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

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

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

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

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

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

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

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

itunes quantified body

What You’ll Learn

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

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

Robb Wolf

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

Recommended Self-Experiments

7-Day Carb Test

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

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

Damien’s 7-Day Carb Test Results

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

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

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

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

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


Blood Ketone Response to 50g of Effective Carbohydrate


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


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



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

Lab Tests, Devices and Apps

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

Tools & Tactics

Diet & Nutrition

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


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

Tech & Devices

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

Other People, Books & Resources


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


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


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

Full Interview Transcript

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

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

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

[Robb Wolf]: Awesome, awesome.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

First of all you were talking about insulin resistance.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Yeah.

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

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

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

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

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

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

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

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

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

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

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

[Robb Wolf]: Yeah, Andrew Bernstein.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Robb Wolf]: Yeah.

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

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

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

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

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

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

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

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

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

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

[Robb Wolf]: Thank you.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Robb Wolf]: Sleep.

[Damien Blenkinsopp]: Okay.

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

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

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

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

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

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

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

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

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

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

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

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

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

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


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Ketone bodies, whether gained from fasting, keto diets, MCTs or exogenous ketones have many potential applications with benefits ranging from performance, to health, to longevity and mitigating symptoms and risks of certain diseases.

There is growing evidence that ketone bodies, whether they come from fasting, keto diets, MCTs or exogenous ketones have potential applications across many areas from longevity to performance, to health and mitigating some of the risks and symptoms of certain diseases like cancer and neurologically inclined deceases. As such the whole ketone body area is what I call a high leverage area due to the many potential upsides.

So I’ve personally been investing more time into experimenting in this area as the payoff for that effort, looks pretty promising. You’ll have noticed that I’ve done a fair amount of fasting and since late 2015, that also includes the exogenous ketones and playing around with the ketogenic diet. More to come on my results with all of those in future episodes.

This interview is a very in depth look at many of the applications of ketone bodies and the nuances of their use in the body.

Ketones have a unique effect of being… anaplerotic… [This] helps to generate the bioenergetic intermediates [including] the Krebs cycle intermediates… to energize the brain when fuel flow is kind of low.
– Dominic D’Agostino

Today’s guest is Dominic D’Agostino. Dominic has something that I found relatively rare but makes for extremely valuable interviews. He has a combined prospective coming from both research and self-experimentation. He has a considerable amount of lab work and research specifically done into ketogenic diets, ketones, ketone driving supplements and a growing number of applications. And he has done a lot of his own self-experimentation for many years in this area.

Dominic is currently an associate professor in the Department of Molecular Pharmacology and Physiology at the University of South Florida, and he’s also a senior research scientist at the Institute for Human & Machine Cognition (IHMC). His research is focused on developing and testing ketogenic diets, ketone supplements, and amino acid formulations for a broad range of therapeutic and performance applications.

His laboratory uses in-vivo and in-vitro techniques to understand the physiological, cellular, and molecular mechanism of nutritional ketosis and supplement formulas. His current efforts are focused on evaluating different methods for inducing and sustaining nutritional ketosis and how this can be optimized to the specific individual and applications. So, we’ll see in today’s interview that there are a lot of nuances and it’s a bit more complex than just boosting your ketones.

Dominic’s research is supported by the Office of Naval Research, The Department of Defense, Support Supplement Companies, and Private Foundations.

Special Note: In the interest of full disclosure, since late 2015 I own a company (Ketosource.co.uk) that develops ketogenic and ketone driving supplements, foods and drinks for the UK.

The episode highlights, biomarkers, and links to the apps, devices and labs and everything else mentioned are below. Enjoy the show and let me know if you want more on this topic in the comments!

itunes quantified body

What You’ll Learn

  • Using exogenous ketones to mitigate some of the impairments of sleep deprivation (all nighters, or jetlag) (5:50).
  • How the stress response from scenarios like jetlag will kick you out of ketosis (and can be compensated for via exogenous ketones) (13:00).
  • Dominic’s background research and how his career has evolved to working on ketone bodies and ketogenic diets and their applications (14:50).
  • Recent research with mice that may indicate that ketosis reduces anxiety (17:00).
  • Screening a range of different naturally derived exogenous ketone agents for their therapeutic and performance benefits (18:40).
  • A once to twice per year fast or nutritional ketosis protocol for potentially activating a range of beneficial genes (37:50).
  • The press-pulse ketone body strategy for the management of cancer (40:40).
  • The benefits of the ketogenic diet for the management of epilepsy over the pharmaceutical alternatives (49:20).
  • Using the ketogenic diet to restore normal appetite regulation (50:15).
  • The various health, performance and longevity applications for ketone bodies (52:00).
  • Potentially reducing tremors in Parkinsons and Alzheimers with the use of ketone bodies (57:10).
  • Evaluating the legitimacy of recently raised safety and effectiveness concerns related to ketone salts and MCTs based on scientific facts and their track record over the last two decades (1:01:10).
  • How racemic exogenous ketones suppress glucose more effectively than non-racemic exogenous ketones (1:13:40).
  • Using MCT oil powder as a staple product for coffee, baking and protein shakes to boost the ketogenic profile of your diet (1:16:00).
  • Avoiding liquid meals in order to be able to elevate protein intake higher while remaining in ketosis (1:18:00).
  • What a typical ketogenic day looks like for Dominic in terms of blood ketone measurements from morning to evening and how he optimizes it (1:20:00).
  • How Dominic has identified his optimum ketone and Glucose-Ketone Index ranges for mental performance (1:21:00).
  • To standardize and control for your blood ketones and glucose you need to be fairly sedentary (1:34:10)
  • Dominic D’Agostino’s recommended self-experiment with the largest potential upside with the tactic to test and biomarkers to track (1:42:00).

Thank Dominic D’Agostino on Twitter for this interview.
Click Here to show him some appreciation for doing this interview!

Dominic D’Agostino

Recommended Self-Experiment

  1. Tool/ Tactic: Start Intermittent Fasting with fasting windows of 18 hours and eating windows of 6 hours each day. Dom recommends listening to Matt Mattson’s talk on IF before you start.
  2. Tracking: Get some baseline lab tests before you start the IF and again 3-4, and/or 6-8 weeks afterwards to see the positive impacts. Your lab tests should include fasting glucose, triglycerides and hs-CRP.

Tools & Tactics

Diet & Nutrition

  • Well Formulated Ketogenic Diet: The high fat, low carb, moderate protein diet that puts you into ketosis with typical blood ketones of between 0.5 and 3 mmol/L depending on execution and the person. Not suggested for children, teens or people in their 20s with good insulin sensitivity in general.
    Foods Dominic Makes Particular Use of:

    • Coconut Cream: Combines the fats with some of the fiber from the coconut flesh. Coconut cream is also known as Coconut Butter.
    • Ghee (Clarified Butter): Butter that has had the dairy proteins removed to leave solely the fats. As such it is considered dairy-free.
    • Wild Sardines
    • Sour Cream with Live Cultures: Didn’t find a link to this – if you know a good source please let me know in the comments.
  • Fasting Protocols

  • Intermittent Fasting: Sometimes referred to as short-term fasting due to the typical 16 hour to 20 hour fasting window. Dom noted that he has spoken to a fair number of high-performing CEOs doing this routinely recently.
  • Fat Fast: A modified intermittent fasting protocol whereby you restrict caloric intake in the fasting window (e.g. 18 hours of day) to some fats, exogenous ketones and/ or MCTs instead of a pure fast (no food or calories). Dom finds this method effective and that he tends to be less hungry going into the eating window (i.e. 6 hour window).
  • Periodic Fasting: Typically refers to fasts spread out by once per week or once per month. We’ve done past self-experiments on the once per month periodic fasting protocols via a 5 day fast, 10 day fast and fast-mimicking diet.

Supplementation & Drugs

Exogenous Ketones

Dominic’s lab has looked at a variety of exogenous ketone formulations in different scenarios and applications. Amongst their papers are included improved blood lipid profiles1 and non-toxic metabolic management of cancer2.

MCTs and C8 (Caprylic Acid)

  • Brain Octane: Pure Caprylic Acid (C8) from Bulletproof Nutrition.
  • Keto8: Pure Caprylic Acid (C8) oil from KetoSports.
  • Quest MCT Powder: MCT powder that Dom is using as one of his staples mixed into coffee for example.

Dominic’s Sleep Deprivation Effects Mitigation Cocktail

  • Exogenous ketone: Take your pick from one of the exo ketones listed above. Is beneficial to combine with MCTs such as C8 or MCT powder.
  • Caffeine: Needs no introduction – use coffee or your other favorite
  • Huperzine A: A nootropic herb used for cognitive enhancement via modification of acetylcholine levels.


  • Metformin: A drug which is used to improve blood sugar regulation in diabetes. Researchers are looking at its wider applications with cancer treatment as it has been found to inhibit insulin secretion.
  • Ringer’s Lactate: The long term use of this racemic solution was noted as evidence as to the safety of racemic ketone salts.

Tech & Devices

  • Hyperbaric Oxygen Therapy: Increasing the amount of oxygen in the body with the use of a hyperbaric oxygen tank which uses air that is more highly saturated with oxygen and which is compressed. Dominic has worked on research with Doctor Thomas Seyfried looking at its application for cancer therapy in combination with ketogenic diets3.



    Glucose/ Ketone Metabolism

  • Glucose: Dom suggests aiming to keep values between 60 and 80mg/dl and that if you can maintain this all other biomarkers should be fine.
  • Glucose Tolerance (OGTT): The Oral Glucose Tolerance Test is a glucose challenge test whereby you take a certain number of grams (e.g. the typical standard is 75 or 100 grams) of glucose and test your body’s ability to regulate glucose and bring your blood glucose back into normal range over a certain time period (e.g. 2 or 4 hours). Dom used the OGTT to assess his insulin sensitivity – the more insulin sensitive you are the quicker your blood glucose returns to normal fasting levels e.g. between 60 and 80mg/dl optimally.
  • HOMA (Homeostatic Model Assessment): An alternative method to the OGTT used to assess insulin sensitivity/ insulin resistance.
  • Glucose-Ketone Index (GKI): This index was conceived by Thomas Seyfried and discussed in detail with him in episode 16. It assesses the weighting of the metabolism towards ketone vs. glucose. Lower values are ketone driven metabolisms and higher value (especially over 20) can be associated with heavy glucose metabolisms associated with chronic disease. Dom brought a new angle to this marker with an optimum everyday target he shoots for of between 2 to 4. Previously we discussed Thomas Seyfried’s recommendation of undertaking a 5 to 7 day therapeutic water fast once or more times per year targeting a GKI value under 1.
  • Lipids

  • Triglycerides: Dom believes this is the most important biomarker to watch. Optimum levels estimated as below 40mg/dl.
  • HDL: Higher HDL levels are said to be protective and beneficial. Dom’s value are around 90 mg/dl.
  • LDL: Dom believes keeping values in the normal to normal high reference range are perhaps optimal. This puts levels at approx. 80mg/dl to 110mg/dl. We previously discussed LDL in more depth in episode 7.
  • Other

  • hs-CRP (high sensitivity CRP): CRP (C-Reactive Protein) is a very common marker of inflammation that is used to assess cardiovascular risk amongst other things. It tends to drop on a ketogenic diet. Dom’s values have been between 0.1 and 0.2 since he quit dairy (Note: Damien’s levels are also at this level).
  • IGF-1: IGF-1 was discussed in more detail in our FMD episode. Dom’s IGF-1 values dropped significantly after quitting dairy.
  • Heart Rate: Typically heart rate is measured as the biomarker Resting Heart Rate (RHR) for standardization, which is an average of the beats per minute. See episode 1 to understand the use of RHR.
  • Blood Pressure: Optimum ranges are for systolic between 90 and 120 and dystolic 60 to 80 expressed as for example 110/70 mm Hg.

Lab Tests, Devices and Apps

Devices for Measuring Glucose & Ketones

The different approaches to measuring ketones provide different perspectives on your ketone metabolism. These can be looked at in terms of the ‘window of snapshot’ that they represent. Some methods have a snapshot of a longer duration, so provide more of an average reading, while others provide a direct status of that exact moment.

Moving from the more average-based value end of the scale to the more direct status end you have:

  1. Measuring ketones via the urine (via the ketone body acetoacetate) has the longest snapshot with it representing your ketone values over the last 5 to 6 hours.
  2. Measuring via the breath (the ketone body acetone) has a smaller snapshot window of the 2 hours leading up to the measurement.
  3. Measuring via the blood (via the ketone body beta hydroxybutyrate) provides you a snapshot of your ketone level at that exact moment.

The various devices available for glucose/ ketones testing and mentioend include:

  • Urine Ketone Strips: . Both hydration status and becoming keto-adapted interfere with the measurement values provided by this. Dominic recommends starting with urine test strips as they are the cheapest and effective until you get keto adapted.
  • Ketonix Breath Meter: Currently the only breath acetone meter. If you are moderate to high on this meter you are effectively in ketosis (i.e. typically over 0.5 mmol/L). Dom recommends this in particular for epilepsy since breath acetone has been correlated with seizure control.
  • Blood Glucose & Ketone Monitoring Systems
  • Precision Xtra: The most popular meter for testing blood glucose and ketones in the U.S. Has a broader reference range than the NOVA providing values for lower blood glucose levels instead of the LOW error.
  • Freestyle Optium Neo: Freestyle Optium Neo is the upcoming replacement for the PrecisionXtra, it comes from the same company and has similar functionality – the only difference in the meters seems to be a rebranding exercise.
  • Novamax Plus: Novamax Plus is a slightly cheaper meter with some greater accuracy and sensitivity concerns than the Precision Xtra or Freestyle Optium Neo.
  • Dexcom G5 CGM: A Continuous Glucose Monitor that Dom is about to start experimenting with for blood glucose optimization. Peter Attia has also been using this tracking device recently to optimize blood glucose regulation. We discussed continuous glucose monitoring and the devices available in episode 43

Other People, Books & Resources




Other Mentions

  • Tim Ferriss: Has been experimenting with the breathe hold extending effects of ketone bodies via ketogenic diet and exogenous ketones.
  • Ben Greenfield: Has been experimenting with using exogenous ketones for free-diving.

Organizations & Companies


Full Interview Transcript

Click Here to Read Transcript
(05:32) [Damien Blenkinsopp]: Dom welcome to the show.

[Dominic D’Agostino]: Thanks for having me, Damien.

[Damien Blenkinsopp]: Yes, it’s great to connect. So you’re just back from a trip to Budapest and you just told me that you’re doing something to bypass the jet lag?

(05:42) [Dominic D’Agostino]: Yeah. Sometimes depending on circumstances I try to prioritize sleep and try to get between six to seven hours sometimes eight on the weekends if I can. But in the absence of sleep, I like to test certain things.

Usually happens once every month or two or I’m going to have to skip one night completely and have to get thrown right back into the fire of work again. I’m doing that now, and testing some different exogenous ketones in combination with caffeine and some Huperzine, and a few other little things in a stack formula that I’m working on.

It seems to be working because I’m functioning and I’ve been able to manage my tasks in a way that allows me to get stuff done.

[Damien Blenkinsopp]: So, this could be a new jet lag formula? Or if you want to keep going on sleep deprivation and work for a night or something…

[Dominic D’Agostino]: Yeah. So, inevitably people will come to the situation where they have to meet a deadline and stay up all night to get something. I don’t recommend doing it all the time because you can get burned out. There is no pill that you can take that will substitute for sleep.

But there are ways to extend your productivity and performance with two or three days of no sleep. I don’t like when those situations arise, but I worked on ways to mitigate some of the impairments that accompany that.

(07:13) [Damien Blenkinsopp]: That’s excellent, that sounds like another application for exogenous ketones I had not thought of. I know there are a whole bunch I want to discuss with you because it seems like there’s quite a few of them. So now if you want to work all night, they can help with that.

I’m tempted actually, what is the mechanism behind that specifically for sleep, is it just a pure energy thing or?

[Dominic D’Agostino]: As far as sleep? Mitigating sleep?

[Damien Blenkinsopp]: Why would exogenous ketones help with?

[Dominic D’Agostino]: Yeah, I think there are several ways that they can help. You can formulate things to provide energy to the brain. There’s various, what we call tricarboxylic acid cycle intermediates, including alpha-Ketoglutarate, creatine – is actually something that could be beneficial to the brain when energy reserves are low, and ketones have a unique effect of being anaplerotic. So if something is anaplerotic it helps to generate the bioenergetic intermediates which include the Krebs cycle or also called the TCA cycle intermediates.

Essentially just helping to energize the brain when fuel flow is low. Many of the TCA cycle intermediates are also precursors to neurotransmitters. For example, alpha-Ketoglutarate is a precursor to glutamate, and then from glutamate through glutamic acid decarboxylase we make GABA.

So, ensuring that we have efficient energy flow to the brain and sort of stimulating anaplerotic reactions and bioenergetic reactions we can replenish the neurotransmitters. Being in a state of ketosis too, can also be glycogen sparing.
I always had the opinion that when we sleep, part of the function of sleep not only restore neurotransmitters but to also restore brain glycogen levels.

Glycogen is actually stored in the astrocytes of the brain. Astrocytes are not just for support cells they have a really important function that pertains to glutamate recycling and sort of dynamic interactions with the synapses and recycling of neurotransmitters and restoring brain glycogen levels is a function when we sleep.

I think we need to look into this more but I have a theory that being in a state of strong ketosis could prevent some of the glycogen depletion that accompanies a normal day in a person that is normally sort of carbohydrate fed.

Where the brain is sucking massive amounts of glucose but if you’re ensuring that it gets a steady fuel flow of ketones it’s going to be glycogen sparing in that way. Sort of like what Jeff Volek is doing with the athletes and it showed in a recent metabolism paper, that being keto-fat adapted and keto-adapted can actually be very glycogen sparing. If you look at the muscles of lead athletes on a carbohydrate restriction, amazingly their glycogen stores are topped off in the muscles.

I think the same thing is happening, I see no reason why it wouldn’t happen in the brain. Our energy reserves in our brain tank, adenosine goes up, neurotransmitters are depleted – we want to sleep. Being in a state of ketosis can slow that process, and exogenous ketones can be a tool in a toolbox to help with that.

[Damien Blenkinsopp]: That’s really fascinating. It’s like the biochemistry of sleep, we’re getting tired and I think we understand on a very basic level but you’ve just broken down quite a few mechanisms which lead to us needing to sleep and how to counter them.

[Dominic D’Agostino]: Yeah, sleep is a really complicated subject. I did my Ph.D. in a pulmonary critical care department that was also a sleep lab. So I sat in on a lot of rounds and meetings with residents and fellows about the mechanics of sleep.

It’s just a fascinating subject, and something I’ll probably get more into research wise. But I do teach the medical students about obstructive sleep apnea and central sleep apnea, that’s some of the research that I did in my Ph.D.

(11:22) [Damien Blenkinsopp]: Excellent, and you’re on a keto-diet as well right still?

[Dominic D’Agostino]: Yeah. I maintain that but I also like to cycle a little bit because I think a lot of the therapeutic and performance enhancing benefits can be achieved with nutritional ketosis but I also think it’s good to have relative changes.

Not to stay on something all the time, but to adjust your macronutrients a little bit, and also maybe your calories a little bit, and occasionally fasting. These relative changes can produce some pretty good performance and therapeutic effects.

[Damien Blenkinsopp]: It’s kind of like exercise like promoting metabolic flexibility, is that where you’re coming from?

[Dominic D’Agostino]: Yeah, that was what I was going to say and relate it back to a hormetic effect where relative changes are good. For a while, I just stayed on the exact same ketogenic diet for a long time and I started adjusting and playing around with different supplements and I realized it’s good to sort of adjust the diet and even adjust your calorie levels sometimes. My life is variable, it kind of fits on with my lifestyle too.

[Damien Blenkinsopp]: I feel the same way. I’m probably doing the something a bit more varied these days. So, it’s just interesting, you said you are basically stacking exogenous ketones for sleep on top of your keto diet. Does that push your levels quite high?

[Dominic D’Agostino]: At least doubles or maybe triples where I would be. I have noticed in the past that if I just stick to my normal diet and I cross time zones. I’ve been in at least a dozen time zones for the last month and a half, two months.

When I do that and I miss a complete night of sleep, coming from Southeast Asia completely flips circadian. I realized that I get a stress response from that I think my cortisol goes up, my sympathetic nervous system can be activated. And I notice that can kick me out of ketosis a little bit or I’ll have levels that are — I would predict there would be much higher based on the macronutrient profile that I’m eating and even fasting.

So, I find that exogenous ketones can sort of help in those situations where I put my body into an unaccustomed stress.

(13:36) [Damien Blenkinsopp]: That’s very interesting. I’ve started to use some of the supplements, exogenous ketones for different scenarios a bit like that situation but we can talk about that later. So, I wanted to give people a background, would you say your focus area is ketones, ketogenic diet? Is that what you’d call your focus area of research?

[Dominic D’Agostino]: Yeah. I’m classically sort of trained as a neuroscientist. I did my PhD in something very specific, it’s patch clamp electrophysiology where you measure from individual neurons and you record the membrane potential, firing frequency input resistance of individual neurons, either in cell culture or in a brain slice, and studying pharmacology and the metabolic activity. I became very interested in observing fundamental neuronal activity.

I became very interested in the metabolism that was supporting that. I realized that the life that I was seeing on the amplifier of the oscilloscope, these neurons firing was completely a result of the electrochemical and the electrical gradients between the neurons, they’re like little batteries.

That was generated completely by the metabolic activity so cells they need to maintain negative 56 kilojoules per mole of energy and they will do anything to do that. Some substrates and some means of generating ATP are more efficient than others. In my early work, I was actually looking at lactate.

I was interested in Ringer’s lactate, so racemic Ringer’s lactate is actually used on the battlefield and also in surgery when people have a lot of massive blood loss. Lactate is extremely efficient fuel, and I studied hypoxia in the brain and ischemia, and I was interested in lactate for that. That got me interested in this whole idea of developing and testing metabolic substrates to preserve and enhance brain energy metabolism in the face of extreme environments.

Our work for the last decade has been funded by the military. So I’m interested in particular situations that would accompany military operations, like a navy seal using a closed circuit rebreather with high levels of oxygen. He’s susceptible to a limitation of his mission, would be oxygen toxicity seizures so the fundamental neuroscience that I learned in my Ph.D.

I applied that to developing and testing metabolic base therapies to preserve that cognitive function and metabolic resilience in the environmental extreme of high-pressure oxygen. That’s sort of a fun thing to do because there’s many ways to do it. I’m always looking for the next, or the optimal formula, of ketones and that’s why we don’t focus on any one particular exogenous ketones. We screen a variety of ketogenic agents or formulas of them to identify the one that’s most neuroprotective or anticonvulsant.

Now, we do cancer studies and we do wound healing, performance applications – and it might be a different ketone for different applications and we’re testing that now. In Budapest, we actually presented some really interesting work on anxiety. So if we induce a state of nutritional ketosis, the anxiety levels go down pretty significantly. In a rodent model, they’ll spend more time in like an open-arm of an elevated plus maze.

Perhaps that reduced anxiety can play a role in reducing seizures too, so it’s another variable that we need to look at. I probably went off on a tangent. My background was neuroscience and now I do what I would call a nutritional neuroscience or metabolic based sort of strategies to target neuronal processes and neuroprotection.

(17:43) [Damien Blenkinsopp]: How many years have you been doing this now?

[Dominic D’Agostino]: I started neuroscience research as an undergraduate in 1997. So, it’s going on about — 1996 or 1997 — so about 20 years now I’ve been into neuroscience research. The office of navy research, post-doctoral fellowship, was the first large grant money that I’ve got, and that was 10 years ago.

It took me about four years to recognize that the most potent strategy for oxygen toxicity for mitigating that, which I was being funded to do would be a ketogenic approach. Then the ketogenic diet at that time was recognized as something very obscure even just six years ago. So the funding agency really wanted a ketogenic diet in a pill per se.

In addition, to our ketogenic diet research which I feel is also very important we have developed these synthetic and actually naturally derived ketogenic agents to mimic the effects of fasting, the ketogenic diet, and also to further augment the therapeutic efficacy of the ketogenic diet. If the ketogenic diet can only get you to one to two millimolar, and we boost it in another one or two millimolar with exogenous ketones. We’ve realized that, that can be very beneficial.

Not everyone can follow a ketogenic diet including performance applications or for therapeutic purposes.

[Damien Blenkinsopp]: People find it quite hard. I don’t think it’s relatively complex to get into it. I speak to a lot of people who think they’re in ketosis but they’re not.

[Dominic D’Agostino]: Yeah, I do too.

(19:25) [Damien Blenkinsopp]: It’s a little bit tricky I think. So, alas comes the supplementation and so on which could make it easier. I think what’s really awesome about you, you self-experiment as well in addition to your research.

You’re always looking for this stuff and I know you’ve been on a keto diet for a long time, when did you start that?

[Dominic D’Agostino]: Yeah, that’s the fun part of this research that I’m really excited about. Well looking back, I did low-carb diets for a while because I was always into powerlifting, fitness, and nutrition. So, I would experiment, and I was under the impression that being on ketosis was bad.

When I did a low-carb diet or what I call the ketogenic diet, I remember smelling like ammonia. Because it was basically a very high protein, zero carb diet, with a normal amount of fat. Then I got educated I guess, being connected with the folks at John’s Hopkins who are using this on a clinical setting. I read the book by John Freeman and Eric Kossoff at John’s Hopkins, which is a great book, ‘The Ketogenic Diet’ for epilepsy and other disorders that’s out there.

There are one or more popular books on Amazon. I realized wow I didn’t know what a ketogenic diet was. I didn’t realize it has this fascinating history. You know written with Travis Christofferson, we wrote a three part of series on Robb Wolf’s blog about the ketogenic diet the history. When I actually got into the 4:1 ratio ketogenic diet, the John’s Hopkins which is like 90% fat.

And I transitioned into a state of nutritional ketosis, it was kind of difficult in the beginning. After about two or three weeks I adapted quite well and started realizing the neurological benefits. The appetite suppression was pretty extreme it was difficult for me to maintain my weight even.

(21:16) [Damien Blenkinsopp]: In terms of losing weight?

[Dominic D’Agostino]: Yeah, because my protein level was really high. I think I was getting probably 300 grams of protein a day which is really high. So, I had to drop that down to about 100 grams of protein a day to hit those macronutrient ratios.

Probably about 120 grams a day of protein, which was a relative change that was really low. When I reduced my protein to 1/3 but elevated my fat, and I still kept going to the gym. But at the time my academic career was sort of going full steam and I was in the gym less, but still making it once or twice a week.

My weights that I was handling on major exercises were maintained so I realized that being in a state of nutritional ketosis had a pretty profound anti-catabolic effect. So, I figured I’d be wasting away if I wasn’t getting my body all these protein. But I was amazed that I could eat.

I even started experimenting and went down to like 60 or 80 grams of protein a day. Even after a couple weeks and months I was able to still move the same weights.

So it really blew my mind that shifting the metabolic physiology to being more fat and keto-adapted had this sort of protein sparing anti-catabolic effect. Which makes sense if you look at it through like an evolutionary lens.

So if we stop eating and we didn’t make ketones to fuel this big, highly energetic organ in our head. If the ketones weren’t providing fuel for our brain we would liberate a lot of gluconeogenic amino acids from the skeletal muscle, and we would quickly waste away probably in a week or two, for a lean individual. That’s important to recognize in the context of using a ketogenic diet for a weight loss strategy and also for body composition.

For example, athletes that need to make weight which many sports do — wrestling, boxing, mixed martial arts – keeping that power to weight ratio is important. We think from the studies that we’ve done, we actually just got a study approved finally for publication yesterday showing elite level athletes or advanced lifters that the ketogenic diet is quite effective for body composition alterations and preserving strength and muscle strength and performance.

So that should be out pretty soon in general strength and conditioning. We realize that the ketogenic diet has far more applications than just pediatric epilepsy, which was it’s original application. We’ve probably studied about 10 different applications now in our lab.

(23:59) [Damien Blenkinsopp]: Excellent. So I wanted to run through some of those applications. First of all taking a step back because you mentioned lactate earlier. I think the majority of us assumes that glucose is the main metabolism. Then we learned about ketones and we think maybe there’re two substrates that we’re using for metabolism.

As I understand it, it’s a lot more complicated right? That we’re using a number of different fuels at any time?

[Dominic D’Agostino]: Yeah. I think the big ones for brain metabolism, which our laboratory originally focused on and now we’ve branched off, would be glucose would be the primary fuel for most people. Then ketones are sort of a backup fuel.

If you’re on a ketogenic diet, you’re running this hybrid engine and you’re using both fuels at the same time. With ketones probably the most efficient of the two. Then lactate too.

When we exercise, we mobilize a lot of lactate and put a lot of lactate back into the bloodstream through what’s called the Cori cycle. We convert that back to glucose and then replenish liver glycogen or muscle glycogen. But that lactate can also go past the blood brain barrier across which is called the monocarboxylic acid transporters and provide a source of energy for our brains.

Lactate metabolism in the brain can also occur under conditions of oxygen deprivation, so it may be beneficial. That was also an interest in my earlier work, using lactate to preserve bioenergetic processes in the absence of oxygen. What we call hypoxia or anoxia, which is a complete lack of oxygen.

Interestingly ketones can generate more ATP per oxygen molecule consumed. In a hypoxic situation, ketone metabolism may also be able to preserve the bioenergetic state of the brain. That’s something that we’re also looking into hypoxia and ischemia protection of the brain with various fuels, ketones, lactate preventing or an alternative substrate to glucose.

In certain situations, neuropathologies and even a hypoxia, stroke, a brain injury for traumatic brain injury can cause a quick impairment of glucose utilization of the brain. By internalization of the GLUT3 transporter and also inactivation or reduced activity of Pyruvate dehydrogenase complex, the PDH complex, can be impaired under certain conditions of brain injury. Even certain viruses that cause neuroinflammation can impair this rate-limiting step for glucose metabolism.

So, alternative energy substrates are a way to bypass that glucose block.

(26:37)[Damien Blenkinsopp]: It’s like a diversification strategy?

[Dominic D’Agostino]: It is, in diving we always talk about being redundance. You need a level of redundancy to ensure safety. I think the brain does that pretty nicely. So we achieve that with fasting.

We have an alternative energy substrates being utilized in the absence of glucose. It’s interesting to be able to delve into that and understand what happens during fasting in different states. From my perspective, it’s a fascinating field of research to develop naturally derived or synthetic agents that can mimic those processes.

(27:17)[Damien Blenkinsopp]: Right. Because we are on a ketogenic diet do we also use fatty acids directly for energy substrates or do they have to be turned into ketones first?

[Dominic D’Agostino]: Yeah. Hepatic gluconeogenesis will be in a state of fasting, completely dependent upon the liberation of fatty acids from adipose tissue. Fat mobilization is directly almost correlated to a ketone production in that fasted state.

Our heart can use fatty acids more efficiently than glucose – our heart is an awesome fat burner. The skeletal muscle is an awesome fat burner especially in the keto-fat adapted athlete, the liver, various organs can use fatty acids quite efficiently. The long-chain fatty acids do not readily cross the blood-brain barrier.

Short chain fatty acids do, and medium chain fatty acids can actually cross the blood-brain barrier. So, that was actually an interest of mine and we did some brain metabolomic studies where we took out the hippocampus of some rodent models that we looked at. We saw a high level of the C8 and the CA10 MCT that we administered to the animals.

I think if you look at the ratio between the blood levels and the brain levels. I think there was a kind of like a 1:5 ratio, so that wasn’t readily getting through but a lot of it was getting into the brain. Of course, the brain was metabolizing it.

Our numbers might have not correlated precisely in a 1:1 ratio in that way. But it’s clear that our body can use fatty acids as fuels, and it’s an incredible fuel for our mitochondria. Because it metabolized exclusively in the mitochondria through oxidative phosphorylation.

(29:03) I would say ketone molecules are I’d like to call water soluble fat molecules, sort of an excessive beta-oxidation or accelerated beta-oxidation in the liver, contributes to the accumulation of acetyl-CoA which drives ketone production, and hepatic ketogenesis. So the acetyl-CoA essentially condenses to form acetoacetate. Then beta-hydroxybutyrate and these spill into the bloodstream.

So it’s interesting that the liver is a massive ketone producer but it lacks certain enzymes that prevent the liver from using the ketones as an energy source so it lacks succinyl-CoA transferase for example.

So, the liver will produce massive amounts of ketones. Then dump it into the bloodstream primarily for our central nervous system to maintain energy flow to the brain, then the central nervous system, and probably the heart too. The liver is a greedy organ, if you fast and you eat, the amino acids and glucose will basically stay in the liver and the liver will take what it needs and put whatever is left into the bloodstream.

But with ketones since the liver does not metabolize ketones it puts them immediately in the bloodstream when it’s burning fat for energy. Looking at it through an evolutionary lens, that function is to ensure that our brain gets adequate fuel flow. In the absence of food, if our brain tanked because we’re hypoglycemic, we wouldn’t be able to hunt.

So, being very lucid and having our brains energized during a period of food deprivation ensure that our species survived. The humans that weren’t able to do that did not get on and live. I think we’re sort of hardwired in a way to function optimally when we’re in a fasted state and that’s important to recognize.

Also, in the context of a society that’s programmed to give three high carbohydrate feedings per day. The metabolic program that is activated during fasting is largely silenced because of the societal norms, associated with our macronutrient profile, but also our eating pattern which is frequent feedings throughout the day.

(31:22)[Damien Blenkinsopp]: Yeah. One of the reasons I ask this is because I’ve had some fear and scared feedback about fasting for instance, which is a bit more of an extreme situation like ketogenic diet normally. One of the things I did was publish some of my own information on YouTube and I got some crazy comments from people saying I was going to die because my glucose was low.

I think it was 3.3 millimolar or something about 54-55 mg/dL. My mother’s a nurse and she saw the numbers and she was quite shocked at the time as well. Everyone thinks that we’re driven solely by glucose metabolism that’s the only thing they look at. So I think it’s really interesting that we have several various fuels that we can be going on, turns out that the glucose isn’t that important.

Someone else just sent me the numbers recently and they were the lowest I’d ever seen, like I was doing a fast and she got 1.8 millimolar with her glucose. I don’t know if you’ve seen anything that low.

[Dominic D’Agostino]: I did. Well, when I fasted for a week I tried some strategies, I probably shouldn’t talk about it here.

[Damien Blenkinsopp]: Okay. In case someone else does it.

[Dominic D’Agostino]: Yeah. After fasting a week, I was staying around the mid-fifties to low fifty’s and occasionally I would dip into the high forty’s depending on my activity and things like that. I did some strategies — I’ll label it as “strategies” — to lower it down to a level that the meter didn’t read, so it just actually was flashing low.

The lowest my meter was able to read was 25 or 26 mg/dL. I assume 25 that’s the limit. I spent a good part of the day with it flashing low and unable to read. I was using the Nova Max meter, and I was using the Precision Xtra Meter and also using the Neo Meter, so I had three different meters and I was scrambling.

[Damien Blenkinsopp]: Is that the Freestyle Optium Neo?

[Dominic D’Agostino]: Yeah. The freestyle like a lower profile sort of meter than the Precision Xtra. So I had three different meters, and I was measuring and I was like, “Oh no I don’t even know what my glucose is. All I know it’s probably under 1 millimolar range.”

I was starting to feel a little bit — using different pharmacological strategies to lower it — but I realized that I was at a level that was universally fatal for everyone if I didn’t have my ketones elevated.

[Damien Blenkinsopp]: Right. But if you had been admitted to the hospital, they’ll put you on the emergency ward most probably if you walked in like that.

[Dominic D’Agostino]: Yeah. During this particular day, I was preparing for a lecture, I was writing a grant it was really a productive day. As I was working I was doing these things and I would do measurements and work for a little bit more and it just goes to show it was a very dramatic demonstration an alternative energy source.

For me, that has tremendous implications therapeutically for someone that’s experiencing insulin shock or a neurological disease with impaired glucose metabolism. So we worked very closely with the glucose transporter type 1 deficiency association. It’s a rare disease where the brain does not have glucose available due to deficiency of the GLUT1 transporter.

There are many different diseases like that. I was also inspired by the work of George Cahill, there was a study that was published in 1967. The first author was Oliver Owen and they fasted subjects for 40 days.

In another report that wasn’t originally published with the original report. I found it in another book they administered insulin, 29 IU of insulin they gave IV. In these fasted subject they lowered the glucose down to 1-2 millimolar and kept it down there.

[Damien Blenkinsopp]: So it’s like 35 mg/dL somewhere around there?

[Dominic D’Agostino]: It’s not even that it was about that 25 range that my meter couldn’t read. So one millimolar would be 18 mg/dL. That inspired me, I was thinking if these subjects can fast for 40 days I could do a week.

It’s about five years ago or so that’s when I did the week long fast and did some experiments on myself. One of the most interesting things that happened to me was my breath hold time. So at the time I was outside a lot.

I was in and out of the pool, taking short walks and trying to stay active, keep my mind off of food. Because the main challenge was just the pleasure of eating was not there. I was swimming I was under the pool and I realized, “Wow,I had been down for quite a while”, and I wasn’t gasping for air.

I got back up to the surface and my girlfriend was there at the time, now my wife, and I started testing my breath hold time. I was like, “Keep an eye on me.” Normally I could do over a minute about 90 seconds, but I was able to stay down for three to four minutes which is remarkable.

I don’t have any kind of specialized training. I’ve been wanting to take a freediver course. I know Ben Greenfield did and we exchanged emails when he was going through that because he was trying exogenous ketones. But I found that after one week of fasting, I had a profound prolongation of my breath hold time. I think that’s fascinating to me.

Fasting does definitely start to shut down your metabolism. I think my body temperature probably went down a degree or two so the metabolic demands just weren’t there. But I think our drive to breath has a lot to do with our CO2 sensitivity.

So there’s receptors in the ventral respiratory group and the ventral surface of the medulla that sense CO2 levels and drive the urge to breathe. We also have the carotid bodies, at the bifurcation of the common carotid artery that sends oxygen and CO2 and they also mitigate or they also play a role in the drive to breath.

I think there’re interesting mechanisms going on there. A desensitization in some way or in combination to just altering our metabolic physiology. I think that has some practical benefits for different sports, maybe military operations.

I want to study that a little bit further with adaptations that happen during fasting.

[Damien Blenkinsopp]: Yes, very interesting. I’m wanting to go and test that out with freediving.

[Dominic D’Agostino]: A number of other people have, I think I might have mentioned it once or twice very briefly, not as descriptive in other podcasts but other people went out there and did it.

I think Tim Ferriss did it. I’m not sure if he’d blogged about it yet but he sent me quite a few texts and emails just saying that dramatically enhanced his breath hold time. So, I’m pretty sure it’s a real phenomenon.

(38:15) [Damien Blenkinsopp]: Very cool, to kind of round that conversation off. I get these emails, like I said, some people are scared because they get injured in fasting particularly a very low glucose levels of 30-35mg/dL.

Do you think that’s something to be concerned about or is it absolutely no problem? Typically, they have ketones like six millimolar, somewhere around there at that stage?

[Dominic D’Agostino]: I wouldn’t recommend that for a long term sustainment of life. Because there are a lot of biological processes that require glucose: red blood cells, your kidney, certain immune cells, and even biosynthetic processes like the generation of certain neurotransmitters are in some part glucose dependent. I think it’s good to get into that level and I’m going out on a limb by saying this to be a mainstream sort of medical college.

I actually think it’s very good to be in a state of nutritional ketosis with sustained hypoglycemia for a period of time, and to do that at least once a year, preferably a couple of times a year. I think what really kicks on a genetic program that activates so many biological processes that I think could be protective from enhanced insulin sensitivity to autophagy, to activating a number of different genes. There’s certain ones obviously, ampakine is activated, mTOR is suppressed.

You put tremendous metabolic stress on glycolytic cancer cells or pre-cancer cells that we may have in our body, sort of an immune activation. I know Dr. Adrienne Scheck is doing some work with the ketogenic diet and she’s doing some elegant work on the immune activation, and from the gist of it and from other bodies of literature it supports the idea that the immune system becomes hyper-vigilant, to recognizing and attacking existing cancer cells when we put our bodies into the state of fasting.

Either prolong fasting or even the ketogenic diet. I think it’s good to do that sometimes. But say if you’re on the ketogenic diet all the time in the state of moderate ketosis and then you fast.

You probably won’t get the same benefits as a person who’s on a high carb diet and did a fast. It would be a lot harder for that person who is on a high carb diet to do a fast. It would be greater stress because it’s that relative change or that pulse.

Thomas Seyfried and I we’re going to work on, it was originally his idea. We talked a lot about this press pulse phenomenon for the metabolic management of cancer. The press would just be a mild state of nutritional ketosis and the pulse could be periodic fasting or some of the things that we’re interested in. Such as hyperbaric oxygen therapy that could be pulsed exogenous ketones to further allow for a greater hypoglycemic response.

Also, you could pulse various cancer-specific metabolic drugs like 2-deoxyglucose, or dichloroacetate, or 3- Bromo Pyruvate] could be used. The press would just be nutritional ketosis and that would metabolically compromise a lot of the highly glycolytic, which corresponds to highly aggressive cancer cells.

(41:41)[Damien Blenkinsopp]: When you say press that would be like something chronic that you’re doing?

[Dominic D’Agostino]: Yeah. We know that being in a state of nutritional ketosis causes suppression of the hormone insulin. The cancer cells that light up on a fluorodeoxyglucose PET scan, a FDG-PET scan. The PET [or PET-CT] scan is really the gold standard technique.

I would say when it’s coupled with the CT scan allows you to precisely locate where that hypermetabolic activity is. So the PET-CT is an incredible, gold standard tool to assess the location and aggressiveness of existing cancer cells. The greater the standardized values that are coming out, like 2.5 would be sort of the normalized value.

If you have a PET scan showing SUVs of a 100 or 250, those cancer cells are very aggressive.

[Damien Blenkinsopp]: So they show up as the big red and yellow blotches?

[Dominic D’Agostino]: Yes.

(42:47)[Damien Blenkinsopp]: Yeah, we spoke to Gene Fine on a previous episode he was talking about the PET scan.

[Dominic D’Agostino]: Oh yeah. Actually Dr. Fine, you probably know he did a study for 28 days. He did a study with a ketogenic diet and he selected patients based on their PET scans. The topic that I was going to touch on is that insulin suppression correlates with ketosis.

I think even the title of his paper didn’t even mention the ketogenic diet, it was something like insulin inhibition therapy can be used to target cancer. It didn’t even talk about the ketogenic diet. But if you read the paper, he basically used the ketogenic diet to suppress the hormone insulin as a therapy for managing these hard to treat cancers or people who have failed the standard of care.

So, that would be the press that I’m talking about. The ketogenic diet limits glucose availability to the cancer cells. It suppresses the hormone insulin which drives IGF-1, mTOR and other factors that cause cancer cell growth and proliferation. I don’t know if Dr. Fine talked about it, but he has a number of publications.

I was inspired by his work and I actually got us to look at exogenous ketones and the effect on cancer cells. We find that if you limit glucose, suppress the hormone insulin and elevate ketones, the ketones themselves have anti-cancer effects. So, we did a study, we published in the International Journal of Cancer.

The first author was my graduate student at the time, Dr. Angela Poff, she’s now a research associate following up on this work. We gave ketones to highly aggressive cancer cells that have a glioblastoma-like origin. When we grew the cancer cells in the presence of ketones, even in the presence of 25 millimolar glucose, it inhibited, it dramatically slowed down cancer growth and proliferation.

(44:47) We did a viability testing where we looked at live cells and dead cells and the ratios of that. We found significantly more dead cells when we grew the cancer cells with ketones even in the presence of glucose. The take home was that ketones were probably turning down or shutting off a lot of some of the glycolytic mechanisms and there’s previous reports suggesting that ketone metabolism can turn down glycolytic metabolism.

So, that would be the press.

[Damien Blenkinsopp]: It sounds like a signal even for the cancer cells?

[Dominic D’Agostino]: Yes.

[Damien Blenkinsopp]: For them to switch them off even if they can’t use the ketones?

[Dominic D’Agostino]: Yeah, we think so. Now, we need to mechanistically dissect those kind of signals that are happening with the ketones because they do high-level sciences. Our lab approaches things a little different. We don’t sort of identify a target and then work up from that.

We screen a lot of things at the top and find out what works. Then, once we found out what actually causes animals to live longer or produce a neuroprotective effect then we go and try to find the mechanism.

(46:00) [Damien Blenkinsopp]: That sounds like a little bit like the pharmaceutical drug research process where they screen many many molecules for doing something. Correct me if I’m wrong. It seems like maybe it’s an efficient process to find things that work by just screening a lot of things and then focusing on the things that are working.

[Dominic D’Agostino]: Okay. So, it’s a little different, with pharmaceutical companies they actually target a mechanism or a biological kind of process and enzyme.

[Damien Blenkinsopp]: So they’re all looking for an end result right?

[Dominic D’Agostino]: Yeah. We’re testing a bunch of things, we don’t even know how they work. We’re testing various ketogenic exogenous ketone formulas and we don’t even have the pharmacokinetic nailed down yet. We don’t even know specifically how they’re metabolized.

We feel that it’s really important to get this research done so we can get these therapeutic agents out there as fast as possible. We screen a lot in various agents, first in human or first in animal, and then we identify what works. But the mechanisms, the metabolism is incredibly complex.

What we find is that it’s not working through one particular mechanism, it’s many different mechanisms working in synergy. The ketogenic diet, you have an increase in the GABA to glutamate ratio or ATP production you have a greater bioenergetic potential of the mitochondria. You have more TCA cycle intermediates.

The list goes on and on. There’s a science paper showing that ketones beta-hydroxybutyrate is a HDAC inhibitor. We published a nature medicine paper showing that inhibits the NLRP3 inflammasome and that’s independent of metabolism.

(47:41)[Damien Blenkinsopp]: So it’s like a huge dynamic system? There’s no way you can see all of the mechanisms going on there? As you’re saying you looked for the end effects and then you started looking for the mechanisms.

All of these mechanisms that you just brought up and started piecing them together to see how it worked after you’ve got the end result that you wanted.

[Dominic D’Agostino]: Yeah. The important thing is that it works and then the secondary important thing is to find out the mechanism. Because once you do know the mechanism, if the majority of the therapeutic effects or performance enhancing effects are due to a particular mechanism, out of many mechanisms. Then we can tweak the molecule of the formula, the pharmacokinetics, to further enhance that particular mechanism.

Then we can go back and tweak the formula, or the molecule to make it hydrolyze faster or to increase the sustainment of it, or deliver it in a certain nanoparticle formula to a particular tissue or something like that.

(48:37)[Damien Blenkinsopp]: So we’ve already spoken about quite a variety of basic applications, benefits of ketone based metabolism, and ketones. Could you just go through the top ones in your mind, maybe the ones that we haven’t already covered? So I know a lot of people are focused on weight loss for instance.

[Dominic D’Agostino]: That probably goes back to what they call the ‘Banting diet’. That even predates some of the work that I first got attracted to in epilepsy. So, epilepsy that would be the big thing.

The ketogenic diet, the only thing that is used for standard of care in mainstream medicine is the management of epilepsy. I always harp on this too, the ketogenic diet is grossly underutilized as a tool for managing epilepsy because it works when drugs fail.

It works in about two-thirds of the population. Imagine the efficacy of it if it was the first line of therapy. If you have a child that’s two or three years old and you load them up with anti-convulsant drugs, we know that these anticonvulsant drugs cause developmental delays. It’s even more important in pediatric epilepsy, I think to start with the ketogenic diet.

I just like to throw that out there. We’ve already talked about epilepsy. So, epilepsy would be the big one and obviously weight loss. You have the original Banting diet. Then Atkins came out with what he said was his famous diet but it was really a playoff with the Banting diet. It allows for effortless weight loss because when you’re in a state of nutritional ketosis the ketones function to control appetite.

It prevents your appetite from controlling you. We don’t really know the mechanisms that regulate appetite control, are incredibly complex. But we think that the ketones are essentially telling the brain it’s in a fed state, that’s the simplistic way to put it.

(50:32)[Damien Blenkinsopp]: Okay. Ketones get converted back into fat? Because people know that you basically pee ketones out when you first get onto a keto diet. Is that one of the mechanisms also?

[Dominic D’Agostino]: Well, yeah. If you collect all the urine of someone that’s on a ketogenic diet and then you look at how many calories are there, it’s pretty marginal. I think Atkins even advertised, “Look you’re peeing out fat, you’re peeing out calories.”

But it only came down to like 50 to a 100 calories or something like that. I think the big effect, the metabolic advantage really, is not that you’re burning more calories. I think there’re different organizations out there that we’re trying to prove if there’s a metabolic advantage to being in ketosis.

I think the big advantage that we need to focus on is appetite regulation. Our current diet of processed carbohydrates contributes to appetite dysregulation. The ketogenic diet is very effective at restoring sort of normal appetite behavior because there’s no fluctuations in blood glucose.

If we’re on a carbohydrate based diet and we go hypoglycemic that’s going to trigger an intense craving for carbohydrate re-feed to re-establish that glycemia. That’s completely abolished on the ketogenic diet.

So when you’re on a well formulated ketogenic diet, the craving that you’d have with hypoglycemia is going to be significantly attenuated if not abolished. We talked about weight loss and type 2 diabetes pretty much every disorder out there. Let’s think cancer, even kidney failure, neurological diseases like Alzheimer’s disease and many other pathologies are sort of linked pathophysiologically to the metabolic dysregulation and also obesity type 2 diabetes.

If a diet does promote a healthy weight loss and sustainment of that weight loss, it’s going to be therapeutic for many other disorders. Some of the things that we study include Alzheimer’s disease, ALS, we have a really active cancer research program in the lab. I have two Ph.D. students right now studying.

One is looking at Metformin and other cancer-specific metabolic drugs but combining it with a ketogenic diet. His main thing is to locate drugs. But we think some drugs will synergize with the ketogenic diet.

In another project is looking at the ketogenic diet or exogenous ketones and branch chain amino acids to mitigate cancer cachexia, which is muscle loss or wasting, so we’re looking at that. Exercise performance we’re looking at that. The most recent data that I’m really excited about because of the pretty robust effect as far as some of the behavioral models that we use.

One particular model is the elevated plus maze which looks at anxiety. We found that being in a state of nutritional ketosis that was induced completely with exogenous ketones stimulates in the elevated plus maze which is like a rodent going out on a catwalk. You can go into a cave or come out into an open area where you’re on a plank and you’re elevated in the air.

It’s a very anxiety producing situation. In our rodent models validate as a very useful model. We’ll spend much more time on the open arm and less more time hiding in the cave. We think that has significant implications for military personnel with PTSD and anxiety in general, and a lot of depression too is also sort of a comorbidity there with anxiety, a lot of depression, and anxiety fueled.

[Damien Blenkinsopp]: You’re saying that they’re willing to go out walk on the plank, take that risk and feel comfortable with it?

[Dominic D’Agostino]: Yeah.

(54:28)[Damien Blenkinsopp]: Do you measure it by time spent on the plank?

[Dominic D’Agostino]: Yeah. Less anti-social behavior I guess. We set up this elevated plus maze and then we have a whole video imaging system above it. We keep the animals as low stress as possible.

We have the same person working with the animals so they’re not experiencing different smells, and things like that. The room is very very quiet. We pay attention to circadian, light on light off things.

There’s a lot of variables that need to be controlled and then we image them in the absence of ketones. We see how much time they’re like in the middle, in the open arm, closed arm and our video camera system sort of can track all that. We have various programs and algorithms that do all the calculations for various things.

We do a bunch of animals just on a standard high carb diet. Then what we’ve been doing is testing various ketogenic agents, or various exogenous ketone and ketone formulas that would be administered 30 minutes prior to being put in this elevated plus maze, and being there for a couple of hours. Then we’ll track all that information, it’s all done blinded.

We have one person who’s, usually two people part of the project that’s administering the agent. The person that does the analysis does not know what the animal is receiving. We’ve got a pretty robust effect with a few of the ketogenic agents on reducing this anxiety behavior.

That’s some new data that we just presented literally less than a week ago in Budapest. That’s what I’m just returning back now. So we want to follow up on that. We used one dose, we need to determine what would be the optimal dose.

There’s a lot of work that we still need to do to optimize that and maybe think about putting together a formula that could be beneficial for people.

(56:30)[Damien Blenkinsopp]: Very cool. One of the ones you didn’t mentioned is Parkinson’s, is that something?

[Dominic D’Agostino]: Yeah. There’s an earlier study I think that was done by Dr. Theodore B. VanItallie. Dr. VanItallie is like 96 years old. We still communicate on the phone and through Email.

He was one of the original ketogenic diet researchers. He did a small sort of pilot study showing that people with Parkinson’s disease can follow a ketogenic diet and that being in a state of nutritional ketosis reduced the tremors associated with Parkinson’s disease and prevented some of the symptoms. Not a cure, but it could help manage some of the symptoms associated with Parkinson’s disease.

There really hasn’t been a good follow-up study to that. I know there was a ketone ester that was developed at NIH and a study at Oxford. There was that group that had a clinical trial open. But I think they might have had some problems recruiting people into that clinical trial, that opened a few years ago.

I know there was a clinical trial looking at the effects of exogenous ketones on Parkinson’s disease. And if we weren’t tied up with so many other projects I would be jumping on that. Because I was able to observe on Alzheimer’s patients when they took a medium chain triglyceride supplement, or even exogenous ketones. They would have pretty dramatic tremors.

And some Parkinson’s disease-like symptoms can be manifested in people with Alzheimer’s, especially advanced Alzheimer’s. I was able to observe and also got feedback from caretakers that when they induced a state of nutritional ketosis it really rapidly stops the tremors associated with that. So, that needs to be followed up on.

The pharmaceutical industry dictates a lot of what studies are done. Because you need a strong financial backing on top of a university, or chain of universities that supports this kind of research. On top of a review board, an IRB, that will prove this kind of research using these nutritional metabolic substances. There are many hurdles that need to happen.

Then you have to recruit patients on top of that and convince them that it’s not a drug but it’s a nasty tasting food that could potentially benefit you. They were like — well, it’s easier for a child, a son or a daughter [who] is bringing in their mom who is typically in a situation — 80 or 90 years old.

They’re not going to want to try to formulate some nasty tasting shake to do that. It’s much easier to just give them a pill. These are some of the things you see, the feedback that you get from people who are trying to implement these kinds of nutritional protocols in patients.

There’s a lot of hurdles. A lot of people ask me, “Well, if it’s so effective, how come science is not using the ketogenic diet or exogenous ketones to treat all these disorders?” I could write a book on the reasons why, but nutritional research is so hard to do.

Because nutrition is really tied into the lifestyle thing, and getting institutional support, getting the expertise needed, ensuring that patients are following through and complying with the protocol. All of these things are hard to do. A supplement, in theory, is a lot easier but we’re at the very initial stages. Because these are just new entities that just developed.

(1:00:16)[Damien Blenkinsopp]: Right, it’s only two and a half years you’ve had the ketone salts for instance, and the esters a bit longer?

[Dominic D’Agostino]: A little bit more than that. I would say the ketone ester was actually developed probably about 20 years ago, if you look into the animal literature. Then they were dropped because it was thought that they’re very expensive to produce and they taste like jet fuel.

Some of the people that originally developed these things, like Henri Brunengraber. He’s like a hardcore metabolic physiologist-scientist who develops a lot of remarkable things. But he kind of drops it and moves on to the next thing.

There’s also sharing the chair of his department and running a billion other things at the same time. So, I dug up some of this research and realized, “Wow, why didn’t anyone follow up on this?” Then I saw some of the work that was funded by DARPA, showing that they were the secret project.

They were using these ketone esters for warfighter performance enhancement. I found some patents and some files on that. I was like, “Well, this is what I need to explore, for use of CNS oxygen toxicity.”

Not only can the ketones potentially mitigate the oxygen seizures but the ketogenic diet was super effective. Even independent of the ideology of the seizures that it tends to work which is really remarkable. But instead of giving an anti-convulsant drug to a warfighter, which can dull your senses and impair your physical and cognitive performance.

You could be giving an anti-convulsant neuroprotective substance that enhances the physical and cognitive performance. It seemed like a win-win situation. I’d rapidly grasped this idea and just went into this manic state of writing grants and writing proposals, and digging up all the research.

Then, I was calling my program officer and I was like, “You need to hear this information and what I’m going to tell you.” We actually had a little meeting at our university and he was like, “We have to do this.” He was very generous to fund some of the initial basic science proof of concept research that demonstrated the efficacy of this ketone ester in mitigating oxygen toxicity.

It worked better than anything we had ever tested or anybody had ever tested, even drug wise. That’s going back in 2009 or 2010. From there, I’m really in safety because I’m really scared about bringing something to market that could potentially harm someone. I know there has been some discussion out there about the quote and quote dangers of a racemic beta-hydroxybutyrate salt.

People need to recognize the difference between someone’s opinion and scientific fact. The scientific fact is that racemic beta-hydroxybutyrate salts have been used for decades for treating a disorder called MAD, Multiple acyl-CoA dehydrogenase deficiency. I get Emails from the patients or from the parents that are treating their kids with this, and it’s like a miracle for them.

I also get Emails from parents that are treating their kids with glucose transporter type 1 deficiency syndrome with a racemic beta-hydroxybutyrate (sodium beta-hydroxybutyrate), which is actually a prescription you can get in Europe.

But they’re also using these commercially available ketone salt products which would be the ones that you might be familiar with. There’s KetoCana from KetoSports, Pruvit makes Keto OS, Forever Green makes Ketopia. The Kegenix product which is the one I’m testing now. It’s a really excellent exogenous ketone product.

This idea which was talked about in various podcasts, I think in Bulletproof podcasts and Ben Greenfield’s that racemic sodium beta-hydroxybutyrate was dangerous and ineffective. It is an opinion and there’s no science to back it up.

If you go back and listen to the podcast you’ll hear the speaker actually reference no actual studies. So, it has an intellectual property supporting the non-racemic, so that needs to be acknowledged and appreciated.

What is appreciated from my end, the science backing up the efficacy and the safety are really profound – like I’ve said on expert panels to approve some of these molecules. And no toxicologist or physiologist could find any evidence that racemic, which is the DL version of beta-hydroxybutyrate, was dangerous in any way.

For example, if you’re a medical doctor or a combat doctor on the field and you’re treating soldiers that have a loss of blood or you’re in the emergency room just talking to the ER doctors, use the Ringer’s Lactate and that’s Racemic lactate.

So, L-lactate would be the natural lactate that you would find in your body. The DL would be in an enantiomer or a mirror image of that lactate. Both of the lactate molecules get metabolized to energy. So, the same things happen with ketones. So the D and the L version get metabolized to ATP, to energy.

A lot of the metabolism has been worked out with very elegant tracer based fate association studies by Dr. Brunengraber at Case Western. Lactate Ringer’s has been used in millions of combat troops and emergency rooms. If there was a danger to using a racemic metabolate, there would be a lot of dead bodies around – and that has not been the case.

Actually, it’s FDA approved, it’s widely used and accepted, and it was even studied the difference between L-lactate and Racemic lactate before it became a standard of care. Actually, it was looked into, and it had exact same effect.

So, if you use the Racemic versus the L-lactate have the same effect at preserving the metabolic activity of the tissues and being protective in that way. So, that needs to be acknowledged that when statements are made, that they could be an opinion and not validated by scientific facts.

The ketone supplements that are on the market now that I’m aware of are very safe and from feedback, they’re very effective. I don’t support any particular ketone supplement that’s out there. I’ve tested all of them and they tend to elevate my beta-hydroxybutyrate and the .5 – 1 millimolar range for one dose.

So, for me to really boost my ketone levels up, I have to take a packet and a half, or a dose and a half, which I can tolerate pretty well. But I think there’s a lot of room for improvement and the products that are out there.

I hope to work with these companies, hoping that they will fund research to support the further development and evolution of these products for different applications.

(1:07:30)[Damien Blenkinsopp]: Excellent. Thanks for going through that because that’s something I have my eye on as well and wanting to get some more facts. Something else that was thrown out, a couple of things was that the racemics were less efficient or were ineffective?

We also have all of the MCTs which people are using to kick up their ketones as well. We have the C8 and C10 of the MCTs, there’re various products around. Another statement that was said they were undesirable and you should avoid those as well unless you really had to take them.

For instance, if you have Parkinson’s it was okay to take them but otherwise you shouldn’t be really taking them. But a lot of people are taking these. Right now, there’s a bulletproof brain octane. I’m sure a lot of people are taking that.

KetoSports has got their own product that I’ve been taking for a long time personally. I don’t know if you have got any comments on that?

[Dominic D’Agostino]: Yeah. I study a lot of very expensive exogenous ketone products. But the more I look into medium change triglycerides, especially the C8 oil which is digested and assimilated much differently than long-chain fatty acids. When you consume it, it basically perfuses the liver.

I mean it goes right to the liver via hepatic portal circulation. It goes right through to liver and is burned as energy. So, they’re poorly astrophied, which means they’re not re-astrophied back and packaged into chylomicrons, like long-chain fatty acids.

Once they reach the liver, it’s basically an obligate oxidation. The medium chains are almost completely oxidized to ketone bodies. Some of them will spill into the bloodstream because we find them in the brain tissue and other tissues.

But it’s independent of the various transporters too. For the medium chain triglycerides to get into the mitochondria there’s various CPT-1, for example, is not needed to get the MCT into the mitochondria. So, they bypass a lot of these rate limiting steps.

And you consume them, it goes right to the liver, you generate a lot of beta-hydroxybutyrate and some of that gets into the bloodstream. So you have the combination of ketones and the medium chain triglycerides going right to the mitochondria. And that can be very therapeutic and beneficial for many different disorders.

You have to realize that the person making that statement that MCTs are dangerous or ineffective, has some underlying personal interests in advancing the commercialization of his particular exogenous ketone, and that needs to be appreciated and understood.

From our perspective, we’re interested in testing that particular ketone formulation and 20 other, and finding out the truth, finding out which is most effective, which is safe. When it comes to the racemic, and the statement that racemic beta-hydroxybutyrate is not as effective. We have not found that out to be the case.

Actually, the first ketone ester that we studied for oxygen toxicity was a monoester of the R-beta-hydroxybutyrate we have formulated. And that did not prevent CNS oxygen toxicity, which actually was very strange to me. But the more research I did I found out that you needed to elevate both the acetoacetate and beta-hydroxybutyrate in the blood to mimic some of what happens naturally, physiologically.

The acetoacetate through spontaneous decarboxylation to acetone, or maybe it has it’s own metabolic effect independently. The elevation of acetoacetate was absolutely critical. It also in the presence of beta-hydroxybutyrate but it was absolutely critical to elevating both ketone bodies to get the anti-convulsing effect.

We published that in the American Journal of Physiology and showed the pharmacokinetics and seizure work with that. So, we screened a lot of agents and found out the particular ketone ester that we found to be most effective was 1,3-Buntanediol acetoacetate diester]. So it was 1,3-Buntanediol that was racemic, so it would make racemic beta-hydroxybutyrate.

But even the non-physiological enantiomer gets broken down and converted to Acetyl-CoA and some of that goes back to the physiological enantiomer so it all gets broken down and metabolized similarly to Ringer’s Lactate which is used in millions of patients.

But the important thing about that particular molecule is that when it’s consumed orally it gets hydrolyzed and it rapidly liberates the acetoacetate. Then the 1,3-Buntanediol gets metabolized in the liver and elevates beta-hydroxybutyrate. So you have both ketone bodies elevated in the blood. We find that it’s absolutely critical to get a certain level of acetoacetate to get the anticonvulsant effect.

(1:12:30) One thing I didn’t talk about was Angelman Syndrome, which is characterized by impairment of motor function and also drug resistant seizures. It’s extremely effective in an animal model of Angelman Syndrome.

If you look at Angelman Syndrome and the ketogenic diet, you come across case reports showing that it basically puts Angelman syndrome patients into remission, at least for seizures. So, it’s highly efficient for that.

So, the first ketone ester we studied was this R in the enantiomer, the hydroxybutyrate, and it was not effective. So it was actually the racemic version of a ketone ester that was most efficacious.

But we’re interested in exploring all different pathologies and finding out which one. So, we have not found out that the R and enantiomer is any more efficacious for any other disorder than the racemic. I think that’s important to acknowledge.

We also found that medium chain triglycerides tend to formulate really well with this exogenous ketones. Not only are they carriers but we think they enhance the transport across membranes and they improve the pharmacokinetic profile, two of many of the ketones salts. So when it’s formulated with MCTs which have the nice advantage of also being ketogenic.

One of the benefits of racemic, the other enantiomer, so there’s D and L. The L-enantiomer tends to impact the liver in a way that reduces hepatic gluconeogenesis. So, you have this hypoglycemic effect that is very well characterized by our laboratory and other peoples laboratory.

[Damien Blenkinsopp]: So you’re saying that ketones go up and the glucose goes down?

[Dominic D’Agostino]: Yeah. It’s more pronounced with the racemic and we don’t know why that is.

(1:14:22)[Damien Blenkinsopp]: Is that beneficial to some of the applications more than others? Weight loss for example?

[Dominic D’Agostino]: Yeah for weight loss, maybe for seizures too. We know that reducing glycolytic metabolism can be beneficial for seizures but also for cancer. As I mentioned, we have pre-active cancer research program.

The lower we can get glucose or glucose response to a meal, the lower we can reduce that, the better therapeutic efficacy we think the agent will have. If we formulate the agent with food, so every time our animal models will eat the food they’re getting a dose of it.

Instead of injecting into the animal or ‘gavaging’ it in the mouth for our cancer studies, we actually take these ketogenic agents and formulate it to about 10 to 20 percent of the weight of the food. Then we count the macronutrient ratio, and then they eat it.

Every time they’re eating the food they’re getting a dose of ketones with the glucose. Because we do a lot of our studies formulating with a high carb diet. Because we want to find out the therapeutic effects of the particular agent and distinguish that between the ketogenic diet.

But we also published a study, about a year ago, where we formulated the ketogenic diet with the ketogenic agent. We did this with a ketone ester and found that it further enhanced the anti-cancer effect of ketogenic diet.

(1:15:48)[Damien Blenkinsopp]: Okay. I’ve got a few questions about this. There’s some MCT powders on the market which combine glucose. Me coming from a ketogenic perspective, that’s not something I want to take with the MCT powder. There’re other powders which don’t have the glucose.

Is there anything to think about or is it not really an issue? Because there’s this effect of the ketones pushing down the glucose anyway? Would it have zero effect? I haven’t tested it myself yet.

[Dominic D’Agostino]: Yeah, the MCT powders on the market like Quest Nutrition?

[Damien Blenkinsopp]: Not Quest, they don’t. It’s basically the generic ones. There’s this cheaper one, generic one, where they’ll put glucose syrup in it and some other glycemic ingredients.

[Dominic D’Agostino]: Yeah, with my interest in the ketogenic diet and staying in ketosis, I would rather get my carbohydrates from things like vegetables, salads, blueberries and dark chocolate. Basically encompasses my carb intake there. So I would avoid that.

A staple product that I use, I have it right by me right now is the Quest MCT oil powder. I did a little bit of beta testing for them as they brought that to market. We went back and forth, and I tested that a lot.

I consumed a lot of that and I did tons of the blood work and got to the point where I was really impressed with the product. There’s not too many products that I consider staple products, maybe about a half a dozen in total that I keep with me all the time.

That MCT oil powder is great, it’s very versatile. You could use it in baking, you could put in my coffee, you can add it to protein shakes to further boost the ketogenic profile of your shakes.

[Damien Blenkinsopp]: Do you take that with you? I take this stuff as well, I’ve got it right next to me as well in my coffee [unclear (1:17:32)]. What I was going to say is that you take that on top of your ketogenic diet?

But I think an interesting thing, I talk to people and they’re taking the exogenous ketones or the MCT powder as a normal diet, or the body builder’s diet where it’s high protein, and they’re not doing a keto diet.

Then there are other people who are interested in getting keto but finding it difficult. They’re using it to ease into the keto diet. So there’re a couple of different applications people use them for different things. I’m just wondering what you’re ideas are in those scenarios.

Dominic D’Agostino]: Yeah. If I put the Quest MCT oil into my coffee or shakes or things like that. I generally try to avoid liquid meals, because liquid meals digest totally different. The only liquid meal that I have would be my coffee, and I would put in some coconut oil and MCT on top of that.

Occasionally, I put in butter or coconut cream. I’ve been using coconut cream instead of full cream. The benefit is that I can elevate my protein a little bit more. I generally eat two meals a day now that I’m home and not traveling.

My meal in the evening is about twice the calorie count. So, I get about a third of my food calories in the morning and about two-thirds in the evening, but I get a lot of fat calories during the day I guess. Because I’ll make my coffee and whip it up and then bring it in a thermos, and drink that mostly in the morning. Then I’ll have a little kicker in the afternoon maybe.

That fat balm, I guess if you want to call it that and occasionally take some exogenous ketones too during the day, if I’m testing different products. It just adds to my total fat macronutrient ratio.

I probably get — with the coconut cream, the butter, and the MCT oil powder — probably get about an extra 100 grams of fat from that. So that allows me to eat a little less fat with my meal in the evening, and that makes it maybe a little bit more palatable because I could add some more protein.

On a typical schedule, I will do my physical activity in the evening. Then I’d like to couple that with a little bit higher protein intake.

(1:19:51)[Damien Blenkinsopp]: Right. So using the exogenous ketones or the MCTs to offset gluconeogenesis? Is that the idea?

[Dominic D’Agostino]: Yeah. This morning I had three or four eggs cooked in coconut oil. I usually have sardines, oysters, chicken, or steak from the night before. Then I’ll have a little bit of green vegetables cooked in fat, and that will be my breakfast.

It will be roughly under a thousand calories, somewhere around 800 – 1000. Then, I’ll get 1,500 – 2000 calories in the evening. During the day, I might even get an extra 500 – 1,000 just of fat or ketones.

I stay semi- fasted, so if I eat 6am or 7am I feel the best when my ketones get highest between like 3pm and 6 or 7pm.

(1:20:53)[Damien Blenkinsopp]: Okay what levels of ketones would you have then?

[Dominic D’Agostino]: I say high but it’s not really that high. In the morning when I wake up it’s maybe 1.0, sometimes .5 if I ate more blueberries or chocolate the night before. Right now, approaching noon, it would start to creep up about 1.5.

Then towards the end of my work day, I’m usually approaching about a 2.0 – 2.5 or somewhere around there. If I’m lucky I budget my time where I can go to the gym so I will be typically be working out. Then if I go home I’ll do some stuff, take my dog for a walk, do some sprints, and that’s when I feel most energetic – when I’m fasted, and in ketosis.

(1:21:40)[Damien Blenkinsopp]: Right, and you’re saying your blood ketones would be 2.5 or something like that and you’d feel that’s when you’re most energetic? Or you feel your best at that time?

[Dominic D’Agostino]: Yeah. I try to subjectively do this too. Basically, I would carry my meter, and I would be like, “When do I feel most energetic, and lucid?”. Then, I would measure my glucose and ketones at that point.

And I find that basically if my glucose is about 3.5 millimolar and my ketones are about 1.5 to 2.0 is when I personally feel the best, as far as energetic. So that would be a glucose-ketone index if we use the Thomas Seyfried’s calculation, of about 2.0. When you’re approaching 1.0, you’re starting to get into that therapeutic range.

But I think for all intensive purposes, for the normal person, if you keep between 2.0-4.0. It would be very abnormal for someone in a normal society to even approach that. If you’re hitting that then you’re doing really well.

You’re in an altered metabolic state. If you can sustain that, I think you’re going to get a lot of therapeutic and performance benefits from that.

[Damien Blenkinsopp]: So 2.0 – 4.0 in the GKI — glucose-ketone index — from Thomas Seyfried?

[Dominic D’Agostino]: Yeah.

(1:22:58)[Damien Blenkinsopp]: Which we covered in his episode in the past. Yeah, the only time I’ve got below 1.0 is when I’d be fasting. I’ve tracked full days as well, every half an hour I’ve tracked, it looks pretty similar to yours.

I’ve heard you say before that over 5.0 millimolar, in terms of ketones has some metabolic downsides. So, I was wondering about the ranges. Are there ranges that people shoot for between this 2.0 – 4.0 basically? You don’t really want to be lower?

Right? Say on the GKI, you don’t want to be going down to 1.0 unless you’re fasting or doing some pulse?

[Dominic D’Agostino]: Yeah, unless you’re really in a total fasted calorie restricted, deprived state, I think between 5.0 and 6.0. I think there was a report in a 60 day fast up to 8.0 millimolar. So that it may be beneficial there for just maintaining that energetic flow to the brain.

But if you’re on an isocaloric diet not calorie restricted. I think staying between 1.0 – 2.0 is probably good. If you’re mildly calorie restricted or maybe towards the end of an intermittent fasting, the fasting portion of an intermittent fasting day, approaching 3.0 may be optimal.

I based this upon thousands of blood measurements that I’ve taken and literally hundreds of blood measurements from other people. Between 1.0 – 3.0 millimolar I think is good. We’ve even seen it in animals, once you dose them up to about over 5.0 they start hyperventilating.

You create a mild metabolic acidosis that needs to be compensated for, so that you get the hyperventilation, they start getting even drunk and sedated, when you really start getting up there and has signs of ketoacidosis. In cases where they’re sedentary, that could be the reason. If you’re approaching 5.0 or 6.0 millimolar and you’re in an all-out sprint, you’re using that.

So maybe in the case of an athlete approaching the higher numbers could be beneficial if you train for that. But say you’re not trained for that and you dose up really high. Your body perceives it as a foreign acidic-metabolic substrate that has to neutralize, your bicarbonate compensates, and you have respiratory-renal compensation that needs to compensate for that.

I just had this discussion in metabolism and physiology with some people that I really respect. They were making the argument that anything above 4.0 or 5.0 is really going to be toxic to the body. I didn’t argue against that but we agreed upon — and there’s some pretty sharp minds in the room — anywhere between 1.0 – 3.0 was probably optimal.

As you know staying in 2.0 – 3.0 range is really hard to do with diet. But staying in a 1.0 range is pretty easy to do with a diet. I do a modified Atkins or modified ketogenic diet, and that’s pretty easy.

Then if I add a little bit of exogenous ketones or some C8 on top of that. I can easily boost that up to 2.0 – 2.5. I think that would give me a metabolic, performance, and cognitive advantage. I’m pretty sure about that.

So, that’s what’s exciting to me. So, not using exogenous ketones in the place of a low carb diet — but you might be able to do that too — I’m actually thinking about doing some experiment of getting off of my ketogenic diet for a period of time.

Not going super high carb but just being out of a state of nutritional ketosis and then adding supplements back in and then doing some blood work and see what happens there. I just haven’t got around to doing it because I enjoy eating ketogenic so much.

[Damien Blenkinsopp]: Right. Once you get into it for a while it’s like you don’t have to eat very often.

[Dominic D’Agostino]: It’s almost like I dread doing it.

(1:26:51)[Damien Blenkinsopp]: I was testing some of the supplements, the different supplements. I don’t think I didn’t do it very well. But what I was doing I was eating in the evening basically a high-carb meal lots of rice to put myself out of ketosis.

I did this for about a week and then tested different supplements in the morning. For the first reason, I don’t think it was a great control because I am basically keto-adapted now. I tend to pop straight back into ketosis relatively quickly.

I’d like your feedback on that whether it’s a decent control. Maybe I’m no good as a control because I’ve been just keto-adapted for a while and also may be I’d have to go for a few days ‘carbing’ it to make it a bit more realistic. What are your thoughts on that?

If you’re trying to do some normal, the first thing is, going back to your point about exogenous ketones. You’re saying like if someone just takes it straight off as some people are doing right now. They’ve been on a carb diet the whole time.

Then they can’t necessarily utilize those because they’re not keto or fat adapted. How long does that take? Should we be taking a lot of these when they haven’t really had that much exposure?

Do they have to take them over a period of a week or longer in order to start getting more benefits from taking them?

[Dominic D’Agostino]: Yeah, that’s a good question. Interestingly, we can use exogenous ketones even if we’re not keto-adapted at all, and that was our first study that we did for CNS oxygen toxicity. It was actually rats eating a standard rodent chow which is 60-70 percent carbohydrates.

We gave a single dose not even feeding it chronically, 30 minutes prior to doing a deep oxygen dive. It worked remarkably well and that really surprised me. So, taking a little bit of a step back, we use the R-enantiomer of the beta-hydroxybutyrate, and it didn’t work.

But then when we found out the ester that did work, that particular compound worked remarkably well. That kind of changed my thinking because I approached it with the understanding or the bias that you really need to be keto-adapted. But if you are adapted to burning fat and ketones for fuel, what has been shown is that you do up-regulate the transporters and the enzymes associated with ketone metabolism.

So, you will theoretically be deriving more benefit from exogenous ketones if you have been previously adapted to a ketogenic diet. I think from a practical standpoint, say you’re on a ketogenic diet and you choose to transition to eating carbs for some reason and then you throw ketones back in. Since you’re adapted to a ketogenic diet already, I think you’ll use those ketones more efficiently even by following a carbohydrate based diet.

We have some evidence to indicate that glucose disposal is enhanced in the presence of ketones. So, it may actually be enhancing insulin sensitivity. The glucose goes does, if you have animals eating a high carb diet and you bolus exogenous ketones, the glucose goes down remarkably low. Much more than you even get with something like Metformin.

What we don’t know why that’s happening, we want to look at the liver metabolimic profile. I think it could be influencing the liver in some way, and may be decreasing hepatic glucose output. Really it’s your liver that dictates your blood glucose, it’s all happening in the liver.

So, if you turn down gluconeogenesis in the liver, you would see a decrease in blood glucose. But also if you’re enhancing insulin sensitivity you would be facilitating glucose disposal and peripheral tissues with ketones. I know Dr. Richard Veech at the NIH has written about that and suggested that ketones actually do enhance glucose uptake and insulin sensitivity.

I get the question, what if you throw ketones on top of carbohydrates? What are the cells going to use? I think the cells will use what’s available to them and we know that the brain might not be able to use the certain types of fatty acids but they can use MCTs.

If you have glucose and ketones in the blood, your cells, your muscle cells, brain cells will be using both fuels. There’s some evidence that suggests that it will be using the glucose more efficiently in the presence of ketones. Because we know ketones can lower reactive oxygen species.

Excess ROS production can decrease insulin sensitivity and cause protein nucleic and lipid peroxidation that can inhibit glucose transporter processes. Even translocation of glucose transporters to the membrane or even PDH complex could be sensitive to the Redox state of the cell.

Ketones tend to normalize or prevent an oxidative environment that could potentially impair glucose transport and insulin sensitivity.

(1:31:56)[Damien Blenkinsopp]: There’s such a wealth of information in this area. It’s not like ketones are a panacea, but there’s just so many applications we’ve spoken about today, so I could go on talking to you for absolute forever. I’m conscious of your time also.

I wanted to round off of a bit of what you do more in terms of optimizing yourself and what you think is effective. For instance, in terms of blood ketones, you said you’re tracking your blood ketones. Have you used the other methods, the urine or the breath method?

The strips for the blood can be a little bit inaccessible in the UK, in the US sometimes, and also they are really expensive. The price varies. I’m sure you have your own ways of getting them but for everyone else it can be a little bit difficult, particularly in the UK I’ve found.

What do you think of the breath? There’s the Ketonix looking at the acetone instead. Do you think that correlates with the blood ketones, and it’s an okay way to try and optimize or not?

[Dominic D’Agostino]: Yeah, it’s a good question. I get this frequently. What I would say the breath, if you’re measuring moderate to high on a breath acetone meter you’re definitely in ketosis. I like it, and I wish it was more quantitative because I’m a numbers guy.

I think we’re all sort of what’s your number? There was like a ketone competition in the lab and my friends like, “You know what’s your ketones today?”. So we like numbers and I wish the unit could be designed.

I believe [unclear (1:33:20)] who’s working on a quantified meter. I like it, and I think it’s great for kids that are trying to manage their epilepsy because breath acetone has correlated with seizure control. So if you give this to a kid and he blows in it and he sees colors and he gets excited, I think that’s great.

It’s giving you a relative level but it’s not a precise level. But it’s also a snapshot of your level of ketosis over the last couple of hours. So your blood, beta-hydroxybutyrate can change.

I’m standing here in front of my desk and talking to you and relatively sedentary. But if I was to go and take a brisk walk on the other side of campus which I do occasionally to get things signed. I’ll come back and measure my ketones, and it’ll be cut in half.

It’ll go from two to one, or below one, just from brisk walk where it should be increased right? Because I should be mobilizing fat, I’m burning fat. But I’ve burnt those ketones for fuel during my movement.

(1:34:25)[Damien Blenkinsopp]: So then it goes into glycogen? I’ve seen this before and I didn’t understand it, that’s why I’m pretty curious.

[Dominic D’Agostino]: Well, it’s burned as fuel. Ketones are substrates, so they’re going to be burned up as fuel. And yes, you may mobilize glycogen from the liver so your glucose can actually go up. You might have some lactic acid from your muscles and through the Cori cycle goes back to the liver and you get some glucose in the blood.

The stress, the sympathetic nervous system from moving and running across traffic and navigating or whatever you do when you walk, that can contribute. What I really found that’s most important is you need to be completely calm and sedentary when you make these measurements to get accurate measurements to prevent the variability.

We have this issue with our rodent studies, we need to pull the food from them for about four to eight hours, to normalize the blood glucose. Because you have some that are nibbling on food, some that have gorged, others haven’t eaten. So the glucose is going to be all over.

To standardize and normalize glucose, you need to remove their food for a little bit and the numbers are tighter. The same thing applies for measuring ketones, especially blood ketones, you need to be fairly sedentary to do it. I really like the urine ketone strips, got a bad wrap, but I like the urine ketone strips.

They’re still used by John’s Hopkins. So, before you go spending a lot of money on getting ketone strips for the meter. You want to first confirm that you’re actually in ketosis on a urine strip.

If you’re registering 15 or 40 mg/dL on a ketone strip then it’s like, “Okay, at least if I take a blood measurement now. I’m going to register something on my blood meter and it’s going to be ‘I’m in ketosis’.” I remember the other meter, I think it’s the Novamax meter, would just give you this annoying, ‘low’, it won’t even read your number on it.

One person went out and bought a couple hundred hours worth of strips and have like 17 lows on there, and have come to find out you’re just eating too much protein or they think it’s okay to drink fruit juice. I forgot what the situation was.

Well first change your diet, then go out and get some urine ketone strips. Once you’re actually in ketosis on the urine strip then go back to the blood meter. And come to find that they tweaked their diet a little bit.

They did it until they were measuring ketones on the urine strip and they went to the blood meter, and bang they get 1.2 and they get all excited. So they could’ve saved a lot of money.

(1:37:04)[Damien Blenkinsopp]: Right. Because the urine gets a bad wrap, because it stops working once you get more keto-adapted. But when you’re first on a ketogenic diet and you’re trying to check that, that’s not going to happen. Right?

[Dominic D’Agostino]: Hydration state too, also plays a role, and less ketones will spill into the urine over time because you’ll conserve them as fuel. The transporters change a little bit. But if your hydration — if you’re drinking lots of water those people who carry water around with them and drinking.

Your urine ketones may register pretty low. Sometimes I wake up dehydrated and I would check my urine ketones will be quite high, whereas my blood ketones would be quite low. So, that’s just an indication of my hydration status.

It’s also a snapshot of what your ketones were over the last four, five, six hours because that urine is collecting in your bladder over time. So it’s sort of a snapshot of what’s happening through the course of the day, whereas your blood ketone is a snapshot of your ketone level at that point in time.

(1:38:04)[Damien Blenkinsopp]: Right, just a bit of information more about you and what you do these days? In terms of tracking things, it seems like you’ve tracked a lot yourself. Are there things that have stood out for you?

Overall, the time that you’ve tracked yourself and you found really useful insights from? Any quants or anything you’ve changed something you do in your life because of that?

[Dominic D’Agostino]: Yeah, I think initially when I started doing the ketogenic diet it was very dairy based. I was taking lots of creams, a stick or two. Two sticks of butter a day. So, I had a really high intake of dairy fat, probably about 200 plus grams of fat per day of dairy.

My LDL went up pretty high and my triglycerides went down a little bit but not really low. Then, I started replacing some of the dairy fat or the whole cream with coconut cream, and just using a little more coconut oil, getting more avocado in from my fats.

I still get dairy fat, by a sour cream that has live cultures in it. I’ll probably get about 50 to 70 grams of fat per day from dairy instead of like 250 grams of fat which I was getting initially. My lab test has improved. I guess you would say, I think my insulin sensitivity is better.

My glucose I can get lower glucose numbers now after eliminating some dairy. My triglycerides are really low now, they stay at 40s to 50s, I think it was 36 at one time. My HDL has improved and better and it’s really high, like 90 something.

My LDL went from really high to normal, but normal high. Now, which I think is completely normal and actually maybe even optimal. My IGF-1 levels are really low now compared to when I was on dairy.

I think dairy may have been contributing a little bit to some insulin resistance or maybe I was just getting a surplus amount of calories. My CRP levels also are the lowest now than they’ve ever been. I mean it’s like 0.1 or 0.2.

[Damien Blenkinsopp]: Right. Basically nothing, that’s the bottom of the range.

[Dominic D’Agostino]: Yeah, it’s like totally bombed out. I just feel better. If I eat a lot of dairy, I do wake up a little bit slightly congested, stuffy in my nose but it’s not bad.

I wouldn’t call it an allergies, and it could be due to allergies. But eliminating that has sort of helped, not eliminating, but reducing the amount of dairy. I don’t get in a whole lot of dairy protein. Maybe a slice of cheese here and there but I limit that. I limit casein. I don’t take away protein anymore.

The dairy that I get is primarily dairy fat. I was actually thinking about, I get very little butter, but I was going to switch to Ghee, and do some clarified butter. The triglycerides I would say for people to look at, for physiological biomarkers, your heart rate, blood pressure, sleep is an important one.

I wear the FitBit Charged. It’s really fun to look at my heart rate during the course of the day and in my sleep, and those sorts of things. I have a Dexcom that I’m going to put in. And I want to…

[Damien Blenkinsopp]: Is that the latest one? Is it the 4 or 5?

[Dominic D’Agostino]: Yeah.

[Damien Blenkinsopp]: I know Peter Attia is playing with that.

[Dominic D’Agostino]: Yeah, the 5 I think it is. So, I’ve just been traveling I just wanted to wait until I was put it in one spot and I can test it. I’m interested in trying that, and maybe working with some companies too, to do a glucose and ketone Dexcom.

I’m hoping to try that. That would definitely fit into your show. Yeah Quantified Self, and get some data for that, that would be good. As far as looking at physical biomarkers, you want to look at blood pressure, heart rates, sleep, and all these things improved when I got on a ketogenic diet.

I think there were various reasons for that. The lab test, the simple ones are probably the most beneficial ones. Triglycerides are the things that I look at the most. My HDL I think is important, and CRP, and of course your blood glucose. If you’re keeping glucose levels between 60 – 80, and doing that pretty much all the time.

Everything else is going to be good, that’s what I find.

(1:42:35)[Damien Blenkinsopp]: You said you did an insulin sensitivity, was that the homo or was it something else?

[Dominic D’Agostino]: No, I didn’t do that. I did the glucose tolerance.

[Damien Blenkinsopp]: Okay, the challenge.

[Dominic D’Agostino]: Yeah. I did like 50 grams, 75 and 100 grams I think. I think that was like over four hours, the 100-gram ones. Yeah, you drink the nasty Slurpee glucose and look at that. I’m extremely insulin sensitive. I dispose of glucose very fast.

I can also get a little bit of a hypoglycemic effect. If I’m on a ketogenic diet, and I go off of it. For example, I get some rice, sushi, or something like that, I will dip down into the low 50s and bounce back up again – very, very insulin sensitive.

(1:43:18)[Damien Blenkinsopp]: Thanks for that. If you were to recommend one experiment. I can guess what you’re going to say. So, we should try to improve the body whether it’s health performance longevity with the biggest payoff.

What would that be? How should they track it to make sure it’s getting that payoff?

[Dominic D’Agostino]: It depends on the person really. I don’t think low carb ketogenic diets are ideal for people in their teens or early 20s because they may be extremely insulin sensitive. I know I have tons of friends and I’ve even measured their glucose levels, and they’re great.

They stay pretty low, the glucose levels and they have adapted really well to a high carb diet. They wouldn’t want to do a ketogenic diet. So, maybe you’re expecting that kind of answer.

But, I think periodic fasting would be an important thing to do. I’ve been talking to some high-level CEO people and they tell me, “Well, I’ve been doing this anyway because I’m so busy. I wake up and I just work all day, and just go home and eat at night.”

But if your pattern of eating — like my patter of eating — I was obsessed with eating every two hours especially when I was really into lifting. I felt I had this preoccupation with food, preparing my meals, carrying it with me. I think it’s very liberating to not have to do that and to realize that your performance, energy levels, are not going to tank if you eat one meal a day.

If you were to do a short term fast, initially, and to do that every once in a while. I think, not only is very good for your metabolic health. I think it’s also good for your state of mind because it tells your body. It tells your mind that you don’t have to be sort of psychologically dependent upon food.

I would go five or six hours, and I’ll be like, “I’m starving I have to eat something.” I have been around people that are like that. My wife is kind of like that, she’s an incredible carb burner.

But if we’re traveling and she’s gone four to five hours without having a meal. I could see it in her mood and in everything. But that’s fine we’ll stop and get something to eat, and usually we’ll have coffee or something like that. But it’s interesting to see, and she sees it in me, “How could you go this long? Aren’t you hungry? What’s wrong with you?”.

She understands it now. She’s watched me do so many tricks and everything. If you’re not a big fan of being hungry. If you’re not a fan of having to eat every two or three hours because you’re hungry. I think doing some intermittent fasting would be a really good experiment for you to do.

I actually interviewed Mark Mattson at IHMC. So, I’m also a research scientist at Institute for Human and Machine Cognition. We interviewed Mattson, I think you did too for a podcast. He really went into the benefits of intermittent fasting and he’s at the National Institute of Health.

If you get a chance, he gave a brilliant lecture, presentation. If you go to IHMC lectures and look up Mark Mattson, he gave a great talk on this. He talks about all the health benefits.

If you do embark — if your listeners embark on [an] intermittent fasting experiment it would be interesting for them to track their blood glucose levels, their ketone levels, their triglycerides and their c-reactive protein. I think in each one of those biomarkers, if you want to call them that, will improve with intermittent fasting. I’ve seen it.

(1:46:51)[Damien Blenkinsopp]: You’re saying the 16-hour window or one day? Because you said short-fast, do you mean like a one day, 16, or 20 hours?

[Dominic D’Agostino]: Yeah. You could do every other day eating. But I think the easiest thing to do for most people would be, what I’d do if I do intermittent fasting maybe once or twice a week now. I eat two meals a day but like once or twice a week I’ll eat one meal a day, and it varies depending on what I’m doing and testing.

But it will be 18 hours of fasting and 6 hours of eating. Actually I get home late, so it ends being about 20 hours of fasting and four hours of eating. So, it will be 7pm – 11pm. I’ve done it [with] water and abstained from putting fat into my coffee.

I’ve also done what I would call ‘fat fast’, so I would put in some MCTs in my coffee and maybe get a ketone supplement during the day. I would still call that a fast because it’s basically non-glycemic.

[Damien Blenkinsopp]: Yeah, probably has very similar ketone and glucose effects.

[Dominic D’Agostino]: Yeah, I actually find that it’s optimal. So, I would call that a modified intermittent fasting protocol, where you would get in some fats and exogenous ketones during that fasting period. I’m a little less hungry once I go into that eating window.

I think that’s good too, so I tend to not over eat that much. My body is still strongly in a state of ketosis that has probably enhanced a bit with the supplementation. It tends to dampen my appetite a little bit so I’m not as ravenous.

But I don’t generally don’t get that ravenous anyway when I eat. But, I would experiment with that the intermittent fasting. I think it’s so easy to do. I mean intermittent fasting is easier to do than the ketogenic diet that’s what I find with people.

So, do some experiment, get some initial blood work, read up about it, listen to Mark Mattson’s talk on [the] IHMC website and you’ll find it there. I’m sure there’s a lot of blogs on the subject and do blood work before and three to four weeks after.

You’ll see pretty big effects, especially six and eight weeks after. You’ll see even bigger effects on your lipid profile and metabolic biomarkers.

(1:49:04)[Damien Blenkinsopp]: Excellent thank you so much for that, that’s a great one. Where would someone look to learn more about your topic? Are there any good books or presentations on the subject you’d recommend if they want to learn more about the whole subject of ketones and ketosis?

[Dominic D’Agostino]: One of the go to book that I would recommend is Jeff Volek’s ‘Art and Science of Low Carbohydrate Performance’. It’s a mandatory reading for students entering the lab just to get a hand on what the ketogenic diet is. The Ketogenic Diet Resource is a website maintained by a friend of mine, Ellen Davis, and I think has a lot of good information on it.

But I maintain a website to throw up links, compile links in there called ketonutrition.org. If you click on resources from the homepage, it will take you to dietary consultants, books, publications, list of podcasts, and lectures on there on a variety of subjects that hit on pretty much all the topics we’ve discussed. I probably need to get on there, but it’s relatively updated. I’ll probably update that in the next month or two.

Metabolic Optimization too, that’s a website that I started with Travis Christofferson who wrote the book ‘Tripping Over the Truth’ which is an excellent book that covers the metabolic theory of cancer. Travis and I maintain the website Metabolic Optimization, and we have Thomas Seyfried on.

We’ve had Adrienne Scheck, we’ve had Bruce Ames actually was our first guy. We’re going to line up a bunch of other speakers on metabolism so that’s another area where they can look up information on these topics.

[Damien Blenkinsopp]: Great, thanks for that. Are you active on Twitter? Where could people also connect with you and keep updated of what you’re at?

[Dominic D’Agostino]: I tried to post at Twitter maybe once or twice a week, not like super active. But on Facebook I post a little bit more. My page is maxed out, I got 500 or 5,000 people following me.

So I’ll probably create a more public page. But you could still follow me because I post things open to the public. I will post usually one or two studies per day, or podcasts or lectures per day on my Facebook page which should be very easy to find.

It’s always sort of topics relevant to the interests or the topics that we covered today. Sometimes I dual post on Twitter and Facebook, important things that pop up as far as studies and lectures and things like that.

(1:51:39)[Damien Blenkinsopp]: Excellent. Of course, we’ll put links to everything you’ve mentioned here in the short notes. Is there anyone besides yourself? You’ve already mentioned a few people, but was there any you would pull out and you would recommend if people wanted to learn more about the subject? Are there are some other people that you would recommend also?

[Dominic D’Agostino]: Yeah. My colleagues, there’s so many of them. I try to stay very active in collaboration. It’s really good for scientists to collaborate to help get their work out there. Also, to get other people to validate the findings that you did in the lab.

So, I know you’ve had Thomas Seyfried. He’s a great friend and colleague of mine. Adrienne Scheck is a fantastic scientist and a pioneer in ketogenic diets and moving the ketogenic diet into clinical trials at Barrow Neurological Institute.

There’s some of the mentors that even got me into this field — would be Dr. Eric Kossoff. He’s a neurologist at Johns Hopkins. He’s been a pioneer in using a ketogenic diet for kids with epilepsy, so look him up.

John Roe who’s a neuroscientist and pediatrician. He was originally at Barrow Neurological Institute and he was the first scientist I ever connected with to discuss this. The use of the ketogenic nutrition for oxygen toxicity.

Dr. Richard Veech he had a profound influence on me when I first got into this area of ketogenic diet and discovered exogenous ketones. It was his reviews on the subject. So if you look up on some of his reviews on ketones and the therapeutic effects of ketones, they’re really good.

Susan Masino has been really supportive of our work and she’s doing some really innovative work looking at the effects of the ketogenic diet on adenosine. Adenosine is a neuroprotective substance that’s elevated, has anti seizure, anti-convulsant, neuroprotective effects.

So, we actually have a lot of these speakers [who] will be coming to our Metabolic Therapeutics’s Conference which will be held either the last week in January or the first week in February. We had a number of speakers, we had Eugene Fine, Colin Champ, David Ludwig, David Diamond, he was a colleague of mine here at USF and [we] talked about cholesterol and statins.

We had Eric Kossoff, Adam Hartman, and a bunch of scientists. So, I would tell your listeners to go to the Metabolic Therapeutic’s website. We’re in the process now of sending out the invitation for speakers.

And pretty soon, I think we might have a preliminary site set up for that, but we’ll be updating that soon with all the different speakers and the topics that are going to be talked about. We really try to emphasize basic science, so you’re going to find lectures on neurophysiology, cancer biology, proteomics, tracer based metabolomics.

Performance — Jeff Volek will be there talking about performance. It will be a mix of things related to not just the ketogenic diet but metabolism in general.

[Damien Blenkinsopp]: Sounds fantastic so anyone can attend that?

[Dominic D’Agostino]: Anyone can attend that, yeah. We should have the registration going up soon. The problem that we had is that last year the venue was small. We wanted originally to keep it small, to cap it at about 250, but we had to turn so many people away.

So, this year we’re going to blow it up a little bit and probably have about maybe 600 – 700 people, hopefully in the same venue. But we’re going to get the whole hotel. You’re going to find a lot of great companies there that are producing these exogenous ketones.

So, Pruvit is going to be there, probably Forever Green, the company Kegenix – they make a great product that I’ve been testing recently during my travels. KetoSports hopefully will be there, and Quest Nutrition has a big footprint in our conference and they have been incredibly supportive of our work.

Scivation, who’s really the leader in branch chain amino acid supplements, will be there. Let me see, we have a lot of good sponsorship supporting this area of research. It’s really exciting to me that it’s becoming so popular it’s easy to find companies that are now emerging that are interested in developing products that can enhance nutritional ketosis.

So it’s fun to see a market for this evolving. They’re are creating products that I think will be very beneficial to patients even that are following nutritional ketosis for managing a disease process.

I do get Emails every single day from patients that are using these products that made a world of a difference. They couldn’t get into ketosis and once they did or their trial did, they started getting all these benefits from the ketones.

[Damien Blenkinsopp]: It’s a super exciting area, you’re very lucky to be right in the center of it.

[Dominic D’Agostino]: Yeah. I do feel lucky.

(1:56:48)[Damien Blenkinsopp]: Just as a quick anecdote, I gave some MCT powders and C8 to my mother because she has tremors. They have been getting worse over time, and they are so much better it seems. She was really surprised by that.

But it is an exciting area, they have so many crazy benefits, so broad compared to the other things we looked at. Which is one of the reasons I’ve covered it several times in different episodes, fasting, ketosis, all of these.

Whereas most topics I don’t cover in many episodes but this one has just so many applications, it’s just interesting. I think it’s worthwhile for people to learn more and more about it.

[Dominic D’Agostino]: Absolutely.

[Damien Blenkinsopp]: Dom, thank you so much for your time. I really appreciate it, we’ve covered such a wealth of topics. I know there’s so much more you could talk about. So, thanks very much for your time.

It’s been great talking to you.

[Dominic D’Agostino]: Thanks for having me Damien. I appreciate it.


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

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

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

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

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

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

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

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

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

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

itunes quantified body

What You’ll Learn

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

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

Andrew Scarborough

Tools & Tactics


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


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

Diet & Nutrition

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



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

Lab Tests, Devices and Apps

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

Other People, Books & Resources


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




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

Full Interview Transcript

Click Here to Read Transcript

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

[Andrew Scarborough]: Thank you for having me.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Andrew Scarborough]: Yes, sorry.

[Damien Blenkinsopp]: Okay.

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

[Damien Blenkinsopp]: Is that a straight MRI?

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: So roughly 28 or 27.

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

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

I thought I was healthy.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

(28:08)[Damien Blenkinsopp]: So what kind of improvements have you seen, what are the biomarkers that stand out for you, the test results that have come back, and been useful?

[Andrew Scarborough]: The first thing I looked at was my vitamin D. When I was first diagnosed it was in a severely deficient range, and now it’s in the suboptimal range. People would say it’s too high now, it’s 200, and previously was 20.

I also have my triglycerides tested, I have my cholesterol done, and all those fun markers. I have a full blood count, my white blood cell count was pretty good, I can’t remember the exact figures. It’s actually better than before I had cancer, which is not typical even years after you had cancer, immunity can be compromised, so your white blood cell count is typically quite low, and I found that quite interesting.

(29:13) [Damien Blenkinsopp]: It’s great to hear about that progression. Let’s talk about the actual things that you’ve done in terms of where you started in your ketogenic diet, because I know that people said they’re ketogenic. Have you been tracking your blood ketones and blood glucose since the start? And have you seen how that’s changed as you’ve changed your diet?

[Andrew Scarborough]: Yeah. The first thing I did I went out and got a glucometer to measure my blood ketones and blood glucose, and I was comparing that to book cancerous [unclear 29:45] disease, and the glucose-ketone index that Thomas Seyfried devised and came up with, with his colleagues. I had a number of conversations with him about it, just over email, and I was amazed that he got back to me.

I found it very interesting, I started with trying to do the fast, to start with, to get me in ketosis quite quickly. But I realized with epilepsy that’s not a great idea. I had quite a few bad breakthrough seizures attempting that.

I decided not to try it that way, I decided to do it gradually and over time I managed to get into the therapeutic range within just a few weeks.

[Damien Blenkinsopp]: When you say therapeutic range what is that?

[Andrew Scarborough]: I was using the glucose-ketone index, which you use a ratio where you divide your blood ketones by the blood glucose, and you come up with a number, and you try and make sure that number is — I think it’s above one. I don’t measure it anymore in that way because I’m consistently in very deep ketosis with very low blood glucose, so I don’t have to do it anymore.

[Damien Blenkinsopp]: Yeah, we actually covered the index with Thomas Seyfried before. I think it’s a glucose divided by ketones, and there’s a couple of other little things you have to do in there, it’s not super straight forward. I put a spreadsheet up for some people who are asking, when he was talking to us he said it was under one.

So I guess that’s what you are aiming for and you seem to be saying you’ve gone…

[Andrew Scarborough]: Yeah at that time, that’s what I was aiming for, but now I’m consistently above 3.5, so I don’t have to worry about that so much.

[Damien Blenkinsopp]: Oh, in the glucose-ketone index?

[Andrew Scarborough]: Well my ketones are typically above 3.5, and the blood glucose is typically hovering around 3.5 — at the very least one to one.

[Damien Blenkinsopp]: Okay, so for the people at home, because in the US the blood glucose measurement isn’t millimolar. So you’re talking around in between 54 and 72 mg/dl, like 3-4 millimolar. I’m guessing you’re hovering around with the Seyfried Index somewhere around 0.6, 0.8.

So it’s well below one that’s what you’re saying because your ketones are so high.

[Andrew Scarborough]: Yeah. In the evenings it goes sky high, well the ketones go sky high, the glucose goes really low.

[Damien Blenkinsopp]: Do you mean from 5 o’clock onwards — it’s interesting because I saw that in some of my fast and some of my earlier experiments also.

[Andrew Scarborough]: Yeah. I guess it’s a hormonal thing that happens, and also because there’s that period of time where I only have typically two meals a day, that’s the in-between period, I guess where it goes that high. So that’s where I’ve unintentionally fasted for that period of time even though the diet’s mimicking fasting itself.

(32:58) [Damien Blenkinsopp]: What is a typical day look? What are you doing now, what is your typical day look like? I’m assuming at the moment you’ve got the most extreme version of your own program for this, is that correct?

[Andrew Scarborough]: Yeah. Typically I have 85% of fat and 15% protein in my diet, but over the last few days, I’ve experimented with 90% fat and 10% protein, and negligible carbs. Typically on my 85% and 15% protocol that I follow which is very similar to the animal studies, and quite similar to very strict ketogenic diet for children with epilepsy.

I restrict my calorie intake to 1,600 calories — calorie restriction is extremely important for brain cancer management. You probably discussed that with other people I’m guessing. What’s also important I think is the other things that I’m doing.

Personally, I think it’s very important to make sure you have correct therapeutic ratio — I like to call it of omega 3 and 6 in the blood, and I have at home testing kit for that which I send off to the lab every few months.

[Damien Blenkinsopp]: Okay, that’s interesting, is that a dry spot test?

[Andrew Scarborough]: Yeah, it is. You just have to collect quite a significant amount of blood, and it gives you a report back just saying what you’re ratios of omega 3 and 6 are in your blood.

[Damien Blenkinsopp]: Which lab are you using for that?

[Andrew Scarborough]: Well, the testing kit is by — if you go on Omegasense.com it comes up. There’s a center called the NutriCentre in London, and I just get it from there. It’s a pretty good test, very accurate.

[Damien Blenkinsopp]: Have you seen that change? This is actually the current levels ratio, it’s not like it’s your diet of the day like we were talking about — the blood glucose and the ketones which are changing all the time. It’s a more stable marker which is evolving over time, so you’re choosing for a range you want to keep it within.

[Andrew Scarborough]: I’m just trying to get us close to 1:1 ratio as possible, and I’ve experimented with a 2:1 and a 3:1 ratio in favor of omega 3 which is quite hard to do, but it’s very interesting. We know that omega 3 fatty acids exhibit neuroprotective properties and can represent a potential treatment for a variety of neurodegenerative diseases. It’s really interesting, we know that they are shown to be cytotoxic to tumor cells themselves.

Ideally, an optimal ketogenic diet for brain cancer should have, in my view a better ratio than omega 3 and 6. I think the standard ketogenic diets that are applied to humans at the moment are way to high in omega 6 which is inflammatory. I struggled when I was doing a standard ketogenic diet because of that.

[Damien Blenkinsopp]: What are you taking in order to raise your omega 3 levels? What are you doing in diet specifically?

[Andrew Scarborough]: Well, initially I was eating lots of brains because they are the best source of omega 3 that you could get, and that’s high in DHA, and one of the main fatty acids in the brain is DHA. The brain is 70% fat, and the rest is mostly water, it just makes sense to me to have in my diet mostly fat and water, that was my main reason for doing that.

We also know that the fatty acid composition of gliomas differs from that founding non-malignant brain tissue quite significantly. The reduction of glioma DHA content is really interesting to view — we know that in gliomas which is what my tumor was, and what a glioblastoma is as well. We know that they have significantly less DHA in and around them.

If we can increase that — the literature shows that it can have a very potent effect, particularly when on a ketogenic diet, in shrinking these tumors.

[Damien Blenkinsopp]: That’s great so you’re still eating brains today, is this a large part of your diet? What types of brains?

[Andrew Scarborough]: I was eating lamb’s brains, but, unfortunately, I’ve stopped eating them because of the very, very low risk of Scrapie which is like a CJD, a Mad Cow disease but the lamb form. Even though it’s a very small risk, and you probably have that same risk if you were to eat any infected tissue of that same animal, I just thought it would be a good idea to avoid it, which is a shame because it’s my favorite type of food on the ketogenic diet.

It’s a perfect ketogenic food, but my second most therapeutic ketogenic food that I found is sweetbreads which is the pancreas and the thymus gland of — in my case I get them from lambs again. I’ve done an experiment which is on YouTube, on my YouTube channel, just look at Andrew Scarborough, and look at my sweetbreads experiment, I’m testing the myoglobin of sweetbreads and it comes up very high on the glucometer for ketones.

When I test my blood after my postprandial blood glucose and my blood ketones after eating, my ketones shoot up very high, and the blood glucose stays more or less the same as before I started eating.

[Damien Blenkinsopp]: That’s interesting. Out of interest, how much do sweetbreads cost? Are they relatively cheap or expensive?

[Andrew Scarborough]: Well I mostly get them for free, sometimes I have to pay a pound for them.

[Damien Blenkinsopp]: Okay, so they are very cheap.

[Andrew Scarborough]: Yeah, because no one wants them.

[Damien Blenkinsopp]: Right that’s what I was thinking.

[Andrew Scarborough]: They’re incredibly nutrient dense, rich in trace minerals such as zinc and selenium, and they’re rich in protein, and omega 3 fatty acids. Like the brain, and like all the fish — the great source of omega 3. They also raise ketones very high.

[Damien Blenkinsopp]: Yeah, that’s very surprising. I don’t know if you’ve heard new supplement ranges which I’ve been playing around with it, exogenous ketones.

[Andrew Scarborough]: Yeah, I take those as well. I take KetoForce, mostly when I’m trying to do exercise because exercise is a huge seizure trigger for me. So yeah I play around with that.

[Damien Blenkinsopp]: It sounds like the sweetbreads are more effective than the KetoForce, KetoCaNa and the other ones.

[Andrew Scarborough]: Yeah. I actually made a supplement, a sludgy juice that the sweetbreads come in because I have them completely fresh straight after the animals are being slaughtered, well not straight after, but not long after, because they have to do a number of things just to make sure they are safe to eat. I made a supplement out of that and tested it, and it was very interesting the results, but it tasted absolutely foul.

[Damien Blenkinsopp]: Is that a downside of sweetbreads, they’re really awesome except they taste bad.

[Andrew Scarborough]: Yeah.

[Damien Blenkinsopp]: Okay.

[Andrew Scarborough]: It’s not the best tasting, you have to boil them for a long period of time, but they’re very nutrient dense and very effective.

[Damien Blenkinsopp]: How do you eat them? Have you got a quick recipe for the people at home, and they’re like, “Oh like a great thing to try out.” But if it tastes horrible is there some way to mask it.

[Andrew Scarborough]: The best thing to do is boil them for about an hour, that’s actually a short period of time typically for sweetbreads. Normally, it’s a lot longer. And then if you add tarragon to it, it actually compliments the flavor, and it actually tastes a lot nicer.

That’s one of the things I do, it goes well with tarragon. I just consume every bit of the animal, and I don’t have any carbohydrate so that’s how I get around possible nutrient deficiencies from not having any fruits and vegetables. And it allows me to not count carbohydrates, so it’s a Paleo-Ketogenic diet.

[Damien Blenkinsopp]: It’s a pure meat diet, right? Basically a pure carnivore?

[Andrew Scarborough]: Meat and fish, and fat, and that’s it.

(41:37) [Damien Blenkinsopp]: I do know there’s a little bit of story behind the reason — first you were on a ketogenic diet and you were doing more of a straight forward one with the coconut oil, and all of these kinds of things, what happened?

[Andrew Scarborough]: I noticed that with certain people with certain types of brain injury, your brain can be more sensitive to salicylates which are found in coconut oil, various vegetables and fruits, especially ones that have seeds. I wasn’t able to have avocados or any of the staple ketogenic foods that you have. I also couldn’t have dairy because I had a reaction to that, and I wouldn’t advise dairy anyway on a ketogenic diet for anyone with cancer let alone — brain cancer, because of IGF-1.

It just doesn’t make sense to me that there’re so many ketogenic diets for cancer management that have been based around dairy.

[Damien Blenkinsopp]: Right. There’s a lot of cheese, cheese is pushed quite hard…

[Andrew Scarborough]: Yeah, loads of cheese and double cream, and it’s not efficacious for me, even though I’m astounded that they get any results with these trans fat. And they do get some results, that’s encouraging for me on my — what I would call a more beneficial and effective ketogenic diet for this circumstance.

(43:06)[Damien Blenkinsopp]: Could you explain quickly the IGF-1, because there are people at home that are not quite up to speed on the IGF-1 and the dairy aspect of it. What’s the problem there?

[Andrew Scarborough]: It activates insulin-like growth factor and that can cause cancer cells to proliferate faster. One of the ways I get around that — I used to eat lots of butter, but because it’s more insulinogenic and it has milk proteins and casein. What I do is I have Ghee, which is clarified butter so the milk solids and the casein have been removed, and it’s much less insulinogenic and I actually get a much better blood ketone readings as a result as well compared to butter.

I find that interesting in itself, and we also know that compared to coconut oil, Ghee has much more omega 3 fatty acids, and coconut oil only has omega 6. If you’re basing a ketogenic diet around — just loads and loads of coconut oil which is just omega 6. Even though coconut oil is fantastic for achieving ketosis, I would advise it in moderate amounts if you can tolerate it because it’s really good.

I would say that making sure that you have enough omega 3 by having more animal fats is more beneficial in terms of the overall nutrient profile than just consuming tons of coconut oil.

(44:44) [Damien Blenkinsopp]: Right. You mentioned you eat all the parts of the animal, I’m guessing you mean all of the organs…

[Andrew Scarborough]: Yep.

[Damien Blenkinsopp]: Do you consume what you would call a variety of these? Do you try to cycle them, and the widest spectrum possible? So what other organs are you eating, are you literally eating all of the different organs on a rotation each week?

[Andrew Scarborough]: Yeah. Literally everything but mostly heart, because it’s very very cheap, it would cost me 60 pence at a time, and you get quite a substantial portion— because lamb hearts are quite fatty, there’s a huge chunk of fat on them. I can just eat them as they are, and I don’t need to add extra fat.

It’s a fantastic source of iron, zinc, selenium, B vitamins, folate, and it’s the best food source of coenzyme Q10. It’s funny how people pay an absolute fortune to get pills that have a coenzyme Q10, and I just get the best source that you could possibly get for 60 pence at a time.

[Damien Blenkinsopp]: There’s a psychological barrier about the taste, and it’s just what we’ve become used to really. I’m definitely nowhere near as far as you — I’ve been eating more organ meats and I’m trying to push it up, I just made another order today from a new company actually. I’m slowly building my way up, and it’s a taste I’m struggling with, recipes I think help with that, learning how to cook and deal with the different tastes, and just getting used to them.

[Andrew Scarborough]: Yeah. I actually did quite well to start with brains, they’re actually the most tolerable in terms of tastes because they just taste like creamy eggs.

[Damien Blenkinsopp]: Oh, I would’ve never thought that.

[Andrew Scarborough]: They taste like creamy salty eggs.

[Damien Blenkinsopp]: You just don’t look at them while you’re eating them.

[Andrew Scarborough]: No. And a number of things I do are just for entertainment, to keep the diet interesting, to make sure I have enough trace minerals. That’s why I added insects to my diet quite early on because anytime you eat the whole animal you’re getting a variety of nutrients. When you eat insects you’re consuming the whole animal — it just makes sense that it would be a beneficial thing to have.

[Damien Blenkinsopp]: How do you consume those? Because I know there are cricket bars out there in the US, how are you consuming insects?

[Andrew Scarborough]: What I do is I get the fattiest insects that are ketogenic, I get waxworms and super worms. Mostly insects that reptiles eat, I get them from a pet shop that sells them for reptiles now, I used to get them online.

[Damien Blenkinsopp]: Oh, man. Okay did you used to buy from [check 47:31 – Bug Grow], was that the specific brand — was that the only place you bought from?

[Andrew Scarborough]: Yeah, I tried a few, I tried silk worm, pupa as well — a few different insects have different medicinal properties, they’re in Chinese medicine. They’re really interesting in terms of the properties that they have. But we largely ignore that, mainly what I do now is I get them from the pet shop.

I just stick them in the freezer to kill them, and then I’ll give them a gentle wash and eat them …

[Damien Blenkinsopp]: You just eat them straight?

[Andrew Scarborough]: The problem, if you get them online is that they’ve been dehydrated and cooked so much that the nutrient profile isn’t as good as if you have them fresh after they’ve been wiggling about. I also grind them up and make my own flour after I’ve frozen them. That makes quite nice breads, I make a zero carb ketogenic bread which is very useful. People actually think it’s proper bread…

[Damien Blenkinsopp]: You don’t tell them right?

[Andrew Scarborough]: I’ve actually offered it to people without telling them, and they quite like it, and then I tell them what it is, and they want to punch me. But it’s actually surprisingly quite nice.

[Damien Blenkinsopp]: A quick story here, I was in Mexico 15 years ago and I went to Taxco. Anyway you go up into the mountains, into this old city and they were selling plastic bags full of live insects for eating. It’s something that we used to do — we don’t do in modern society. . .

[Andrew Scarborough]: If you look at anthropology, and how we evolved, it’s largely ignored especially with these Paleo diets — we evolved primarily eating a variety of insects, and in quite a large amount. It suggested that the man would go out and go hunting — would only about a 20% success rate catching these larger animals.

The woman would be mainly collecting insects for food. Seasonally they would collect nuts and berries, but it’s a fact in anthropological studies that we did consume a large amount of insects before we moved closer to the coast to eat fish, and that’s how our brains developed more. It’s an ignored fact.

(50:16)[Damien Blenkinsopp]: It’s really interesting, we’ll get there. There’ll be people writing books — maybe you, about the missing parts of the Paleo diet, Paleo upgraded. You did mention that, when you exercise you’re taking exogenous ketones, because of your epilepsy, why is that?

[Andrew Scarborough]: When I exercise my blood ketones go down, lower than my individual therapeutic reading for seizure control for me personally. I have to do that, and I also have to take another experimental treatment of mine which is proved effective, which I learned from the literature on epilepsy. It’s a magnesium chloride solution that I mix into water, and I have a specific amount that reverses auras.

An aura for me is when you have all symptoms that you’re about to have a more serious type of seizure. An aura is a partial seizure in itself.

[Damien Blenkinsopp]: Okay. Maybe you would loose your words a little bit?

[Andrew Scarborough]: I would get pins and needles in my mouth and throat, and I would feel very dizzy, and faint. I have this horrible feeling like I’m going to collapse and have a tonic-clonic seizure. When I take the magnesium solution that I take three times a day, it actually reverses that aura, it is a potent preventative measure that I found to control seizure activity extremely effectively.

People with any kind of epilepsy, their levels of magnesium drop very low, and there are certain types of the day that magnesium is at its lowest, and typically that’s when seizure threshold is also at its lowest. If we can control that, we can control seizures very effectively. Also, on a ketogenic diet, supplemental magnesium — particularly magnesium chloride are found most effective.

It acts as a natural statin, it has a beneficial effect not only on cholesterol, in a natural way not like a typical statin where it’s actually destroying that process, it’s working with your body to do it naturally. I find that it also controls blood glucose — it regulates blood glucose very effectively too. I see it as my replacement for my medication that I was on previously, and the medication interestingly actually causes magnesium deficiency as well as calcium deficiency, deficiency in vitamin B-12 and vitamin D.

[Damien Blenkinsopp]: Which medication where you on?

[Andrew Scarborough]: I was on the maximum dose of Levetiracetam, which the brand name is Keppra and Sodium Valproate the brand name for that is, Epilim. I was both on those and the highest possible amount that you could be on. You can imagine the side effects of that, and the nutrient deficiencies that caused were just quite substantial.

When you’re withdrawing from those drugs you could actually get breakthrough seizures if you don’t address those nutritional deficiencies, and those seizures can actually cause SUDEP — it’s shorthand for sudden unexpected death in epilepsy. I was told consistently that I was highly likely to have that if I was to — not only come off my medication which is what I eventually did but reduced the medication. I have to reduce that medication for a period of almost two years.

I had to do it very slowly, and adding these nutrients and trace elements so that I was not having these breakthrough seizures that were life-threatening. It was a difficult balance, but I achieved it.

(54:50) [Damien Blenkinsopp]: It makes it easier when you titrate down slowly, but still you’ve been courageous in pushing for all of these things when you’re getting this pushback which is saying it’s really dangerous. Just in terms of the exercise, how do you bump your ketones up – is it the KetoForce?

[Andrew Scarborough]: Yeah. I consume that throughout my workout but I tend to mostly just do quite a light bodyweight exercise because I don’t want to stress my body too much. Thomas Seyfried himself recommends that cancer patients don’t push themselves too much with exercise, because it just puts too much stress on the body and on the brain. Mostly I just go for long walks, in an area with lots of oxygen, and I’m actually going to start having hyperbaric oxygen therapy fairly soon.

I’m in discussions with a number of facilities about that, and I’m going to start doing case studies on patients. I’m actually working part-time at the moment with Imperial College London in Charing Cross Hospital, to start-up clinical trials hopefully next year with brain cancer patients using — what I would call an optimal ketogenic diet.

We’re looking at magnesium for these brain cancer patients, we’re looking at the omega 3 and 6 ratios in the blood, we’re looking at C-reactive protein as a marker for a systemic inflammation, and we’re able to measure that for over a period of time to see how that changes while on a ketogenic diet.

[Damien Blenkinsopp]: With cancer is that typically high the hs-CRP because of the inflammation, or is that just a. . .

[Andrew Scarborough]: Yeah. It’s typically higher than normal, but one of the main ideas of measuring that is to have a marker that you can measure over time. I’m a huge fan of testing and I know that even if these things have no effect on cancer, they have an effect on epilepsy and blood glucose management.

We know that these are prognostic factors and they’re also effective at managing epilepsy which many brain cancer patients have as a result. I’m very keen to start doing this in patients more, and I’m working very hard to do that.

[Damien Blenkinsopp]: It’s very exciting that you’re able to work in hospitals. This is starting next year you said, potentially?

[Andrew Scarborough]: Yes. It would also be featured in, New Scientist magazine early next year. My story and my approach will be featured, and that’s very exciting as well because it’s getting the message out there and we can then have the actual data on humans which is missing. It would be — as I’ve said before it will be efficacious.

We’ll be able to not just translate the diets that have been used for children with epilepsy which I don’t believe …

[Damien Blenkinsopp]: As good, as they could be?

[Andrew Scarborough]: I don’t think that they’re translatable for brain cancer patients because I think it’s just very different. For example, when I was on the standard type of ketogenic diet, they did include those ingredients. I developed symptoms that were similar to Temporal Arteritis, where my temporal arteries became so inflamed that I nearly went blind and I was prescribed steroids for it.

But instead of taking the steroids what I did is I looked at how much omega 6 I was taking in my diet, and even though my blood glucose and ketones looked fantastic, and the ketogenic diet is anti-inflammatory in itself. I was having these inflammatory responses which were only controlled and reversed when I re-addressed the balance of omega 3 and 6 ratios. That in itself is quite powerful.

(59:15)[Damien Blenkinsopp]: Interesting. Where did your omega 6 ratio start? We read studies where the standard American diet, for example, is you can get ratios of 20:1, 10:1 — quite far off.

[Andrew Scarborough]: I’ve read up to 40:1.

[Damien Blenkinsopp]: Were you not so bad because you said you had a reasonable — you were trying to have a reasonably healthy diet before. I wouldn’t expect you’d have the sad numbers.

[Andrew Scarborough]: Yes, prior to initiation of the diet, I would say I was most likely about a 10:1 ratio. But, on the ketogenic diet, it was probably quite similar actually because it was including lots of nuts, coconut oil, coconut milk, coconut cream, lots of vegetables that were high in omega 6. I just thought it could be done better — then I transferred on to what I like to call a, fishogenic diet.

I was consuming a lot more fish, and I felt instantly much better and then as I cut down on the vegetables – cut them out completely. I had an instant response where I can’t even remember the last time I had a headache, even a mild headache.

(60:32)[Damien Blenkinsopp]: Great to hear. I’m conscious of your time I know that you’re really busy currently. But there’re a couple of things — I do want to make sure we cover before you go. We didn’t speak about glutamine and I know that an important part you mentioned up front that’s something you had to restrict quite sharply. But how did you do that practically?

[Andrew Scarborough]: Well, the first thing I did was limit protein quite significantly, and I did a number of therapeutic fasts, and it wasn’t until then that I actually saw the greatest response in my MRI scans, in terms of the complete remission. One of the other things that’s quite effective is with the magnesium it has an effect on that as well. I need to find the study for that, but I can send it to you if you’re interested in reading it.

Another thing that I’m actually looking into for the long term is Metformin, because Metformin on a ketogenic diet has quite a potent effect. It has a number of mechanisms which I can’t remember all of them off the top of my head, but that’s one thing that I’m playing around at the moment. It gets an effect on MAMP and a few other things.

It’s quite hard to explain, it’s quite technical.

[Damien Blenkinsopp]: In terms of the fast, you said that’s when you really started seeing the effects, so that would mirror — we had Thomas Seyfried on here and he was talking about the importance of the fast. How many days — was that a pure water fast? Was it a seven or five day fast?

[Andrew Scarborough]: It’s interesting because I think that — when these researchers are talking about fasting for brain cancer patients particularly if they have epilepsy, what they fail to note is that there’s ionic changes that are happening in the brain when you’re doing these fasts. A patient with epilepsy can’t — especially if they have brain cancer in my opinion shouldn’t just do water-only fast.

I think that they need to do what I call, a ’magnesium fast’. When I fast I have my magnesium water solution that I make up myself, and that prevents me from having breakthrough seizures while I’m fasting because I have such low body fat percentage. My longest fast has only been nine days. I aimed for 10 but I couldn’t do more, I’ve done that a few times but I need to have my magnesium-chloride solution or I instantly have breakthrough seizures, not the good kind either.

I found out the hard way initially, but now it’s just the easiest thing that I do.

[Damien Blenkinsopp]: You’re taking specifically magnesium chloride, is that because it’s a spray kind or is it actually the magnesium chloride specifically — there’s something about the chloride which is helping?

[Andrew Scarborough]: It has something to do with hydrochloric acid and how you digest it. I’d say it’s more bioavailable and it seems to me to be just in my personal experiences that it seems to get the brain very quickly. The literature doesn’t actually say that, but personally, I found that — even though there is not much in the literature about that.

[Damien Blenkinsopp]: Are you buying a specific brand? We’ve talked about using magnesium spray transdermally, but I’m just wondering if you’re using one of those sprays? How much you’re taking of it?

[Andrew Scarborough]: It’s designed to be primarily used transdermally this particular type, and I just get it from a health food shop, it’s mainly people who do sports who take it, which is interesting and funny. I typically take about five sprays three times a day. I can’t remember exactly how much that is, for 10 sprays it’s 150 milligrams of magnesium.

It’s variable depending on how mixed up the solution is — typically around 230 milligrams in a day that I would take. If you consider our water is too high in calcium and not high enough in magnesium. It’s addressing that imbalance that we have, we know that we should have at least a 2:1 ratio of magnesium to calcium, that addresses that imbalance.

We know that in the mornings after we wake up, magnesium levels are lowest. Primarily take it in the morning, after waking up in the afternoon, and before I go to bed.

[Damien Blenkinsopp]: Have you checked your RBC magnesium levels?

[Andrew Scarborough]: I haven’t because I don’t think it’s an accurate measure. I just go by how I feel, and sometimes — I see the epilepsy as a blessing because everything to do with epilepsy with brain cancer is typically very similar to what would work for treating the cancer. If something is working for the epilepsy, you’ve got a pretty good idea that it’s beneficial for the cancer, and most of the things that I actually research about what helps in terms of my epilepsy, experimentally and otherwise.

I found incidentally that it has quite potent anti-cancer benefits as well. It’s really interesting the relationship. It’s quite empowering as well. What I would call spectacular results because I still can’t believe I’m not having these horrific seizures all the time without medication. It’s quite empowering to know that it’s potentially having the same benefit on the cancer.

(1:06:44)[Damien Blenkinsopp]: Yes, it’s pretty amazing your journey. I don’t know if you’ve come into contact with other people with similar stories to tell — I know that some other people who had cancer, you said, unfortunately, they’ve passed away — the ones you were relating to. But if you come across any other people who have been experimenting like yourself.

[Andrew Scarborough]: Yeah. I actually have a group of friends now who I came into contact with just through seeking out long-term survivors, and I have a group of long-term survivor friends who had glioblastoma many years ago, and now have no sign of disease. I have a group of friends with various other cancers who are still here now. They’ve mostly done a drug cocktail treatment on themselves, which is very interesting.

Personally, I wanted to try and copy that drug cocktail treatment but do it in a natural way just using diet.

[Damien Blenkinsopp]: When you say drug cocktail, is that chemo or is that more Metformin and things like that?

[Andrew Scarborough]: It’s more Metformin and statins, and phosphates, and various other DCA, and other very interesting drugs. Personally, the only one I’m considering is Metformin, and potentially a few others, but mainly Metformin and Curcumin which I take in tablet form with DHA because they work synergistically. Curcumin actually increases uptake of DHA to the brain.

Because we know that around these tumors, or where the tumor was – DHA is very low. We know that if you have Curcumin and DHA that’s a powerful combination. Curcumin is cytotoxic to the cells. We know that DHA is, and is essential for brain functioning.

[Damien Blenkinsopp]: You really have built a whole lot of armory against this — it sounds like you’re doing really well. On the Curcumin – there’s many forms available on the market today, you’re taking one of the bioavailable forms…

[Andrew Scarborough]: Yeah, it has piperine in it as well.

[Damien Blenkinsopp]: Okay.

[Andrew Scarborough]: It’s a component of black pepper. I have a number of strategies that I use, and I’m constantly optimizing my metabolic formula.

(1:09:14)[Damien Blenkinsopp]: Do you feel constant improvement? I don’t know if there are any symptoms because it seems like you’ve got most of it under control. Do you think you’re going to be able to repair your body, do you feel any signs of that in terms of potentially resolving the epilepsy?

Do you think this is more likely something that you’re just going to optimize and maintain so that it never bothers you, so you never get the actual symptoms?

[Andrew Scarborough]: As my brain has been visibly healing at a very fast rate on these scans while I’ve been utilizing this protocol, I’ve also found my symptoms have improved with that quite substantially as well. I had facial paresthesia constantly all throughout the day, everyday, and a number of other debilitating symptoms I couldn’t even go out and walk a few steps. The fatigue was horrendous as well.

Being able to do what I am now and this non-stop activity, and just doing so many different things, and having my seizure activity controlled in such a great way that’s much better than before — even before when I was doing all these things I was still getting more activity. I haven’t actually done that many more things if I compare to even just a few months ago. Definitely improving in quite a dramatic way, despite having to keep up with all these things.

It’s getting easier to control, to the point where I have days now that I have no symptoms at all, but if I get overconfident and I forget to have my magnesium drink or do something that’s just out of my routine, I’d definitely have more seizure activity coming. Even though it’s not to the degree that I used to have.

[Damien Blenkinsopp]: I guess really say why you’re saying epilepsy is a bit of a bonus for you because it’s early warning detection system for you…

[Andrew Scarborough]: Yeah.

[Damien Blenkinsopp]: — Whereas cancers can creep up on you and you won’t know unless you’re watching the scans and even the scans aren’t showing a small progression. So right now you can still have a small amount of cancer left, but you can’t see it. It does seem like a pretty nice little tool, even though it’s not nice to have it, in the longer term it sounds like it’s a beneficial thing for you.

[Andrew Scarborough]: Yeah, I can see it as beneficial now, I couldn’t before but it definitely is.

(1:11:47) [Damien Blenkinsopp]: Well Andrew this has been an amazing — it’s very inspiring episode today. I can really say that — I’m totally going to take some of the things that you have been trying and start testing them out myself. I would like to ask you — where to look first if they would like to learn about this topic if they’re facing cancer or epilepsy?

Are there good books or presentations on the subject, the first places to go to, to start learning themselves about this?

[Andrew Scarborough]: I would thoroughly recommend the book, Cancer as a Metabolic Disease by Thomas Seyfried. I think that’s a great starting point. For anyone starting a ketogenic diet I would recommend, Keto Clarity, that’s a good resource to use. I would also go to www.ketogenic-diet-resource.com — that has answers to just about all the questions that you could have.

For help to a dietician, if you live in the UK I would recommend the charity, Matthew’s Friends. In the US, I would recommend the Charlie Foundation which is the sister organization of Matthew’s Friends in the UK. It has recently started to see — it’s mainly brain cancer patients that they see because they get around with that by saying that they’re treating the epilepsy.

I would also go on Clinicaltrials.gov to see what clinical trials are happening globally to do with the ketogenic diet and different cancers.

[Damien Blenkinsopp]: Right, so if they’ll just search for a ketogenic diet on there…

[Andrew Scarborough]: Yeah, if they search for ketogenic diet and cancer on Clinicaltrials.gov they can see all of the clinical trials that are currently happening in terms of ketogenic diets for different cancers. It’s very exciting that more and more of these are popping up, and I hope to — I have a meeting on Thursday to discuss having proper official ketogenic diets, using the right approach in this country, and that’s really exciting new development.

[Damien Blenkinsopp]: Is that with the government, NHS or some other body that’s going to help promote it.

[Andrew Scarborough]: This is in conjunction with brain tumor research, they’re one of the very few cancer charities that actually are going all at it with this metabolic research, and they’re doing that with Imperial College London. It’s a small charity that’s doing this, it’s quite incredible what they are able to do being such a small organization.

[Damien Blenkinsopp]: It’s great they’re starting to be – some grounds building from the bottom and up.

[Andrew Scarborough]: Yeah, and I’m going to start-up my own individual research with a few of my lecturers at my university because I want to get these things happening much faster than if it’s going through clinical trial protocol. I want to do this myself with lower grade gliomas, so that we can see a long-term response to try and shrink these tumors hopefully, because they are not as aggressive, but, they still are incurable.

I want to see what effect that we can have on them rather than having to go through all the standard treatment to go through clinical trials. I think that’s very exciting going forward.

(1:15:25) [Damien Blenkinsopp]: That sounds really exciting, and I’m sure anyone who – maybe affected would be very interested to know more. What are the best ways for people to connect with you and learn about you, and keep up with you when you’re doing these things, they can stay up to date on them. Are you on Twitter, you mentioned you had a YouTube channel?

[Andrew Scarborough]: Yeah, my Twitter name is @ascarbs, and I’m on Facebook if people want to add me on there, Andrew Scarborough. I also am working on a website at the moment which is www.metabolictherapy.co.uk, and that has a holding page at the moment, but it should be live shortly. I have a YouTube channel, Andrew Scarborough, and I have a blog, My Brain Cancer Story that’s the title of it.

People search for Andrew Scarborough and My Brain Cancer Story, they should find it.

[Damien Blenkinsopp]: Excellent. We’ll put all those links on the show notes of course also, make sure all of that is there. Is there anyone besides yourself you’d recommend to learn more about the stuff that you mentioned, Thomas Seyfried, is there anyone else that people should look to?

[Andrew Scarborough]: I would look at the research by Dominic D’Agostino, also I would recommend Dr. Colin Champ, I’ve had various discussions with him online which are very interesting. He’s very interested in my approach and he is very unique, he’s a radiation oncologist who is very supportive of this metabolic treatment. Very similar to my oncologist who – it’s quite a rare thing to find – but it’s very encouraging.

There’s Dr. Adrienne Scheck, who I’m having a meeting with on Thursday she’s coming overseas from the Barrow Neurological Institute in the US, and she’s the one that does the rodent studies using the ketogenic diet. It’s great to be able to discuss with her.

(1:17:29) [Damien Blenkinsopp]: Great, great, thank you for those. Some quick items on your – just a personal approach on what you would advise people to get started with – are you still tracking any biomarkers, on a routine basis?

[Andrew Scarborough]: Only occasionally with MRI spectroscopy but we’ve stopped doing that now just because it looks a bit boring and nothing’s really changing. It all looks really good, that’s why we’re not monitoring it anymore.

[Damien Blenkinsopp]: So maybe once in every six months or once a year?

[Andrew Scarborough]: Yeah, just to keep an eye on it, but everything that you would expect to be elevated but would be a bad thing isn’t showing up – it sounds like a good thing. It’s very new research, we don’t know too much about it, but it’s very promising for the future.

Because if we can see these things before they show on the scan, in terms of enhancement or just showing in an obvious way then it’s – that can only be good for the patient really. Then we can intervene in a non-toxic way.

[Damien Blenkinsopp]: So if you were to recommend one experiment, basically you’ve done many experiments to get to this point – they’re not proven recommendations by doctors and so on. What would you recommend that someone with brain cancer or potential other cancer – what would be the first thing they should try, the biggest payoff from all of the things that you’ve mentioned, what should their first step be?

[Andrew Scarborough]: The first step should definitely be reducing carbohydrate intake. The second step would be reducing protein intake to maintenance levels, and therapeutic fasts are very important. But the main thing, I would say is the omega 3 to 6 ratio, I believe that they should be an omega 3 to 6 index, just like with the glucose-ketone index, and they should work together, as a synergistic therapy.

Because you could even argue the ratio of omega 3 to 6 is even more important than the ketones. I would also say, the magnesium is very important with that too, those three things. Therapeutic ketosis, the omega 3 to 6 ratio and the magnesium I would say are very important for brain cancer patients.

[Damien Blenkinsopp]: Great, thank you, that’s some great takeaways for people at home. Andrew, I’ve got to say this has been really amazing interview – it’s amazing all of the different avenues you’ve run-down and all of these different aspects that you found to improve your situation. I know it’s going to be an inspiring story for the audience.

Thank you very much for being on the show.

[Andrew Scarborough]: No problem, we did cover a lot but we got there in the end.

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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.



  • 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


  • 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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