’t have it. But if you do have it you may still have to, in some cases, go on and do a invasive biopsy in order to determine what’s actually there.

[Damien Blenkinsopp]: So I guess, just to be practical for anyone at home that might be related to some cancer case or perhaps working with cancer patients. So if it does come up a positive PET scan, it may be worth using a ketogenic diet, a low carbohydrate diet as one of the tools. Could you just confirm more, and tell me that that’s not correct. And then talk a little bit about your recharge trial, where you were actually looking at this.

[Gene Fine]: Sure, okay. I think that it’s hard to generalize. I have spoken, patients have found me on the internet and have called me and discussed their particular cancer situation. And I don’t consider myself explicitly an advocate for this, simply because a 10 patient study — which I’ll talk about in a minute, our recharge trial — is a very small study, and it’s pretty hard to generalize from a study of 10 patients.

But it’s not appropriate to make a scientific conclusion when generally the standard of evidence is that you have to do large, randomized controlled trials. However, that would be the direction I’d like to go to find out more information. And also the fact that it certainly is uncertain whether this works in all patients with PET positive cancers.

But I can talk a little bit about the recharge trial, as preliminary as it is. And what we did was we studied 10 patients with advanced cancers, which is to say they all had PET positive studies and they all had failed several rounds of chemotherapy and were still progressing. So they had had chemotherapy, they were therefore eligible for an experimental trial of the diet, because nothing really was working anyway.

And these patients signed informed consent and they were told that we didn’t know what the outcome was going to be, but we were going to put them on a 28 day trial diet of very low carbohydrate. And so the patients agreed to this, and for 28 days under nutritionist and dietitian guidance they were taught to change their diet.

They had a two to three day trial diet, just to see if they hated it, to make sure. If they didn’t hate it then they could go ahead, but we didn’t want to have people who were clearly not going to be able to complete the diet. We limited it to 28 days because change in diet is hard for anybody. It’s not easy. However, just about anyone can stay on a diet for a month.

So we figured that this would give all the patients a chance to succeed. And principally, the first goal we had to have was safety and feasibility. Was this actually safe? There wasn’t really a lot of reason to believe that it wasn’t safe, but you still have to try that out before you can do anything else.

And it was, there were no unsafe adverse effects. The worst effects that sometimes were reported in this, that we did see were some patients had some reversible constipation — as I say reversible — and reversible fatigue within a couple of weeks. And that’s generally the worst that happened.

So the patients were able to span the diet. Half the patients stopped a little short of 28 days, like 26 or 27 days. We considered that really a successful completion. They didn’t stop because of the diet, they stopped because these were patients with advanced cancers who had planned before they had heard about this trial to go on vacation.

They had bought tickets and thought this might be the last vacation they would be taking. So we weren’t going to interfere with that, and we got the PET scan two days earlier than we had expected and they then left the next day for vacation. So really everyone completed the trial without any adverse effects.

Now, what we did see was that, and we measured ketosis as the standard for how compliant they were. Patients would report their food intake and they would tell us what they ate, and the dietitians would record that. But food recall can be inaccurate.

The most reliable way we could determine whether they were on a ketogenic low-carb diet would be to measure ketone bodies in the blood. And we did find that all of the patients were ketotic. In fact all of them became ketotic — and we measured this weekly for four weeks, a baseline and then four weeks — patients became ketotic really by the end of the first week. So we know that they were ketotic for the period of the four week trial.

[Damien Blenkinsopp]: Were you measuring blood levels?

[Gene Fine]: Yes, these were blood levels. We felt that that was going to be a more accurate measure because urine levels can be influenced by hydration state. If you’re very hydrated you’ll dilute your urine, if you’re dehydrated you’ll concentrate it. So this is more accurate.

[Damien Blenkinsopp]: Yeah, absolutely. We discussed this with Jimmy Moore, who you know well, in a previous episode.

[Gene Fine]: Oh yeah, that’s right. And he actually interviewed me one time as well. That’s right.

So the goal, as I say, was the 28 day diet. And what we did find was that, one patient we actually had to exclude from analysis because, it took us four years to recruit 10 patients. Most patients are on chemo and they don’t really have this opportunity.

And we also didn’t want patients who were too thin because that would have trouble getting past the investigational review board. These are thought of as weight loss diets and you don’t want a cancer patient to lose too much weight. So we had to restrict our patients to patients who were normal weight or above.

Now finding patients with advanced cancer who had not lost too much weight took a long time to get this group of patients together. It took four years to recruit them, there was a lot of time in that.

So beggars can’t be choosers, and we didn’t notice that one patient had had advanced breast cancer with chest wall invasion, but she’d had it for 14 years. And this was different from all the other nine patients, who had failed multiple chemotherapies. She’d had this for 14 years and had never sought any treatment for it at all. She had no surgery, she had no radiation therapy and she’d had no chemo.

So in retrospect we realized, oh my gosh, this patient clearly has much more indolent disease. Even though it’s advanced, it’s progressing so slowly we would have to exclude this patient from analysis because in one month she wouldn’t show change.

She was stable from that point of view, so we couldn’t show progression of disease in this patient in a one month diet. And it turns out she wasn’t very compliant with the diet anyway, and she showed very little change. So the reality was we had to exclude this patient. So we really only evaluated nine patients.

Anyway, getting to the gist of that, of the nine patients the results on the face of it were really not terribly impressive; five patients showed, well four patients showed stable disease, one patient showed a partial remission on the PET scans. We had a baseline PET scan indicate the patients had glucose dependent cancers, and we had a follow up PET scan to monitor the change in the PET scan as an index of whether these patients responded in some way.

But four patients had continued progressive disease. So on the face of it, this is really not that impressive. However, the interesting thing about the difference between these patients is that the patients who had the stable disease or partial remission had three times the levels of ketosis compared to those who didn’t.

So the fact was that whether this was an issue of compliance or metabolic effect, whatever that was with the level of compliance they achieved, the reality was that the patients who showed the best responses were those who had the most ketosis. So that was also consistent with our hypothesis that the ketone bodies and the effect of low insulin levels, which would include ketosis, would have some varying on the outcome.

[Damien Blenkinsopp]: So did the same thing show up? The higher the inhibition of insulin the better the result?

[Gene Fine]: Yes,that’s essentially what we’re saying. That the more it was inhibited, it’s effects were best measured by measuring ketone bodies. Insulin itself varies so rapidly that unless you time it exclusively the same way, timing after a meal and so forth, you have to be very careful. So we use ketone bodies as a more robust measure of the effects on insulin inhibition.

[Damien Blenkinsopp]: So is that pretty concrete then? That there will always be an inverse correlation? That that’s been established very well in science?

[Gene Fine]: An inverse correlation between ketone bodies…

[Damien Blenkinsopp]: Because as you say, insulin can go up and down very quickly so it’s kind of difficult to know where it is. But in scientific studies it’s been pretty well established that insulin is inverse to ketone bodies, so then it’s okay to assume that.

[Gene Fine]: Right, but they act on different time scales. Insulin spikes very rapidly after a meal, and ketone bodies gradually build up over a period of days after chronic low insulin levels.

So you can go out of ketosis fairly quickly, but not as quickly as you can spike. You can spike an insulin level pretty level and the ketone bodies will decrease over a period of hours, the insulin levels change rapidly over a period of minutes. It’s a little bit different time scales, but yes there is a general inverse relationship for chronic insulin levels and ketosis.

The other thing I wanted to mention about this is that the patients who did show progressive disease also showed evidence of, which we weren’t really looking at, we wanted patients who did haven’t coincident other diseases, particularly diabetes because we didn’t want to be treating two conditions at the same time. So we basically made sure that the patients were not diabetics and were not taking diabetic medications.

However, in retrospect we did notice that the patients who showed progressive disease had evidence of pre-diabetes. That these were patients who were the four heaviest, they actually were the four heaviest of the group of 10 patients. They also had baseline glucose levels 100 and above.

There was more evidence of pre-diabetes in this group than there was in the group that showed a response. And there were lower levels of ketosis. So, overall, we don’t know for a fact that this is the way to screen patients, whether this is actually a biomarker. I would suggest that it makes sense that in patients who have pre-diabetes, pre-diabetes is marked by high insulin levels, and it takes quite some [time].

So that in this group, a low-carb diet didn’t seem to have much benefit. In fact, it didn’t have any benefit at all, they had progressive disease.

Now of course the way you want to treat, at least the way I like to treat patients with pre-diabetes, is put them on a low-carb diet. But I think that that would take several months to improve their insulin insensitivity, and if they already have cancer that’s probably not what you want to do in this particular group. If they have cancer and they have pre-diabetes, you’d probably have to treat the cancer as a separate entity.

[Damien Blenkinsopp]: Right, because it’s going to take a longer time to have the metabolic impact that you want.

[Gene Fine]: Right, and you don’t want the cancer to be progressing during that time, so you probably have to make your choices in that case.

[Damien Blenkinsopp]: So, from your study I remember one thing you were doing was in order to assess the better performers was you were looking at the relative ketone change.

[Gene Fine]: That’s right. And we actually, we used relative ketosis, interestingly, rather than absolute. Now, the absolute ketosis was not very different in the two groups. But I actually believe the relative ketosis is more important, mainly because — let’s see if I can describe that succinctly.

When you looked at the baseline ketosis, baseline levels of ketone bodies, absolute values.

[Damien Blenkinsopp]:: So this is before you start the low-carb diet?

[Gene Fine]: Fasting levels, right.

There were some patients who had issues of values, who had like 0.04 millimolar. And then there were others who had 0.4 millimolar. So that’s factor of 10.

Now, the absolute levels of ketosis rose in most patients to about 1.0 millimolar. A patient that only went from 0.4 to 1.0 went up by a factor of just two and a half. A patient that went from 0.04 to 1.0 went up by a factor of 25. So there is a much bigger change in the overall metabolism, and the change of the metabolism in a patient that started at a lower value.

I would propose — and this is what I actually believe — is that the patients who were living with a baseline ketone body level of 0.4 were actually acclimating their cancers to a higher level of ketosis during the period of the cancer’s growth, initiation, and development. And in fact that these cancers may be well acclimated, in other words adapted to, that they grew up in a level in which they were used to these levels.

And so that you can’t expect — well, put it this way. Whereas I do believe that people who live in environments where they eat mostly meat and fat during the year — let’s just say Inuits for example that haven’t been exposed to McDonalds and Laps living in northern Finland and live on reindeer meat all day long — that people who live under those conditions I would suggest, and I don’t know what the evidence is exactly, that they will have lower incidences of cancer.

However, should a person under those circumstances develop cancer, you know you sure as heck would not put them on a low-carb diet, because you know that they developed cancer already on a low-carb diet.

So that’s what I’m basically saying. If you have somebody who already is in a state of higher levels of ketone bodies and cancer develops in a person like that, then you certainly wouldn’t expect that patient to be as responsive to a low-carb diet.

[Damien Blenkinsopp]: It’s interesting because there’s a lot of things in biology, like somatic signals, where, like if you think about the treatment of antibiotics, right, you basically have to pulse it. You have to pulse it and do it one go has to be done effectively. If you get chronic antibiotics for a while then it stops having it’s impact, and you don’t get the benefits, and so on.

So it’s interesting that you identified this mechanism where a body could be a lot more beneficial to, let’s say do something. I mean I’m sure you’re aware that Dr. Seyfried recommends a five day fast, which is a more extreme version of what you did in your study, and potentially may be more beneficial because it is more extreme. As you said, and maybe there will be a higher therapeutic value.

[Gene Fine]: Yeah, that’s right. And Dr. Seyfried is one, also Valter Longo in California has recommended calorie restriction and fasting as well. And I think that those methods may have some other unique benefits that carb restriction may not have. They also may not be as easy to implement, but I think that they’re all in the ballpark, and there may be values for all of them.

[Damien Blenkinsopp]: So one thing I did want to bring up is when we were talking to Dr. Seyfried he mentioned he’s using an index now, which is called the glucose ketone index. I don’t know if you’ve spoken to him about that, or come across it.

It’s simply glucose divided by ketones in millimolars. And he’s been using that to look at his approach to metabolic therapy and see if it’s effective. I’m just wondering if you could compare that to the relative ketones. Would that make sense for you, or you haven’t looked at this?

[Gene Fine]: I haven’t done that, so I really don’t feel up enough to comment on it. I didn’t do that. I actually might want to go back and calculate that as well in these patients to see if I can get those numbers and make some correlations. But I haven’t actually done that yet.

[Damien Blenkinsopp]: Yeah, it strikes me it just might be interesting because, as you said, some of the diabetic patients went up, potentially high glucose. So you might see something similar there. Based on it.

[Gene Fine]: Yeah, that’s right. I was just thinking about that.

[Damien Blenkinsopp]: Great, great.

There’s a few things I wanted to bring up here in terms of the other tactics people might use. Which I don’t know, you may not have an opinion on these. But there are other things that can change the levels of ketones in our body. You can use MCT oil, or ketone esters, exogenous ketones basically, or a high fat diet.

My personal experience with these, for instance, is I’ve been on a high fat diet for a while and in my fasting insulin tests, my insulin is pretty low compared to the average. And I understand that that’s pretty standard. So I was just wondering what you thought of these kind of approaches. Also, if you’ve seen anything that might say there would be similar impact. Because they’re basically mimicking the effects of a low carbohydrate diet.

[Gene Fine]: Well yeah, I actually don’t know what way a high fat diet is distinguished from a low-carb diet. There are three macro nutrients, and basically a low-carb diet is a high fat diet. I don’t know if a high fat diet necessarily is also a low-carb, but it must be lower in carbs because you don’t really make up the difference in protein.

[Damien Blenkinsopp]: Right, you’re right. The question is the protein. That’s the missing…

[Gene Fine]: Right. And as I say, I haven’t tested the protein values. We didn’t restrict protein in our group. I think we could have.

We were dealing with patients who, as I say, had advanced cancers, and we were getting them as through referrals from their oncologists as volunteers, and we really didn’t want to give them something too complicated to do, so we just tried to [simplify it]. But yes, protein, certainly restriction might have had further benefit.

But as far as inducing ketosis with medium chain triglycerides, coconut oils and the like, ketone esters, I think these are interesting approaches. They can certainly, possibly offer more convenience, rather than going through a low-carb diet. And that I think has value.

The other thing to note is that they don’t actually mimic the full effects of a low-carb diet because they don’t inhibit insulin. So, there is that aspect of it. While there may be value, I’m not sure that they’ll produce the full effect.

[Damien Blenkinsopp]: Great, great. Thanks for the commentary.

Now the other thing I wanted to just bring up was metformin, I don’t know if you’ve looked at all at that.

[Gene Fine]: Well, yeah. I mean, I’m aware that this is being used, at least in trials, as another potential mimicker. And it has it’s own value. I think what it does for me is it illustrates the value of low-carb diets, because what it really does, metformin, is it limits glucose and thereby insulin secretion. So, it’s fine. To me it’s major mechanism is the same mechanism as a low-carb diet.

It has some independent mechanisms. It seems to up-regulate AMP kinase, which happens also to be done by low-carb diets. So metformin may have some advantages. It’s a drug. It’s a very well tolerated drug, but it’s not a universally well tolerated drug.

There are some side effects that have been reported. Not frequently, but some patients develop lactic acidosis, which can be very serious. And some patients develop hypoglycemia. So, I think overall it would be considered a very safe approach, it just has to be tested, like everything else.

[Damien Blenkinsopp]: Great. Thank you.

I was wondering if you had any opinion on calorie deficit versus high intake of calories. I could be on a high fat diet, or a low carbohydrate diet, and still have a surplus of calories versus a deficit. Do you think that’s anything that could be either affecting your results, or something to look at?

[Gene Fine]: Yes, it is something, definitely, to look at. The calorie restricted approach has been advocated…well, it’s just been advocated. I can’t say exactly whether the mechanism is the same, overlapping, or somewhat different.

But I can just say this, that in our study we actually wanted patients to not lose weight. We encouraged them to overeat. Overeat a low-carb diet, but overeat. So to eat as many calories as they needed to sustain their weight.

So the only comment I can make about this is that all the patients lost weight. We did not intend for them to lose weight, that was not our goal. We encouraged them, we would be weighing them weekly and we’d tell them, “Eat more, eat more. You’re making these shakes, add more cream to it. Add more oil to your foods. Put butter on everything.”

Well anyway, whatever it is that we encouraged them to do, all 10 of them lost weight. They lost on average about four percent of their initial body weight. The interesting thing about that, I just suppose that this is why these diets are effective as weight loss diets.

No one knows exactly why they work, but you certainly can speculate some pretty plausible mechanisms. One is that ketosis may inhibit appetite. Another is that your inhibiting insulin, and insulin, as I say, under the influence of carbohydrate makes you fat and keeps you fat. The absence of insulin does the opposite. It releases lipids from your fat cells, and metabolizes them in the liver. So the fact is that low-carb diets intrinsically may be weight loss diets.

We believed in our study that it’s possibly to defeat this. That there’s such a thing as overfeeding, and maybe if one is particularly conscious about this, one can do this. But the other interesting factor is that seven out of the 10 patients were above a body mass index of 25, which is to say they were overweight. Only three of them were in the normal weight range, between 20 and 25.

And as it happens, the patients who lost the most weight were the heaviest. Frankly they were delighted with their weight loss, even though we were trying to maintain weight just for the principles of our study.

The patients who were in the normal weight range, the two who were the higher two in the normal weight range — I should say, the heaviest patients lost about five to six percent of their body weight. The patients who were in the normal weight range, the two heavier of them — 25 BMI and 23 — lost about three percent of their body weight. And the patient who was 20 lost no body weight at all.

So what this tells us is something we all know also, which is that the closer we approach our ideal body weight, the harder it is to lose weight. I don’t know whether you’ve observed that yourself, whether you have gained, lost or are stable in terms of your body weight, but I believe that high fat diets do not necessarily cause weight loss, particularly in people who are approaching their ideal lean body weight.

[Damien Blenkinsopp]: I’ve been on this diet for many years, just as an n=1 experiment. I think I lost a bit of weight when it first started, but ever since I’ve been really stable, ever since. And I’ve never paid attention to the number of calories. Sometimes I’m sure I’m eating a lot of calories, and sometime I’m not eating so many, for whatever it’s worth.

[Gene Fine]: I should also mention one other thing, which is that in our study, when we calculated what the calorie intake was on the basis this is of course on the patients self-reports, that all the patients reduced their calorie intake as well. Now, we didn’t want them to, but the measured calorie intake on the basis of their self reports was reduced, in fact by about one third.

The other interesting thing though is that the stable disease effect and partial remission, those patients who showed stable disease or partial remission had three times the ketosis. But the degree of weight loss in the two groups was the same. They both lost about four percent. So although there was weight loss in all the patients, weight loss, or calorie deficit, did not appear to correlate with the effects that we saw.

[Damien Blenkinsopp]: Well that’s a great point then.

I think the other point you illustrated, if we’re talking about your studies, is how difficult it is to set a good cancer study up, given the situation with the patients and you’re trying to control for a lot of things. So, as you say, it took you four years to recruit the patients for the last study. So I think it gives us a much better appreciation of how difficult it is to do these types of studies.

[Gene Fine]: Yeah. I think it is the fact that physicians are trained to treat with drugs and that’s very understandable. Drugs generally work well. And in cancer, it would be naive to start off with the assumption that diet is going to be a successful therapy. It has to be tested.

And so, whereas there was some reluctance, there wasn’t entirely, and many of the oncologists were very helpful and cooperative and referred patients when they were on a chemo holiday, or chemo break. That’s what was needed to get this study done. And also the fact that I didn’t want patients who were too thin and too sick.

But I think going forward, I think that we can count on, perhaps, some additional support. And we are actually aiming for human studies going forward as well. Right now, as I say, we’re also trying to couple diet with drugs in animal studies. So this combination, we hope, will lead us somewhere.

[Damien Blenkinsopp]: Yeah, Great. So is it the first time someone’s been trying to couple chemotherapy with diet? Or are there existing studies that you’re basing your current work on?

[Gene Fine]: Coupling a low carbohydrate diet with other therapies has been done. I know that Colin Champ and Doug Spitz, I believe, have coupled low-carb diets with radiation therapy. As far as coupling with drugs, I’m not actually immediately aware that anyone has done that. I think that we may be the ones who are looking at that right now.

[Damien Blenkinsopp]: Great. Wrapping up a bit, thanks so much for your time today.

Where could we learn more about this subject? Are there other people you would look to to learn more about this? Perhaps people you’ve worked for who are doing a lot of studies in this area. You mentioned Valter Longo, of course who was mentioned in Dr. Seyfried’s as well. Or are there any books or presentations on the subject that are good?

[Gene Fine]: I’m trying to think, other presentations. I know that there are some other people working in the area that I know have been doing good work.

Dominic D’Agostino in Florida. I think he has a website, and it would be interesting to look at some of the work that he’s done. A somewhat, I hope, accessible discussion of what we’ve talked about.

I have a couple of guest blog posts that I wrote. My colleague Richard Feinman has a generalized biochemistry and metabolism web blog, and he invited me to write some guest blog posts for his web blog. So I wrote two.

One which is on the general hypothesis, which I didn’t even discuss today. I mean, I discussed it in the broadest forms, but I didn’t discuss some of the details. And the other one is more on the clinical trial, on the recharge trial. So it gives more detail on that.

And I think Colin Champ has an interesting website as well, Caveman Doctor. I think I’d look at that. These are other resources. I think I’ve mentioned most of those that I know.

[Damien Blenkinsopp]: Great, great. So, we’ll put links to all of that in the show notes, thank for those.

Well how about you? What are the best ways for people to connect with you? I mean you mentioned the blog posts, which we’ll put in. Is there anything else? Do you have a website, or are you on Twitter? Is there anywhere you are active where people could learn more about what you’re up to?

[Gene Fine]: Let’s see. The website that I have is my website at Albert Einstein. You can also, through the blog posts that I mentioned it gives other links to papers that I’ve written as well as to my website. So I think that probably the most complete portal, you can look me up just at Albert Einstein and find my website there. And that will also link me to the dietary studies and the blog posts and the papers. They all connect to each other.

[Damien Blenkinsopp]: Great, great. We’ll put those on the show notes.

Something we spoke about just before the interview, your perspectives are a little bit different to Dr. Thomas Seyfried that we’ve already had on the show. Could you briefly summarize where you think you might have a different opinion?

[Gene Fine]: Well, I just think that we really are in the same camp. I think that we both believe in metabolic therapy, as do the other people that I’ve mentioned. I think that he believes that when he describes cancer as a metabolic disease, he believes that the fundamental problem is it starts as a metabolic disease in abnormal mitochondria. That may be true.

The only thing that I think that I would differ is that that abnormality in the mitochondria, I believe, is a genetic abnormality, even in the mitochondria. That you still have, what’s happening in the mitochondria is that, to me the fundamental problem in cancer is actually a genetic mutation that leads the cells to increased proliferation and growth and unlimited growth and immortality, and so forth.

The source of these mutations, I believe, could certainly be in the mitochondria, but in fact if it is, and that would make sense to me, it would be increased reactive oxygen species. And increased reactive oxygen species can cause mutations in the genetic portions of the mitochondria, and that would cause abnormal mitochondria. Or it could cause mutations in the DNA of the cell. Certainly hydrogen peroxide, peroxide can migrate over distances and can migrate into the nucleus.

So, I actually believe that the fundamental problem that leads to the cancer may initiate in the mitochondria with reactive oxygen species, but nonetheless results in the fundamental change of cancer is in a mutation. So I think that [in a] certain sense we’re describing the same phenomenon, but we have a different emphasis on which syllable we’re emphasizing.

[Damien Blenkinsopp]: Right. Potentially where it starts and where it finishes, and so on.

[Gene Fine]: Yeah, yeah.

[Damien Blenkinsopp]: Great. Great, thanks for that clarification.

Before you go, I just wanted to look at a bit of what you do on a personal level with your body data. I was just wondering if you track any metrics at all for your own health, biomarkers, or anything like that on a routine basis. Maybe yearly, or more so?

[Gene Fine]: When I started studying this in, around 2003, and I got interested in it, by the way, from my friend and colleague Richard Feinman. He’s a biochemist, and he’s been interested in this principally from the point of view of the effects on metabolic syndrome, diabetes, lipid disorders, and so forth.

However, I came in from the nuclear medicine background, and PET scanning and Warburg effect, and hypoxic cells. For me it was attractive for the possibility that this may have some effect, low-carb diets in inhibiting glycolosis, and as I mentioned earlier through the uncoupling protein 2 having a unique inhibitory effect on cancers while sparing normal cells.

So in 2003 when I got interested in this, and I decided that — you know, I never really had a weight problem, but I had gradually put on a few pounds over the years. And I have a small frame, so I’m about five foot nine, and 165 pounds. For me that was carrying excess fat.

So I figured well, you know, if I’m going to study this in others I might as well experience what it’s like for myself. And maybe I’ll even have some benefit in terms of overall body composition.

To make a long story short, I’ve been on a low-carb diet of various degrees of strictness over the years. In some cases I’ve been ketogenic, I’ve been very strict. In other cases, I’ve just been low-carb, but not likely ketogenic. I haven’t been under 50 grams a day, I’m not quite sure.

But the short story is that over a period of now, what 2003, really 2004, about 11 to 12 years, I’ve lost 33 pounds. Sometimes it’s been in fits and starts, but I’m very, very happy and comfortable with my weight right now. I like myself at 132. I have a small frame. I feel that for me I am lean and fit, and that’s a good thing.

There’s that aspect of it. In terms of other biomarkers, the numbers that I like to look at, in particular, are those that have risk profiles for, well my glucose and my hemoglobin A1C has dropped. In addition, my fasting blood glucose.

[Damien Blenkinsopp]: So if you remember, where did they start and where are you at now? And are you happy with the numbers now?

[Gene Fine]: Well yeah. I mean, I think I’ve been stricter lately and more consistent, so I’ve only been monitoring them really. I don’t think I’ve really been taking very close watch of them.

But I think over the past year or two my blood glucose, a couple of years ago had actually been at 100, and my hemoglobin A1C I think at one time was around 5.7. I’m sorry, this was only about one year ago.

The hemoglobin A1C changes slowly, but in two successive measurements, I’m about to come up with a third, it’s dropped to 5.7 to 5.6 now to 5.5, and I’m expecting it will continue to be going down because I’m doing this. And my fasting blood glucose is now about 94. So it’s dropping, and I’m satisfied with that.

I used to eat what was recommended. I used to eat a low fat diet, which of course means a high-carb diet, and I think I suffered the consequences. But little by little that has been reversing.

From the point of view of my lipid profile, the things that I’m most interested in are those that are atherogenic, that contribute to risk of cardiovascular disease. And I think the current thinking, which makes some sense to me, is that it’s not so much LDL which is targeted by the cardiologist, because LDL is a mixed bag.

Low density lipoproteins really consist of two major fractions. One of the light, buoyant LDL, which is really not harmful, and the other is the small dense LDL, which is. And what happens on a low-carb diet is you reverse the ratio. You reduce the amount of small dense LDL.

And the good measure of that, because it’s hard to get that measurement directly. There are only a few labs in the world that actually measure small dense LDL directly. You have to send away to specialized testing for them. However, there’s a good index of it and it’s the ratio of your triglycerides over your HDL.

[Damien Blenkinsopp]: So there’s a proxy?

[Gene Fine]: There’s a proxy for small dense LDL, yeah.

[Damien Blenkinsopp]: Oh, great.

[Gene Fine]: And so when I started, I guess when I first measured my triglycerides to small dense LDL when I had been not very compliant at all, my triglycerides at one point were about 150, and my HDL was about 50. So the ratio was about three. And since going on a low-carb diet, my triglycerides fell in half, to 74, and my HDL went from 50 to 75. So basically my ratio is now one.

[Damien Blenkinsopp]: That’s pretty high.

[Gene Fine]: So all the things went in the right direction. I’m very pleased that the HDL went up, without any major increase in exercise, just the diet alone. And my triglycerides fell in half. So those are both just exactly what you would expect on a low-carb diet, and what you want.

[Damien Blenkinsopp]: Great, thanks for those.

They’re very useful, especially the triglyceride HDL ratio. Because it is difficult to get the, I guess you were talking about the NMR, nuclear magnetic resonance. We spoke about that in a previous episode. And then there’s the LDLP to get the number of particles. But as you say, there’s only a few specialized labs, so it’s not as accessible. So it’s great to know that there’s a proxy to use also.

Last question here. What would be your number one recommendation to someone trying to use some kind of data to track, whether it’s biomarkers or something else, to make better decisions about their own health?

[Gene Fine]: Yes, well I mean it depends on what aspect of the health you’re talking about. But I don’t know if ketosis is necessary.

As I mentioned, any change of diet can be difficult to sustain over the long term. I don’t even know what it takes. Willpower is something that, what is it. So, it’s hard to know how to do that.

And by and large the reason I would say it’s hard to change diet is people eat what they like. And you want to eat what you like, and so changing your diet means you’re, by definition, changing it to something that you didn’t prefer. So it seems as though there’s a fundamental issue there.

On the other hand, I think that if you have a weight issue that you’re not happy with, or your doctor reports blood lipid markers or glucose markers that you’re not happy with and evidence of pre-diabetes or diabetes, and you’re on meds, so forth — let’s not consider meds yet. Let’s just talk about without being on meds. Because low-carb diets, if you can actually go on them and you’re also on meds, you have to do that under supervision because you might actually become hypoglycemic, and you have to be careful about that.

But without considering meds if you just want to, say, improve your health in terms of obesity or aspects of metabolic syndrome, lipid disorders, blood glucose levels, pre-diabetes. Without going on a strict low-carb ketogenic diet it’s not as hard, I think anyway, to reduce the quantity of carbohydrates that you eat.

You can have a breakfast where, you can cut out, well cut in half the size of the desserts that you eat. You can cut in half the amount of mashed potatoes that you eat. You can eat one slice of bread instead of two, or you can not eat bread. Although that sometimes is hard for people, but if you eat the bread and don’t eat the mashed potatoes, you’ve reduced the number of carbs that you eat.

So if you just start by reducing certain portions of carbohydrates. And I actually found I still have carbohydrates a little bit now. I have a sort of modified Atkins Plus, I call it, or South Beach Plus. I have a little ice cream at night. It’s my treat.

Overall, I probably eat about 60 grams of carbs a day. But, I treat myself to a little bit of ice cream at night. I’ll find out what that’s done to my lipid profile, by the way. But I don’t think it’s going to have a major effect. I think that overall it’s going to be still pretty good.

So the idea of reducing the overall quantity of carbs, I think, is actually important. I think that with the average American diet, I don’t know if the same is true in UK but probably, that overall consumption of carbs is 300 to 400 grams a day. And that’s really quite a lot. And if that could be cut in half to 150, that would be a big improvement.

So, I think that that would be lower stimulation of insulin secretion. Yeah, I think that that would be my principle recommendation in terms of health.

Now as far as exercise is concerned, exercise is also something that many people do but can’t stick to an exercise regime. And overall, I think that even if you look at the overall impact on insulin sensitivity and improving metabolic profile, there’s no question that exercise helps. But it really comes a distant second to diet in terms of having a dramatic impact on insulin sensitivity and these other biomarkers of lipids and glucose and so forth.

So that, while you’ll never hear me discourage anyone from wanting to do exercise, I think that if you want to have an immediate and more dramatic effect, the thing to do would be to reduce carbohydrates in the diet somehow.

And that’s probably the best I can say at the present time, because as I say, I don’t think anyone has a magic bullet as to how to help someone go on a diet. It’s never easy, but if you can find a way to reduce carbohydrates, you’re off to a start.

And if you feel encouraged by the results that you see, you tend to continue it.

[Damien Blenkinsopp]: Absolutely. Thank you for bringing that up, because we’re introducing changes here, new habits. And as you say, it’s super difficult.

I feel one of the things that helps people is making it clearer how helpful it can be in different areas of their life. Once you’ve heard it 10, 20 times from different people who are studying these things, like yourself, in different areas. I think it makes it easier for people, just because of the repetition, for the clarity in their heads.

I think part of the problem is the mystery and the misunderstanding, especially in the media and the press. The more times you’ve heard five different stories, the less you feel like taking action against any one of them, because you’re just not sure, you’re hesitant.

So thank you for your time today, because it’s certainly helping with these type of things.

[Gene Fine]: Thank you. I’m glad that you have this program, really, to spread the word through interviewing people who are active in the field.

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An in-depth look at using heart rate variability biofeedback with slow breathing to reduce stress, enhance athletic performance and provide therapeutic support for some chronic health issues.

Heart rate variability biofeedback is being used primarily to reset the nervous system and thus as an antidote to different types of stressors. These include modern-day chronic stress, aka the all-time-on syndrome, or infections or other problems in our lives.

In this episode we compare the use of breathing techniques to other tools like meditation to improve HRV (Heart Rate Variability), and the use of biofeedback to optimize the benefits.

Biofeedback enables us to learn what yogis historically spent decades learning in a matter of weeks. And the applications are multiple. It can be applied to improving athletic performance, productivity, health issues such as headaches, irritable bowel syndrome, insomnia, asthma, inflammation and on and on.

It turns out that everybody has their own unique pace, where breathing in and breathing out at that pace produces the biggest peaks and valleys, the exact right phase angle between respiration and heart rate, and when you go into that particular rhythm, it seems to have tremendously beneficial effects. Again, we often see this as a brand new idea that’s 2500 years old because this is exactly what these yogis were doing.
– Richard Gevirtz

For the HRV biofeedback topic our guest is Professor Richard Gevirtz, PhD, professor of health psychology at Alliant International University. He has been working in HRV biofeedback for nearly 30 years and he’s published over 40 papers on biofeedback during that time in areas such as mind-body feedback, stress disorders, clinical protocols for the biofeedback, anxiety disorders and autonomic control. This was a great interview; I thoroughly enjoyed it. I hope you enjoy it too.

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 early days of biofeedback – key discoveries in conscious control over autonomic functions of the body (6:12).
  • How the science on the benefits and mechanisms of various yogi techniques needs to improve – to produce more quality studies and reliable data (11:05).
  • The degree of complexity in HRV biofeedback and the applicability of various beat-to-beat analysis in studying mechanisms of stress response (14:19).
  • Optimizing breathing and heart rate rhythms has beneficial effects on the cardiovascular system (19:26).
  • Why standard metrics do not apply for slow breathing, because this category is a low frequency range of approximately 4-7 breaths per minute (26:54).
  • Overviewing the ups and downs of available beat-by-beat biofeedback devices (32:25).
  • An average training session aimed at determining optimal breathing frequency during slow breathing. How to optimize measuring equipment and make people feel comfortable during the HRV tracking exercise (42:31).
  • Performance benefits of practicing breathing exercises, with examples in sports and music (46:33).
  • For optimal results, during practicing slow breathing you should be non-judgmental and self-observant at the same time (50:09).
  • How the brain and heart integrate physiological feedback in the body and how this system is negatively affected by anxiety and stress (52:35).
  • Positive effects on gastrointestinal health in kids with inflammatory bowel disorders, who practice slow breathing techniques (57:55).
  • In most studies on depression, improvements in HRV biofeedback are accompanied with beneficial effects (1:00:01).
  • Slow breathing training helps for anxiety and urge – control, by inhibiting stress response centers in the brain (1:03:52).
  • Data on cortisol (the stress hormone) indicates beneficial effects of slow breathing practice in fighting stress (1:04:30).
  • When practicing meditative slow breathing, it is important to measure EEG waves in low frequency ranges – in order to clearly demonstrate beneficial effects on heart performance (1:05:16).
  • Gratitude and compassion mindfulness exercises are broadly related to HRV performance, but optimizing slow breathing is a practicable and improvable skill to be learned and trained (1:08:47).
  • In the future, the team and Prof. Richard will continue to research outcomes of HRV studies, physiological mechanisms of slow breathing, and standardizing yoga breathing practices by beneficial effects (1:10:48).
  • How to best obtain information of Prof. Richard’s research and career (1:14:27).
  • People and lines of research related to Prof. Richard’s interests. Additional practical advice on integrating HRV biofeedback with your performance goals (1:14:27).

Prof. Richard Gevirtz

Tools & Tactics

Interventions

  • HRV Breathing: Modern science is increasingly focused on beneficial effects of meditation and slow or diaphragmatic breathing techniques – practiced at the pace of 4-7 breaths per minute. During slow breathing, heart rate and breathing rhythms synchronize – in a way that produces resonance in the autonomic nervous system. This concept is known as a meditators’s peak. The unique slow breathing pace at which it occurs in different individuals (for most people between 5.5 – 6 breaths per minute) can be determined using HRV biofeedback tracking tools. When tracking Low Frequency (LF) HRV ranges (see below), the meditators’s peak occurs as a single spike of great magnitude (in graphical form) and is followed by smooth overlaps between the peaks and valleys of waves representing breathing and LF HRV rhythms.
    Over time, slow breathing exercises produce flexibility in the autonomic nervous system. Essentially, practicing breathing at a specific, disciplined, rate synchronizes respiratory and cardiac systems to increase resilience to physical or psychological stress, improve autonomic balance, and sharpen mental clarity. These tools can be used to fight against stress related medical conditions such as Irritable Bowel Syndrome (IBS), hypertension, depression etc.
  • Acceptance and Commitment Therapy (ACT): Prof. Gevirtz has successfully applied this psychological therapy in his practice. A recent scientific review of all available research on ACT concluded that it is more effective than placebo, or standard treatment, in dealing with anxiety disorders, depression, and addiction.

Tracking

Biomarkers

  • Heart Rate Variability (HRV): HRV is the measure of the change in the heart’s rhythm over time based on changes between sympathetic and parasympathetic activation. HRV was previously covered in the context of managing stress using HRV in Episode 6 with Ronda Collier, in using hormesis to improve HRV in Episode 8 with Todd Becker, and in using HRV as a biomarker for longevity in Episode 20 with Dr. Joon Yun.
  • Time-Domain HRV

  • Standard Deviation of Normal to Normal R-wave Beat (SDNN): The most statistically simple measure of HRV – simply measuring beat-to-beat variability.
  • Root Mean Square of the Successive Differences (RMSSD): A measure used to calculate HRV that has proven to be reliable and is used in a lot of research studies. An integral measure that seems to be a little bit more dominated by the parasympathetic nervous system, compared to SDNN.
  • Frequency-Domain HRV

  • HRV may be broken into frequency components that compose the overall variability. Low Frequency (LF) is association with sympathetic activation; High Frequency (HF) is associated with parasympathetic activation. Frequencies of different rhythms can be detected over time in the heart rate. How much any of the frequencies is present in overall variability is indicative of heart performance and factors which influence this performance. For example stress is associated with high LF with respect to HF (high LF/HF ratio).

Lab Tests, Devices and Apps

    Biofeedback Devices

  • HeartMath: The company has developed products for tracking HRV. Devices include emwave2 and Prof. Gervitz’s preferred device – Inner Balance for iOS.
  • My Brain Solutions: The company offers products which track HRV including MyCalmBeat.
  • Muse: The Brain Sensing Headband: This device provides brain feedback data and allows users to determine when they are in a fully meditative state.
  • Breathing Timing Apps

  • MyCalmBeat App: Over 30 brain exercises for training slow breathing and improving HRV in managing stress.
  • Breathe2Relax: This is a portable stress management tool which provides instructions and practice exercises for using slow breathing techniques and managing stress.
  • Breath-Sync Music CD Suite: The suite includes six CDs with slow-breathing music, each at a different rate (from 4.5 to 7.0 breaths per minute).
  • Multi-Channel HRV Biofeedback

  • NeXus-4 by Mind Media: This instrument can be used to simultaneously track various biofeedback signals coming from photoplethysmogram (PPG) sensors. These sensors optically determine heart rate by illuminating the skin with the light from a light-emitting diode (LED) and then measuring the amount of light transferred to an opposite end of a finger – clipped sensor. Changes in light are indicative of changes in blood flow – which result from changes in hearth beat rhythm.
  • Stress Control Suite by Thought Technology: This software integrates information from multiple sensors relevant for tracking HRV and autonomic nervous system functionality. The Stress Control Suite works with the ProComp2, a physiological monitoring device which can be plugged to Temperature Sensors and Skin Conductance Sensors.
  • Multiple Channel ECG reader by J&J Engineering: This product connects to a computer and is able to monitor ECG, skin conductance, temperature, and respiration rates, at the same time. Price: $1,995.
  • HRV Analysis Software

  • Kubios HRV

Other People, Books & Resources

People

  • Peter J. Lang, PhD: A research scientist who was one of the founders in the field of psychophysiology (linking psychological phenomena with physical states of the body).
  • Our guest, Prof. Gevirtz, collaborated with Marks Schwartz PhD, Paul Lehrer PhD and with Dr. Stephen Porges during the early days of biofeedback.
  • Dr. Robert Freedman: Because of his interests in Raynaud’s disease, Dr. Freedman experimented with biofeedback as a way for people to learn to control blood flow in cold areas of the body – as a therapeutic means.
  • Neal Elgar Miller: An American experimental psychologist whose studies showed that animals and people could control all kinds of autonomic functions. Numerous studies of his have not been able to be replicated, leading to controversy. Regardless, Neal E. Miller’s legacy stems form inspiring future and current researchers to dig deeper into psychophysiology and behavioral studies.
  • Dr. Elmer Green has traveled to India and done extensive research on the physiology of yogis. He discovered that, through meditation and slow – breathing techniques, yogis could control a range of autonomic phenomena. Notably one yogi could warm one ear and then switch to warming the other, at will.
  • Laura Schmalzl PhD: Prof. Gevirtz recommends a recently published scientific review article by Laura Schmalzl on the topic of neurophysiological and neurocognitive mechanisms underlying the effects of yoga-based practices.
  • Dr. Ary L. Goldberger: A beat-to-beat heart rate is characterized by many different oscillators that are contributing to a healthy pattern. Dr. Goldberger is a pioneer of analyzing complex patterns in cardiology and in detecting how these vary in different heart diseases.
  • Lionel Messi: A world famous football player, currently playing for FC Barcelona. His coaches optimize his training using the gold-standard for HRV tracking – every morning in bed, right after waking up.
  • Prof. John Gruzelier: A researcher who makes use of brainwave feedback and slow-breathing techniques to bring benefits for recitals and dance performers.
  • Prof. Mihaly Csikszentmihalyi: A leading researcher in the psychology of flow (aka. optimal experience).
  • Tim Harkness: A club psychologist for FC Chelsea. His approach includes positive psychology, cognitive perception training, and psychophysiology.
  • Evgeny Vaschillo PhD: A Russian cosmonaut physiologist who started studying hearth rhythms in the very low frequency range – at approximately 3 breaths per minute.
  • Dr. Luciano Bernardi: At Italian cardiologist arguing that music offers beneficial effects in managing cardiovascular disease. Our guest shares the story of how Dr. Bernardi traveled to mountains in Bangalore accompanied by twelve yogi. He discovered the yogis’ slow breathing techniques had significantly increased their baro reflex (the ability to withstand high altitude without experiencing symptoms of altitude sickness).
  • Mark Stern: One of Prof. Gevirtz’s students who students who created a video to explain the basics of HRV Biofeedback and its Applicability.
  • Inna Khazan PhD is a clinical psychologist using mindfulness and biofeedback in her therapy. Prof. Gevirtz recommends her book on combining mindfulness with biofeedback (see below).
  • Dr. Kevin J Tracey: A neurosergant who is the president and CEO of the Feinstein Institute for Medical Research. His research focuses on inflammation and how neurons control the immune system.
  • Rollin McCraty PhD: Executive Vice President and Director of Research for the company HeartMath.

Organizations

  • Western Association of Biofeedback and Neuroscience: Formerly called the Biofeedback Society of California, was founded in 1974 and is the oldest and largest state neurofeedback biofeedback society.
  • Association for Applied Psychophysiology and Biofeedback (AAPB): AAPB’s mission is to advance knowledge about applied psychophysiology and biofeedback, to improve health through research, education and practice.
  • Mayo Clinic: Mayo Clinic is a nonprofit medical practice and medical research group based in Rochester, Minnesota.
  • The Wingate Institute: An interdisciplinary research unit focusing primarily on biofeedback and psychophysiology of gastrointestinal diseases. Notably, their research has shown that slow breathing exercises protects patients from lowered esophagial pain thresholds, thus lowering the conscious perception of pain.

Books

Full Interview Transcript

Click Here to Read Transcript

[DAMIEN BLENKINSOPP]: Richard, thank you so much for joining us today.

[RICHARD GEVIRTZ]: Glad to be here.

[DAMIEN BLENKINSOPP]: I wanted to get a quick background behind what you do. How did you learn to do what you do, these studies and this area; how did you first get into it and learn to do it?
[RICHARD GEVIRTZ]: Well I started as an undergraduate studying with a famous psychophysiologist named Peter Lang, who was one of the founders of the field of psychophysiology, which is basically different from neurophysiology because we’re looking at physiological measures indicating psychological parameters. In those days we were measuring heart rate, but not beat-by-beat heart rate, just average heart rate, and muscle tension, temperature and respiration.

Then I went to grad school and got waylaid a little bit into another topic, but eventually I came back to psychophysiology and began working. I was in Minnesota at the time and I was near the Mayo Clinic, and I ended up working with a guy who’s been a lifelong friend, Marks Schwartz, at Mayo Clinic and doing biofeedback. It was the beginning days of biofeedback.

In those days we were doing just muscle tension and temperature and breathing, not even heart rate in those days. That was interesting; we were doing work on chronic pain mostly, and then relaxation techniques with finger temperature. I did that for a number of years but became a little unhappy with it because it seemed very limiting.

I had a background in heart rate, and as the technology got better, we realized that we could measure heart rate in a much more sophisticated way. Actually, in the beginning, I was collaborating with Paul Lehrer, my colleague at Rutgers University, and we were fascinated by this. Also we were good friends with Stephen Porges, who is this Polyvagal Theory guy. We were fascinated by this idea that the action wasn’t in the sympathetic nervous system as much as in the parasympathetic nervous system for day-to-day stress. That went against everything we had been doing up till then, which was really calming down the sympathetic nervous system.

So, as the technology built, and we realized it was really an incredible amount of information in the beat-by-beat heart rate, he and I began developing this idea of looking at beat-by-beat heart rate and feeding it back to people.

At the same time, in cardiology, the measurement of the beat-to-beat heart rate was growing rapidly, and so we benefitted a lot from all of the cardiology research showing a healthy heart as a very complex, somewhat chaotic-looking pattern to them, and that represented mostly the parasympathetic nervous system.
(0:06:12)[DAMIEN BLENKINSOPP]: Great. To take a step back a bit, what is biofeedback and what are the benefits that you’re seeking through using that?

[RICHARD GEVIRTZ]: Biofeedback, in general, is feeding back physiological information to a client or a subject and having them try to modify their physiology based on what they see, based on either wiggly lines on a screen or some analogue – a rocket ship going up or a train moving, or some other visual or other signal.

In the early days, what we were doing was teaching people to relax their muscles more profoundly than they might be able to do naturally, and we did that by feeding back information from voluntary muscle activity from electromyographs. Then we used finger temperature because it turned out that by learning to warm your hands, you could shut down the sympathetic nervous system. The sympathetic activity produces vasoconstriction. As you learn to vasodilate, it generally accompanies relaxation.

[DAMIEN BLENKINSOPP]: People would focus on their hands?

[RICHARD GEVIRTZ]: Yeah, they would focus on mental techniques to warm their hands.

[DAMIEN BLENKINSOPP]: It’s interesting.

[RICHARD GEVIRTZ]: And it turned out that they could both cool and warm their hands at will. A colleague of ours, Bob Freedman, in Detroit, was interested in Raynaud’s disease, so he was starting to look at biofeedback as a way that people could learn to warm their hands, even without getting relaxed they could learn to vasodilate. He studied the mechanisms of that and actually found fairly detailed mechanisms of how people could warm and cool their hands with different mechanisms. But they could definitely do it; medical students, even while playing a game of bridge, they could warm or cool their hands when a signal told them to do it at, will. Not a lot, but to some degree.

Everybody was fascinated by the plasticity idea that people could really control these supposedly non-controllable autonomic phenomena. So actually the original impetus was Neil Miller’s studies in ’69 that showed that animals and people could control all kinds of autonomic functions, although most of that has not been able to be replicated, interestingly enough. But it’s a famous study in ’69 and we knew Neil Miller. He was a great pioneer in his field. So even though it hasn’t been replicated, it’s still got us all thinking about control of autonomic phenomena.

At the same time, a colleague, Elmer Green, went to India and studied yogis, and showed that yogis have remarkable control of autonomic function. Though he didn’t exactly know how they did it at the time, they certainly could do all kinds of things. They could warm one hand and not the other hand, they could warm one ear and not the other ear, and they could do a trick that looked like they were stopping their heart, which is actually just a muscle tension that hid the ECG.

[DAMIEN BLENKINSOPP]: So the ECG wouldn’t pick it up because of the way they were beating their heart?

[RICHARD GEVIRTZ]: Yeah. It looks like they’re actually stopping their hearts – they weren’t. But it’s still pretty amazing. And they also had great control over heart rate and they could control heart rate, so it looked like maybe people could learn to control heart rate, and that was our first foray into that idea.

[DAMIEN BLENKINSOPP]: Did you ever look into how the yogis had learnt that? Was it meditation or mindful?

[RICHARD GEVIRTZ]: Purely meditation, yeah. It was various kinds of yogic meditation with a lot of breaths, a lot of pranayama.

[DAMIEN BLENKINSOPP]: Was this like the fire breathing, the fast breathing and things like that?

[RICHARD GEVIRTZ]: All kinds of breathing techniques: fast breathing, nasal, alternation with nasal breathing, slow breathing, but the thing we eventually discovered was if we asked the yogis to do what they do to get calm and centered, whatever language we could use for that, they always did the same thing. They always breathed very slowly, somewhere between four and a half and seven breaths a minute – whatever breath rate they chose, they always used exactly the same breath rate, within a half a breath, and they could do it even during distraction.

One of our colleagues had this one yogi who had put skewers through his tongue and through his arm and his neck, and still maintained this exact breath rate through the whole thing.

[DAMIEN BLENKINSOPP]: Wow. Was he making new holes in himself with those?

[RICHARD GEVIRTZ]: Yeah, little tiny holes, but he could prevent bleeding. It wasn’t a fake because I was right there next to him and I felt those skewers and I saw him do it. I think he learned certain places to put them that didn’t bleed and would quickly close up again, but they could do this without any outward sign of pain, without any physiology changing, is just remarkable.

We realized that there was some potential for control and that set us off on this pathway.
(0:11:05)[DAMIEN BLENKINSOPP]: I actually used a machine where they look at the blood flow in your forehead. I don’t know if you’ve seen that it’s a biofeedback mechanism – you can play this little computer game and it will go in the right direction when you’re increasing the blood flow.

[RICHARD GEVIRTZ]: Yeah. The question about that technique is whether it’s really just measuring forehead and dura blood flow, maybe peripheral blood flow, or is it really going deeper into the brain to measure cortical blood flow, and I think that’s still to be decided. The claims are that you’re getting the first centimeter of the cortex – I don’t think that has been shown, myself. But something varies, there’s no doubt about it, and people can learn to control it.

Blood flow was one of those techniques that yogis could control. Remarkably sometime there was one yogi who could make one ear get very warm and the other ear stay the same and then he’d switch ears. How he did that, he could never tell us. He just willed it. But that’s pretty remarkable. Physiologically, you’re not supposed to be able to do that. There’s no evolutionary reason why we should be able to control an autonomic function like blood flow, so somehow the brain could learn to do this through some remarkable meditative techniques.

[DAMIEN BLENKINSOPP]: This is pretty spectacular. I’d read a lot of the yogi books and some of the books on the science of yoga, and I wanted to try it but I wasn’t sure there were actual benefits and I didn’t know what the benefits were, and it went through all the history and stuff – quite interesting to see that some of that matches up, that’s spurred on your interest in the area.

[RICHARD GEVIRTZ]: Right. Actually we’re trying to encourage better science, because they think they know it all and they can cure everything, and I think the chances are that they are definitely on to some very remarkable things, but others probably not.

[DAMIEN BLENKINSOPP]: Yeah, because it’s interesting because it’s split into different types of yoga and all of this, and which came from the actual practices. I understand that some people injure their lower backs and things like that, so there are some parts which are seen as not good and other parts, which as you say, could be good. So there’s a way to go to figure that out.

[RICHARD GEVIRTZ]: It’s very tricky for science because they don’t have standardized methods. We just got a paper from a group about a kind of a yoga called reflective exercise. It’s got some Indian name and it’s claiming fantastic results with athletes. Here it’s just a completely different one – they use reverse diaphragmatic breathing – and with all kinds of claims, with really not much science behind it.

I’m an associate editor of the journal Applied Psychophysiology and Biofeedback and we try to encourage people to send us some good scientific papers. We would love to see what the mechanisms are. There is just a recent paper coming out in Frontiers, looking at the neurophysiological mechanisms of yoga – a pretty extensive review by a woman named Schmalzl. There’s lots to be learned, that’s for sure, but I think it’s an area that will be studied more frequently.
(0:14:19)[DAMIEN BLENKINSOPP]: Great. Thanks for the reference on that paper, too. That will be interesting to read.

So you’ve been focused on the heart rate variability biofeedback for a while. What is that in comparison to the other stuff we’ve been talking about?

[RICHARD GEVIRTZ]: Firstly, the important point for the listeners is that heart rate variability measurement is completely different than heart rate variability biofeedback. The measurement is a very big field, very dominant in parts of cardiology, and the underlying idea is that healthy hearts have tremendous complexity in their patterns of beat-to-beat activity – and you have to actually look at a beat-to-beat to see this. If you go to the gym and do your average heart rate, that doesn’t pick it up at all.

A beat-to-beat healthy heart rate is characterized by great amounts of complexity – many different oscillators that are contributing to the pattern. For some heart disease things, you need a non-linear message to look at these really complex patterns. Ary Goldberger is pioneering this in cardiology and has amazing results with different heart disease, in terms of seeing how it varies.

The measurement is of interest to us because we do measurements on people with different disorders. The disorders we are interested in are more psychophysiological or stress-related disorders and they do show up with poor heart rate variability quite often.

[DAMIEN BLENKINSOPP]: Are we talking about RMSSD here?

[RICHARD GEVIRTZ]: Yes. There are three classes of measurement. One is called time domain measures, which are fairly simple, they just look at the beat-to-beat variability. The most common one is SDNN, standard deviation of the normal to normal R-wave beat. A little more sophisticated and one of the same type is called RMSSD, root mean square of successive differences. The difference between the two is that the second is an integral measure that seems to be a little bit more dominated by the parasympathetic nervous system. SDNN is simply all forms of variability, it’s just the standard deviation of beat-to-beat differences.

It’s quite simple really. You just get a column of interbeat intervals in milliseconds and take the standard deviation. That’s still very widely used and is a powerful epidemiological measure. RMSSD is a little bit more sophisticated because it picks up a little bit more of the parasympathetic nervous system.

Then there are frequency domain measures, a second class of measures, and that’s where you look at what the frequencies are of different rhythms over time in the heart rate. It gets a bit more complex then. So you have to print out a sequence of beat-to-beat heart rates and then look at the frequency characteristics of them, and those frequency characteristics then can be sorted by how much of each frequency. The advantage to that is that in one realm, what’s called high frequency power, is a pretty good analogue to the vagal tone.

The tenth cranial nerve is the vagus nerve, which is the parasympathetic nerve that controls heart patterns. At rest, it’s the dominant source of heart patterns. By being able to measure the amount of vagal tone, we can look at things that are of interest to us, especially psychophysiological disorders or anxiety disorders, depression, because those things are all diminished in those disorders.

[DAMIEN BLENKINSOPP]: So better vagal tone is better, more control?

[RICHARD GEVIRTZ]: Exactly, yes, good vagal tone is, in general. A rebound vagal tone, like in asthma, which is too much vagal tone and it shuts down the airways, but that’s just a poor amount of flexibility in the autonomic nervous system.

The goal is very flexible, resilient, autonomic nervous system; not necessarily more tone overall. We do see less vagal tone, however, in a number of disorders.

[DAMIEN BLENKINSOPP]: I think another scenario where high vagal tone may not be a good thing is adrenal fatigue – we’ve discussed it on the show before.

[RICHARD GEVIRTZ]: Yeah, that could be, and as I say, asthma, if you get a sympathetic surge followed by a giant parasympathetic rebound, it shuts down the airways and that’s not healthy. There are some situations like that. Some kinds of stress are vagal stress. For instance, if you show somebody a video of a fake shop accident, where the shop teacher is putting a piece of wood through a circular saw and we see him just about to saw off his finger, people rate that as very stressful, but they don’t get a sympathetic surge, they get a parasympathetic surge from that.

[DAMIEN BLENKINSOPP]: Interesting.

[RICHARD GEVIRTZ]: Similarly for a vasovagal response, people faint when they see blood or needles; that’s a parasympathetic response, not a sympathetic response. So the system is adaptive to what’s important. The vagal system is trying to preserve blood and shut things down, but that can be a stressful response too, so we don’t want you to just think stress is sympathetic.

(0:19:26)[DAMIEN BLENKINSOPP]: Right. In terms of the heart rate variability mechanism you’re looking at, which approach have you been using?

[RICHARD GEVIRTZ]: The measurements we use are the same as everyone else. I’ll tell you an anecdote – it’s a fun anecdote. Paul Lehrer went to Russia; went to visit his son who works for the state department, and there met some people doing some of this heart rate stuff. They had kids breathing very slowly and improving their vagal tone in front of computers in St. Petersburg. He couldn’t understand why that would work because it seemed like it would kill them if they had asthma. These are all asthmatic kids – but they were getting better.

He tried to understand that better and eventually that led him to a guy named Evgeny Vaschillo, who was the cosmonaut physiologist. He was observing heart rates and respiration rates in the cosmonauts. By some chance, one of the cosmonauts was a bit of a meditator and every day in space he would suddenly see these patterns of heart rate that were completely unusual. Big peaks and valleys, very slow big peaks of waves and valleys. Again, he called up and thought the guy was dying or something, and he said, “No I’m just meditating.” So, luckily he was also an engineer and a physiologist and he began studying these patterns.

At the same time, we were doing the same thing, but we didn’t quite understand it. But he helped us understand that at certain slow breathing rates there is a resonance produced in the cardiovascular system, between several different oscillatory systems. The main one is called respiratory sinus arrhythmia. It’s like a brake accelerator and every time you breathe in, the brake goes off; when you breathe out, the brake goes on. If you think about it, it makes sense: the brake goes off, heart rate speeds up; when the brake goes on, heart rate slows down.

Why wouldn’t you want heart rate to be speeding up when you have oxygen available for gas exchange, and then when you’re breathing out, there’s no oxygen available? Actually it saves you something like 350 million heartbeats over a lifetime. This rhythm is called respiratory sinus arrhythmia, RSA, and it’s a normal pattern that we can see in a normal resting heart rate. But when you breathe somewhere between four and a half and seven breaths a minute, that pattern becomes greatly exaggerated.

What Vaschillo figured out, and we’ve built on, was that at those rates, you’re getting the phase angle between the baroreceptor, the blood pressure rhythm in your body, and the breathing rhythm in your body at exactly a 180 degree phase angle. What’s happening is you’re breathing in and heart rate is going up, then it’s going up even further because blood pressure is at the exact right angle for blood pressure to go down to make heart rate go up; and then when you breath out, the opposite happens in the other direction. So, these unexplainable shifts in the cosmonaut, where it was going from 65 beats a minute to 95 beats a minute in each rest cycle – giant peaks and valleys.

[DAMIEN BLENKINSOPP]: So you can’t get that by – people would think based on the description you gave – I breathe in and it goes up? So I can’t take a really, really big breath, hold it for 20 seconds and breath out, and get a higher peak and trough.

[RICHARD GEVIRTZ]: No because the timing isn’t right. It’s like a metronome, and you have to push on both ends of that metronome to make those big peaks and valleys. You’ve got to get exactly the right pace to do that.

There is an artifact in there. When you breathe more deeply, you do produce an artificial pressure that does affect the heart a little bit. It’s not really the one we’re interested in. We’re interested in what happens during restful breathing at certain paces. That’s where the benefits seem to come. In fact, the danger of really deep breathing is people hyperventilate and then that has negative effects on them. So we really try to prevent hyperventilation at all costs.

It turns out that everybody has their own unique pace, where breathing in and breathing out at that pace produces the biggest peaks and valleys, the exact right phase angle between respiration and heart rate, and when you go into that particular rhythm, it seems to have tremendously beneficial effects. Again, we often see this as a brand new idea that’s 2500 years old because this is exactly what these yogis were doing.

These yogis have remarkable cardiovascular systems. None of them are hypertensive – we’ve never found one that’s hypertensive. If you take them to high altitude, none of them get altitude sick. A colleague Luciano Bernardi, a cardiologist in Italy – it’s a funny story – he went to Bangalore and found twelve yogis and got them to agree to go up to high altitude. The first thing he found out is that yogis are prima donnas, they wanted to be pampered. He thought they were going to be really stoic and not care what material – no, they wanted a certain kind of cot, a certain kind of food. So as they drove up to the Himalayas, the Italian crew was all getting altitude sick, having a tough time, and these guys are just complaining about the food!

We realized that what they’re doing is they’re strengthening the baro reflex tremendously, by 30 percent. Practicing every day, you strengthen this reflex in the cardiovascular system that has really powerful benefits for cardiovascular health, and that’s why they all have fantastic cardiovascular health because they breathe tons of time at these slow breath rates. They also do other breathing techniques too, but they do – do this as well.

[DAMIEN BLENKINSOPP]: Are there any studies on heart disease, cardiac issues in yogis?

[RICHARD GEVIRTZ]: These yogis don’t have heart disease, but of course they’re also vegetarians, who knows.

[DAMIEN BLENKINSOPP]: Right, there are other co-factors.

[RICHARD GEVIRTZ]: Yeah, lots of factors, but it’s unknown in these people that do this. There is a lot of evidence now in cardiac rehab that people that get a lot of vagal stimulation – nowadays the big money is in vagal nerve stimulators – that’s healing to the heart. There’s a study at Cleveland Clinic where they’re using the HRV biofeedback instead of left ventricular assist devices for people who are getting a transplant, and when they harvest the heart for the transplant, the old heart is much healthier than they would have expected. It’s well known that vagal input to the heart repolarizes the cells and is healing to the heart and overloading sympathetic system is very detrimental to the heart.

[DAMIEN BLENKINSOPP]: I don’t know if you have done studies, but we tend to be higher sympathetic basis? Everyone talks about it but I was just wondering about the studies and if we’ve actually looked at that?

[RICHARD GEVIRTZ]: The more chronically stressed your life is, the more sympathetic dominance there is. That generally plays out in poor cardiovascular health. The veterans coming back from the Gulf Wars have horrible looking cardiovascular systems. They look like they’re 70 years old – and they’re going through 18 months of chronic stress – and that’s really bad for your heart. So there are efforts underway to try to teach them techniques to prevent that.

(0:26:54)[DAMIEN BLENKINSOPP]: Coming back to the metrics you’re using.

[RICHARD GEVIRTZ]: The metrics don’t apply anymore when you’re doing slow breathing, that’s a hard thing for people to understand. So when you’re breathing normally, you want most of the activity to be in the high frequency – between 12 and 20 cycles per minute. That’s what’s called high frequency HRV. But when you’re breathing slowly, you’re purposefully moving out of that, into a lower frequency range. At rest, a low frequency range is indicative of poor vagal tone and high sympathetic activity, but when you’re breathing slowly, you’re artificially moving into that period of time during that slow breathing.

It’s like any kind of exercise. If you measure someone’s physiology when they’re exercising physically, they look like they’re quite sick during the exercise – their heart rates are flying high, they’re sweating – but, of course, we know that when they stop, then everything gets more resilient and more fit. The same thing is true for the autonomic nerve system. This is a kind of exercise for the autonomic nervous system. On a regular basis, you produce quite a lot of resilience, flexibility and health in that system.

The metrics fall apart completely when we do the biofeedback. We have to completely ignore them and start looking at a different sort of metric then. So then what we want is actually all the activity in the low frequency range, which is in the four to seven range. The activity we look at, there’s one known as meditator’s peak in that range – it’s a single peak of great magnitude in that low frequency range. If that was your normal breathing, that would be a sign of ill health, but during this slow breathing, it’s a sign of accomplishment, of being able to do the technique.

[DAMIEN BLENKINSOPP]: So it’s a specific frequency? Basically, nearly all of your heart beats are within this specific frequency range?

[RICHARD GEVIRTZ]: It’s exactly where you’re breathing. Let’s say you’re breathing in five breaths a minute, then it will be a little less than 0.1 Hz. If you’re breathing in at six breaths a minute, it will be exactly 0.1 Hz. If you’re breathing in seven, it will be a little bit higher than that, or something in-between those. That’s exactly what you see – breaths dominate that peak and then you want that peak to be the exclusive peak in the heart rate, and as high as it can be, during slow breathing.

[DAMIEN BLENKINSOPP]: Does it matter exactly where it is?

[RICHARD GEVIRTZ]: Yeah, for each person it matters because they have to find their resonance frequency. What heart math calls the point of coherence, we call resonance frequency. We think coherence is not exactly the right word because it means two things going together. It is two things aligning together – breath and heart rate – but they don’t measure breath, so we think really what you are doing is producing true physical resonance in the system between the baroreceptors and the breathing rhythms, and that’s where the big benefits come during that slow breathing.

[DAMIEN BLENKINSOPP]: Is it different for different people?

[RICHARD GEVIRTZ]: Yeah. We get some people at four and a half breaths a minute, that’s where their peak is; some at five; some at five and a half; some at six; some at six and a half; some at seven. We’ve done various studies to see where the frequencies are. They tend to be in the five and a half to six range for most people. Smaller people tend to have a little bit higher frequencies, very tall people have lower ones – it’s like a violin versus a cello, with different resonances. That’s not a perfect relationship.

What we do in the biofeedback is we test at every breathing frequency. With the other systems, what you do is just trial and error to try and find something that produces the most coherence. We actually systematically don’t do that; we systematically go through in some order. I like to start at seven and we do a few minutes of breathing at seven, then six and a half, then six. At some point, the pattern falls apart – it’s too slow – so we go back up another half beat until we find somewhere within a half a beat of the proper frequency for that person.

[DAMIEN BLENKINSOPP]: Where they’re getting their highest peak and trough?

[RICHARD GEVIRTZ]: Exactly, and the phase angles are correct, and it’s also the one with the smoothest heart rate patterns. That does show up – at our school they’re using a seismograph just to look at the pulse beats, but I think it does hold up that the smoothest, biggest peak-valley differences is usually where it will be.

[DAMIEN BLENKINSOPP]: Does that work with smooth breathing as well?

[RICHARD GEVIRTZ]: Yes, and we try to teach diaphragmatic breathing – smooth, restful, diaphragmatic breathing works better. If you overdo it, you hyperventilate and then you lose the effect. If you can breathe with your diaphragm, it’s much easier to breathe more slowly if you actually get your diaphragm in the action.

[DAMIEN BLENKINSOPP]: I think some people would know the heart math device, the M wave, already, in a sense, because that’s very consumer focused. With that one you have a score – basically, you get to 11, 16, if you’re getting higher. So mapping that to what you’re saying is the higher the S-score just the higher the peak and the trough.

[RICHARD GEVIRTZ]: Yes, well, what they do is actually measure the frequencies and then they take the low frequency that’s in the range of their breathing divided by all the other frequencies, so it’s just a percentage of activity in the low frequency range, which correlates very highly to the peak-trough difference as well.
(0:32:25)[DAMIEN BLENKINSOPP]: I see. If we compare that to what you do, do you use a specific device or devices?

[RICHARD GEVIRTZ]: Yeah, so we use one of many different biofeedback devices. The advantage we have is we measure four channels usually or five: we measure heart rate beat-to-beat, based on EKG not a PPG. So you can either do it based on a pulse – the problem with a pulse is that you have to decide when the pulse starts and stops – versus an R-wave of an ECG, which is a very distinct event to start and stop the clock. If possible, it’s good to use an ECG, which we do. So we use beat-to-beat heart rate, we use respiration – we have strain gauges for respiration. We look at finger temperature and skin conductance – that’s sweatiness on the palms of your hands. All of those are useful indices for what’s happening.

If you can, the devices that just use the single channel heart rate – the emWave, MyCalmBeat, a number of other ones that are out now–are fine, they work, but it’s certainly not as good an information as if you’re using devices that have the four channels.

[DAMIEN BLENKINSOPP]: Right. So you’re using clinical machines?

[RICHARD GEVIRTZ]: Right. But some of those clinical devices are getting down into the 600-700 dollar range now. The ones we use range from about 3000 dollars to about 11,000 dollars.

[DAMIEN BLENKINSOPP]: Very clinical!

[RICHARD GEVIRTZ]: That’s not for consumers. But, there are a number of devices now that are coming out that are going to be with those four channels, that will be ECG, that will be in the 600-700 dollar range. But for everyday people, the emWave device that really works well is the Inner Balance, the one that runs off an iPhone. It’s a beautifully designed device and you can have it on an iPhone and it’s tremendous to manage.

[DAMIEN BLENKINSOPP]: Yeah, because it’s convenient.

[RICHARD GEVIRTZ]: It works well but you’ve got to be sitting in front of a PC, which is a big difference, but it’s cheap and it works well.

[DAMIEN BLENKINSOPP]: I’ve had both the emWave and the Inner Balance – is it Inner Balance or the Inner Sense?

[RICHARD GEVIRTZ]: The Inner Balance is a Hearth Math device; it’s the one that goes on the iPhone. The other Heart Math ones either run on a PC or they have a handheld stand alone.

[DAMIEN BLENKINSOPP]: I find it so much more convenient, I basically keep it in my jacket pocket. I’ll be on a train or anywhere where I’ve got a bit of free time and I’ll just pop it on.

[RICHARD GEVIRTZ]: Right, absolutely. There are also some free apps. What we do usually is we don’t advise people to buy those devices because we find their resonance frequency with our instruments and then we give them one of three or four different ways of practicing at that pace.

MyCalmBeat has a free app for pacing. There’s another one we like called Breathe2Relax – these are free apps – or there’s a musical pacer, that does cost some money but it’s very nice, called Breathe Sync. It has five different musical tracks at your particular pace, so we have a separate CD for each person. We let people choose the ones they want, whatever is the most convenient. It’s really important that it’s something they can practice with.

[DAMIEN BLENKINSOPP]: So this isn’t biofeedback – this is once you have done the biofeedback, you’re just giving them the timer?

[RICHARD GEVIRTZ]: Exactly. And some people just count. I can do it now – I’ve done it enough that I can get exactly to my resonance frequency pace just by counting.

[DAMIEN BLENKINSOPP]: And then you become like a yogi basically, you’ve just learned a lot quicker to do it.

[RICHARD GEVIRTZ]: Yeah, I learned to do it but I don’t do it hours a day so I’m not quite like a yogi. I do it ten minutes a day.

[DAMIEN BLENKINSOPP]: Is there any danger of overdoing this, like if you did too much of it?

[RICHARD GEVIRTZ]: Not that we know of. Some people do get anxious when they try to do it, but usually that only takes a bit of practice until they get out of that. As far as we know, there doesn’t seem to be any ill effects of this, but people have worried about it and perhaps overstimulating the parasympathetic system. But it doesn’t really do that – it just gets you better balance in the system.

[DAMIEN BLENKINSOPP]: Right. Because when you said it was like exercise, like hormesis in a way, right? I’m just wondering as we can overdo exercise.

[RICHARD GEVIRTZ]: Well, the yogis are the ones who overdo it. They breathe many hours a day and they don’t seem to be in bad shape from it. I don’t know. There’s tens of thousands of the emWave devices that have been used and I’m sure some people must overuse them, but I know of no reports of any really ill effects of it. There might be but I don’t know.

[DAMIEN BLENKINSOPP]: It sounds like a very simple approach you have, just covering a slightly low and a slightly high and then just finding the optimum by moving around by testing. One of those devices – the 600-700 dollar ones – are there any names of those that are coming out?

[RICHARD GEVIRTZ]: The two companies that make them, they’re not quite out yet, they’re coming soon, one is J&J Engineering, which has a new device coming out in that range that will do those four channels, but it’s not a portable device – it’s a PC device. The other company is called Thought Technology, that’s a big biofeedback company. They’ve got a little device that’s coming out that’s a fingertip PPG, just a pulse amplitude but it also measures temperature and skin conductance, and it bluetooths it to a tablet. Then it has an accelerometer so you can put it on your chest and it will also give you the breaths measurement. So those two are in that range of price and they’re coming out fairly soon. I think one is out but not with all the channels yet, so I’m not sure where they are exactly.

The other company that doesn’t have a cheaper one yet is called Nexus, a Dutch software package. Thought Technology and Nexus have very expensive systems, but they do many more things than that – they do all kinds of bells and whistles.

J&J is a bit cheaper, it doesn’t have as many bells and whistles, but they also have a 3000 dollar device that measures many channels as well, but it doesn’t have as many displays, so probably for the consumer, none of these are of interest.

I’d say right now, the consumer device that is far and away the best for portability, is Inner Balance from Heart Math. They’ve mastered some things that nobody else has mastered. That system seems to work extremely well. I have yet to find someone that doesn’t get an adequate pulse from their earlobe, whereas we used to get a lot of problems with pulses and not everybody could get a good pulse.

[DAMIEN BLENKINSOPP]: The only problem I’ve ever had with – I think it was the emWave – was I was living in Spain – very, very bright sunlight – and if I was in the sun, it wasn’t working. I had to be in some kind of shade. That’s the only thing I ever came up with.

[RICHARD GEVIRTZ]: That’s true for any of the PPG devices. I haven’t ever really tried it in a really bright sunlight. So those are the devices, but we’re not sure that people need to spend the money on those things if they can figure out what their pace is and then just practice on a regular basis. Twenty minutes a day is ideal but people will practice ten minutes a day.

[DAMIEN BLENKINSOPP]: What are other ways? If I don’t want to buy the device, do some physicians have these kits or some other kind of specialist, so I could basically go for a session? I don’t know how long it takes to do this, an hour or something, and they would figure out my perfect?

[RICHARD GEVIRTZ]: Yeah, there’s a guy near you in St. Albans at the Open University who does it. There are people around who do this. We do a lot of trainings with people all over the world. I was just in Rome training people from all over Europe, so there are a lot of people who do this. And probably even more people who aren’t very well trained but who have the emWave devices who probably give close to enough to be quite beneficial.

[DAMIEN BLENKINSOPP]: For you, would it be worthwhile one session even if you’ve been doing emWave? Would it be worthwhile doing one session? It depends how extreme we are about these things.

[RICHARD GEVIRTZ]: Well you know what, it’s very convincing when you see it on the screen. So even if you were able to get exactly the right pace yourself, seeing the actual physiology change is amazingly persuasive.

With our clinical clients, we take a baseline at normal breath rates and then show it to them again after they’re done with the training, and they get emotional. They’re seeing that their physiology really has changed; their baseline physiology has changed dramatically over the course of six or seven weeks of training. That’s one big advantage of it.

[DAMIEN BLENKINSOPP]: And, of course, you’re cross-referencing lots of different data, so you’re seeing the change across the whole body. Is there ever a case where you see the change in just the EKG and you don’t see it in the other areas? Are you cross-referencing that data or is it more just to make sure?

[RICHARD GEVIRTZ]: We do cross-reference it with fingertip temperature and skin conductance. Sometimes we don’t get those, that’s true. Sometimes they don’t click and that may just be they’re being nervous in the session or something while we’re measuring them. And some people get very small changes in heart rate variability, especially older people. It’s actually a very small quantitative change, but they seem to get the same clinical benefits.

As we get older, those peaks and valleys definitely go down. Even if you’re quite fit – I’m a bicyclist, I ride 110 miles a week. I’ve been monitoring mine for twenty years – it’s going down despite my best efforts.

[DAMIEN BLENKINSOPP]: Even with all the training. So you’re not able to get the same peaks anymore?

[RICHARD GEVIRTZ]: Right. It used to be 15 – the value of the peak for me, 16. Now it’s 11, it just little by little by little it goes down. But, the good news is that in terms of the clinical benefits, it doesn’t seem to matter, as long as you’re training at that right frequency, you seem to gain the clinical benefits of it. It doesn’t necessarily mean you’ll live forever, but it seems to help with a lot of parameters.

[DAMIEN BLENKINSOPP]: So that’s similar to RMSSD, which declines over age as well.

[RICHARD GEVIRTZ]: Exactly, and that’s exactly why it does. Any of those indices would be measuring somewhat the same thing.
(0:42:31)[DAMIEN BLENKINSOPP]: So you spoke about people doing this for a number of training sessions. For someone wanting to do this, how long would it take? What’s the typical protocol you’d put them through to learn when you take them on?

[RICHARD GEVIRTZ]: We need one session to make sure we have the right frequency. Then we send them home with the practice techniques, any of the ones they want. Then they come back the next week and we just make sure we’ve got everything right, because sometimes one week of practice will change it a half a beat and we want to just fine tune it. Some people are very sensitive to that, others are not. The rest of the time is depending on what they’re coming in for, so if they’re athletes, we now start to use some sports psychology to integrate it into sports psychology.

I work with a lot of rhythmic gymnasts who get very nervous before they go on – those are the ones with the hoops and the clubs, that funny sport; these are little girls basically and they get nervous.

[DAMIEN BLENKINSOPP]: You mean they’re quite young?

[RICHARD GEVIRTZ]: Yeah they’re 11 or 12. The coaches are Bulgarian usually.

[DAMIEN BLENKINSOPP]: They’re quite tough on them.

[RICHARD GEVIRTZ]: So we teach them the technique, they come back, make sure they have the technique–these kids are fantastic at it, they get giant peaks and valleys. They’re so fit and good at this stuff. Then we sort of integrate it into the cues in their routine where they tend to get nervous, pairing them together with some sort of sports psychology intervention, so that might take a few more sessions.

[DAMIEN BLENKINSOPP]: Are you getting them to trigger it at just the right moment where they would normally get a bit more anxious, but you trigger it just before something?

[RICHARD GEVIRTZ]: Exactly, and we have to work out how to do that. But for somebody who just wanted to do it for their own benefit, we probably could do it in two sessions, as long as they keep practicing, they’d do very, very well.

[DAMIEN BLENKINSOPP]: So they come back for a session of half an hour, an hour?

[RICHARD GEVIRTZ]: They come back for an hour. That’s what our standard session is, but we usually talk about other things during that hour. We also want to get a baseline again and so we try to distract them and just get them breathing normally. One of the problems is that if people don’t breathe normally, you can’t get an adequate baseline from them. So if they breathe slowly, it messes up their RMSSD data. It messes up all their data, so suddenly they don’t have any high frequency data. You have to make sure they’re breathing at their normal breathing pace when you’re getting baseline or follow-up data, and then when they do the slow breathing, then that changes everything.

[DAMIEN BLENKINSOPP]: Right, just to make sure you’re comparing to that – you’re getting a real control basically.

[RICHARD GEVIRTZ]: Exactly.

[DAMIEN BLENKINSOPP]: This is how they are in real life or this is how they are just before they’re going to compete, in the other example.

[RICHARD GEVIRTZ]: Yeah.

[DAMIEN BLENKINSOPP]: So would you give them a heart strap and monitor their athletic when they’re actually doing it?

[RICHARD GEVIRTZ]: We do do that, and that would be just for research purposes. We don’t do it for them. They’re not usually allowed to have that in a real competition anyway. It depends how they are, and it depends on what we’re doing.

Another application that’s not biofeedback but it’s an interesting HRV technique is for detecting over-training. FC Barcelona has got Leo Messi every morning doing five minutes of heart rate variability measurements, right in bed in the morning, and the training director monitor that. When they see dips in heart rate variability, they decide that it’s over-training and they ease up his training protocol. So if he has a couple of games in a week, they’ll monitor that and try to see, because over-training generally produces poor performance.

[DAMIEN BLENKINSOPP]: Absolutely.

[RICHARD GEVIRTZ]: So that’s catching on like crazy. The sports psychologists are so competitive- if anybody gets anything, they all do it, just immediately.

[DAMIEN BLENKINSOPP]: They see it as a competitive advantage. I was thinking, you said they’re not allowed to wear those during competitions. Well I can understand why – if you’re getting biofeedback, it’s kind of like cheating. I don’t know if it’s cheating but you’ve got a competitive advantage.

[RICHARD GEVIRTZ]: Could be, yeah.
(0:46:33)[DAMIEN BLENKINSOPP]: What’s the performance benefit of being able to put yourself in this restful state? Say I’m just about to compete; is there a study showing there’s a performance benefit or another benefit, or is it just keeping their mental focus?

[RICHARD GEVIRTZ]: Yeah. It has to be for sports that are single action kind of sports, so golfing, gymnastics, baseball hitting, cricket batting, possibly penalty kicks in football; things like that. For aerobic sports, there’s no parasympathetic at all – they’re all in the aerobic range. It probably doesn’t make much difference for those, although it gives them a little bit of a psychological edge – it’s hard to detect the benefits there.

For baseball, one of my former students is in whole practice dealing with Major League Baseball players for hitting, because you’ve got a split second to make up your mind. The ball is coming at 95 miles an hour, and you have to be in exactly the right arousal level to be able to flow through that swing. It’s a way of getting an optimal flow state in things like that. Also in dancing and music, there’s a guy in London, John Gruzelier, who does it with dancing and music and combines it with brainwave feedback, and gets benefits for recitals and dance performances and things like that.

[DAMIEN BLENKINSOPP]: So it sounds like it’s eliminating nerves, is that the application?

[RICHARD GEVIRTZ]: Well, trying to get people into their optimal – to try to get them from over-aroused to the medium level. There’s a famous curve called Yerkes-Dodson Law, which is an inverted U-shape and the y-axis is performance, on the x-axis is arousal. Imagine an upside down U – people do the best in the middle, too high or too low isn’t good. We don’t want them to be relaxed, we want them to be psyched, but if they’re over-aroused then opposing muscles don’t work well, they began to get a certain choking mentality, they start thinking “What if I screw up?”, things like that.

[DAMIEN BLENKINSOPP]: I don’t know if you know about the science of flow and the books around flow. I can never pronounce the guy’s name, it’s very long and complicated – Csikszentmihalyi.

[RICHARD GEVIRTZ]: We think that we’re trying to go for the same thing. But it turns out, I was just at this conference in Rome and there were a lot of sports psychologists. One of the points they made, and it’s actually rare for athletes to be in the flow state during a performance, it’s definitely the ideal. These are people dealing with Olympic athletes, the most elite athletes in the world, and their experience is that maybe ten or fifteen percent of the time they actually get into their flow state. Now they’re saying the important part is if you don’t get into the flow state, don’t panic and go into the complete opposite quadrant where you’re really choking completely. But work on getting through the routine and the best arousal you can. That’s the first I’d actually heard that – I thought it was pretty interesting.

[DAMIEN BLENKINSOPP]: Right, so that’s more like limiting the downside, or focusing on not getting the troughs?

[RICHARD GEVIRTZ]: Exactly. There’s a guy working in London with FC Chelsea doing that, Tim Harkness. Chelsea has got a big room full of expensive biofeedback equipment, called “the Mind Room”. He works with all these multi-millionaire players. So it’s interesting to see.

Try to be self-observant, non-judgmentally observing your thoughts and breaths as you do it
[DAMIEN BLENKINSOPP]: One of the things I’ve done with Heart Math – you can tell me if this fits with exactly what you said – is I’ve tried many things to get my peak higher, of course, and get my highest score. I do think that what you’re doing with your mind seems… For me personally, I’ve had the biggest peaks and troughs over time by actually focusing on the wave in the device, so just watching the wave go up and down and then I breath at a specific point in that curve, which I found works for me.

[RICHARD GEVIRTZ]: Yeah, and I should have said that, so for some people, we don’t use the pacing at all – we do exactly what you do. We just show them their heart rate and respiration, we have the advantage of one more channel for them to look at, because you can see their breathing.

[DAMIEN BLENKINSOPP]: When you say one more channel, what would that be showing?

[RICHARD GEVIRTZ]: It’s showing a wave form of breathing, just a nice, smooth wave form of the breathing rate – so when you breathe in, it goes up; when you breathe out, it goes down.

[DAMIEN BLENKINSOPP]: In addition to the heart?

[RICHARD GEVIRTZ]: It could be smooth or jumpy and you want it to be smooth.

[DAMIEN BLENKINSOPP]: Right.

[RICHARD GEVIRTZ]: We would say exactly the same thing for a certain percentage of people: just make those two go up as high as they can, and down. Some people absolutely prefer that, they get their best results. I think partially because it takes away any performance anxiety, you’re just trying to match it as opposed to trying to breathe to a pacer. Some people really have a hard time breathing to a pacer, so we absolutely leave that as an opening – just do that, kind of thing.

We do try to promote a mindful mental set as well, so we try to say, “Try to be self-observant, non-judgmentally observing your thoughts and breaths as you do it.” I think there are some real benefits to doing that. I’m not sure it shows up exactly in the heart rate patterns, as we said earlier. I think that remains to be seen. If it does, it’s a pretty subtle difference.

[DAMIEN BLENKINSOPP]: If I started thinking about something stressful, like work, some problem I had at work, would that tend to put me off or would you think that would have a minimal impact compared to breathing, as long as your breath remained the same?

[RICHARD GEVIRTZ]: Right. It probably would be very hard to see as long as your breath stayed exactly in that same pattern. Oh, of course, it might interfere with your breath pattern too. Then you’d see it for sure; but if you maintained your breath pattern exactly the same, you’d probably have a very hard time seeing very much in there. Whatever it is – is subtle. If there is something to that, it’s probably quite subtle.
(0:52:35)[DAMIEN BLENKINSOPP]: What do you think about the connection between the brain and the breathing pattern in this case? By taking on this physiological breathing, do you think it will naturally affect the brain? I don’t know if there’s any research related to that, that it will put you in a different state of mind as well, as long as you maintain that.

[RICHARD GEVIRTZ]: We’re working on that now and we’re definitely finding pretty dramatic effects. Eighty percent of the vagal fibers are afferent – they go from the heart to the brain; only 20 percent of them are efferent – from the brain to the heart. This is something Heart Math has definitely pointed out and we agree with them on this completely, and it’s interesting. So the brain is listening to the heart more than the heart is listening to the brain, which seems counterintuitive. But they’re both part of a central autonomic system that integrates frontal lobe and some limbic system activities into the brain function. So really, it’s silly to treat them as separate systems – they’re an integrated system.

It appears that this technique has a powerful effect on the vagal afference going into the brain, so the brain states are quite dramatically affected. We recently published one study, and we’re just about to publish another, where we look at a brain wave called an evoke potential, it’s a very short – just for 800 milliseconds, and you do it for repeated stimuli. In this case, we take the filters off. Usually when they do EEG, you put a big filter on to get rid of that R-wave and the heart rate, because it messes up the EEG. But we take that off and let it mess it up, and you can see a very giant spike in the EEG for every heartbeat. Well there’s another wave that comes right after that – 250 milliseconds after. It appears to be the brain processing the information from the heart and it’s called a heart period evoked potential.

We measured that during positive emotions, negative emotions, baseline, slow breathing and resonance breathing. Resonance breathing had by far the biggest effect on it. Negative emotions did diminish that wave, so if your brain is busy thinking about the worst thing that ever happened to you, it doesn’t pay attention to your heartbeat anymore. During the slow breathing we got a dramatic improvement in this processing of the R-wave. It also correlates with people’s ability to be able to detect their heartbeat. There are some German studies that had people try to guess what their heart rates where. They were much better at it if they had that big wave at the 250 milliseconds.

So yes, I think the other powerful part of this is that we’re bombarding the parts of the brain that I think are beneficial to us with a very positive wave form – it goes up into the frontal cortex and the part of the brain we think that controls depression possibly – and this would be the basis for the claims of positive mental states coming from the heart rate itself. I think there’s a lot to that – we’re continuing to do more research on that. The results we got from both studies were very dramatic.

[DAMIEN BLENKINSOPP]: You mentioned a few use cases. What are the other most beneficial use cases that you have been working on over the years and you feel like the best applications for it are?

[RICHARD GEVIRTZ]: We mostly focus on autonomically mediated disorders, which are giant amounts of medical disorders. That would be things like functional gastrointestinal disorders like irritable bowel syndrome, reflux, functional abdominal pain, diarrhea, constipation. Those are massive familiar disorders and they’re greatly affected by the autonomic nervous system. There’s actually an institute right there in London, Wingate Institute (it might be a good thing for one of your podcasts actually), where they actually look at esophageal pain thresholds, with a nasal tube down the throat, and how they’re affected by autonomic function. They’re dramatically affected, and slow breathing changes the pain thresholds: it protects you from lowered pain thresholds. That probably is the low-hanging fruit in terms of applications.

We see about 15 kids a week with functional abdominal pain from our children’s hospital and we get tremendous results with those kids.

[DAMIEN BLENKINSOPP]: Is it therapeutic or is it just lowering the pain?

[RICHARD GEVIRTZ]: No, it’s therapeutic because the functional abdominal pain is actually caused by an imbalance in the autonomic nervous system. There’s no pathology that’s detected, these kids have been scoped, there’s nothing wrong they could find, but your gut needs a lot of parasympathetic input to function, and if you take that away… The kids that get this are all “internalizers,” they’re a little bit anxious kids – they’re great kids, they’re achievers, but they tend to be a little bit nervous, they worry about getting into a good university in third grade and things like that.

[DAMIEN BLENKINSOPP]: The famous insecurity overachievers.

[RICHARD GEVIRTZ]: Yeah, they’re lovely kids to work with, we love them, and they do very, very well. Adults don’t do as well but they still do well.
(0:57:55)[DAMIEN BLENKINSOPP]: You mentioned IBS as well. I think this is becoming a lot more common these days, a lot of people are getting these kinds of conditions and gut issues. Is it therapeutic also for those areas? Because a lot of people talk about probiotics, the microbiome, gut lining damage, gluten intolerance and all of these kinds of things related to these disorders, so I’m just wondering if you have had therapeutic benefits there.

[RICHARD GEVIRTZ]: Yeah, the relationship between the biome is complicated. I don’t think we know it, but it is definitely a parasympathetically connected system. We’re not quite sure whether we’re correcting it or whether it corrects us. The problem is the probiotics – there was a Cochrane Review on probiotics – apparently they are not near enough probiotics to have much effect, to really change the biome. But the biome definitely affects the brain, there’s no doubt about that, and probably through the autonomic nervous system. In fact we know it does through the vagal afferent system. So I think in the future, we will be pairing up with better techniques for improving the flora of the gut with these kinds of techniques that we use.

[DAMIEN BLENKINSOPP]: To kind of come at it from two different angles.

[RICHARD GEVIRTZ]: Both ways, I think that would be quite powerful.

(0:59:09)[DAMIEN BLENKINSOPP]: So you are seeing a permanent improvement in these cases, like IBS and stuff? But do they have to keep up the practice in order to maintain it?

[RICHARD GEVIRTZ]: We thought they did but then we did a follow-up and we asked them more in-depth questioning, and it turns out they just use the technique whenever they feel symptoms coming on – they don’t actually continue to practice very often. Some kids do, but a lot of them said, “Oh yeah, I keep on practicing,” and we asked them, “So what does that mean?” and they said, “Well, whenever my stomach gurgles, I do my slow.”

[DAMIEN BLENKINSOPP]: Okay, but that’s a good thing. That means that there is something that you’re fixing, basically, and so you don’t have to constantly – just maintain the practice in order to maintain it.

[RICHARD GEVIRTZ]: The kids with these disorders are at much greater risk for adult IBS – a lot of studies show that. We don’t know if we’re preventing that risk, but we think we are. We’ve had some five or six year follow-up with some kids and they seem to be doing just great at that point, so hopefully that will move on through their lives to be quite beneficial.
(1:00:01)[DAMIEN BLENKINSOPP]: Are there areas that you’ve looked at where it wasn’t effective? You mentioned depression – has it been effective in those kinds of neurological things?

[RICHARD GEVIRTZ]: I didn’t think it would be, but my students wanted to try it – I have a lot of doctoral students and we keep on consistently seeing beneficial effects on depression, probably through that vagal afference system. We are consistently seeing that and we’re doing more studies, and I think every study so far has shown a beneficial effect on depression. Sometimes they’re combined with psychotherapeutic techniques – in most of the studies they are. In one study they weren’t, they just did nothing but the biofeedback, and they got improvements, though there was no control group in that study. But the other studies, they are just adding it to cognitive behavioral therapy or one of the mindfulness-based therapies, and it seems to add a definite benefit to it.

In one study in China, they compared just slow breathing, without finding the right frequency, to finding the right frequency, and the frequency finding had better results than just slow breathing, even though that did help.

There are some indications that technique specifically might be beneficial. It probably is no more helpful than palliative techniques for chronic pathology like nerve pain, probably not very beneficial for people with Crohn’s or chronic IBD, inflammatory bowel disease. There is possibly an effect on the inflammatory system. There’s a guy called Kevin Tracey that has traced this cholinergic immunological system. There’s a lot of interest in that now, but we have not been able to show yet that it has any benefit on immunological function, but it may be.

There’s research coming out now that is indicating it might have an effect on one part of the immunological system. There’s a vagal part of that system that may help, and if it does work, it would probably be that it would be helping the system from going bonkers. Sometimes people’s immunological system turns on and doesn’t turn off again – autoimmune diseases – and nobody knows quite why that is, but it looks like strengthening this vagal system might prevent that. That would be that it might help to reset it; there are some claims of that. I would say the evidence is just beginning now.

Other disorders, it doesn’t seem to help for atrial fibrillation for some reason, that’s kind of a nerve induction of the heart itself. Pacemakers aren’t involved. At my age, all my friends are getting atrial fibrillation. I’ve tried it on all of them and it doesn’t seem to help very much. Then there are probably a number of physical disorders that it doesn’t really help. If it’s an autonomically-mediated disorder it seems to be quite effective.
(1:02:52)[DAMIEN BLENKINSOPP]: I guess what we haven’t spoken about is people’s emotional happiness and things like that. Are there any evidence that it improves satisfaction or happiness or stops angry outbursts?

[RICHARD GEVIRTZ]: Yeah, we have a couple of studies that show it helping with urge control. The pathway back up into the brain seems to go through the places that have inhibitory neurological control of emotion, so we have some reason to believe that if you can improve those inhibitory circuits, that would help a lot with anxiety, help a lot with urge.

We’re doing one now with smoking, people who are in smoking cessation programs, to try and help them with their cravings. There’s a food craving study that showed benefits for food craving and we’re doing another one of those right now actually. So there’s some reason to believe it might help with some of those kind of impulsive urge kinds of things.

I’ve used it with clients with anger control and they’ve reported the results, but there are no studies that I’ve seen, so it may be helpful for anger control. But we don’t just do it alone; we always combine it with a lot of other techniques. It’s going to be hard to show that by itself it’s a beneficial technique.

Heart Math has all kinds of studies on stress, self-reported stress, and self-reported life satisfaction that always show benefits but it’s hard to know how much of that is placebo and how much of that is the actual technique. I think it helps people, but the studies are hard to do and it’s self-reported – you have to put in a sham control of some sort to make them think they’re getting something that they’re not – but it’s hard to do those.
(1:04:30)[DAMIEN BLENKINSOPP]: Right, that is hard. Have you seen anything with cortisol levels or something like that, hormonal?

[RICHARD GEVIRTZ]: There’s a little bit of data in burned out cortisol patients with long periods of rehab – they do better. But there again, we don’t just do that, we do it with integrated exercise, with activity management, with sleep management. Those are the things that all go together in these syndromes and I would never just do the biofeedback. But biofeedback is the part they like the best.

[DAMIEN BLENKINSOPP]: There are benefits to that if they’re actually interested in coming into the physician’s office.

[RICHARD GEVIRTZ]: Exactly. We say it’s the “Trojan horse technique” – it gets people in, they don’t resist it. That’s true for a lot of disorders. With veterans we get them in by saying we’re doing biofeedback before we do any psychotherapy with them.

(1:05:16)[DAMIEN BLENKINSOPP]: The part you brought up about resisting impulses, so impulse shopping; we can think about lots of things we do on impulse. Personally, for performance at work and with my businesses and everything, I find that extremely important. Basically, in the morning, if I do some meditation, perhaps do some Heart Math, I do feel more in control and I’m less likely to work on something that is a waste of time for a couple of hours, rather than exactly the right thing that was going to bring the best results. So I find it from a performance perspective to be very, very important.

There’s a big trend in meditation. I also have a device which I can use – I don’t know if you’ve seen this – the Muse. It’s an EEG, you place it on your head and it tells you how calm you are in terms of alpha waves and so on. I’ve used both and I’m not sure, sometimes I’m left wondering “Which one shall I use today?” or “Which one shall I do this morning?”. I’m not exactly sure which one would be the most beneficial, so I’m just wondering if you have any perspective on it, or if it’s worth doing both, or one on one day and one the other day?

[RICHARD GEVIRTZ]: If you hook then both up, I think you would see that your optimal alpha state will come very quickly when you’re in resonance frequency, which to me is much easier to do. But, and I’m interested in your feedback, do you think the feedback on the EEG is as beneficial to you as on the emWave?

[DAMIEN BLENKINSOPP]: I feel like it’s different, honestly. I’m actually using Inner Balance on that now. I used to use the emWave before. With that one, I tested meditating, so I’m doing mindfulness meditation, and I didn’t get good scores in the Heart Math device. However, I definitely used breathing when I’m using the alpha wave thing and it definitely does help. So, it’s interesting, and I’ve heard that from other people using this – if they use their standard meditation, they don’t tend to do well on the Heart Math.

[RICHARD GEVIRTZ]: No absolutely. It’s because you’re not breathing in the low ranges with that. What is your standard meditation, is it a mantra-based one?

[DAMIEN BLENKINSOPP]: I’ve tried different ones. I’ve tried the mantra, and just the breathing mindfulness. The worst I would say, mantra is worse.

[RICHARD GEVIRTZ]: We get nothing from mantra people, even with years and years of mantra work – it doesn’t tend to train their breath. We did transcendental meditation with 30 year meditators and we were looking at brain scans at the same time. They had dramatic effects on their brain scans. Their mantras really affect their [unclear 1:07:45] a lot. But, we saw no effect on their breathing whatsoever, which is sort of good for the scanner because if you change your breath, it changes the BOLD response in the FMRI, which is an artifact. So then suddenly you don’t know what the heck you’re measuring. But in breath meditators, it just seems to vary a lot, so some of them do breath in the resonance range so they absolutely get both going together.

The Muse will definitely teach you how to get into an alpha state, independent of breath. Those are two separate things, so it’s interesting that you say that. To me though, if I hook myself up to an EEG, it’s so much easier for me to get into alpha by just breathing slowly than it is by paying attention to the EEG feedback that I don’t bother with.

[DAMIEN BLENKINSOPP]: Right, because you’ve potentially learnt. I’d love to run them both, but I need two phones because they both interface with the iPhone and you can only run one app at a time, unfortunately. So I’ll have to get an additional phone. It will be interesting to see how that works out.
(1:08:47) The last thing is–we did touch on it just before the interview – there’s a lot of people talking about gratitude types of meditation and empathy and that kind of thing, and that having an impact. How do you feel that connects or it doesn’t connect?

[RICHARD GEVIRTZ]: I think it only mildly connects, but I think it’s an independent, important thing to do. In our clinical training, we start with the biofeedback and we end up with mindfulness-based techniques, that’s pretty much all we do. We don’t do cognitive behavioral therapy at all anymore – the kind we like is called “acceptance and commitment therapy,” ACT. It’s another one of many, and it has a strong compassionate meditation, strong mindfulness component. I think most of those have the same kind of strong component.

I think it’s important for your brain functioning to learn those things. It doesn’t seem to have much impact on the heart rate variability, as we were saying before. I don’t see a ton of impact on heart rate variability and that’s mainly because breath is such a dominant factor in what we’re saying on that screen. As we get more sophisticated, we might be able to tease out some non-linear components or something once your brain is in a mindful state – it should show up somewhere.

The thing right now is like you walk into a room full of people talking loudly and trying to hear someone across the room whisper. It’s hard to pick it out because it’s a small component in the overall picture of heart rate. But, certainly there’s a lot of evidence now from brain scanning type techniques and EEG techniques that people do benefit from repeating it. It’s a skill, it’s very important to know it’s a skill, and the more you practice those mindfulness, compassion and forgiveness type skills. The evidence is strong that for instance forgiveness produces beneficial health outcomes, no doubt about it, and so does compassion. Those are things that we know are beneficial in some ways but probably in somewhat independent channels.
(1:10:48)[DAMIEN BLENKINSOPP]: Great. What’s coming next? You mentioned a few things, so in the future, are there any things you are looking forward to in this area or directions you’re moving in to? You mentioned a couple of things over the period.

[RICHARD GEVIRTZ]: I have a slew of students so we’re all doing this kind of research, so we generally focus on maybe three things. One is just outcome data from heart rate variability biofeedback. We keep on doing studies and trying to see what it works for, and we’ve got a bunch on those going so we’re always looking at how does it work compared to other techniques and compared to other controls, and we tend to get very positive results out of that. I just published a literature review on that and we have quite a number of applications where it looks like it works. We don’t have much big funding so we have to do little small studies – big pharma is not too interested in this technique, as you might guess, as “skills and not pills” is our motto.

The second one is mechanisms, so we make reference to how does it work? What are the other mechanisms here? There’s a whole bunch of new stuff on that. Vaschillo, that Russian guy, is looking at rhythms in the very low frequency range and seeing what happens to the blood pressure systems when you breathe at like three per minute, and there’s some really interesting data coming out on that. We’re trying to understand both psychological and physiological mechanisms of why this works, how does it work – we’re going to do many more studies looking at how the brain is affected.

The third one is, I’ve sort of been dragged kicking and screaming into this by my students, but looking at yoga and trying to standardize yoga and see what are the mechanisms by which yoga works. The other mechanism that I think is important but we have not been able to pin down, is the postures. We know the pranayama component of yoga is very important–that’s what we study, and it’s real easy to study that–but when we look at the postures, the body was evolved for movement so there are massive afferent pathways from muscles back to the brain and we’re quite interested in what are those pathways and how does the movement complement the breathing. The thousands of years of looking at movement-breathing complementarity – there’s probably something to it, but it’s very hard to study that and it’s very hard to figure out how to study those afferent muscle pathways. There’s not a good way to study it non-invasively – so that’s an issue.

We’re doing yoga studies for IBS right now, seeing how much heart rate variability changes. These are students who are very proficient in yoga, they were instructors and they beat me up until I let them [unclear 1:13:27] on yoga. There are assorted other topics that come up.

There are a lot of parametric things we don’t know, like [check 01:13:36] Hubbard inhalation-exhalation ratio: is it important to breathe 40% in, 60% out? That’s what everyone thinks but now there’s one study that shows that no that’s not very important, 50/50 is okay. Another study showed that 40/60 is better, so we want to look at that. We want to look at lying down versus sitting up. So these are little studies we do, parametric studies, so the students can get a scientific poster out of it and we present it at a meeting, and if it comes out, then we try to publish it. These are things that really nobody is studying and we really need to know those things.

Tight-fitting clothing – it looks like women who wear very tight-fitting waists don’t breath diaphragmatically at all, and it looks like it has a detrimental effect on them.

[DAMIEN BLENKINSOPP]: These are useful things. You find the answers to these, you can improve a whole bunch of lives.

[RICHARD GEVIRTZ]: Right.

(1:14:27)[DAMIEN BLENKINSOPP]: Mass market kinds of lives. I came across you first in a presentation video. I’m just wondering, what are the best ways to learn more about you and your work? Are there presentations you have got up online? Are you on Twitter? Do you have a website? Where’s the best place to connect with you?

[RICHARD GEVIRTZ]: We have some YouTubes out there. I avoid Twitter like the plague. One of my students, Mark Stern, did a very nice YouTube explaining heart rate variability biofeedback – it’s fairly recent. If you just Google “Mark Stern HRV BSC” (Biofeedback Society of California), it’s the first one that pops up as it’s got a long address. He goes through and explains how the biofeedback works and some of the stuff we’ve been talking about.
HeartMath has a lot of stuff too, so a lot of their stuff is really good.
(1:14:27)[DAMIEN BLENKINSOPP]: Great, so I’ll put all of that in the show notes.

Is there anyone besides yourself – you’ve mentioned a few people already, but is there anyone else you would recommend that people look up to learn more as well?

[RICHARD GEVIRTZ]: There are websites – the one you saw probably was from Thought Technology, because they keep on doing things with me and putting them up there. My website – I have a hard time keeping it recent, but there’s a lot of stuff from the Association for Applied Psychophysiology and Biofeedback, AAPB. We’re just coming out with another magazine, a whole magazine and all the articles on HRV, and they tend to be lower level, not quite as scientific. And we publish things in regular journals all the time.

There’s a woman named Inna Khazan in Boston who published a book of combining biofeedback with mindfulness techniques. That’s a really nice book. I hope to review it for the publisher, and she did a very nice job on that book. She’s using our techniques pretty much, she’s taken our workshops, but she’s quite an accomplished mindfulness-based therapist and she put that altogether in a book that she has published.

[DAMIEN BLENKINSOPP]: That sounds great. Thank you for that. So just a little bit about you and how you approach data in your life. I’m just wondering if there are any biomarkers or anything you track in your life – could be HRV, could be other things – and use it to make decisions or just to keep track of where you are at personally?

[RICHARD GEVIRTZ]: Well, I do check HRV but it’s kind of discouraging since it goes down as I get older. I do it sometimes because it’s easy just to hook myself up. I do the breathing on my own, I don’t need the devices anymore to do it so I do the breathing myself. I have a heart rate monitor for my bicycling, which is a little bit useful actually. By now I know exactly which hills produce which heart rates, so I actually don’t bother with it a lot of times. I know exactly where my heart rate is from my bicycling.

I monitor my blood pressure regularly, just because it’s a risk with aging. But that’s all I do; I don’t monitor any other biomarkers. I suppose I could do over-training, but I don’t think I’m in danger of over-training. Possibly I do; sometimes on Saturday I ride with a group that pushes me too far. I probably would have lower heart rate variability on Sunday morning, but I know that because I feel crappy.

[DAMIEN BLENKINSOPP]: We’ve talked a lot about HRV on this show, as you’ve probably seen, and there are some situations where I find I’ll have a low HRV in the morning and I feel okay and it will hit me probably at lunch or a little bit later. So at four in the morning I was okay, and my HRV says “You’re not okay.” There are a few times like that it’s been a – how do you say – a forerunning signal for me.

[RICHARD GEVIRTZ]: Yeah because what it’s picking up is vagal withdrawal. One of the implications of this is what makes people have ill effects, unless they’re in war or something, is not sympathetic over activation as much as vagal withdrawal. So the minute you get up and you have a big busy day of stressful things in front of you, you don’t get a big surge of sympathetic activity usually, and maybe during a presentation you might, but what happens is your brake goes off, so your vagal brake is off. If it’s off for about 90 minutes, your body doesn’t like that so it will show up in whatever the most vulnerable body system you have is.

For the gut problems, it shows up in gut problems for those people, but if you have a trigger point, it will show up in trigger point pain. Or if you have performance issues, it will show up with not feeling sharp in your performance. So I think that’s what you’re picking up. Probably it would be a good idea if you wake up with it to do some biofeedback, try to get yourself back on track. Or break up the morning sometime with ten minutes of slow breathing, maybe combined with some alpha, and just to do that as a middle of the day break is really powerful. That will put you back in balance and then you’ve got another 90 minutes of messing it up again before it will start to affect you again. 90 minutes is a total guess but that’s what we say.

[DAMIEN BLENKINSOPP]: That’s great, thanks. There are some very useful tactics there to keep me performing.

Just the last question here, what would be your number one recommendation for people if they want to use data in some way in their life to improve their health, what would be the one way you would recommend doing that?

[RICHARD GEVIRTZ]: Well, the Inner Balance actually has a – it’s tricky but you can get heart rate variability data out of it. If you wanted to monitor your heart rate variability on a daily basis, this would probably be interesting to some people; it’s a lot of trouble. There’s a free software program that you can load it into called Kubios HRV. It’s a Finnish program – it’s free, you can download it on your PC. Then you can actually export Heart Math data or any of those device’s data to that–for resting level data – and it will give you, actually a very respectable heart rate variability profile with all the measures we talked about and many more.

If somebody was really into it, they could do that on a regular basis. It’s a little tricky how to get the Inner Balance to output that data. You have to write to Rollin McCraty and he’ll give you something to load that’s not meant for that, but you can do it. Or if it’s one of the other devices, it will do it easily. That might be something that would be worth keeping track of, although I think really, in the long run, just how you feel, you know what’s going on and if you know what’s going on and you just intervene properly, you’d probably be just as well off.

[DAMIEN BLENKINSOPP]: Yeah, self-awareness. Great. Well thank you so much for your time. I’ve found it really interesting. There were some things I wasn’t expecting–the yogis, a great story as background to how you got into this and the 1000 year old knowledge was an input into all of this. Thank you so much for your time, it’s been a lot of fun.

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A look at a collection of high impact endurance tools and tactics – and the top biomarkers to watch for optimization. Vetted by an endurance athlete with years of experiments and competitions behind him.

Today’s episode is about endurance training and using high-impact tools to get the most out of it. We look at self-tracking in diet and exercise when aiming to optimize your body to perform at peak capacity.

We discuss factors playing a role in improving endurance through a healthy progression. What self-quantifying strategies are useful for tracking overall performance and health?

This episode features actionable takeaways on dealing with a variety of obstacles commonly experienced by endurance athletes.

How to make use of ketogenic dieting in maximizing fat-burning efficiency during physically demanding exercise? Which biomarkers are important for tracking individual organ-systems functionality in the body? How to maintain a healthy hormonal status?

Overall, we look to beneficial and practical tactics for athletes wishing to upgrade their performance and discuss common pitfalls to avoid in cultivating endurance.

On this full-on ketosis diet… the endurance payoff was huge. The amount of focus that I had for long periods of time. My ability to just hop on a bike and ride for hours with no fuel at all, with just water. It was pretty profound, because you produce all these ketones as a bi-product of fatty acid oxidation, and they’re used as the preferred fuel… while you’re out exercising. And that’s a huge boon to an endurance athlete.
– Ben Greenfield

Today’s guest is Ben Greenfield who is a professional competitor in endurance-demanding events, including triathlon and Ironman races. Ben has 11 years experience coaching athletes and fitness professionals.

Throughout his athletic career, he has researched physiology of upgrading endurance using a quantified approach. He has performed numerous self-experiments targeted towards understanding his performance parameters, and towards optimizing his diet and exercise.

Ben is the author of a New York Time’s best-selling book titled “Beyond Training: Mastering Endurance, Health, and Life”, which was published in 2014. His top-ranked iTunes podcast is called BenGreenFieldFitness.

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

  • Ben uses his biohacking experience to coach people on living healthy and attempting on-the-edge extreme exercise (4:46).
  • Ben’s interests in endurance training and research developed over time. No big eureka moments, just meaningful experiences (7:12).
  • Important biomarkers in endurance training specifically, and practical reasons for these picks in exercise self-tracking (11:24)
  • Why regulation of sex-hormones and cortisol (the stress hormone) are important to track in endurance training (15:50).
  • Why standard reference ranges for free testosterone are often not applicable to endurance athletes (16:48).
  • Liver enzymes, kidney parameters, Vitamin D, and digestive track inspections are also key biomarkers for healthy endurance training (18:20).
  • The digestive track plays an upstream role in multiple athlete pains and discomforts (21:18).
  • How to fight thyroid system dysfunction in endurance training (24:17).
  • The key lessons Ben learned from his 12 months ketosis dieting experiment (26:10).
  • The biomarkers for detecting adrenal fatigue symptoms (27:22).
  • Biomarkers and tests for autonomic nervous system functionality and distinguishing adrenal fatigue from thyroid system dysfunction (28:03).
  • Incorporating Heart Rate Variability (HRV) tracking in endurance training (31:39).
  • HRV is Ben’s ultimate marker for optimizing endurance training and quantifying overall health (33:23).
  • Success in endurance training requires optimization between high-volume achievements and short-duration precisely aimed tasks (34:29).
  • Dealing with negative effects of endurance exercise and ketogenic dieting (39:01).
  • Maximizing ketogenic dieting benefits and potentially useful supplements (44:34).
  • Breath ketones are an easy way to test for purposeful ketosis (46:20).
  • Tracking important biomarkers and avoiding excessive ketosis (47:20).
  • Why oxaloacetate can be used as a supplement with ketogenic dieting (48:25).
  • Why cold thermogenesis works for athletes’ bodies, for recovery and for overall performance (50:27).
  • The portal outlining Ben’s work and relevant people recommended by Ben (53:17).
  • Ben’s most-important advice on living healthy is being grateful several times per day (54:48).

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Ben Greenfield, Greenfield Fitness Systems

Tools & Tactics

Interventions

  • Cold Thermogenesis: Can be achieved through a variety of cold exposure methods such as cold showers or dipping into cold water streams . In cold thermogenesis hormesis is used to promote positive adaptations in the body as we saw in episode 8. Amongst other improvements it can help to burn fat more efficiently and improve blood vessel functionality in part by promoting development of your Brown Adipose Tissue (BAT). BAT is a type of fat which is active tissue and able to generate heat.

Tech

  • Heart Math Gratitude exercises: The Institute of Heart Math promotes using specific gratitude exercises to optimize the HeartMath Heart Rate Variability (HRV) score. We’ve discussed the HeartMath form of HRV previously in episode 6. This exercise can be done with one of either of their two HRV feedback devices: Inner Balance for iOS or emwave2.

Supplementation

  • Thyro-Gold: Thyroid glandular extract produced by the New Zealand company Natural Thyroid Solutions. This supplement is used as a biohack to correct thyroid-system dysfunction, sometimes caused by ketogenic dieting – especially with very low carbohydrate intake and endurance exercise.
  • AndroGel: Although the use of testosterone hormone-containing products is illegal in professionally-sanctioned sports events, this supplement is sometimes used because free-testosterone levels often drop in a ketosis state.
  • Ketosports KetoForce: KetoForce contains the endogenous ketone body beta-hydroxybutyrate (BHB) in sodium and potassium salt form. The compound BHB can be used as an energy source by the brain when blood glucose is low. Ingesting KetoForce raises the levels of blood ketones for 2.5-3.0 hours after ingestion. (Note: A similar product from same company is Ketosports KetoCaNa).
  • benaGene: This supplement, oxaloacetate, was previously covered in depth in episode 30 in an interview with its creator Alan Cash.
    Greenfield uses this specifically to increase the rate at which his liver synthesizes new glucose molecules, during a low-carbohydrate ketogenic diet including exercise. The goal is to take advantage of its ‘glycogen sparing’ effect, since glycogen is less available in ketogenic diets, and thus get more intensity out of workouts.

Diet & Nutrition

  • Ketogenic Diet: A ketogenic diet is low in carbohydrates intake and high in fat intake. As such, it induces a state of ketosis in the body – the condition in which the body burns fats and uses ketones instead of glucose for fuel. Previously, we discussed measuring ketones and ketogenic dieting in Episode 7 with Jimmy Moore.
    To provide scientific support in favor of ketogenic dieting for endurance, Ben suggests the research of a University of Connecticut team investigating athletic training and human performance. For more information, see this recent scientific review authored by them on using fat as fuel for endurance exercise.
  • Cyclic-Ketogenic Diet: In some people, full ketogenic diets can lead to hormonal or organ dysfunction (e.g. thyroid). The cyclic-ketogenic diet is the solution often used to avoid these downsides. This is a low-carbohydrate diet with intermittent periods of high or moderate carbohydrate consumption (e.g. a refeed with carbohydrates every weekend). It is used as a way to maximize fat loss while maintaining the ability to perform intense exercise during a ketosis state.
  • Based on his 12 month ketosis self-experiment, Ben has concluded that eating anti-inflammatory food, as well as increasing intake of food containing medium-chain triglycerides (MTCs) and resistant starches, are all beneficial in reducing the potential negative side effects of ketogenic dieting.

Exercise

  • Polarized Training: Polarized Training is scientific terminology for the concept of easy-hard training. Researchers from the University of Stirling in Scotland have concluded that using an approach which excludes medium-intensity training is more beneficial for building endurance compared to an approach that includes medium-intensity training. The polarized training model (80% low-intensity; 0% medium-intensity; 20% high-intensity training) produces more positive results in endurance athletes, compared to the competitor threshold model (57% low-intensity; 43% medium-intensity; 0% high-intensity training).
  • Murph Workout: “Murph” is a CrossFit workout named after Navy Lieutenant Michael Murphy, who was killed in Afghanistan June 28th, 2005. He was awarded the Congressional Medal of Honor after his death. It first appeared on the CrossFit site 18 August 2005. This workout consists of (in order): 1 mile run, 100 pull-ups, 200 push-ups, 300 squats, and a 1 mile run at the end.

Tracking

Biomarkers

  • Heart Rate Variability (HRV): HRV is the measure of the change in the heart’s rhythm over time based on changes between sympathetic and parasympathetic activation. HRV was previously covered in the context of optimizing training workouts using HRV in Episode 1 with Andrew Flatt and using HRV as a biomarker for longevity in Episode 20 with Dr. Joon Yun.
  • Triglyceride to High Density Lipoprotein (HDL) ratio: Researchers have shown that using the triglyceride to HDL ratio is a better predictor of coronary disease risk factors, compared to tracking total cholesterol (which includes HDL and other lipoprotiens). A ratio of 2 : 1 or less is considered optimal.
  • High-Sensitivity C-reactive protein (hs-CRP): CRP is a protein that increases in the blood with inflammation and is used as a marker for cardiovascular health (high levels over 1 mg/l are indicative of higher cardiovascular risk). Both diet choices and overtraining can lead to high levels of hs-CRP (over 1).
  • Ketones: Ketone concentrations can be tested in blood, breath and urine samples to determine if you are in ketosis (burning ketones for fuel) and to what extent. We covered these markers extensively in episode 7 – how to measure ketones.
  • Creatinine and Blood Urea Nitrogen: These two biomarkers are often elevated above normal levels in endurance athletes, without being indicative of a health risk. In endurance training, creatinine levels lower than about 1.1 mg/dl do not pose a health risk. It is also relatively normal to have BUN levels over 20mg/dL.
  • Liver Function Tests: When excessive exercise is present, the blood levels of liver enzymes Alanine Transaminase (ALT), Aspartate Transaminase (AST), and Alkaline Phosphatase (ALP) are elevated above normal.
  • The 25-hydroxy Vitamin D Blood Test: The most accurate way to measure how much vitamin D is bioavailable to be used by your body is the 25-hydroxy vitamin D blood test. Optimum vitamin D levels range between 50-70 ng/ml.
  • Salivary cortisol to Dehydroepiandrosterone (DHEA) ratio: An increase in DHEA levels is highly suggestive of adrenal dysfunction because DHEA is produced exclusively by the adrenal glands. Excessive exercise stresses the body to produce very high levels of cortisol, which causes a depletion of endogenous DHEA. This results in an elevated cortisol to DHEA ratio. Testing for this ratio several times per day provides a more complete image of adrenal function, compared to a snapshot provided by simple monitoring of blood cortisol levels. A normal cortisol : DHEA ratio is approximately 5:1 to 6:1.
  • Thyroid Functional Test Panel: A TFT panel typically includes thyroid hormones such as Thyroid Stimulating Hormone as well as the thyroid hormones triiodothyronine (T3) and thyroxine (T4). Excessive exercise can stress the body to produce high-levels of cortisol (the stress hormone) which inhibits the conversion of thyroid hormone from inactive (T4) to biologically active (T3). This can result in lower levels of active thyroid hormone despite normal or up-regulated levels of TSH. Thus, testing for (active) T3 hormone concentrations is more relevant for endurance athletes self-tracking. Optimal reference ranges for TSH are 0.4 – 2.5 milliunits per liter (mU/L). Optimal reference ranges for free (bioavailable) T3 range between 350 – 780 pg/dL.
  • Sex Hormone Binding Globulin (SHBG) and free testosterone: The standard reference ranges for SHBG are 0.2-1.6 mg/dL for non-pregnant adult females and 0.1-0.6 mg/dL for adult males. Changes in SHBG levels affect the amount of free hormone that is available to be used by tissues, including the levels of free testosterone. In case SHBG levels are in abnormal ranges, then free (bioavailable) testosterone should be tested (reference ranges 1.0-8.5 pg/mL for females and 50.2-210.3 pg/mL for males).
  • Tests for detecting adrenal fatigue and thyroid system insufficiency

  • Iris Contraction Test: This test consists of you looking at the pupil of your eye in a mirror while shining a bright light at your eye. The light should cause the pupil (center black spot of your eye) to contract or become more narrow. The contraction should be sustained for longer than 20 seconds before the pupil starts to flicker or dilate. Otherwise, if the pupil starts to flicker immediately upon shining light, this is a good indication that you have adrenal fatigue – mainly because your adrenal gland is functioning properly in managing blood pressure.
  • Dizziness Test: If you lay down or you sit down and you stand up quickly and you get dizzy, then this is a sign of blood pressure mismanagement. Importantly, problems with blood pressure often accompany adrenal fatigue because one of the main functions of the kidneys is to regulate blood pressure via production of hormones in the adrenal gland.
  • Broda Barnes, MD Temperature Test: This test was developed by Dr. Broda Otto Barnes, who was best known for developing novel perspectives on hypothyroidism – a type of thyroid system disease. In essence, you do oral and armpit measurements every morning in bed upon waking up and keep a graph of the results. If your temperature is consistently low, then this is an indication that your thyroid system is dysfunctional even in the absence of a blood thyroid test.

Lab Tests, Devices and Apps

Other People, Books & Resources

People

  • Dr. Terry Wahls: Dr. Terry Wahls is a a clinical professor of medicine at the University of Iowa. Previously, Dr. Wahls was kind to participate in the third episode of our show, where we focused on linking mitochondrial health to autoimmune and chronic disease.
  • Alan Cash: Alan Cash is the CEO of Terra Biological. Previously, he has been a guest on our podcast in Episode 30, where we discussed the potential for using oxaloacetate as an anti-aging supplement.
  • Joe Friel: Joe Friel holds a masters degree in exercise science and is a USA Triathlon and USA Cycling certified elite-level coach. For Joe’s blog click here. For his Twitter click here.
  • Sami Inkinen: Sami Inkinen is a balanced person. He is a successful businessman and a top-age Ironman competitor. For his Twitter click here.
  • Dr. Peter Attia: Dr. Peter Attia is a scientist who is knowledgeable in healthy endurance exercise and self-quantification. For Dr. Attia’s Eating Academy Blog click here. For his Twitter click here.

Books

Other

Full Interview Transcript

Click Here to Read Transcript
[04:46] [Damien Blenkinsopp]: Ben, welcome to the podcast.

[Ben Greenfield]: Hey, thanks for having me on man. And I’ve got to ask you, is it Damien, or Damion? Or Dami-something else?

[Damien Blenkinsopp]: Or Damian? It depends where you come from, I guess.

[Ben Greenfield]: Okay. Just checking. I don’t want to stick my foot in my mouth.

[Damien Blenkinsopp]: Yeah. You can call me Dam. I tell people to call me Dam, just to avoid all those questions.

[Ben Greenfield]: There we go. I want to sound like I’m cursing the entire episode.

[Damien Blenkinsopp]: Yeah. But it even works in Asia, tried and tested.

[Ben Greenfield]: Nice.

[Damien Blenkinsopp]: I mean you’ve got a three letter name. That works well.

[Ben Greenfield]: Yeah, totally. Ben.

(05:12) [Damien Blenkinsopp]: So, Ben, you’re into triathletes, Ironman, and basically the way I look at you is you go around searching for tactics and tools to give you an edge in these areas that you’re interested in. Is that a fair kind of back story to who you are and what you’re doing?

[Ben Greenfield]: Yeah, I do a lot of that I guess n=1 guinea-piging myself. Going out and doing crazy things like training with the Navy SEALS or doing these Spartan Races or Ironman triathlons, things like that.

But then I also think I learn just as much via a lot of the coaching and consulting that I do, just because people typically come to me for one of two reasons.

They either want to do some crazy feat that’s completely unnatural for the human body to do, like they want to go run 100 miles in the wilderness or something like that, and figure out how to do it without destroying themselves. So my job is to figure out how to do that from a nutrition and a physiology and an exercise standpoint.

Or they come to me because they basically want to live as long as freaking humanly possible, and want me to manage how do you sleep when you want to do something like that, how do you exercise, what do you measure, what do you pay attention to in your blood and your gut. And so there’s that kind of biohackiness that I get into.

And I’ve got to admit, for me personally it’s a little bit of both, really. I certainly do want to live as long as possible. I also want to do as many crazy events as I can during the process, see as much of the world as I can at the fastest pace possible. And so for myself, personally, I’m doing a little bit of both.

But sometimes people come to me and want to do something that I know nothing about, so I’ve got to go and learn it. So part of it is that, too. That, or if it’s not coaching someone it’s writing about that. Because I’ve done a lot of writing recently. This morning [I] published a big article on my website about how to use marijuana to get performance enhancing gains.

And I never really would have delved into that if I hadn’t been asked by so many people, especially here in the US with the growing legality. It’s like, can I use this while I’m exercising? That type of thing. So it’s a little bit of everything.

[07:12] [Damien Blenkinsopp]:Yeah, great. So [what was] the event that started the whole Ben Greenfield fitness podcast, and the blog and everything? How’d you get involved in that? Because you’re obviously very passionate about it.

[Ben Greenfield]: Yeah. Well there’s, I mean I get that question a lot, and frankly – nothing against you – but it annoys me, because I hate when people go, “When did you decide to do this? When did you decide to do that?” I never make decisions. I don’t have a 10 year business plan. I don’t have some ‘Come to Jesus’ moment where I said, “Oh hey, I want to learn how to exercise.”

It’s just that I live my life. I do things that I’m passionate about, or that other people who I’m helping are passionate about and tend to fall into whatever I might fall into based on that. I’m getting into hunting right now – well specifically bow hunting and hunting competitions – before that obstacle racing, before that Ironman Triathlon, before that water polo, before that body-building, before that I was a collegiate tennis player.

It’s just like life is a series of chapters and moving targets. It’s never just like one commitment to do one thing. But I would say, to give you a rough answer to your question, the very first time I decided to something a little bit more endurance orientated – which I would define as something that has a nutrition rate.

You don’t see people dropping out of baseball or cricket games because of fatigue and heat stroke and lack of nutrition. That’s very rare, but you see it all the time in marathons and Ironman triathlons and things like that. So I would say the first time I started to get into that side of sports would have been my first Ironman Triathlon that I did back in the city of Portalane, Idaho in 2007.

And up until that point I’d been primarily an explosive power athlete. Like body-building and tennis and stuff like that. But my girlfriend, who is now my wife, was a runner. She ran cross-country for University of Idaho. So I kind of had to take up running, to a certain extent, just to be able to woo her.

And she dragged me to a triathlon one day and she actually had me run the running leg of the triathlon, which hurt like hell. I was a body builder; my boobs were bouncing up and down and my lower back was locking up and it was horrible. But it kind of got me interested in this high that you can get from endurance sports.

And so I wound up doing a few triathlons and doing, what I would say, is the biggest mistake for anyone who wants to avoid getting into endurance, that is I went and watched an Ironman Triathlon. And after watching Ironman and watching these intense feats of physical performance and the huge feeling of satisfaction and self-completion that these people were experiencing as they threw up their arms when they crossed the finish line I was like, I want that. I want to experience that.

And so I signed up for an Ironman and began taking everything I had been studying. At that point I had a Master’s Degree in Exercise Physiology and Nutrition and I was able to start applying that stuff to my training, and experimenting with a lot of what I was finding in research and sports science and seeing what worked and what doesn’t.

For example, all laboratory studies, or most of them, done by the white coats in their little labs will tell you that the body can take on about 200 to 250 calories of fuel during exercise. You can oxidize 200, 250 calories of carbohydrates while you are exercising. But for anyone, especially anyone who’s above about 150 pounds who has tried to go out and do an Ironman Triathlon, you completely bonk after about five hours on that number of calories, and you technically need about twice that in order to be able to get by in an Ironman race in most cases.

So, it’s a situation where what they’re saying in the lab and textbooks actually doesn’t work once you get out in real life and you try this stuff in the streets, in the trenches. So, that’s been kind of fun too, figuring out from research what works, and what doesn’t.

[Damien Blenkinsopp]: Right. Yeah, we often talk on here about n=1 experiments are often going to be different to the research, for a variety of reasons like the ones you brought up, and the use of averages, and other things like that.

[11:24] So, anyway, in terms of endurance training, since we’re there, what kind of biomarkers have you found to be the most useful to track your performance? Or what do you track around your capabilities for endurance training, and see as important?

[Ben Greenfield]: Oh, for endurance specifically?

[Damien Blenkinsopp]: Yeah.

[Ben Greenfield]: So for endurance specifically, that’s a great question. So one would be your level of HSCRP, which really that’s just for exercise in general. Or high sensitivity C-reative protein, just to make sure that your levels aren’t straying too high above 0.5. And the reason for that…

[Damien Blenkinsopp]: So that’s kind of your benchmark? You try to keep them under there? Where do yours tend to hover around?

[Ben Greenfield]: I actually fall below 0.2 now for HSCRP, probably because I eat a very anti-inflammatory diet, very clean. And I won’t insult your listeners’ intelligence by defining what a clean diet or an anti-inflammatory diet is, because it’s pretty easy to go out and figure that out with Dr. Google.

But I eat very clean. I also use a lot of anti-inflammatories. Like I make ginger tea, and I use a ton of turmeric, usually combined with black pepper to increase the efficacy of it, and I use percumin and I consume a lot of very dark and colorful vegetables with very limited amounts of dark and colorful fruits, and wild caught fish, and fats, and things that really help with inflammation.

And I’m also very careful with my training, where I do extremely focused and intense, but short, bouts of training with a specific purpose. I never go out and just pound the pavement for the hell of it, which is a great way to build up a lot of voluminous training based inflammation.

And so I have a very precise, dialed in training program that also includes things that help to mitigate inflammation, like foam rolling, and cold soaking, and these things that can help to remove a lot of these byproducts of metabolism that can create inflammation. So, inflammation is a biggie. Honestly, it doesn’t take a rocket scientist to figure out that if you keep your inflammation controlled, it’s a good thing.

So, a few others that I’ll pay attention to for endurance. When we’re talking about labs, as far as blood goes, TSH, preferably a full thyroid panel, is pretty prudent to pay attention to simply because high level endurance training can inhibit conversion of inactive to active thyroid hormone.

And because of the high amounts of cortisol that can potentially be produced through an improper training program can stress the body out enough to where you experience some hypothalamic pituitary adrenal axis insufficiencies, particularly high cortisol, creating a feedback loop that reduces the conversion of inactive to active thyroid hormone and thus an increase in thyroid stimulating hormone. So your body turns out a bunch more thyroid stimulating hormone to try and get more T4 present, even though a lot of that T4 isn’’t getting converted into T3.

And by monitoring TSH, if you see a pattern or a rise in TSH many times it’s concomitant with an increase in cortisol and stress, and often also accompanies a not enough eating period. Sometimes not enough carbohydrates is the biggest culprit, but in many cases just not enough damn calories, period. Damn, not referring to your first name but to the curse word. Just so we’re clear.

That’s another one is TSH. Cortisol, I alluded to, but when we’re looking at a hormonal panel, I also like to pay attention to sex hormone binding globulin. Because the body has this interesting mechanism where when it’s stressed out, when it’s in a time of famine, in a time of need, under high amounts of stress, doing a lot of migrating, a lot of moving with low amount of calorie intake, the last thing you want the body to do is produce a bunch of babies at that point.

And so sex hormone binding globulin often rises simultaneous to cortisol to keep total testosterone bound, and keep it from being available as free testosterone. So even if your testes are working just fine, or your pituitary gland is working just fine, –obviously talking about the males more than the females now– and even the leydig cells in your testes are producing testosterone just fine, if sex hormone binding globulin levels are really, really high that’s all for naught. And so that’s another really, really important one to keep an eye on. And that’s typically addressed by addressing cortisol.

[15:50][Damien Blenkinsopp]: Right. So, why would you look at SHBG versus free testosterone, or that marker? The [unclear 15:56]?

[Ben Greenfield]: Well, because if free testosterone is low, but if you look upstream perhaps it’s because total testosterone is low because the leydig cells in your testes are not producing enough hormone because you’ve got low levels of luteinizing hormone. In contrast to that, perhaps your luteinizing hormone production is fine, your leydig cells are producing enough testosterone just fine, your total testosterone is high, but it’s more of a cortisol issue than it is a central nervous system issue or a glandular issue.

So that’s why you test that versus just looking at free testosterone.

[Damien Blenkinsopp]: So basically, free testosterone could be many, there’s more reasons behind it, but the SHBG is more specific to endurance and specific dynamic.

[Ben Greenfield]: Yeah. Really, two reasons behind it. Either you aren’t producing enough total testosterone, or you are producing enough total testosterone but it’s not getting converted. So those are really the two main things to look at.

[16:48] [Damien Blenkinsopp]: So, are you looking at the standard reference ranges for that, or do you look for something a bit more precise?

[Ben Greenfield]: A lot of times you have to look at symptoms synonymous, because standard reference ranges are going to vary widely.

I’ve worked with a lot of endurance athletes who have very high libido levels, show no signs of over-training, have very robust nervous systems, high heart rate variability, low cortisol, and even low sex hormone binding globulin, but their total testosterone is in like the high 300s. Which, for a body builder they would scoff at that and say, oh that’s rock bottom low. Even though a lot of times hypogonadism is levels below 100.

And you’ll get many people who just feel like fricking crap at 300, and some people will be closer to 500, and some people will need levels of 700, 800, or even 1000. So it kind of depends. It varies widely, I suspect based on genetics as a big part of it.

So ultimately it’s really tough to hold things up to reference ranges. I mean, you can ballpark it. You can say well if total testosterone is starting to get below 300, that’s where we would really start to get a little bit concerned. But it really is kind of tough. A lot of times it’s a moving target based off of a cluster of other symptoms.

If someone’s complaining of low libido and low motivation, and lack of energy, etc, and their testosterone is at 400, well that’s a pretty good sign that 400 is not going to be adequate for them. So I know that’s one of those deals where it’s total soft science, but it does really depend. That’s one of those ‘it depends’ answers, but that is definitely a variable that I will look at.

[18:20] Liver enzymes is another one, like alkaline phosphatase, aspartate aminotransferase, the ALT, the AST, some of these liver markers just because a lot of times they can be elevated when excessive exercise is present. And so that’s another one to pay attention to. It doesn’t have to be excessive exercise; sometimes it can be alcohol, pharmaceutical intake, things of that nature. But liver enzymes are the one that I’ll look at.

Kidneys, a lot of people say to look at kidneys, but frankly it’s very rare for me to see an athlete who doesn’t have slightly elevate creatinine and blood urea nitrogen levels, which are two common markers in the kidneys that a physician will get concerned about if they see elevated, but that are very common to see elevated if an athlete is exercising anywhere in the 48 hours leading up to a blood panel.

So, as long as creatinine levels aren’t much higher than about 1.1, and as long as blood urea nitrogen isn’t through the roof and – I apologize, but off the top of my head I don’t remember the lab reference ranges for blood urea nitrogen. The reason being that I do most of my coaching for blood panels with a company called WellnessFX. It’s basically more like a dashboard with graphs, more than it is hard numbers, so occasionally I’m looking at graphs more than I am numbers.

[Damien Blenkinsopp]: And they just have those red zones.

[Ben Greenfield]: Yeah, exactly. They’ve got red, yellow, green, which actually annoys me some of the time. Because they’ll flag high LDL as red when I purposefully try to get my LDL high. So there’s some issues with the whole red yellow green type of quantification. But anyways, blood urea nitrogen and creatinine, even though a lot of people talk about those, they’re not super duper important in my opinion, because they’re always going to be a little bit elevated.

Vitamin D, that’s another one that I’ll look at just because of it’s importance. As you can suspect, a lot of these aren’t just specific to endurance, they’re specific to exercising period. Just as a hormone and a steroid, vitamin D is another important one that I’ll look at.

And then as far as other things, I typically will have most of the athletes I work with or the people I advise do at least once a year a full gut panel. You know, a comprehensive gut panel that includes parasitology, measurement of pancreatic enzyme production, measurement of yeast and fungus and any type of bacterial overgrowth in the digestive tract because I find that, especially when you’re jogging your body up and down for 10 plus hours while racing, having a really, really good gut and GI system and very efficient digestion is incredibly important.

And so I will look at things like presence of yeast or fungus, like Candida Albicans, or the presence of H pylori, or absence of hydrochloric acid, or absence of pancreatic enzymes, or overgrowth of specific bacteria, or lack of short chain fatty acids in the digestive tract, in the colon, and a lot of those things that tend to influence an athlete’s performance or their feelings of well-being. So that’s another thing I’ll pay attention to.

[21:18][Damien Blenkinsopp]: Right. A lot of people wouldn’t think of that as something performance related, more like a chronic issue related.

Have you got any case studies where you saw people, basically not performing but not having any negative symptoms in terms of GI distress or anything that they would have noticed, but when you put through these tests some negative results came?

[Ben Greenfield]: Sure. Now we’re delving a little bit more deeply. And I mean, obviously explosive diarrhea halfway through a marathon can be a good sign of digestive enzyme insufficiency, but so can, for example, vitamin B12 or vitamin D deficiencies, or even if you go more advanced and run like an organic acids profile, or an amino acid profile, severe imbalances of a lot of micro-nutrients.

Well if you’re not digesting your food efficiently, for example, if you’re not producing adequate hydrochloric acid, you’re not activating pepsin to break down proteins, beginning in the stomach an moving on to the small intestine, then you’re going to: a. have undigested protein fragments winding up in the bloodstream causing some auto-immune issues, and that can include fuzzy thinking, which no athlete wants.

But then you also can get amino acid deficiencies, like deficiency in the ability to create neurotransmitters, and also deficiencies in the ability to repair and regenerate skeletal muscle tissue, because you aren’t breaking down the proteins that you’re eating.

And the same could be said for something like inflammation in the digestive tract from wearing down of the microvilli. So perhaps you’re not producing adequate levels of lactase, so you’ve got some lactose issues and bloating and gas. Or you’ve got inflammation that is resulting in malabsorption of fat-soluble vitamins, so vitamins A, D, E, and K aren’t getting absorbed properly, or bacteria aren’t helping you to produce those, and so you experience hormonal deficiencies, or steroid deficiencies.

And so, yeah the gut is incredibly important, and that’s one of the things I’ve been kind of getting on companies like WellnessFX, for example, to do is to not just use the strategy of blood testing but also really pay attention to the gut. I mean, in an ideal scenario, what I would like to see is a done-for-you system.

And for me right now, what I do is just kind of string this together for the athletes who I work with. But a done-for-you system where you get your blood testing, you get your gut testing, and you get your genetic testing so we can look at everything from genetic snips to bacterial imbalances in the gut to all the blood and biomarkers, and have all of that done with either one panel or one service.

That would be really nice, because right now you’ve got to go to typically three different places. You’ve got to go to whatever DNAFit, or 23andMe, and you’ve got to go to DirectLabs, or Metametrix for GI affects, and then you’ve got to go to WellnessFX for whatever else. And then if you want to do food allergy testing, well then you’ve got to throw in a Cyrex panel, or something like that.

So maybe it’s a first world problem to want all this stuff to be available in one central location, but it certainly would be nice.

[Damien Blenkinsopp]: Yeah. It’s so near the early days from that perspective. There’s a lot of specialized, it’s still kind of specialized in terms of the labs. Each is in their little separate box and everything.

[Ben Greenfield]: Yeah.

[24:17] [Damien Blenkinsopp]: So, in terms of the kinds of decisions you’ve made, or you’ve advised a client based on some of these values, some of this data that’s come back, what have been the biggest changes that you’ve implemented to optimize training?

[Ben Greenfield]: You mean as far as training?

[Damien Blenkinsopp]: So, say the TSH came up too high, what would you do about that?

[Ben Greenfield]: Oh okay, so for high TSH, obviously it’s never a shotgun approach. It’s never a multivitamin. So for high TSH it may be looking at your carbohydrate intake. That’s the first thing that I’ll look at.

Even before you look at total amount of calories, you just make sure nobody is on some low, like 40 gram per day carbohydrate diet, because frankly a lot of the ‘low carb’ or ‘ketosis’ based diets that are out there were created for sedentary people. Even the bulletproof diet. I love the whole bulletproof philosophy, but it was written by a computer programmer, not by an athlete.

And so the levels of carbohydrate, and even the levels of calories in that diet, have to be adjusted and modified for a hard-charging athlete, especially an endurance athlete. So, otherwise with caloric depletion and carbohydrate depletion, you basically lose a lot of your ability to convert inactive to active thyroid hormone.

And in the case of calories, as you would deduce through common sense, when you send your body a message that calories are insufficient but you’re still requiring it to move a lot, your body down regulates metabolism. And one of the main ways it does that is by down regulating thyroid.

So, I look at carbohydrates, I look at calories, and then I also look at dietary intake of organ meats and fat soluble vitamins, which can also assist with thyroid health. So in my case, because I did an n=1 experiment about a year and a half ago where I did 12 months of ketosis.

Not cyclic ketosis, not cycling carbohydrates in and out throughout the day, but full on eating only 5-10 percent of my total daily intake from carbohydrates. Very low carbohydrate diet. Too low, in my opinion, for most endurance athletes who want to maintain optimal levels of health elsewhere.

[26:10] [Damien Blenkinsopp]: Did you see negative effects from that over the 12 months?

[Ben Greenfield]: Yeah, and that’s what I’m getting at with the thyroid. I started taking thyroid glandular extract. I took one called Thryo-Gold, which is made from New Zealand cows, that are like an A2 cattle.

A lot of A1 cattle has proteins in it that cause an immune reaction within the human body, but cattle that are breed via A2 are cattle that contain this A2 genetic profile that is more bio-compatible with the human body. And so I basically took a T1, T2, T3, and T4 combo, and that seemed to turn my thyroid around. But that was after I had already done a number on it.

So for thyroid, that would be an example of what I would do with something like thyroid, would be increase calories, increase carbohydrates, increase intake of organ meats and fat soluble vitamins. And then for a really hard-charging athlete who insists upon doing something like restricting carbohydrates to tap into the performance enhancing effects of ketosis, understand that you’ve got to get on extra help from the thyroid.

Since your body isn’t going to make T3, dump it into the body. And preferably get it from a whole source, like levothyroxine or synthroid. But a source that contains other elements of thyroid in addition to just T3, so you’re not creating an imbalance.

[27:22] [Damien Blenkinsopp]: Great. Well, connected with the thyroid issues, I was wondering if you’ve come across adrenal fatigue also. If that’s every come up with you or with anyone else.

[Ben Greenfield]: Absolutely. Adrenal fatigue, gosh. There’s like four chapters of my book on that alone. But adrenal fatigue, well what do you want to know about it?

[Damien Blenkinsopp]: Well first of all, have you looked at some of the tests? I’ve done some of the salivary tests.

[Ben Greenfield]: Oh yeah. Yeah, like an adrenal stress index is kind of gold standard, cortisol DHA. If you look at the cortisol DHA curve, that’s much, much better when you’re addressing something like adrenal fatigue versus a blood cortisol measurement, which is just a snapshot. You want to see a moving target of salivary cortisol levels, preferably matched to salivary DHEA levels, throughout the day.

[28:03][Damien Blenkinsopp]: I was just thinking, based on it’s endurance exercise, and it has this tendency to raise cortisol, that that would be more of an issue and something that you would keep an eye on. Or by monitoring TSH, does that kind of take care of itself? If the TSH is alright then you tend not to have an adrenal issue as well?

[Ben Greenfield]: No, not necessarily.

You can still have adrenal fatigue and have a thyroid that’s managed properly. Because what you would typically see in that case is someone is eating boatloads of calories and taking care of themselves from an energetic standpoint, but simply outputting too much energy. They’re just training way too much. Even though they’re supplying their thyroid with what it needs, there’s just too much training still.

And a lot of times you’ll see inflammation high, but yeah. Cortisol DHEA, and that adrenal stress index can be a good measurement. And there are less quantitative measurements. You could do a pulst test, where you look in a mirror and you shine a bright light at your eyes, and your pupils should stay dilated. But if it stays dilated and then just starts flickering rapidly.

[Damien Blenkinsopp]: Have you tried that one?

[Ben Greenfield]: I have, yeah.

[Damien Blenkinsopp]: Because I was just wondering. I did try it and I find it a little bit difficult to judge.

[Ben Greenfield]: Yeah, it’s certainly not as precise as a salivary measurement, but once you’ve done it a few times you can definitely see the pupil, and whether or not it’s actually flickering versus staying dilated. If you look at if for long enough, it’s just going to start flickering period, but if it starts flickering after just a few seconds, that’s typically a sign that your kidneys are not producing enough aldosterone, which is synonymous, or can accompany, adrenal fatigue.

The other one is just the dizziness test. If you lay down or you sit down and you stand up quickly and you get dizzy, that can be a sign of blood pressure mismanagement that often goes hand-in-hand with adrenal fatigue. And again, these are the super cheapo poor man’s methods, but it can give you clues.

And then there’s temperature tests for thyroid, the Broda Barnes Temperature Test, where you do oral and axillary measurements of your temperature in bed every morning, and keep a running graph. And if it’s consistently low, that can be a pretty good indication that even if you haven’t done a blood thyroid test that your thyroid might be having issues.

So, there are a lot of things. One of the best ones I like though is just pure heart-rate variability. Testing the interplay between your sympathetic and your parasympathetic nervous system by using something like a Bluetooth enabled heart rate monitor and one of these heart rate variability apps, and simply paying attention to whether heart rate variability is high or low on any given day.

And if it’s consistently low, and you see consistent suppression of both sympathetic and parasympathetic nervous system feedback, then that can be a pretty good sign that you’re on the cusp of adrenal fatigue illness or injury, and so that’s another really good one to pay attention to. And I do that one every day myself.

[Damien Blenkinsopp]: Do you do it in the morning as soon as you wake up?

[Ben Greenfield]: Yes, that’s gold standard, because that’s where most of the studies have been done on heart rate variability were five minutes resting in the morning.

[30:45] [Damien Blenkinsopp]: Right, right. I believe you use the HR…what’s the name of the company?

[Ben Greenfield]: SweetBeat?

[Damien Blenkinsopp]: Yeah, SweetBeat.

[Ben Greenfield]: Yeah, but because I want to build up that technology and add some features and stuff like that, I’ve actually white labeled their technology. And so I use the app called NatureBeat now, but it’s the SweetBeat technology.

[Damien Blenkinsopp]: Great, great. Yeah, she’s been on the show.

[Ben Greenfield]: Yeah.

[Damien Blenkinsopp]: So I was using that for a long time, and then I just recently started using iFleet, because I also talked to the guys at iFleet, and it does have this other thing that they just added recently. You might just want to check out.

It’s kind of interesting. It shows how high your energy levels are on a given day, so it kind of does this matrix thing. So it shows you if your in the bottom right corner, it means something a little bit different. So I’ve been checking it out. I’m still trying to understand what it means each day. But I do find that when I’m at the bottom, low energy, those days tend not to be good. Even if I have a high HRV.

[31:39] So anyway, out of interest, what is your HRV levels? Because you think normally endurance athletes have higher HRV, right?

[Ben Greenfield]: Yeah. Usually higher HRV, which isn’’t necessarily a good thing if you’ve got what are called HF to LF ratio imbalances.

You want your HF to LF ratio to be pretty close to one. That’s sympathetic and parasympathetic nervous system feedback. And if parasympathetic nervous system feedback, which would be your high frequency number, if that’s super duper depressed, and your LF is really high that can be an indication of aerobic based over-training, or vice versa.

So ideally you’ve got high HRV and a pretty close to a 1-1 ration between HF and LF. That’s what you want to go to. And you want both HF and LF to be up in the thousands. That’s a sign of a really robust nervous system.

So, my values tend to be between about 92 and 98, with HF and LF values that vary between about 4,000 to 8,000, around in there. Generally with a 1-1 ratio, depending on what my previous day’s training had looked like.

And I would expect, for example, this Tuesday I’ll do a CrossFit’s Murph and I’ll do that with a 20 pound weighted vest on, and just crush myself. And that will take me about an hour to do, and I guarantee my LF value will be tanked the next day. But I also won’t be doing any sympathetic nervous system training for like 48 hours afterward.

[Damien Blenkinsopp]: So you recover within 48 hours?

[Ben Greenfield]: 48 to 72 hours, depending.

[Damien Blenkinsopp]: These scores recover for you pretty quickly?

[Ben Greenfield]: Yeah, but I mean, if I were to do something epic, right? Like, usually something that gets you to the state of glycogen depletion. Or let’s say instead of Murph, I do double Murph, or I do a Murph with a 5k sandwiched on either end rather than just a mile, then it can take me several days to recover, for sure.

[33:23] [Damien Blenkinsopp]: If you had to pick one marker to optimize your endurance training by and make decisions on, which one of the ones we’ve talked about would it be?

[Ben Greenfield]: HRV.

[Damien Blenkinsopp]: Okay, great.

[Ben Greenfield]: Just because it’s easy, right? You don’t have to give blood.

And maybe at some point, once we’ve got the lab and chip technology finalized, and I can put a drop of blood onto a little dongle that will plug into my iPhone and I can measure, let’s say, testosterone cortisol ratios, maybe that will become a more valuable metric for me. But at this point, I would have to say something simple and easy to utilize and relatively inexpensive, the HRV would be the one that I’d choose.

If I had to choose an actual blood biomarker, tough to say. Tough to say. I guess I’d probably have to go with HSCRP, again. Just because inflammation is generally going to be high when cortisol is high. It’s generally going to be high when diet is crappy, it’s going to be high when triglycerides are high, it’s going to be high when omega-3 fatty acids are low. So, that’s a pretty good one to measure.

[Damien Blenkinsopp]: Yeah. So it catches a lot of things. Mainly whenever something starts going wrong.

[Ben Greenfield]: Yeah.

[34:29] [Damien Blenkinsopp]: Well so you’ve referred to over training quite a bit over this as something that you’d have to change. So HRV would be one of the first places you’d see over training.

Are there any other tell-tale markers, and what do you suggest, more to the point, because you mentioned earlier that you do very – is it short, intense kind of endurance exercises. And I think a lot of people when they’re thinking about endurance, they’re thinking about very high-volume, kind of long duration activity.

So how do you approach it, and avoid over training? What are the top things you’ve taken in over time?

[Ben Greenfield]: First of all, one of the common pitfalls that people fall into with endurance training is doing the long voluminous training every weekend. It’s very stereotypical that you’ll see in a lot of athletes these Saturday long bike rides and then Sunday long run, for example. Or in a marathon, the Saturday long run.

I’ve found that in most cases, you can maintain endurance really, really well. Unless you’re a professional athlete trying to perform at the peak of performance, most people can perform just fine. With doing digging into the well like that, really, really, deep for like a death march, a really long ride or something like that, you typically only need to do that one to two times a month. Not every weekend.

I’m a bigger fan of using shorter, very temporal based intervals. So to give you an example, for the Ironman triathletes that I work with, while their peers are out doing a five hour ride followed by an hour long run, my athletes will be doing two hours of 20 minutes at race pace followed by 5 minutes recovery. So a very focused activity with a specific goal in mind. And then they’ll finish that up with a 15 minute tempo run at a cadence of 90 plus.

So it’s all extremely high quality. And then once a month they’ll go out and do something big, something long, something voluminous that builds the mental tolerance to training, but that doesn’t dig so deep into the well as doing it every week.

And the reason for that is based off of the human body’s natural slow twitch muscle fibers. The human body’s ability to cool because we’re upright and not covered in fur and hair. Our ability to sweat, rather than pant, to reduce heat. And a cluster of other factors.

We’re pretty good at going for long periods of time. And when training for endurance, bigger limiters are things like power, speed, cadence, strength, the integrity of the fascia connective tissue, the intelligence to be able to use nutrients and calories properly.

And really pointing in one direction, and going for long periods of time is not that much of a weakness for the human body, but the problem is that it’s easy. And people take pride in it. They’re like, “Oh I persevered today. I did my three hour run.”

And my question to you is well yea, but what did you accomplish side from being on your feet for long periods of time? Which frankly I could stand up at my standing workstation and write an article for three hours and get the same amount of time on my feet as you just did out pounding the pavement. So it would be better in that case to do something with intervals at race pace for a shorter period of time.

Focus on cadence. Allow enough time before and after for a good warmup. Maybe some meditation and breath work. Some good recovery. And so that’s where the more intense, more quality, lower volume approach nine times out of ten trumps the voluminous approach.

The exception to that fact would be the person who has a lot of time on their hands to train: the professional athlete. Professional athletes, assuming they’re using this 80-20 approach, it’s called polarized training. 80 percent of your training is done aerobically, with about 20 percent done high intensity.

That approach works very well, and it is what a lot of the elite cross-country skiers and marathoners and cyclists etc. will use, but what is important to understand about that approach is it requires many, many hours per day.

That approach can require two to four hours per day of training, and even more than that, on weekends, for example. And the majority of folks simply don’t have the luxury of time available to utilize that approach effectively. That in a nut shell is my approach to training.

I’ve got a couple of athletes who I work with who are more, what I would consider to be on the professional level, who have that luxury of time. And I do train them with that aerobic approach, where they’re out doing long voluminous sets of training at a controlled heart rate aerobically, putting lots of time in the saddle or time on the pavement. But its very few and far between that I’ll recommend an athlete to train like that.

[Damien Blenkinsopp]: Great, great, thanks. That’s a great summary of it.

[39:01] I wanted to move on to, because I know you did this 12 months of ketogenic dieting. Could you talk a little bit about that? Give us an overview. What was your approach to that, what were you actually eating, and was there any specific goals to track over the year?

[Ben Greenfield]: Well yeah, for that specific diet, that was for a study at University of Connecticut that was done on, basically, a group of athletes who followed a high-carb/low-fat diet, versus a group of athletes who followed a high-fat/low-carb diet.

And it was basically a measurement of fat oxidation during exercise. And they also did muscle biopsies before and after exercise to see the rate of glycogen use as well as the rate of glycogen replenishment following the post work out meal to just see if the body does a better job at oxidizing fat, or at sparing glycogen during exercise when you’ve eaten a high-fat diet.

And it did turn out in that study that the athletes who followed the high-fat diet were oxidizing a lot of fat. The textbooks tell you that you can burn about 1.0 grams of fat per minute, and the group of athletes who followed the high-fat diet were burning 1.5, 1.6, 1.7 grams of fat per minute. Literally rewriting the textbooks when it comes to how much fat you can burn during exercise.

I haven’t seen the muscle biopsy data yet to see how much glycogen conservation actually took place, or whether or not the body became more glycogen depleted when using primarily fatty acids as a fuel. But ultimately, what that diet consisted of was really controlling carbohydrates.

Whereas I would normally – and this is what I do now – I would carb-cycle, or I would do cyclic-ketogensis or cyclic-ketosis, where I don’t eat carbohydrates all day long and at the very end of the day, typically in the post-workout scenario, with dinner I’ll eat anywhere from 75 to 200 grams of white rice, red wine, sweet potatoes, sourdough bread. You know, safe starches, not like pizza and ice cream, but good carbohydrates. And then the rest of the day just high fat and moderate protein.

Whereas on this full on ketosis diet, it was pretty much just things like bulletproof coffee, and high fat shakes and lots of coconut milk and coconut oil, and heavy cream and MCT oil and seeds and nuts, and just fats, fat, fats. Bone broth and avocados, and olives, and you name it.

And frankly, in my opinion, it wasn’t that enjoyable to have to not have sweet potato fries, and not have, even coconut ice cream has cane sugar in it. So you have to make your own with chocolate stevia. And so it’s a little bit laborious and a little bit tough, but I mean at the same time the endurance payoff was huge.

The amount of focus that I had for long periods of time. My ability to just hop on a bike and ride for hours with no fuel at all, with just water. It was pretty profound, because you produce all these ketones as a bi-product of fatty acid oxidation, and they’re used as the preferred fuel by the brain, by the heart, by the liver, by the diaphragm while you’re out exercising. And that’s a huge boon to an endurance athlete.

And like I mentioned, there’s some blow-back. Like the TSH could take a hit, the testosterone could take a hit. But ultimately, it’s a cool little bio-hack. If I could go back and do it over again, I would definitely start taking thyroid glandular earlier to stave off some of those thyroid issues.

I would,– it’s not legal – but I would really encourage folks to pay attention to testosterone. And I mean like, you can’t use testosterone in a WADA, or a USADA or like an NCAA sanctioned event, but my testosterone dropped so much during that experiment with ketosis, I would say if you’re not competing, use AndroGel or just some kind of testosterone support because your testosterone is going to fall to pieces.

And then the question becomes well is it really worth it to you if you’re doing this thing and you’re not even competing.

[Damien Blenkinsopp]: Yeah. Did you feel different?

[Ben Greenfield]: Oh, yeah.

[Damien Blenkinsopp]: Because we talk about testosterone with things like anxiety, your drive, your libido, of course. And so did you get any kind of low testosterone symptoms?

[Ben Greenfield]: Oh yeah. Absolutely. I mean even something as simple as only having to shave every four or five days, whereas normally I would just shave every one to two days.

[Damien Blenkinsopp]: That’s a benefit.

[Ben Greenfield]: I mean, little things like that, but you notice. Yeah, potentially. You save money on razors.

Yeah, the libido, sex drive, number of times having sex per week, desire to have sex, quality of the erection, all of those kind of things certainly they took a hit during ketosis. They weren’t good. But that was, mind you, ketosis in the presence of high amounts of physical activity. Even doing the ‘low volume approach’ it’s still a massive amount of work, right?

[Damien Blenkinsopp]: Right.

[Ben Greenfield]: You’re still working out 60 to 90 plus minutes every day, and longer than that on the weekends.

And you look at something like Dr. Terry Wahls and her ketosis approach for managing MS. Well sure. I mean, that’s going to work just fine for managing MS. I mean, going on a walk with your dog every morning, and maybe lifting easy weights, three sets of 10 for 20 minutes twice a week.

But once you jump into hard exercise, it’s a whole different type of ketosis.

[Damien Blenkinsopp]: Right, right. Just to be clear, were you getting better times? Did you feel like you were competing better?

[Ben Greenfield]: Oh, I was competing way better. Yeah. Absolutely.

[Damien Blenkinsopp]: Right. But it’s just the downsides to your lifestyle, to all the other things, were too great to do this on a constant basis.

[Ben Greenfield]: In my opinion, yes, because I don’t like being cold all the time, I don’t like not having libido. So again, I’m not saying you can’t do it properly, even though it’s way, way tougher once you get into training, but I think that you basically have to use supplementation pretty intensively.

[44:34] [Damien Blenkinsopp]: Did you kind of see the benefits evolve and get much better as the months passed, or is this something someone could do on a month basis, one month on and one month off?

[Ben Greenfield]: For exercise, you barely even see any benefits until you’ve been doing it consistently for about six months, and the real benefits start to manifest after one to two years.

But the other thing to realize is that right about the time I finished up the experiment, companies like KetoForce started coming out with beta hydroxybutyrate salts that could be consumed to elevate your ketone bodies, even in the presence of a lot of carbohydrates or glucose. And so it’s possible that now, since the experiment that I did, you could get the best of both worlds.

And I actually have some bottles of the beta hydroxybutyrate salts and the resistance starches, and a lot of the things that, if I had to go back and do it all over again, I would try to get the best of both worlds. I would eat more carbohydrates, but then I would also hack myself into ketosis by consuming actual ketones bodies.

The question there becomes a matter of long term health and gut health and how that actually manifests in terms of actual symptoms or the way you felt, or even I would definitely pay close attention to blood and biomarkers.

Were I to delve into that type of bio-hack? I potentially may. I could see myself, and obviously I’m at a point in my athletic career where I’ve still got a good eight years of hardcore performance left in my body, and I could see one of those years being spent utilizing a ketonic approach again, but with the incorporation of beta hydroxybutyrate salts, resistance starches, even higher amounts of MCT oils, particularly like the C8s and the C10s. And a little bit more attention paid to ways to get into ketosis that go above and beyond just carbohydrate restriction and exercise.

[Damien Blenkinsopp]: This is great Ben, this is a wealth of information.

[46:20] In terms of the biomarkers you would track, you said you would track some biomarkers if you were going to do this again what kinds of ones that we haven’t spoken about already would you look at? Did you track your blood ketones?

[Ben Greenfield]: Yeah. Breath ketones. I mean, urinary ketones become, many times, absent after a few weeks in ketosis just because you’re utilizing your ketones. Blood ketones are accurate but expensive and invasive to test, and breath ketones are pretty [easy].

There are breath testing monitors like the Ketonix device that, one breath and you know your ketones, and you’re good. So breath testing is a really good way to go as far as measurement of ketones. You look for values anywhere from 1.0 up to 3.0 millimolars. You’ll finish exercise as high as 7.0 millimolars.

You’ll rarely see ketoacidosis, which would be like 10 plus millimolars. It is a non-issue. I have yet to see any athlete I work with go under ketoacidosis, which would be an actual deleterious biological state. Not something you need to worry about unless you are letting yourself become severely hypoglycemic.

[47:20] [Damien Blenkinsopp]: So again, is that something you saw evolve over the months? Like your ketones ratings would get higher.

[Ben Greenfield]: Yeah. You get to the point where it’s just super duper easy to get into ketosis. Yeah. And your ability to go for long periods of time without eating just goes through the roof.

So ultimately, the biomarker I would say, in addition to what we’ve already talked about, would be breath ketones. And then pay attention to triglycerides too, because they’ve shown that compared to total cholesterol values, a better predictor of your coronary disease risk factors is your triglyceride to HDL ratio, specifically keeping that at one or lower in terms of your number of triglycerides versus HDL.

But I’ve found that some people will switch to a high-fat diet and have such a high intake of vegetable oils, and even an imbalanced high intake of animal based oils, like butter for example, versus olive oil and avocados. Their triglycerides go through the roof.

Pay attention to that HDL ratio. That’s my advice is make sure that that thing isn’t getting much above one, that would be another important thing to pay attention to, especially on a higher fat intake.

[Damien Blenkinsopp]: Great, great. Excellent points.

[48:25] So there are a couple of other things I’ve noticed you’ve done in your experiment. I read your book of course. One of the things that we’ve come across before – I spoke to Alan Cash from benaGene –oxaloacetate, and I was wondering what you’ve done with that and if you’ve tracked anything or learned anything about that.

[Ben Greenfield]: Yeah, obviously if you talked to Alan Cash your listeners can go back and listen to that to learn more about what oxaloacetate is. But in a nutshell, the reason that I used it was because it can increase the turnover rate of lactic acid into pyruvate, and increase the rate at which lactic acid is shuttled back up into the liver to be reconverted into glucose.

And so if you are eating a low-carbohydrate diet anyways, that by nature means you might not be taking as much exogenous glucose in, or might not even have as high a level of glycogen stores, but you can still take the lactic acid that you’re producing as a byproduct of metabolic activity anyways and have that reconverted into usable glucose sources to have a glycogen sparing effect and to get a little bit more intensity. And so the way that would be achieved if you’re going to increase the rate of that cycle, which is called the Cori cycle, would be via the use of oxaloacetate.

And so, I actually did use that. I don’t use it right now. It’s one of those things where it’s just like, I would benefit from it its just one more supplement to remember to take. But I certainly used it through that entire ketotic experiment with the oxaloacetate just to increase the conversion of lactic acid into glucose.

[Damien Blenkinsopp]: Right, it sounds like it would help specifically in that ketogenic diet state when you’re exercising.

[Ben Greenfield]: Exactly.

[Damien Blenkinsopp]: So you designed it that way? You decided to take it before, or was it something you came up with afterward to help?

[Ben Greenfield]: I talked to Alan at one of the Bulletproof bio-hacking conferences. We talked about the physiology of oxaloacetate, and then based on that I just kind of had a little light bulb moment, where I realized that if I was restricting carbohydrates anyway, that this was one more way that I could create endogenous glucose more quickly.

[Damien Blenkinsopp]: Great, great.

[50:27] Cold thermogenesis. Do you still play around with that? Is there anything like, for instance, have you seen your HSCRP any time, potentially when you first started it or did it a bit more intensively, change with that?

[Ben Greenfield]: Yes. I have not done a dedicated experiment with cold water exposure, cold temperature exposure, or the use of ice baths or cold showers to see the direct effects on HSCRP, although reduction of inflammatory cytokines has been observed in literature when it comes to cold thermogenesis and inflammation.

What I use cold thermogenesis for is increased conversion of white adipose tissue to brown adipose tissue. Simply because it’s very difficult to kill fat cells, but you can convert fat cells into energy utilizing and heat producing tissue. And that’s one thing that cold thermogenesis is good for. That would mean cold baths, cold showers, cold soaks, etc.

Also very useful for increased production of endothelial nitric oxide synthase, which can cause your blood vessels to dilate much more readily, which is good for everything from exercise to sex to heating your body when it needs to be heated. And then there’s also increased tolerance to the mammalian dive reflex, which is that activation of our sympathetic fight-or-light nervous system in response to stress.

And when you are able to withstand cold stress without taking that sharp influx of breath, that means that you have become more resilient and more resistant to subconscious activation of that fight-or-flight nervous system. You’re better at controlling stressful events that happen.

And so, what I do is I never take a warm shower. I do a cold shower in the morning, cold shower in the evening. I do once per week a 30 minute cold soak that gets me up to shivering level, typically needing to shiver for one to two hours afterward in order to regain warmth. And those are the ways that I use cold thermogenesis. I also keep my house relatively cold. My office is at about 55 degrees. In my home, typically I’ll sleep at 60 to 65 degrees.

It’s just a really, really good way to make yourself tough, to burn fat, and to increase blood vessel health. And it’s just super simple. And frankly, the other cool thing is when I go hunting or when I have long periods of time outdoors or when I’m at the beach and evening comes and I forgot my coat, I don’t get as bothered, which is just kind of nice. You’re just more tough.

[Damien Blenkinsopp]: It sounds like the only time it was an issue when you were doing you ketogenic thing. What was the issue there? Were you getting a lot colder, or?

[Ben Greenfield]: Yeah, but that was because of the thyroid. If you have hypothyroidism, cold thermogenesis is going to be very uncomfortable. Heck, even normal temperatures you’re colder during. So I was still doing cold thermogenesis then but it was quite unpleasant. It was hard for the body to get warm again.

[Damien Blenkinsopp]: Okay. Right, great.

[53:17] Some quick fly questions that I have just to finish off here.

First of all, if people want to connect with you and learn more about you and what you’re up to, where is the best place? Twitter, your website?

[Ben Greenfield]: Bengreenfieldfitness.com, because if you go there, you’ll find links to my Twitter, Facebook, Instagram, my blog, my podcast, etc. So that’s a good place to go as a portal.

[Damien Blenkinsopp]: Great, great. And who besides yourself would you recommend to learn more about endurance training, or some of the other topics we spoke about today? Ketogenic diets and so on?

[Ben Greenfield]: As far as people who have their head screwed on straight who are paying attention to the research, I’d say three people come to mind.

Number one would be Joe Friel. He’s coached a lot of professional cyclists, but also has just been in the sport a long time and pays attention to the science and the research and has a pretty good unbiased view of things.

Sami Inkinen, who is a top age group for Ironman competitor. He’s a higher fat diet, pays attention to quantified data, and is a smart, well spoken person who performs well.

And then Dr. Peter Attia, who I would not say is on the pointy edge of physical performance, even though he’s in much better shape than the average, general population. He’s not out doing Ironman triathlons or anything. But, as far as the science goes, he probably knows the science better than just about anybody else when it comes to being able to speak to these things, and he also does quite a bit of self-quantification himself.

So, those would be three people that would be good resources for this.

[Damien Blenkinsopp]: Great, thanks so much for that.

[54:48] Beyond everything, like all the biomarkers we’ve spoken about today, are there any other biomarkers you pay specific attention [to] on a routine basis, I don’t know whether it’s monthly –that you feel are important that we haven’t spoken about?

[Ben Greenfield]: I’ll finish with this because it’s important. And many times in our type of circles it’s not talked about, and it’s not quantifiable to a great degree, as far as I know. And that would be simply paying attention to your levels of gratitude every single day, and multiple times per day.

For me, I guess you could kind of quantify it – at least six times per day I’m grateful. Because I’m journaling, and at the beginning of the day I journal three things I’m grateful for, and at the end of the day I journal three amazing things that happened to me that day. So there’s at least six times per day that I’m being grateful for things.

And then I practice quick coherence technique, which is something you can read about at heartmath.org, which increases heart rate variability and decreases stress. And that’s where you simply think of something that you love or someone you hold dear, and you imagine intense feelings of gratefulness washing over your body and going into your heart after you feel those feelings of gratefulness.

Saying thank you to people, saying I love you to people, randomly calling up people and telling them how much you appreciate them. If you listen to my voicemail, I ask people to end their voice message by telling me one thing that they’re grateful for that day.

It’s certainly something that’s not super duper quantifiable, again, but it is one thing, not a biomarker, but certainly something I pay attention to every day is gratefulness for being alive, for the people in my life, for the experiences that I’ve had, and for simply being able to take one more breath.

[Damien Blenkinsopp]: Excellent. Thanks for that, that’s not the typical, but definitely something really important. So I can see how that would be useful. I do a meditation gratitude every morning too, and I find that really, really useful.

So Ben, thanks so much for your time today. It’s been really stock full of biomarkers and hacks and everything, so it’s really been a great episode. Thank you for your time.

[Ben Greenfield]: Awesome. Well thanks for having me on, Dam.

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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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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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