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 brings ketone supplements previously unavailable in the United Kingdom, such as exogenous ketones, to the UK.

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

itunes quantified body

What You’ll Learn

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

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

Dominic D’Agostino

Recommended Self-Experiment

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

Tools & Tactics

Diet & Nutrition

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

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

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

Supplementation & Drugs

Exogenous Ketones

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

MCTs and C8 (Caprylic Acid)

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

Dominic’s Sleep Deprivation Effects Mitigation Cocktail

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

Drugs

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

Tech & Devices

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

Tracking

Biomarkers

    Glucose/ Ketone Metabolism

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

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

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

Lab Tests, Devices and Apps

Devices for Measuring Glucose & Ketones

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

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

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

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

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

Other People, Books & Resources

Books

People

Researchers

Other Mentions

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

Organizations & Companies

Other


Full Interview Transcript

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Dominic D’Agostino]: Yeah, I do too.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Dominic D’Agostino]: Yes.

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

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

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

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

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

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

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

So, that would be the press.

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

[Dominic D’Agostino]: Yes.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Dominic D’Agostino]: Yeah.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Dominic D’Agostino]: Yeah.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Dominic D’Agostino]: Yeah.

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Okay, the challenge.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Dominic D’Agostino]: Absolutely.

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

It’s been great talking to you.

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

References:

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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

Interventions

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

Supplementation

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

Diet & Nutrition

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

Tracking

Biomarkers

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

Lab Tests, Devices and Apps

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

Other People, Books & Resources

People

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

Organizations

Books

Other

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

Full Interview Transcript

Click Here to Read Transcript

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

[Andrew Scarborough]: Thank you for having me.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Andrew Scarborough]: Yes, sorry.

[Damien Blenkinsopp]: Okay.

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

[Damien Blenkinsopp]: Is that a straight MRI?

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: So roughly 28 or 27.

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

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

I thought I was healthy.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Andrew Scarborough]: Yeah. I guess it’s a hormonal thing that happens, and also because there’s that period of time where I only have typically two meals a day, that’s the in-between period, I guess where it goes that high. So that’s where I’ve unintentionally fasted for that period of time even though the diet’s mimicking fasting itself.

(32:58) [Damien Blenkinsopp]: What is a typical day look? What are you doing now, what is your typical day look like? I’m assuming at the moment you’ve got the most extreme version of your own program for this, is that correct?

[Andrew Scarborough]: Yeah. Typically I have 85% of fat and 15% protein in my diet, but over the last few days, I’ve experimented with 90% fat and 10% protein, and negligible carbs. Typically on my 85% and 15% protocol that I follow which is very similar to the animal studies, and quite similar to very strict ketogenic diet for children with epilepsy.

I restrict my calorie intake to 1,600 calories — calorie restriction is extremely important for brain cancer management. You probably discussed that with other people I’m guessing. What’s also important I think is the other things that I’m doing.

Personally, I think it’s very important to make sure you have correct therapeutic ratio — I like to call it of omega 3 and 6 in the blood, and I have at home testing kit for that which I send off to the lab every few months.

[Damien Blenkinsopp]: Okay, that’s interesting, is that a dry spot test?

[Andrew Scarborough]: Yeah, it is. You just have to collect quite a significant amount of blood, and it gives you a report back just saying what you’re ratios of omega 3 and 6 are in your blood.

[Damien Blenkinsopp]: Which lab are you using for that?

[Andrew Scarborough]: Well, the testing kit is by — if you go on Omegasense.com it comes up. There’s a center called the NutriCentre in London, and I just get it from there. It’s a pretty good test, very accurate.

[Damien Blenkinsopp]: Have you seen that change? This is actually the current levels ratio, it’s not like it’s your diet of the day like we were talking about — the blood glucose and the ketones which are changing all the time. It’s a more stable marker which is evolving over time, so you’re choosing for a range you want to keep it within.

[Andrew Scarborough]: I’m just trying to get us close to 1:1 ratio as possible, and I’ve experimented with a 2:1 and a 3:1 ratio in favor of omega 3 which is quite hard to do, but it’s very interesting. We know that omega 3 fatty acids exhibit neuroprotective properties and can represent a potential treatment for a variety of neurodegenerative diseases. It’s really interesting, we know that they are shown to be cytotoxic to tumor cells themselves.

Ideally, an optimal ketogenic diet for brain cancer should have, in my view a better ratio than omega 3 and 6. I think the standard ketogenic diets that are applied to humans at the moment are way to high in omega 6 which is inflammatory. I struggled when I was doing a standard ketogenic diet because of that.

[Damien Blenkinsopp]: What are you taking in order to raise your omega 3 levels? What are you doing in diet specifically?

[Andrew Scarborough]: Well, initially I was eating lots of brains because they are the best source of omega 3 that you could get, and that’s high in DHA, and one of the main fatty acids in the brain is DHA. The brain is 70% fat, and the rest is mostly water, it just makes sense to me to have in my diet mostly fat and water, that was my main reason for doing that.

We also know that the fatty acid composition of gliomas differs from that founding non-malignant brain tissue quite significantly. The reduction of glioma DHA content is really interesting to view — we know that in gliomas which is what my tumor was, and what a glioblastoma is as well. We know that they have significantly less DHA in and around them.

If we can increase that — the literature shows that it can have a very potent effect, particularly when on a ketogenic diet, in shrinking these tumors.

[Damien Blenkinsopp]: That’s great so you’re still eating brains today, is this a large part of your diet? What types of brains?

[Andrew Scarborough]: I was eating lamb’s brains, but, unfortunately, I’ve stopped eating them because of the very, very low risk of Scrapie which is like a CJD, a Mad Cow disease but the lamb form. Even though it’s a very small risk, and you probably have that same risk if you were to eat any infected tissue of that same animal, I just thought it would be a good idea to avoid it, which is a shame because it’s my favorite type of food on the ketogenic diet.

It’s a perfect ketogenic food, but my second most therapeutic ketogenic food that I found is sweetbreads which is the pancreas and the thymus gland of — in my case I get them from lambs again. I’ve done an experiment which is on YouTube, on my YouTube channel, just look at Andrew Scarborough, and look at my sweetbreads experiment, I’m testing the myoglobin of sweetbreads and it comes up very high on the glucometer for ketones.

When I test my blood after my postprandial blood glucose and my blood ketones after eating, my ketones shoot up very high, and the blood glucose stays more or less the same as before I started eating.

[Damien Blenkinsopp]: That’s interesting. Out of interest, how much do sweetbreads cost? Are they relatively cheap or expensive?

[Andrew Scarborough]: Well I mostly get them for free, sometimes I have to pay a pound for them.

[Damien Blenkinsopp]: Okay, so they are very cheap.

[Andrew Scarborough]: Yeah, because no one wants them.

[Damien Blenkinsopp]: Right that’s what I was thinking.

[Andrew Scarborough]: They’re incredibly nutrient dense, rich in trace minerals such as zinc and selenium, and they’re rich in protein, and omega 3 fatty acids. Like the brain, and like all the fish — the great source of omega 3. They also raise ketones very high.

[Damien Blenkinsopp]: Yeah, that’s very surprising. I don’t know if you’ve heard new supplement ranges which I’ve been playing around with it, exogenous ketones.

[Andrew Scarborough]: Yeah, I take those as well. I take KetoForce, mostly when I’m trying to do exercise because exercise is a huge seizure trigger for me. So yeah I play around with that.

[Damien Blenkinsopp]: It sounds like the sweetbreads are more effective than the KetoForce, KetoCaNa and the other ones.

[Andrew Scarborough]: Yeah. I actually made a supplement, a sludgy juice that the sweetbreads come in because I have them completely fresh straight after the animals are being slaughtered, well not straight after, but not long after, because they have to do a number of things just to make sure they are safe to eat. I made a supplement out of that and tested it, and it was very interesting the results, but it tasted absolutely foul.

[Damien Blenkinsopp]: Is that a downside of sweetbreads, they’re really awesome except they taste bad.

[Andrew Scarborough]: Yeah.

[Damien Blenkinsopp]: Okay.

[Andrew Scarborough]: It’s not the best tasting, you have to boil them for a long period of time, but they’re very nutrient dense and very effective.

[Damien Blenkinsopp]: How do you eat them? Have you got a quick recipe for the people at home, and they’re like, “Oh like a great thing to try out.” But if it tastes horrible is there some way to mask it.

[Andrew Scarborough]: The best thing to do is boil them for about an hour, that’s actually a short period of time typically for sweetbreads. Normally, it’s a lot longer. And then if you add tarragon to it, it actually compliments the flavor, and it actually tastes a lot nicer.

That’s one of the things I do, it goes well with tarragon. I just consume every bit of the animal, and I don’t have any carbohydrate so that’s how I get around possible nutrient deficiencies from not having any fruits and vegetables. And it allows me to not count carbohydrates, so it’s a Paleo-Ketogenic diet.

[Damien Blenkinsopp]: It’s a pure meat diet, right? Basically a pure carnivore?

[Andrew Scarborough]: Meat and fish, and fat, and that’s it.

(41:37) [Damien Blenkinsopp]: I do know there’s a little bit of story behind the reason — first you were on a ketogenic diet and you were doing more of a straight forward one with the coconut oil, and all of these kinds of things, what happened?

[Andrew Scarborough]: I noticed that with certain people with certain types of brain injury, your brain can be more sensitive to salicylates which are found in coconut oil, various vegetables and fruits, especially ones that have seeds. I wasn’t able to have avocados or any of the staple ketogenic foods that you have. I also couldn’t have dairy because I had a reaction to that, and I wouldn’t advise dairy anyway on a ketogenic diet for anyone with cancer let alone — brain cancer, because of IGF-1.

It just doesn’t make sense to me that there’re so many ketogenic diets for cancer management that have been based around dairy.

[Damien Blenkinsopp]: Right. There’s a lot of cheese, cheese is pushed quite hard…

[Andrew Scarborough]: Yeah, loads of cheese and double cream, and it’s not efficacious for me, even though I’m astounded that they get any results with these trans fat. And they do get some results, that’s encouraging for me on my — what I would call a more beneficial and effective ketogenic diet for this circumstance.

(43:06)[Damien Blenkinsopp]: Could you explain quickly the IGF-1, because there are people at home that are not quite up to speed on the IGF-1 and the dairy aspect of it. What’s the problem there?

[Andrew Scarborough]: It activates insulin-like growth factor and that can cause cancer cells to proliferate faster. One of the ways I get around that — I used to eat lots of butter, but because it’s more insulinogenic and it has milk proteins and casein. What I do is I have Ghee, which is clarified butter so the milk solids and the casein have been removed, and it’s much less insulinogenic and I actually get a much better blood ketone readings as a result as well compared to butter.

I find that interesting in itself, and we also know that compared to coconut oil, Ghee has much more omega 3 fatty acids, and coconut oil only has omega 6. If you’re basing a ketogenic diet around — just loads and loads of coconut oil which is just omega 6. Even though coconut oil is fantastic for achieving ketosis, I would advise it in moderate amounts if you can tolerate it because it’s really good.

I would say that making sure that you have enough omega 3 by having more animal fats is more beneficial in terms of the overall nutrient profile than just consuming tons of coconut oil.

(44:44) [Damien Blenkinsopp]: Right. You mentioned you eat all the parts of the animal, I’m guessing you mean all of the organs…

[Andrew Scarborough]: Yep.

[Damien Blenkinsopp]: Do you consume what you would call a variety of these? Do you try to cycle them, and the widest spectrum possible? So what other organs are you eating, are you literally eating all of the different organs on a rotation each week?

[Andrew Scarborough]: Yeah. Literally everything but mostly heart, because it’s very very cheap, it would cost me 60 pence at a time, and you get quite a substantial portion— because lamb hearts are quite fatty, there’s a huge chunk of fat on them. I can just eat them as they are, and I don’t need to add extra fat.

It’s a fantastic source of iron, zinc, selenium, B vitamins, folate, and it’s the best food source of coenzyme Q10. It’s funny how people pay an absolute fortune to get pills that have a coenzyme Q10, and I just get the best source that you could possibly get for 60 pence at a time.

[Damien Blenkinsopp]: There’s a psychological barrier about the taste, and it’s just what we’ve become used to really. I’m definitely nowhere near as far as you — I’ve been eating more organ meats and I’m trying to push it up, I just made another order today from a new company actually. I’m slowly building my way up, and it’s a taste I’m struggling with, recipes I think help with that, learning how to cook and deal with the different tastes, and just getting used to them.

[Andrew Scarborough]: Yeah. I actually did quite well to start with brains, they’re actually the most tolerable in terms of tastes because they just taste like creamy eggs.

[Damien Blenkinsopp]: Oh, I would’ve never thought that.

[Andrew Scarborough]: They taste like creamy salty eggs.

[Damien Blenkinsopp]: You just don’t look at them while you’re eating them.

[Andrew Scarborough]: No. And a number of things I do are just for entertainment, to keep the diet interesting, to make sure I have enough trace minerals. That’s why I added insects to my diet quite early on because anytime you eat the whole animal you’re getting a variety of nutrients. When you eat insects you’re consuming the whole animal — it just makes sense that it would be a beneficial thing to have.

[Damien Blenkinsopp]: How do you consume those? Because I know there are cricket bars out there in the US, how are you consuming insects?

[Andrew Scarborough]: What I do is I get the fattiest insects that are ketogenic, I get waxworms and super worms. Mostly insects that reptiles eat, I get them from a pet shop that sells them for reptiles now, I used to get them online.

[Damien Blenkinsopp]: Oh, man. Okay did you used to buy from [check 47:31 – Bug Grow], was that the specific brand — was that the only place you bought from?

[Andrew Scarborough]: Yeah, I tried a few, I tried silk worm, pupa as well — a few different insects have different medicinal properties, they’re in Chinese medicine. They’re really interesting in terms of the properties that they have. But we largely ignore that, mainly what I do now is I get them from the pet shop.

I just stick them in the freezer to kill them, and then I’ll give them a gentle wash and eat them …

[Damien Blenkinsopp]: You just eat them straight?

[Andrew Scarborough]: The problem, if you get them online is that they’ve been dehydrated and cooked so much that the nutrient profile isn’t as good as if you have them fresh after they’ve been wiggling about. I also grind them up and make my own flour after I’ve frozen them. That makes quite nice breads, I make a zero carb ketogenic bread which is very useful. People actually think it’s proper bread…

[Damien Blenkinsopp]: You don’t tell them right?

[Andrew Scarborough]: I’ve actually offered it to people without telling them, and they quite like it, and then I tell them what it is, and they want to punch me. But it’s actually surprisingly quite nice.

[Damien Blenkinsopp]: A quick story here, I was in Mexico 15 years ago and I went to Taxco. Anyway you go up into the mountains, into this old city and they were selling plastic bags full of live insects for eating. It’s something that we used to do — we don’t do in modern society. . .

[Andrew Scarborough]: If you look at anthropology, and how we evolved, it’s largely ignored especially with these Paleo diets — we evolved primarily eating a variety of insects, and in quite a large amount. It suggested that the man would go out and go hunting — would only about a 20% success rate catching these larger animals.

The woman would be mainly collecting insects for food. Seasonally they would collect nuts and berries, but it’s a fact in anthropological studies that we did consume a large amount of insects before we moved closer to the coast to eat fish, and that’s how our brains developed more. It’s an ignored fact.

(50:16)[Damien Blenkinsopp]: It’s really interesting, we’ll get there. There’ll be people writing books — maybe you, about the missing parts of the Paleo diet, Paleo upgraded. You did mention that, when you exercise you’re taking exogenous ketones, because of your epilepsy, why is that?

[Andrew Scarborough]: When I exercise my blood ketones go down, lower than my individual therapeutic reading for seizure control for me personally. I have to do that, and I also have to take another experimental treatment of mine which is proved effective, which I learned from the literature on epilepsy. It’s a magnesium chloride solution that I mix into water, and I have a specific amount that reverses auras.

An aura for me is when you have all symptoms that you’re about to have a more serious type of seizure. An aura is a partial seizure in itself.

[Damien Blenkinsopp]: Okay. Maybe you would loose your words a little bit?

[Andrew Scarborough]: I would get pins and needles in my mouth and throat, and I would feel very dizzy, and faint. I have this horrible feeling like I’m going to collapse and have a tonic-clonic seizure. When I take the magnesium solution that I take three times a day, it actually reverses that aura, it is a potent preventative measure that I found to control seizure activity extremely effectively.

People with any kind of epilepsy, their levels of magnesium drop very low, and there are certain types of the day that magnesium is at its lowest, and typically that’s when seizure threshold is also at its lowest. If we can control that, we can control seizures very effectively. Also, on a ketogenic diet, supplemental magnesium — particularly magnesium chloride are found most effective.

It acts as a natural statin, it has a beneficial effect not only on cholesterol, in a natural way not like a typical statin where it’s actually destroying that process, it’s working with your body to do it naturally. I find that it also controls blood glucose — it regulates blood glucose very effectively too. I see it as my replacement for my medication that I was on previously, and the medication interestingly actually causes magnesium deficiency as well as calcium deficiency, deficiency in vitamin B-12 and vitamin D.

[Damien Blenkinsopp]: Which medication where you on?

[Andrew Scarborough]: I was on the maximum dose of Levetiracetam, which the brand name is Keppra and Sodium Valproate the brand name for that is, Epilim. I was both on those and the highest possible amount that you could be on. You can imagine the side effects of that, and the nutrient deficiencies that caused were just quite substantial.

When you’re withdrawing from those drugs you could actually get breakthrough seizures if you don’t address those nutritional deficiencies, and those seizures can actually cause SUDEP — it’s shorthand for sudden unexpected death in epilepsy. I was told consistently that I was highly likely to have that if I was to — not only come off my medication which is what I eventually did but reduced the medication. I have to reduce that medication for a period of almost two years.

I had to do it very slowly, and adding these nutrients and trace elements so that I was not having these breakthrough seizures that were life-threatening. It was a difficult balance, but I achieved it.

(54:50) [Damien Blenkinsopp]: It makes it easier when you titrate down slowly, but still you’ve been courageous in pushing for all of these things when you’re getting this pushback which is saying it’s really dangerous. Just in terms of the exercise, how do you bump your ketones up – is it the KetoForce?

[Andrew Scarborough]: Yeah. I consume that throughout my workout but I tend to mostly just do quite a light bodyweight exercise because I don’t want to stress my body too much. Thomas Seyfried himself recommends that cancer patients don’t push themselves too much with exercise, because it just puts too much stress on the body and on the brain. Mostly I just go for long walks, in an area with lots of oxygen, and I’m actually going to start having hyperbaric oxygen therapy fairly soon.

I’m in discussions with a number of facilities about that, and I’m going to start doing case studies on patients. I’m actually working part-time at the moment with Imperial College London in Charing Cross Hospital, to start-up clinical trials hopefully next year with brain cancer patients using — what I would call an optimal ketogenic diet.

We’re looking at magnesium for these brain cancer patients, we’re looking at the omega 3 and 6 ratios in the blood, we’re looking at C-reactive protein as a marker for a systemic inflammation, and we’re able to measure that for over a period of time to see how that changes while on a ketogenic diet.

[Damien Blenkinsopp]: With cancer is that typically high the hs-CRP because of the inflammation, or is that just a. . .

[Andrew Scarborough]: Yeah. It’s typically higher than normal, but one of the main ideas of measuring that is to have a marker that you can measure over time. I’m a huge fan of testing and I know that even if these things have no effect on cancer, they have an effect on epilepsy and blood glucose management.

We know that these are prognostic factors and they’re also effective at managing epilepsy which many brain cancer patients have as a result. I’m very keen to start doing this in patients more, and I’m working very hard to do that.

[Damien Blenkinsopp]: It’s very exciting that you’re able to work in hospitals. This is starting next year you said, potentially?

[Andrew Scarborough]: Yes. It would also be featured in, New Scientist magazine early next year. My story and my approach will be featured, and that’s very exciting as well because it’s getting the message out there and we can then have the actual data on humans which is missing. It would be — as I’ve said before it will be efficacious.

We’ll be able to not just translate the diets that have been used for children with epilepsy which I don’t believe …

[Damien Blenkinsopp]: As good, as they could be?

[Andrew Scarborough]: I don’t think that they’re translatable for brain cancer patients because I think it’s just very different. For example, when I was on the standard type of ketogenic diet, they did include those ingredients. I developed symptoms that were similar to Temporal Arteritis, where my temporal arteries became so inflamed that I nearly went blind and I was prescribed steroids for it.

But instead of taking the steroids what I did is I looked at how much omega 6 I was taking in my diet, and even though my blood glucose and ketones looked fantastic, and the ketogenic diet is anti-inflammatory in itself. I was having these inflammatory responses which were only controlled and reversed when I re-addressed the balance of omega 3 and 6 ratios. That in itself is quite powerful.

(59:15)[Damien Blenkinsopp]: Interesting. Where did your omega 6 ratio start? We read studies where the standard American diet, for example, is you can get ratios of 20:1, 10:1 — quite far off.

[Andrew Scarborough]: I’ve read up to 40:1.

[Damien Blenkinsopp]: Were you not so bad because you said you had a reasonable — you were trying to have a reasonably healthy diet before. I wouldn’t expect you’d have the sad numbers.

[Andrew Scarborough]: Yes, prior to initiation of the diet, I would say I was most likely about a 10:1 ratio. But, on the ketogenic diet, it was probably quite similar actually because it was including lots of nuts, coconut oil, coconut milk, coconut cream, lots of vegetables that were high in omega 6. I just thought it could be done better — then I transferred on to what I like to call a, fishogenic diet.

I was consuming a lot more fish, and I felt instantly much better and then as I cut down on the vegetables – cut them out completely. I had an instant response where I can’t even remember the last time I had a headache, even a mild headache.

(60:32)[Damien Blenkinsopp]: Great to hear. I’m conscious of your time I know that you’re really busy currently. But there’re a couple of things — I do want to make sure we cover before you go. We didn’t speak about glutamine and I know that an important part you mentioned up front that’s something you had to restrict quite sharply. But how did you do that practically?

[Andrew Scarborough]: Well, the first thing I did was limit protein quite significantly, and I did a number of therapeutic fasts, and it wasn’t until then that I actually saw the greatest response in my MRI scans, in terms of the complete remission. One of the other things that’s quite effective is with the magnesium it has an effect on that as well. I need to find the study for that, but I can send it to you if you’re interested in reading it.

Another thing that I’m actually looking into for the long term is Metformin, because Metformin on a ketogenic diet has quite a potent effect. It has a number of mechanisms which I can’t remember all of them off the top of my head, but that’s one thing that I’m playing around at the moment. It gets an effect on MAMP and a few other things.

It’s quite hard to explain, it’s quite technical.

[Damien Blenkinsopp]: In terms of the fast, you said that’s when you really started seeing the effects, so that would mirror — we had Thomas Seyfried on here and he was talking about the importance of the fast. How many days — was that a pure water fast? Was it a seven or five day fast?

[Andrew Scarborough]: It’s interesting because I think that — when these researchers are talking about fasting for brain cancer patients particularly if they have epilepsy, what they fail to note is that there’s ionic changes that are happening in the brain when you’re doing these fasts. A patient with epilepsy can’t — especially if they have brain cancer in my opinion shouldn’t just do water-only fast.

I think that they need to do what I call, a ’magnesium fast’. When I fast I have my magnesium water solution that I make up myself, and that prevents me from having breakthrough seizures while I’m fasting because I have such low body fat percentage. My longest fast has only been nine days. I aimed for 10 but I couldn’t do more, I’ve done that a few times but I need to have my magnesium-chloride solution or I instantly have breakthrough seizures, not the good kind either.

I found out the hard way initially, but now it’s just the easiest thing that I do.

[Damien Blenkinsopp]: You’re taking specifically magnesium chloride, is that because it’s a spray kind or is it actually the magnesium chloride specifically — there’s something about the chloride which is helping?

[Andrew Scarborough]: It has something to do with hydrochloric acid and how you digest it. I’d say it’s more bioavailable and it seems to me to be just in my personal experiences that it seems to get the brain very quickly. The literature doesn’t actually say that, but personally, I found that — even though there is not much in the literature about that.

[Damien Blenkinsopp]: Are you buying a specific brand? We’ve talked about using magnesium spray transdermally, but I’m just wondering if you’re using one of those sprays? How much you’re taking of it?

[Andrew Scarborough]: It’s designed to be primarily used transdermally this particular type, and I just get it from a health food shop, it’s mainly people who do sports who take it, which is interesting and funny. I typically take about five sprays three times a day. I can’t remember exactly how much that is, for 10 sprays it’s 150 milligrams of magnesium.

It’s variable depending on how mixed up the solution is — typically around 230 milligrams in a day that I would take. If you consider our water is too high in calcium and not high enough in magnesium. It’s addressing that imbalance that we have, we know that we should have at least a 2:1 ratio of magnesium to calcium, that addresses that imbalance.

We know that in the mornings after we wake up, magnesium levels are lowest. Primarily take it in the morning, after waking up in the afternoon, and before I go to bed.

[Damien Blenkinsopp]: Have you checked your RBC magnesium levels?

[Andrew Scarborough]: I haven’t because I don’t think it’s an accurate measure. I just go by how I feel, and sometimes — I see the epilepsy as a blessing because everything to do with epilepsy with brain cancer is typically very similar to what would work for treating the cancer. If something is working for the epilepsy, you’ve got a pretty good idea that it’s beneficial for the cancer, and most of the things that I actually research about what helps in terms of my epilepsy, experimentally and otherwise.

I found incidentally that it has quite potent anti-cancer benefits as well. It’s really interesting the relationship. It’s quite empowering as well. What I would call spectacular results because I still can’t believe I’m not having these horrific seizures all the time without medication. It’s quite empowering to know that it’s potentially having the same benefit on the cancer.

(1:06:44)[Damien Blenkinsopp]: Yes, it’s pretty amazing your journey. I don’t know if you’ve come into contact with other people with similar stories to tell — I know that some other people who had cancer, you said, unfortunately, they’ve passed away — the ones you were relating to. But if you come across any other people who have been experimenting like yourself.

[Andrew Scarborough]: Yeah. I actually have a group of friends now who I came into contact with just through seeking out long-term survivors, and I have a group of long-term survivor friends who had glioblastoma many years ago, and now have no sign of disease. I have a group of friends with various other cancers who are still here now. They’ve mostly done a drug cocktail treatment on themselves, which is very interesting.

Personally, I wanted to try and copy that drug cocktail treatment but do it in a natural way just using diet.

[Damien Blenkinsopp]: When you say drug cocktail, is that chemo or is that more Metformin and things like that?

[Andrew Scarborough]: It’s more Metformin and statins, and phosphates, and various other DCA, and other very interesting drugs. Personally, the only one I’m considering is Metformin, and potentially a few others, but mainly Metformin and Curcumin which I take in tablet form with DHA because they work synergistically. Curcumin actually increases uptake of DHA to the brain.

Because we know that around these tumors, or where the tumor was – DHA is very low. We know that if you have Curcumin and DHA that’s a powerful combination. Curcumin is cytotoxic to the cells. We know that DHA is, and is essential for brain functioning.

[Damien Blenkinsopp]: You really have built a whole lot of armory against this — it sounds like you’re doing really well. On the Curcumin – there’s many forms available on the market today, you’re taking one of the bioavailable forms…

[Andrew Scarborough]: Yeah, it has piperine in it as well.

[Damien Blenkinsopp]: Okay.

[Andrew Scarborough]: It’s a component of black pepper. I have a number of strategies that I use, and I’m constantly optimizing my metabolic formula.

(1:09:14)[Damien Blenkinsopp]: Do you feel constant improvement? I don’t know if there are any symptoms because it seems like you’ve got most of it under control. Do you think you’re going to be able to repair your body, do you feel any signs of that in terms of potentially resolving the epilepsy?

Do you think this is more likely something that you’re just going to optimize and maintain so that it never bothers you, so you never get the actual symptoms?

[Andrew Scarborough]: As my brain has been visibly healing at a very fast rate on these scans while I’ve been utilizing this protocol, I’ve also found my symptoms have improved with that quite substantially as well. I had facial paresthesia constantly all throughout the day, everyday, and a number of other debilitating symptoms I couldn’t even go out and walk a few steps. The fatigue was horrendous as well.

Being able to do what I am now and this non-stop activity, and just doing so many different things, and having my seizure activity controlled in such a great way that’s much better than before — even before when I was doing all these things I was still getting more activity. I haven’t actually done that many more things if I compare to even just a few months ago. Definitely improving in quite a dramatic way, despite having to keep up with all these things.

It’s getting easier to control, to the point where I have days now that I have no symptoms at all, but if I get overconfident and I forget to have my magnesium drink or do something that’s just out of my routine, I’d definitely have more seizure activity coming. Even though it’s not to the degree that I used to have.

[Damien Blenkinsopp]: I guess really say why you’re saying epilepsy is a bit of a bonus for you because it’s early warning detection system for you…

[Andrew Scarborough]: Yeah.

[Damien Blenkinsopp]: — Whereas cancers can creep up on you and you won’t know unless you’re watching the scans and even the scans aren’t showing a small progression. So right now you can still have a small amount of cancer left, but you can’t see it. It does seem like a pretty nice little tool, even though it’s not nice to have it, in the longer term it sounds like it’s a beneficial thing for you.

[Andrew Scarborough]: Yeah, I can see it as beneficial now, I couldn’t before but it definitely is.

(1:11:47) [Damien Blenkinsopp]: Well Andrew this has been an amazing — it’s very inspiring episode today. I can really say that — I’m totally going to take some of the things that you have been trying and start testing them out myself. I would like to ask you — where to look first if they would like to learn about this topic if they’re facing cancer or epilepsy?

Are there good books or presentations on the subject, the first places to go to, to start learning themselves about this?

[Andrew Scarborough]: I would thoroughly recommend the book, Cancer as a Metabolic Disease by Thomas Seyfried. I think that’s a great starting point. For anyone starting a ketogenic diet I would recommend, Keto Clarity, that’s a good resource to use. I would also go to www.ketogenic-diet-resource.com — that has answers to just about all the questions that you could have.

For help to a dietician, if you live in the UK I would recommend the charity, Matthew’s Friends. In the US, I would recommend the Charlie Foundation which is the sister organization of Matthew’s Friends in the UK. It has recently started to see — it’s mainly brain cancer patients that they see because they get around with that by saying that they’re treating the epilepsy.

I would also go on Clinicaltrials.gov to see what clinical trials are happening globally to do with the ketogenic diet and different cancers.

[Damien Blenkinsopp]: Right, so if they’ll just search for a ketogenic diet on there…

[Andrew Scarborough]: Yeah, if they search for ketogenic diet and cancer on Clinicaltrials.gov they can see all of the clinical trials that are currently happening in terms of ketogenic diets for different cancers. It’s very exciting that more and more of these are popping up, and I hope to — I have a meeting on Thursday to discuss having proper official ketogenic diets, using the right approach in this country, and that’s really exciting new development.

[Damien Blenkinsopp]: Is that with the government, NHS or some other body that’s going to help promote it.

[Andrew Scarborough]: This is in conjunction with brain tumor research, they’re one of the very few cancer charities that actually are going all at it with this metabolic research, and they’re doing that with Imperial College London. It’s a small charity that’s doing this, it’s quite incredible what they are able to do being such a small organization.

[Damien Blenkinsopp]: It’s great they’re starting to be – some grounds building from the bottom and up.

[Andrew Scarborough]: Yeah, and I’m going to start-up my own individual research with a few of my lecturers at my university because I want to get these things happening much faster than if it’s going through clinical trial protocol. I want to do this myself with lower grade gliomas, so that we can see a long-term response to try and shrink these tumors hopefully, because they are not as aggressive, but, they still are incurable.

I want to see what effect that we can have on them rather than having to go through all the standard treatment to go through clinical trials. I think that’s very exciting going forward.

(1:15:25) [Damien Blenkinsopp]: That sounds really exciting, and I’m sure anyone who – maybe affected would be very interested to know more. What are the best ways for people to connect with you and learn about you, and keep up with you when you’re doing these things, they can stay up to date on them. Are you on Twitter, you mentioned you had a YouTube channel?

[Andrew Scarborough]: Yeah, my Twitter name is @ascarbs, and I’m on Facebook if people want to add me on there, Andrew Scarborough. I also am working on a website at the moment which is www.metabolictherapy.co.uk, and that has a holding page at the moment, but it should be live shortly. I have a YouTube channel, Andrew Scarborough, and I have a blog, My Brain Cancer Story that’s the title of it.

People search for Andrew Scarborough and My Brain Cancer Story, they should find it.

[Damien Blenkinsopp]: Excellent. We’ll put all those links on the show notes of course also, make sure all of that is there. Is there anyone besides yourself you’d recommend to learn more about the stuff that you mentioned, Thomas Seyfried, is there anyone else that people should look to?

[Andrew Scarborough]: I would look at the research by Dominic D’Agostino, also I would recommend Dr. Colin Champ, I’ve had various discussions with him online which are very interesting. He’s very interested in my approach and he is very unique, he’s a radiation oncologist who is very supportive of this metabolic treatment. Very similar to my oncologist who – it’s quite a rare thing to find – but it’s very encouraging.

There’s Dr. Adrienne Scheck, who I’m having a meeting with on Thursday she’s coming overseas from the Barrow Neurological Institute in the US, and she’s the one that does the rodent studies using the ketogenic diet. It’s great to be able to discuss with her.

(1:17:29) [Damien Blenkinsopp]: Great, great, thank you for those. Some quick items on your – just a personal approach on what you would advise people to get started with – are you still tracking any biomarkers, on a routine basis?

[Andrew Scarborough]: Only occasionally with MRI spectroscopy but we’ve stopped doing that now just because it looks a bit boring and nothing’s really changing. It all looks really good, that’s why we’re not monitoring it anymore.

[Damien Blenkinsopp]: So maybe once in every six months or once a year?

[Andrew Scarborough]: Yeah, just to keep an eye on it, but everything that you would expect to be elevated but would be a bad thing isn’t showing up – it sounds like a good thing. It’s very new research, we don’t know too much about it, but it’s very promising for the future.

Because if we can see these things before they show on the scan, in terms of enhancement or just showing in an obvious way then it’s – that can only be good for the patient really. Then we can intervene in a non-toxic way.

[Damien Blenkinsopp]: So if you were to recommend one experiment, basically you’ve done many experiments to get to this point – they’re not proven recommendations by doctors and so on. What would you recommend that someone with brain cancer or potential other cancer – what would be the first thing they should try, the biggest payoff from all of the things that you’ve mentioned, what should their first step be?

[Andrew Scarborough]: The first step should definitely be reducing carbohydrate intake. The second step would be reducing protein intake to maintenance levels, and therapeutic fasts are very important. But the main thing, I would say is the omega 3 to 6 ratio, I believe that they should be an omega 3 to 6 index, just like with the glucose-ketone index, and they should work together, as a synergistic therapy.

Because you could even argue the ratio of omega 3 to 6 is even more important than the ketones. I would also say, the magnesium is very important with that too, those three things. Therapeutic ketosis, the omega 3 to 6 ratio and the magnesium I would say are very important for brain cancer patients.

[Damien Blenkinsopp]: Great, thank you, that’s some great takeaways for people at home. Andrew, I’ve got to say this has been really amazing interview – it’s amazing all of the different avenues you’ve run-down and all of these different aspects that you found to improve your situation. I know it’s going to be an inspiring story for the audience.

Thank you very much for being on the show.

[Andrew Scarborough]: No problem, we did cover a lot but we got there in the end.

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Part 3 in our series of Fasting Self-Experiments. In this longer 10 day water fast I tracked results with a broad set of biomarkers (ketones, glucose, weight, hormones and cognitive performance panels).

This is a long post – if that scares you, jump directly to what you’re looking for:

  1. Why Do a 10 Day Water Fast? (The health benefits that we’re optimizing for)
  2. 10 Day Water Fast Results (Weight, metabolism, cognitive performance, hormones)
  3. 10 Day Water Fast Experience (Anecdotal thoughts, symptoms, and my post-fast rookie mistake)
  4. The Tracking (Details on all the biomarkers tracked and lab tests used)
  5. Tools & Tactics (Details on the exact fasting protocol I used, and some supplements taken)

Video Recorded on Day 10 of Fast Just Before Refeed

Note: I was yet to realize the post-fast rookie mistake I was making!

I’ve been fasting once per month for 5 days since my first water fast experiment in June 2015. If you are new to fasting, you can get all the why and how basic details in that post.

The results from my 5 day fast cycles have been so positive that I couldn’t help but wonder if More is Better when it comes to fasting.

This led me to ask:

“Will I benefit from a 10 day fast programmed into my life once per quarter or twice per year?”

To get an answer to that I broke that down into the following questions I was going to try to answer with this first 10 day fast:

  1. Can I remain productive during a 10 day fast?
    (10 days is a big chunk of time to strike off from work and life – far too big for my taste! Let’s be sure I’m not throwing away the equivalent of 40 productive days a year with this habit)

    • Would my mental performance suffer? Perhaps leading subtly to worse decisions, or perhaps just slower thinking?
    • Would my energy levels remain the same or decrease? Would there be a change in how many hours I could comfortably work per day?
    • How about concentration, focus and drive?
  2. Is “10 day fasting” every quarter sustainable? Specifically, where I’m doing monthly cycles of 5 day fasts in between?
    • Would I double the weight loss of a 5 day fast? And thus make it difficult to recover the weight within the following month? (The question here: Does weight loss follow a linear path based on number of days fasted?)
    • Would a 10 day water fast be as easy, psychologically and physiologically, as the 5 day water fasts? Or would I hate it? (Nothing we hate is going to get done repeatedly)
    • Is there any downside impact on “adrenal health” or cortisol regulation from fasting? (this is a question I’ve been attempting to answer since I started long duration fasting)

itunes quantified body

To try to answer these questions I tracked cognitive performance, hormones, metabolism and weight throughout the fast.

I also committed to following a normal rhythm of life and work during the fast this time. I would run life as usual, and let the chips fall where they may – I would see if the fast got in the way.

(Note: Please do not take this as advice to do this at home yourself – I’m not a doctor, and would be extremely upset if you hurt yourself – please be cautious with fasting.)

The outcome we’ll get to in the results in a second, but but first “the Why”…

Why Do a 10 Day Fast?

We’ve covered the benefits and whys of fasting well in previous episodes, however, as a quick reminder here’s the list:

  • Anti-Cancer: Leveraging the metabolic theory of cancer and Dr. Thomas Seyfried’s work, fasting may be an effective tactic to reduce our future risk of cancer.
  • Immune System Effectiveness: Cyclic fasting has been shown to regenerate immune system cells which deteriorate ‘naturally’ as we age or via environmental or other insults. Thus, it may reduce or stave off some of this natural deterioration and keep us healthier.
  • A Stronger Body: Lean body mass gains including bone density increase and muscle mass increase have also been tracked in studies and myself.
  • Body Fat Removal: Fasting or cycles of fasting can be a useful tactic for removing unwanted excess body fat.

The 10 Day Water Fast Results

Metabolism on 10 Day Fast Looks Similar to 5 Day Fast

In 5 day fasts I consistently see glucose drop to between 50 and 60 mg/dL and ketones rise to between 5 and 7 mmol/L. In the additional 5 days it seems you shouldn’t expect any big change. My numbers came back largely the same.

My ‘switch time’ from glucose to ketone metabolism continues to edge forward to happen slightly earlier with each fast I do. This time just past the 48 hour mark the switch took place – my blood ketones jumped up and glucose dropped down to their fasting equilibrium levels. My metabolism had switched to ketone burning.

10 day waterfast ketones glucose
A few interesting points:

  • There was a slight glucose upwards blip on days 6 and 7 where it rose back up to between 60 and 70 mg/dL. This was most likely caused by the sleep disruption I experienced from day 5 (see sleep details). Low quality sleep tends to impair glucose regulation – thus higher (but still low) glucose.
  • On day 7 and 9 I got several “HI” errors for my ketone readings, meaning that my ketones were over 8 mmol/L, the upper limit of the ketone meter’s range.
  • For the first 3 days post fast, days 10 to 13, my ketones were still spiking high in the evenings and quite erratic – this was most likely an anomaly this time around due to my Post-Fast Rookie Mistake.

Despite the glucose uptick on day 5, I stayed well within the therapeutic range to provide anti-cancer benefits outlined by Dr Thomas Seyfried (see explanation via my interview with him in Episode 16).

So long as you remain under a Glucose Ketone Index of 1, you are assumed to be within the therapeutic range as per chart below where I’m shown to have had a complete 8 days of therapeutic anti-cancer action.
10 day water fast glucose ketone index

Weight Loss: How Much & How Long to Gain it Back?

Over the 10 days I lost a total of 5kg (ll lbs) of weight. The weight loss was at a consistent daily rate as usual, except for Days 8 and 9 where it stalled at a weight loss plateau, before a further drop on the morning of the last day.

I regained all the lost weight by the 18th day after the end of the fast – and this was despite some digestion re-startup issues for the first 3 days post fast (see the post-fast rookie mistake for the details). So the weight was really recovered via 15 days of normal eating.

Weight Loss 10 Day Water Fast

Testosterone on a Fast: Big Drop & Libido Changes

It makes sense that you shouldn’t expect to be on top of your ‘libido’ game while fasting. When food is scarce we should have evolutionarily had more important things on our mind – like finding food to survive.

This was certainly part of my experience. The longer the fast, the less interest I had in women or sex. By day 5 my testosterone levels (DUTCH Test – see in labs) had dropped below the 20 to 40 year old male reference range.

A couple of studies I found corroborated this with testosterone dropping significantly during fasts (and then rebounding strongly with refeeding)1,2.

The Takeaway: NOT a good idea to fast on honeymoons or dates. The day after ending the fast – great idea.

Testosterone: 10 day fast

Is it OK to Fast with Adrenal Fatigue?

In previous fasting episodes I’ve noted that I’m working on “low free cortisol” levels that I’ve been tracking for a couple of years. A situation that I expect, based on symptoms I now understand dates back to as much as 10 years ago.

One of my concerns with repeated fasting (considered a stressor) was that it may not necessarily help with this situation – when you look at it through the lens of “Adrenal Fatigue”.

Specifically, I was referring to the idea that Low Free Cortisol = “Adrenal Fatigue”. Thus adding more stress could exacerbate the issue, reasoning that the adrenal glands are already overstretched in a normal everyday scenario without that added stressor.

In this fast I learned that there’s less reason for concern than I’d initially considered. You need a bit of background to understand why.

Historically, people from the functional medicine realm have referred to “adrenal fatigue” as a state of fatigue of the adrenal glands, whereby you typically have low energy in the afternoons. This can happen to me at times. It is documented and diagnosed via 4-point free cortisol salivary tests like the one from Biohealth that I’ve done previously (See the results from previous adrenal labs in this episode).

However that name doesn’t have a very accurate definition or explanation. The term is used quite vaguely for the most part. We can’t scan an adrenal gland and see it in a withered state for example. We don’t have a specific test that can show the state of ‘adrenal gland fatigue’ that ties it back to the adrenal gland itself.

So a new term that is surfacing for the situation of low free cortisol is “cortisol dysregulation” as a result. It provides at least a ‘less wrong’ definition. Cortisol isn’t normal, it’s lower than it should be – and thus is driving some fatigue symptoms. It’s dysregulated. Another term you may have heard is HPA Axis dysregulation.

The DUTCH test I used to track my hormones is useful where it comes to investigating and better understanding cortisol metabolism as it looks at both free and metabolized cortisol. Metabolized cortisol is a proxy for total cortisol output. The traditional salivary tests used look only at free cortisol levels. Thus, DUTCH enables you to assess whether your total levels of cortisol are low (the adrenal output is lower, or if it’s just free cortisol that is low, and total cortisol is normal).

As you can see below my total cortisol (metabolized cortisol) is right in the middle of the normal reference range.

Metabolized Cortisol Levels (Baseline and Fasted)

10 Day Fast Total Cortisol (Metabolized Cortisol)

So in my case, it turns out that I have above average metabolized cortisol levels – so in fact total cortisol output is well within the normal range. It’s just my free cortisol levels that continue to come back below the reference range (now cross-checked with two labs, DUTCH test + Biohealth #201).

I don’t have reduced adrenal output, I have normal adrenal output – which would fit the old definition “adrenal fatigue”.

That’s good news.

Nonetheless, the low free cortisol has to be troubleshot. The most likely explanation behind this is that I’ve been subjected to a long term stressor and my body has compensated to lower free cortisol levels. That maps to other information – that underlying stress, is most likely high ongoing inflammation levels that I have documented over several years now.

24 Hour Free Cortisol Levels (Baseline and Fasted)

10 day fast 24hr free cortisol

The Takeaway: Rather than just relying on propping up my adrenals with adaptogens, it’s pretty clear that the end game is to continue to explore and resolve all causes of stress. Inflammation is my obvious first target, although it’s another reminder to keep up my lifestyle stress management practices (adaptogens, meditation, circadian rhythm and sleep).

Note: For those who like to dig into the data – here’s an explanation of the cortisol results from the DUTCH test.

Did Mental Performance Keep Up During the Fast?

Although I’ve always “felt productive” when fasting, I wasn’t as sure that my mental performance was the same. This time round I planned to try to capture this information properly. Unfortunately the results weren’t very clear.

I used Quantified Mind, the tool we covered in Episode 33 to track my cognitive performance in terms of Working Memory and Attention Control.

The main issue I was advised to eliminate by Yoni Donner, founder of Quantified Mind was the practice effect. As we perform any mental test repeatedly we get better – to understand if a fast was impacting me cognitively, I needed to try to eliminate that. To do this I used the same test repeatedly during the few months before the fast, due to travel this wasn’t as consistent as I would have liked. The idea is that eventually you peak out, and any practice based improvements will have dried up or be minimal.

10 Day Fast Mental Performance

As you can see in the data above it looks like there were some pretty strong practice effects taking place throughout and after the fast. The fasting period is shaded out in blue.

As a result, I’ll be continuing to use the same test panel in future fasts, and in between, to see if I can separate these out. With continued repetition I should be able to isolate any fasting effects.

The 10-Day Fast Experience

With repeated cycles of fasting I have become a lot more comfortable with “how it feels” – both body and mind do feel different on the water fast – the first experience I was cautious due to this – not knowing if I had new limitations that I shouldn’t cross.

Now that I have got used to fasting, I basically run life as usual. I don’t restrict my activity level or my schedule, or need to plan for it. In this fast of course I committed to making this a goal in itself to understand if fasting limits me.

As a result, during the 10 day fast, I was out meeting friends, business contacts – and even went on a date to an art exhibition.

Nonetheless there are things to note…

Physical Weakness

I experienced less of the feeling of physical weakness than in previous fasts – a heaviness or lack of refined motor control of the arms and legs.

I tested this a bit further on day 2 with one set of 55 push ups (my current 1 set max). This didn’t feel much different to doing it in a non-fasted state.

During this fast as I was going about my days I had times when I actually felt ‘physically strong’ and was naturally walking around at a rapid pace. This was more so on the last 5 days of the fast, so that difference may simply be related to the fast being longer. In many ways the last 10 days were more physically comfortable than the first 5 days.

Sleep – My Next Challenge

On most of my fasts the biggest downside is sleep disruption. After a few days on the fast I tend to start to have interrupted sleep.

This fast was no exception. From day 5 I began to get night wakings as early as a couple of hours after going to sleep. After some of these I wouldn’t be able to get back to sleep for hours. The exception was the last night – on day 10 – I had perfect sleep, longer duration, and deeper than usual judging by the drowsy feeling combined with how refreshed I felt in the morning.

Sleep disruption and night wakings are shown to impair glucose metabolism. So it’s the likely cause of the slight rise in glucose I experienced on day 5 and 6 also.

For future fasts I’ll be making sleep a priority to investigate, track and optimize.

The Mind Retreat

The mental experience of fasting for 10 days allowed me to appreciate more clearly aspects that I’d noticed in shorter fasts. Fasting promotes a less rushed, more practical and more bigger picture thinking state of mind for me.

The contrast of this with the typical more frenetic ‘getting things done’ focus of life is very attractive. In my mind it presents a great counter balance to keep your decisions in check once a month. It enables you to look at life, work from this other perspective once per month (if you’re doing the cyclic fasting) and that strikes me as a good thing for decision making.

This was far more noticeable on the 10 day fast. Some of this may be related to the drop in testosterone (and libido!) I tracked.

The Post-Fast Rookie Mistake

If you’re thinking of undertaking a 10 day water fast yourself. This is possibly the most important section – pay attention – I made the mistake and paid for it.

For 3 days after the fast I suffered from gut and toilet problems. Severe pain the first night to discomfort and the inability to keep anything actually inside me for the 3 following days.

It was a simple mistake. I assumed that what works post-fast for 5 days, should be okay for 10 days despite having spoken with people having done 10 or more day fasts that advised caution.

The biggest difference between the 5 and 10 day fast is how you start to refeed. I prepare and eat a couple of bowls of bone broth after my 5 day fasts without issue. I’ve found it to be a great high micronutrient way to ease back into eating.

However, with the 10 day fast, this turned out to be a disaster. My body simply was not able to deal with high levels of fat found in bone broth. My appetite didn’t return as a result either, so I was having to push myself to squeeze in small meals. After 3 days of failing to get my digestion back to normality with a variety of food combinations I thought would work (vegetable soup, scrambled eggs, etc) I had to rethink my strategy.

I resorted to drinking exclusively blended green vegetable smoothies.

The turnaround was amazing. All my digestion issues disappeared literally with the first couple of glasses, and my digestion issues were completely resolved within the next 24 hours. I kept that program up for a few more days nonetheless, to make sure I was past the issues.

So my strong recommendation to anyone trying this – and myself for future long duration fasts – will be to start with exclusively vegetable smoothies for the first 24 hours as a minimum (better 48 hours). That should lay the digestive foundation to be able to move back to your usual eating patterns.

Symptoms – The Back Rash

I’ve experienced some slight rashes during fasts before. With this longer fast it was a lot more extreme.

By day 10 my whole back was covered with a rash of spots – just the back. It was quite stunning – it made me think back to the time I caught chicken pox.

This rash disappeared just as quick within a couple of few days of refeeding it was completely gone again.

The Takeaways

So coming back to the questions we want to answer:

  1. Can I remain productive during a 10 day fast?
    • Would my mental performance suffer? Perhaps leading subtly to worse decisions, or perhaps just slower thinking?
      Answer: It’s not clear as yet. It doesn’t look like there was any drastic mental performance impact on working memory or attention control. Future testing will need to be done with future fasts to further validate
    • Would my energy levels remain the same or decrease? Would there be a change in how many hours I could comfortably work per day?
      Answer: There was no noticeable big change in energy levels or hours worked during the fast. If anything I felt a little more wired, and thus had to reduce my intake of caffeine.
    • How about concentration, focus and drive?
      Answer: Testosterone is often associated with these attributes in men. Low testosterone tends to reduce these attributes, however while my testosterone dropped during the fast, that’s not something I experienced. In a future 10 day fast I’ll track testosterone on the last day (day 10) to see if the hormonal impact is greater than the mid fast impact (day 5).
  2. Is “10 day fasting” every quarter sustainable? Specifically, where I’m doing monthly cycles of 5 day fasts in between?
    • Would I double the weight loss of a 5 day fast? And thus make it difficult to recover the weight within the following month?
      Answer: Weight loss wasn’t exactly linear – there was a leveling off at one point so weight loss per day was slightly less than with that I’ve experienced with the 5 day fast. The weight was easily regained within 15 days – so there doesn’t look to be an issue with not being able to maintain my equilibrium weight when I introduce 10 day fasts every quarter in between the monthly cyclic 5 day fasts.
    • Would a 10 day water fast be as easy, psychologically and physiologically, as the 5 day water fasts? Or would I hate it?
      Answer: If anything the 10 day fast was easier and got easier as I got into it. This could be due to my growing experience with fasting – “practice effects”, or that fasts do get easier the longer you’re on them. I think it’s probably a bit of both of these.
    • Is there any downside impact on “adrenal health” or cortisol regulation from fasting? (this is a question I’ve been attempting to answer since I started long duration fasting)
      Answer: My total cortisol and 24hr free cortisol were slightly lower on day 5 of the fast compared with baseline. Despite having done many fasts my 24hr free cortisol levels have not dropped from the original values I tracked a year previously – they’re stable. My total cortisol is also well within normal output ranges. So my inclination is to say no. I’d like to check in a future 10 day fast the cortisol metabolism on day 10 to see if there is a ‘declining slide’ in cortisol output over longer duration fasts.

Episode Question: Are you convinced about the rewards of water fasting to try it yourself yet? If not, what else would you need to know to get you there? Let me know in the comments.

Tracking

Biomarkers

  • Blood Ketones (Beta-Hydroxybutyrate / β-hydroxybutyrate): Blood ketones are the gold standard for measuring your state of ketosis. During the fast, ketones are expected to peak in the range of between 6 and 8 mmol/L. Dominic D’Agostino mentions that metabolic acidosis with values over 5 mmol/L place an additional burden of processing on your body, so in non fasting states keeping values between 1 and 5 mmol/L may be optimum.
  • Blood Glucose (mg/dl): A measure of the level of glucose in the blood at one point in time. Values of between 50mg/dL and 60mg/dL are standard for fasts. Non-fasting values should be below 80mg/dL ideally, and at least 92mg/dL.
  • Glucose-Ketone Index (GKI): The ratio between the concentration of glucose in the blood to ketone bodies in the blood. The calculation is Glucose (mmol)/ Ketone (mmol). Dr. Seyfried created the index as a better way to assess metabolic status. Therapeutic efficacy is considered best with index values approaching 1.0 or below. Patients with chronic disease like cancer have consistent index values of 50 or more.
  • Weight (lbs): Standard scales measurement of weight in morning without clothes (to avoid biases).

Lab Tests, Devices and Apps

  • Blood Ketone/ Glucose Monitors: The Precision Xtra in the U.S. or Freestyle Optium Neo in the UK are the current recommended monitors. You’ll need lancets, ketone strips and glucose strips also.
  • DUTCH (Dried Urine Test for Comprehensive Hormones): This advanced hormone test panel from Precision Analytical is currently the most comprehensive and convenient test looking at cortisol metabolism and sex hormones. I used it to track baseline and fasting hormones. You can download my complete lab test results here: Baseline test results / Day 5 of fast test results.
  • Quantified Mind: The free online tool used to track cognitive performance during the fast – you can learn more about using the tool in this episode with its creator Yoni Donner. I used two short tests Yoni recommended to use for a mental performance check-in requiring a minimum of time (~5 minutes):
    • Color Word Inhibition: A test that measures attention control via the stroop effect.
    • Self-Paced 2-Back: A version of the N-Back game used to assess working memory.
  • Muse Calm: Mentioned as one of the better return on effort items discovered through the Quantified Body’s exploration so far. Interview with the founder, Ariel Garten, in previous episode here.

Tools & Tactics

Fasting Protocols

  • Water Fast: “Water fasts” are the standard fast protocol used in most of the research studies, including those looking at cancer inhibition or therapy for cancer patients. People are more or less extreme with the definition of what a water fast consists of. I personally am looking for the ‘biological effects’ or results. I’m not concerned with sticking to purely water unless that’s what is required to gain those results. So my version in this fast includes some supplement support which should not interfere with the beneficial fasting mechanisms – see below in Supplements for details.
    • 5 Day Water Fast: A minimum of 3 days is required to flip most people’s metabolic switch between glucose and ketone metabolism, and attain the benefits of the fast. For this reason a good place to start with water fasting is 5 days, which incorporates 2 days of therapy time (i.e. after the 3 day lead time to switch the metabolism). You can see this effect taking place in my first 5-day water fast self-experiment. The 5 day fast is also manageable on a cyclic monthly basis: 25 days of normal life, and 5 days of fasting per month.
    • 10 Day Water Fast: To provide a deeper dose of therapy (i.e. 7 days) people are extending their fasting times to 10 days, or beyond. As per my interview with Dr. Thomas Seyfried this may be more effective with respect to the anti-cancer effects. Depending on your risk profile, this may be something you consider doing from time to time.
  • Fast Mimicking Diet (FMD): A diet designed by researcher Valter Longo to maximize activation of the beneficial fasting mechanisms while still allowing you to eat to an extent. The details of this type of fast were covered in my FMD self-experiment in episode 31.

Supplements

My goal with this fast was to support my body without interfering with the beneficial fasting mechanisms, and to stay productive throughout (work wise and socially). So this is actually what I did:

  1. Mineral supports: This was the main supplementation I took covering a broad spectrum of minerals.
    • Real Salt: I sprinkled real salt into the filtered water I was drinking throughout the fast.
    • Quinton Hypertonic: A seawater electrolytes solution with a broad spectrum of minerals.
    • Pure Encapsulations Minerals 650: Capsules containing a broad spectrum of minerals.
    • (Both of the above recommended to me by Chris Shade from this episode)

    • Ancient Minerals Magnesium Spray: Typically I apply this to my skin daily after showers for absorption via that route. However, I’ve also started to spray it into my drinking water along with the Real Salt, and continued this during the fast (Note: Spraying the oil in drinking water was a tip from Andrew Scarborough in an upcoming interview – Episode 44).
  2. Drinks: Besides water I also consumed some other drinks during the fast, primarily for productivity purposes. My usual routine is to have a coffee in the morning, with the obvious caffeine jolt – so I kept to that usual routine, just keeping it to simple no calorie versions.
    • Black Coffee: For the first 5 days I took a black coffee in the morning, however I typically found that I naturally didn’t finish it. As the first continued I increasingly felt the caffeine from this single coffee was too much of a stimulant, the effect seemed to be magnified. So half way through I switched to…
    • Teas: Mostly Green Tea, also some Rooibos and Camomile tea. I found the green tea didn’t over-stimulate as much although I was still maxed out on 1 or 2 cups. More than that and I got the jitters.

Personal Note: Background on Using Minerals in Fast

There was another, more personal, reason I included a good amount of mineral supplementation during the fast. Since the episode with Chris Shade I’ve been following his mercury and heavy metals removal protocol.

Part of that protocol requires that you take a break from time to time to halt the process and remineralize the body since a side effect of the protocol is removing needed minerals along with the heavy metals.

I wasn’t going to be following the Shade protocol during the 10 day water fast (I stop all other experiments and protocols while fasting), so it made sense for efficiency to use that time for remineralization.

Other People, Books & Resources

People

  • Dr. Thomas Seyfried: See episode 16 for a discussion of his theories and work.
  • Dominic D’Agostino: Dominic has led some of the research into the benefits of ketone bodies and metabolic therapies, he is now turning much of his research effort towards cancer similarly to Thomas Seyfried.
  • Chris Kresser: Damien first learned about the benefits of the DUTCH test at Chris’ recent seminar in London.

References:

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

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

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

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

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

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

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

itunes quantified body

What You’ll Learn

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

Eugene J. Fine, MD

Tools & Tactics

Drugs & Supplements

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

Diet & Nutrition

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

Tracking

Biomarkers

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

Lab Tests, Devices and Apps

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

Other People, Books & Resources

People

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


Full Interview Transcript

Click Here to Read Transcript

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Gene Fine]: Yes.

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

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

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

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

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

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

[Gene Fine]: Yeah, sure.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Gene Fine]: Yes, true.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Great, great.

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

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

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

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

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

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

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

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

[Gene Fine]: Yes.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Were you measuring blood levels?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Gene Fine]: Fasting levels, right.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Great, great.

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

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

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

[Damien Blenkinsopp]: Right, you’re right. The question is the protein. That’s the missing…

[Gene Fine]: Right. And as I say, I haven’t tested the protein values. We didn’t restrict protein in our group. I think we could have.

We were dealing with patients who, as I say, had advanced cancers, and we were getting them as through referrals from their oncologists as volunteers, and we really didn’t want to give them something too complicated to do, so we just tried to [simplify it]. But yes, protein, certainly restriction might have had further benefit.

But as far as inducing ketosis with medium chain triglycerides, coconut oils and the like, ketone esters, I think these are interesting approaches. They can certainly, possibly offer more convenience, rather than going through a low-carb diet. And that I think has value.

The other thing to note is that they don’t actually mimic the full effects of a low-carb diet because they don’t inhibit insulin. So, there is that aspect of it. While there may be value, I’m not sure that they’ll produce the full effect.

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

Now the other thing I wanted to just bring up was metformin, I don’t know if you’ve looked at all at that.

[Gene Fine]: Well, yeah. I mean, I’m aware that this is being used, at least in trials, as another potential mimicker. And it has it’s own value. I think what it does for me is it illustrates the value of low-carb diets, because what it really does, metformin, is it limits glucose and thereby insulin secretion. So, it’s fine. To me it’s major mechanism is the same mechanism as a low-carb diet.

It has some independent mechanisms. It seems to up-regulate AMP kinase, which happens also to be done by low-carb diets. So metformin may have some advantages. It’s a drug. It’s a very well tolerated drug, but it’s not a universally well tolerated drug.

There are some side effects that have been reported. Not frequently, but some patients develop lactic acidosis, which can be very serious. And some patients develop hypoglycemia. So, I think overall it would be considered a very safe approach, it just has to be tested, like everything else.

[Damien Blenkinsopp]: Great. Thank you.

I was wondering if you had any opinion on calorie deficit versus high intake of calories. I could be on a high fat diet, or a low carbohydrate diet, and still have a surplus of calories versus a deficit. Do you think that’s anything that could be either affecting your results, or something to look at?

[Gene Fine]: Yes, it is something, definitely, to look at. The calorie restricted approach has been advocated…well, it’s just been advocated. I can’t say exactly whether the mechanism is the same, overlapping, or somewhat different.

But I can just say this, that in our study we actually wanted patients to not lose weight. We encouraged them to overeat. Overeat a low-carb diet, but overeat. So to eat as many calories as they needed to sustain their weight.

So the only comment I can make about this is that all the patients lost weight. We did not intend for them to lose weight, that was not our goal. We encouraged them, we would be weighing them weekly and we’d tell them, “Eat more, eat more. You’re making these shakes, add more cream to it. Add more oil to your foods. Put butter on everything.”

Well anyway, whatever it is that we encouraged them to do, all 10 of them lost weight. They lost on average about four percent of their initial body weight. The interesting thing about that, I just suppose that this is why these diets are effective as weight loss diets.

No one knows exactly why they work, but you certainly can speculate some pretty plausible mechanisms. One is that ketosis may inhibit appetite. Another is that your inhibiting insulin, and insulin, as I say, under the influence of carbohydrate makes you fat and keeps you fat. The absence of insulin does the opposite. It releases lipids from your fat cells, and metabolizes them in the liver. So the fact is that low-carb diets intrinsically may be weight loss diets.

We believed in our study that it’s possibly to defeat this. That there’s such a thing as overfeeding, and maybe if one is particularly conscious about this, one can do this. But the other interesting factor is that seven out of the 10 patients were above a body mass index of 25, which is to say they were overweight. Only three of them were in the normal weight range, between 20 and 25.

And as it happens, the patients who lost the most weight were the heaviest. Frankly they were delighted with their weight loss, even though we were trying to maintain weight just for the principles of our study.

The patients who were in the normal weight range, the two who were the higher two in the normal weight range — I should say, the heaviest patients lost about five to six percent of their body weight. The patients who were in the normal weight range, the two heavier of them — 25 BMI and 23 — lost about three percent of their body weight. And the patient who was 20 lost no body weight at all.

So what this tells us is something we all know also, which is that the closer we approach our ideal body weight, the harder it is to lose weight. I don’t know whether you’ve observed that yourself, whether you have gained, lost or are stable in terms of your body weight, but I believe that high fat diets do not necessarily cause weight loss, particularly in people who are approaching their ideal lean body weight.

[Damien Blenkinsopp]: I’ve been on this diet for many years, just as an n=1 experiment. I think I lost a bit of weight when it first started, but ever since I’ve been really stable, ever since. And I’ve never paid attention to the number of calories. Sometimes I’m sure I’m eating a lot of calories, and sometime I’m not eating so many, for whatever it’s worth.

[Gene Fine]: I should also mention one other thing, which is that in our study, when we calculated what the calorie intake was on the basis this is of course on the patients self-reports, that all the patients reduced their calorie intake as well. Now, we didn’t want them to, but the measured calorie intake on the basis of their self reports was reduced, in fact by about one third.

The other interesting thing though is that the stable disease effect and partial remission, those patients who showed stable disease or partial remission had three times the ketosis. But the degree of weight loss in the two groups was the same. They both lost about four percent. So although there was weight loss in all the patients, weight loss, or calorie deficit, did not appear to correlate with the effects that we saw.

[Damien Blenkinsopp]: Well that’s a great point then.

I think the other point you illustrated, if we’re talking about your studies, is how difficult it is to set a good cancer study up, given the situation with the patients and you’re trying to control for a lot of things. So, as you say, it took you four years to recruit the patients for the last study. So I think it gives us a much better appreciation of how difficult it is to do these types of studies.

[Gene Fine]: Yeah. I think it is the fact that physicians are trained to treat with drugs and that’s very understandable. Drugs generally work well. And in cancer, it would be naive to start off with the assumption that diet is going to be a successful therapy. It has to be tested.

And so, whereas there was some reluctance, there wasn’t entirely, and many of the oncologists were very helpful and cooperative and referred patients when they were on a chemo holiday, or chemo break. That’s what was needed to get this study done. And also the fact that I didn’t want patients who were too thin and too sick.

But I think going forward, I think that we can count on, perhaps, some additional support. And we are actually aiming for human studies going forward as well. Right now, as I say, we’re also trying to couple diet with drugs in animal studies. So this combination, we hope, will lead us somewhere.

[Damien Blenkinsopp]: Yeah, Great. So is it the first time someone’s been trying to couple chemotherapy with diet? Or are there existing studies that you’re basing your current work on?

[Gene Fine]: Coupling a low carbohydrate diet with other therapies has been done. I know that Colin Champ and Doug Spitz, I believe, have coupled low-carb diets with radiation therapy. As far as coupling with drugs, I’m not actually immediately aware that anyone has done that. I think that we may be the ones who are looking at that right now.

[Damien Blenkinsopp]: Great. Wrapping up a bit, thanks so much for your time today.

Where could we learn more about this subject? Are there other people you would look to to learn more about this? Perhaps people you’ve worked for who are doing a lot of studies in this area. You mentioned Valter Longo, of course who was mentioned in Dr. Seyfried’s as well. Or are there any books or presentations on the subject that are good?

[Gene Fine]: I’m trying to think, other presentations. I know that there are some other people working in the area that I know have been doing good work.

Dominic D’Agostino in Florida. I think he has a website, and it would be interesting to look at some of the work that he’s done. A somewhat, I hope, accessible discussion of what we’ve talked about.

I have a couple of guest blog posts that I wrote. My colleague Richard Feinman has a generalized biochemistry and metabolism web blog, and he invited me to write some guest blog posts for his web blog. So I wrote two.

One which is on the general hypothesis, which I didn’t even discuss today. I mean, I discussed it in the broadest forms, but I didn’t discuss some of the details. And the other one is more on the clinical trial, on the recharge trial. So it gives more detail on that.

And I think Colin Champ has an interesting website as well, Caveman Doctor. I think I’d look at that. These are other resources. I think I’ve mentioned most of those that I know.

[Damien Blenkinsopp]: Great, great. So, we’ll put links to all of that in the show notes, thank for those.

Well how about you? What are the best ways for people to connect with you? I mean you mentioned the blog posts, which we’ll put in. Is there anything else? Do you have a website, or are you on Twitter? Is there anywhere you are active where people could learn more about what you’re up to?

[Gene Fine]: Let’s see. The website that I have is my website at Albert Einstein. You can also, through the blog posts that I mentioned it gives other links to papers that I’ve written as well as to my website. So I think that probably the most complete portal, you can look me up just at Albert Einstein and find my website there. And that will also link me to the dietary studies and the blog posts and the papers. They all connect to each other.

[Damien Blenkinsopp]: Great, great. We’ll put those on the show notes.

Something we spoke about just before the interview, your perspectives are a little bit different to Dr. Thomas Seyfried that we’ve already had on the show. Could you briefly summarize where you think you might have a different opinion?

[Gene Fine]: Well, I just think that we really are in the same camp. I think that we both believe in metabolic therapy, as do the other people that I’ve mentioned. I think that he believes that when he describes cancer as a metabolic disease, he believes that the fundamental problem is it starts as a metabolic disease in abnormal mitochondria. That may be true.

The only thing that I think that I would differ is that that abnormality in the mitochondria, I believe, is a genetic abnormality, even in the mitochondria. That you still have, what’s happening in the mitochondria is that, to me the fundamental problem in cancer is actually a genetic mutation that leads the cells to increased proliferation and growth and unlimited growth and immortality, and so forth.

The source of these mutations, I believe, could certainly be in the mitochondria, but in fact if it is, and that would make sense to me, it would be increased reactive oxygen species. And increased reactive oxygen species can cause mutations in the genetic portions of the mitochondria, and that would cause abnormal mitochondria. Or it could cause mutations in the DNA of the cell. Certainly hydrogen peroxide, peroxide can migrate over distances and can migrate into the nucleus.

So, I actually believe that the fundamental problem that leads to the cancer may initiate in the mitochondria with reactive oxygen species, but nonetheless results in the fundamental change of cancer is in a mutation. So I think that [in a] certain sense we’re describing the same phenomenon, but we have a different emphasis on which syllable we’re emphasizing.

[Damien Blenkinsopp]: Right. Potentially where it starts and where it finishes, and so on.

[Gene Fine]: Yeah, yeah.

[Damien Blenkinsopp]: Great. Great, thanks for that clarification.

Before you go, I just wanted to look at a bit of what you do on a personal level with your body data. I was just wondering if you track any metrics at all for your own health, biomarkers, or anything like that on a routine basis. Maybe yearly, or more so?

[Gene Fine]: When I started studying this in, around 2003, and I got interested in it, by the way, from my friend and colleague Richard Feinman. He’s a biochemist, and he’s been interested in this principally from the point of view of the effects on metabolic syndrome, diabetes, lipid disorders, and so forth.

However, I came in from the nuclear medicine background, and PET scanning and Warburg effect, and hypoxic cells. For me it was attractive for the possibility that this may have some effect, low-carb diets in inhibiting glycolosis, and as I mentioned earlier through the uncoupling protein 2 having a unique inhibitory effect on cancers while sparing normal cells.

So in 2003 when I got interested in this, and I decided that — you know, I never really had a weight problem, but I had gradually put on a few pounds over the years. And I have a small frame, so I’m about five foot nine, and 165 pounds. For me that was carrying excess fat.

So I figured well, you know, if I’m going to study this in others I might as well experience what it’s like for myself. And maybe I’ll even have some benefit in terms of overall body composition.

To make a long story short, I’ve been on a low-carb diet of various degrees of strictness over the years. In some cases I’ve been ketogenic, I’ve been very strict. In other cases, I’ve just been low-carb, but not likely ketogenic. I haven’t been under 50 grams a day, I’m not quite sure.

But the short story is that over a period of now, what 2003, really 2004, about 11 to 12 years, I’ve lost 33 pounds. Sometimes it’s been in fits and starts, but I’m very, very happy and comfortable with my weight right now. I like myself at 132. I have a small frame. I feel that for me I am lean and fit, and that’s a good thing.

There’s that aspect of it. In terms of other biomarkers, the numbers that I like to look at, in particular, are those that have risk profiles for, well my glucose and my hemoglobin A1C has dropped. In addition, my fasting blood glucose.

[Damien Blenkinsopp]: So if you remember, where did they start and where are you at now? And are you happy with the numbers now?

[Gene Fine]: Well yeah. I mean, I think I’ve been stricter lately and more consistent, so I’ve only been monitoring them really. I don’t think I’ve really been taking very close watch of them.

But I think over the past year or two my blood glucose, a couple of years ago had actually been at 100, and my hemoglobin A1C I think at one time was around 5.7. I’m sorry, this was only about one year ago.

The hemoglobin A1C changes slowly, but in two successive measurements, I’m about to come up with a third, it’s dropped to 5.7 to 5.6 now to 5.5, and I’m expecting it will continue to be going down because I’m doing this. And my fasting blood glucose is now about 94. So it’s dropping, and I’m satisfied with that.

I used to eat what was recommended. I used to eat a low fat diet, which of course means a high-carb diet, and I think I suffered the consequences. But little by little that has been reversing.

From the point of view of my lipid profile, the things that I’m most interested in are those that are atherogenic, that contribute to risk of cardiovascular disease. And I think the current thinking, which makes some sense to me, is that it’s not so much LDL which is targeted by the cardiologist, because LDL is a mixed bag.

Low density lipoproteins really consist of two major fractions. One of the light, buoyant LDL, which is really not harmful, and the other is the small dense LDL, which is. And what happens on a low-carb diet is you reverse the ratio. You reduce the amount of small dense LDL.

And the good measure of that, because it’s hard to get that measurement directly. There are only a few labs in the world that actually measure small dense LDL directly. You have to send away to specialized testing for them. However, there’s a good index of it and it’s the ratio of your triglycerides over your HDL.

[Damien Blenkinsopp]: So there’s a proxy?

[Gene Fine]: There’s a proxy for small dense LDL, yeah.

[Damien Blenkinsopp]: Oh, great.

[Gene Fine]: And so when I started, I guess when I first measured my triglycerides to small dense LDL when I had been not very compliant at all, my triglycerides at one point were about 150, and my HDL was about 50. So the ratio was about three. And since going on a low-carb diet, my triglycerides fell in half, to 74, and my HDL went from 50 to 75. So basically my ratio is now one.

[Damien Blenkinsopp]: That’s pretty high.

[Gene Fine]: So all the things went in the right direction. I’m very pleased that the HDL went up, without any major increase in exercise, just the diet alone. And my triglycerides fell in half. So those are both just exactly what you would expect on a low-carb diet, and what you want.

[Damien Blenkinsopp]: Great, thanks for those.

They’re very useful, especially the triglyceride HDL ratio. Because it is difficult to get the, I guess you were talking about the NMR, nuclear magnetic resonance. We spoke about that in a previous episode. And then there’s the LDLP to get the number of particles. But as you say, there’s only a few specialized labs, so it’s not as accessible. So it’s great to know that there’s a proxy to use also.

Last question here. What would be your number one recommendation to someone trying to use some kind of data to track, whether it’s biomarkers or something else, to make better decisions about their own health?

[Gene Fine]: Yes, well I mean it depends on what aspect of the health you’re talking about. But I don’t know if ketosis is necessary.

As I mentioned, any change of diet can be difficult to sustain over the long term. I don’t even know what it takes. Willpower is something that, what is it. So, it’s hard to know how to do that.

And by and large the reason I would say it’s hard to change diet is people eat what they like. And you want to eat what you like, and so changing your diet means you’re, by definition, changing it to something that you didn’t prefer. So it seems as though there’s a fundamental issue there.

On the other hand, I think that if you have a weight issue that you’re not happy with, or your doctor reports blood lipid markers or glucose markers that you’re not happy with and evidence of pre-diabetes or diabetes, and you’re on meds, so forth — let’s not consider meds yet. Let’s just talk about without being on meds. Because low-carb diets, if you can actually go on them and you’re also on meds, you have to do that under supervision because you might actually become hypoglycemic, and you have to be careful about that.

But without considering meds if you just want to, say, improve your health in terms of obesity or aspects of metabolic syndrome, lipid disorders, blood glucose levels, pre-diabetes. Without going on a strict low-carb ketogenic diet it’s not as hard, I think anyway, to reduce the quantity of carbohydrates that you eat.

You can have a breakfast where, you can cut out, well cut in half the size of the desserts that you eat. You can cut in half the amount of mashed potatoes that you eat. You can eat one slice of bread instead of two, or you can not eat bread. Although that sometimes is hard for people, but if you eat the bread and don’t eat the mashed potatoes, you’ve reduced the number of carbs that you eat.

So if you just start by reducing certain portions of carbohydrates. And I actually found I still have carbohydrates a little bit now. I have a sort of modified Atkins Plus, I call it, or South Beach Plus. I have a little ice cream at night. It’s my treat.

Overall, I probably eat about 60 grams of carbs a day. But, I treat myself to a little bit of ice cream at night. I’ll find out what that’s done to my lipid profile, by the way. But I don’t think it’s going to have a major effect. I think that overall it’s going to be still pretty good.

So the idea of reducing the overall quantity of carbs, I think, is actually important. I think that with the average American diet, I don’t know if the same is true in UK but probably, that overall consumption of carbs is 300 to 400 grams a day. And that’s really quite a lot. And if that could be cut in half to 150, that would be a big improvement.

So, I think that that would be lower stimulation of insulin secretion. Yeah, I think that that would be my principle recommendation in terms of health.

Now as far as exercise is concerned, exercise is also something that many people do but can’t stick to an exercise regime. And overall, I think that even if you look at the overall impact on insulin sensitivity and improving metabolic profile, there’s no question that exercise helps. But it really comes a distant second to diet in terms of having a dramatic impact on insulin sensitivity and these other biomarkers of lipids and glucose and so forth.

So that, while you’ll never hear me discourage anyone from wanting to do exercise, I think that if you want to have an immediate and more dramatic effect, the thing to do would be to reduce carbohydrates in the diet somehow.

And that’s probably the best I can say at the present time, because as I say, I don’t think anyone has a magic bullet as to how to help someone go on a diet. It’s never easy, but if you can find a way to reduce carbohydrates, you’re off to a start.

And if you feel encouraged by the results that you see, you tend to continue it.

[Damien Blenkinsopp]: Absolutely. Thank you for bringing that up, because we’re introducing changes here, new habits. And as you say, it’s super difficult.

I feel one of the things that helps people is making it clearer how helpful it can be in different areas of their life. Once you’ve heard it 10, 20 times from different people who are studying these things, like yourself, in different areas. I think it makes it easier for people, just because of the repetition, for the clarity in their heads.

I think part of the problem is the mystery and the misunderstanding, especially in the media and the press. The more times you’ve heard five different stories, the less you feel like taking action against any one of them, because you’re just not sure, you’re hesitant.

So thank you for your time today, because it’s certainly helping with these type of things.

[Gene Fine]: Thank you. I’m glad that you have this program, really, to spread the word through interviewing people who are active in the field.

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A look at a collection of high impact endurance tools and tactics – and the top biomarkers to watch for optimization. Vetted by an endurance athlete with years of experiments and competitions behind him.

Today’s episode is about endurance training and using high-impact tools to get the most out of it. We look at self-tracking in diet and exercise when aiming to optimize your body to perform at peak capacity.

We discuss factors playing a role in improving endurance through a healthy progression. What self-quantifying strategies are useful for tracking overall performance and health?

This episode features actionable takeaways on dealing with a variety of obstacles commonly experienced by endurance athletes.

How to make use of ketogenic dieting in maximizing fat-burning efficiency during physically demanding exercise? Which biomarkers are important for tracking individual organ-systems functionality in the body? How to maintain a healthy hormonal status?

Overall, we look to beneficial and practical tactics for athletes wishing to upgrade their performance and discuss common pitfalls to avoid in cultivating endurance.

On this full-on ketosis diet… the endurance payoff was huge. The amount of focus that I had for long periods of time. My ability to just hop on a bike and ride for hours with no fuel at all, with just water. It was pretty profound, because you produce all these ketones as a bi-product of fatty acid oxidation, and they’re used as the preferred fuel… while you’re out exercising. And that’s a huge boon to an endurance athlete.
– Ben Greenfield

Today’s guest is Ben Greenfield who is a professional competitor in endurance-demanding events, including triathlon and Ironman races. Ben has 11 years experience coaching athletes and fitness professionals.

Throughout his athletic career, he has researched physiology of upgrading endurance using a quantified approach. He has performed numerous self-experiments targeted towards understanding his performance parameters, and towards optimizing his diet and exercise.

Ben is the author of a New York Time’s best-selling book titled “Beyond Training: Mastering Endurance, Health, and Life”, which was published in 2014. His top-ranked iTunes podcast is called BenGreenFieldFitness.

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

itunes quantified body

What You’ll Learn

  • Ben uses his biohacking experience to coach people on living healthy and attempting on-the-edge extreme exercise (4:46).
  • Ben’s interests in endurance training and research developed over time. No big eureka moments, just meaningful experiences (7:12).
  • Important biomarkers in endurance training specifically, and practical reasons for these picks in exercise self-tracking (11:24)
  • Why regulation of sex-hormones and cortisol (the stress hormone) are important to track in endurance training (15:50).
  • Why standard reference ranges for free testosterone are often not applicable to endurance athletes (16:48).
  • Liver enzymes, kidney parameters, Vitamin D, and digestive track inspections are also key biomarkers for healthy endurance training (18:20).
  • The digestive track plays an upstream role in multiple athlete pains and discomforts (21:18).
  • How to fight thyroid system dysfunction in endurance training (24:17).
  • The key lessons Ben learned from his 12 months ketosis dieting experiment (26:10).
  • The biomarkers for detecting adrenal fatigue symptoms (27:22).
  • Biomarkers and tests for autonomic nervous system functionality and distinguishing adrenal fatigue from thyroid system dysfunction (28:03).
  • Incorporating Heart Rate Variability (HRV) tracking in endurance training (31:39).
  • HRV is Ben’s ultimate marker for optimizing endurance training and quantifying overall health (33:23).
  • Success in endurance training requires optimization between high-volume achievements and short-duration precisely aimed tasks (34:29).
  • Dealing with negative effects of endurance exercise and ketogenic dieting (39:01).
  • Maximizing ketogenic dieting benefits and potentially useful supplements (44:34).
  • Breath ketones are an easy way to test for purposeful ketosis (46:20).
  • Tracking important biomarkers and avoiding excessive ketosis (47:20).
  • Why oxaloacetate can be used as a supplement with ketogenic dieting (48:25).
  • Why cold thermogenesis works for athletes’ bodies, for recovery and for overall performance (50:27).
  • The portal outlining Ben’s work and relevant people recommended by Ben (53:17).
  • Ben’s most-important advice on living healthy is being grateful several times per day (54:48).

Thank Ben Greenfield on Twitter for this interview.
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Ben Greenfield, Greenfield Fitness Systems

Tools & Tactics

Interventions

  • Cold Thermogenesis: Can be achieved through a variety of cold exposure methods such as cold showers or dipping into cold water streams . In cold thermogenesis hormesis is used to promote positive adaptations in the body as we saw in episode 8. Amongst other improvements it can help to burn fat more efficiently and improve blood vessel functionality in part by promoting development of your Brown Adipose Tissue (BAT). BAT is a type of fat which is active tissue and able to generate heat.

Tech

  • Heart Math Gratitude exercises: The Institute of Heart Math promotes using specific gratitude exercises to optimize the HeartMath Heart Rate Variability (HRV) score. We’ve discussed the HeartMath form of HRV previously in episode 6. This exercise can be done with one of either of their two HRV feedback devices: Inner Balance for iOS or emwave2.

Supplementation

  • Thyro-Gold: Thyroid glandular extract produced by the New Zealand company Natural Thyroid Solutions. This supplement is used as a biohack to correct thyroid-system dysfunction, sometimes caused by ketogenic dieting – especially with very low carbohydrate intake and endurance exercise.
  • AndroGel: Although the use of testosterone hormone-containing products is illegal in professionally-sanctioned sports events, this supplement is sometimes used because free-testosterone levels often drop in a ketosis state.
  • Ketosports KetoForce: KetoForce contains the endogenous ketone body beta-hydroxybutyrate (BHB) in sodium and potassium salt form. The compound BHB can be used as an energy source by the brain when blood glucose is low. Ingesting KetoForce raises the levels of blood ketones for 2.5-3.0 hours after ingestion. (Note: A similar product from same company is Ketosports KetoCaNa).
  • benaGene: This supplement, oxaloacetate, was previously covered in depth in episode 30 in an interview with its creator Alan Cash.
    Greenfield uses this specifically to increase the rate at which his liver synthesizes new glucose molecules, during a low-carbohydrate ketogenic diet including exercise. The goal is to take advantage of its ‘glycogen sparing’ effect, since glycogen is less available in ketogenic diets, and thus get more intensity out of workouts.

Diet & Nutrition

  • Ketogenic Diet: A ketogenic diet is low in carbohydrates intake and high in fat intake. As such, it induces a state of ketosis in the body – the condition in which the body burns fats and uses ketones instead of glucose for fuel. Previously, we discussed measuring ketones and ketogenic dieting in Episode 7 with Jimmy Moore.
    To provide scientific support in favor of ketogenic dieting for endurance, Ben suggests the research of a University of Connecticut team investigating athletic training and human performance. For more information, see this recent scientific review authored by them on using fat as fuel for endurance exercise.
  • Cyclic-Ketogenic Diet: In some people, full ketogenic diets can lead to hormonal or organ dysfunction (e.g. thyroid). The cyclic-ketogenic diet is the solution often used to avoid these downsides. This is a low-carbohydrate diet with intermittent periods of high or moderate carbohydrate consumption (e.g. a refeed with carbohydrates every weekend). It is used as a way to maximize fat loss while maintaining the ability to perform intense exercise during a ketosis state.
  • Based on his 12 month ketosis self-experiment, Ben has concluded that eating anti-inflammatory food, as well as increasing intake of food containing medium-chain triglycerides (MTCs) and resistant starches, are all beneficial in reducing the potential negative side effects of ketogenic dieting.

Exercise

  • Polarized Training: Polarized Training is scientific terminology for the concept of easy-hard training. Researchers from the University of Stirling in Scotland have concluded that using an approach which excludes medium-intensity training is more beneficial for building endurance compared to an approach that includes medium-intensity training. The polarized training model (80% low-intensity; 0% medium-intensity; 20% high-intensity training) produces more positive results in endurance athletes, compared to the competitor threshold model (57% low-intensity; 43% medium-intensity; 0% high-intensity training).
  • Murph Workout: “Murph” is a CrossFit workout named after Navy Lieutenant Michael Murphy, who was killed in Afghanistan June 28th, 2005. He was awarded the Congressional Medal of Honor after his death. It first appeared on the CrossFit site 18 August 2005. This workout consists of (in order): 1 mile run, 100 pull-ups, 200 push-ups, 300 squats, and a 1 mile run at the end.

Tracking

Biomarkers

  • Heart Rate Variability (HRV): HRV is the measure of the change in the heart’s rhythm over time based on changes between sympathetic and parasympathetic activation. HRV was previously covered in the context of optimizing training workouts using HRV in Episode 1 with Andrew Flatt and using HRV as a biomarker for longevity in Episode 20 with Dr. Joon Yun.
  • Triglyceride to High Density Lipoprotein (HDL) ratio: Researchers have shown that using the triglyceride to HDL ratio is a better predictor of coronary disease risk factors, compared to tracking total cholesterol (which includes HDL and other lipoprotiens). A ratio of 2 : 1 or less is considered optimal.
  • High-Sensitivity C-reactive protein (hs-CRP): CRP is a protein that increases in the blood with inflammation and is used as a marker for cardiovascular health (high levels over 1 mg/l are indicative of higher cardiovascular risk). Both diet choices and overtraining can lead to high levels of hs-CRP (over 1).
  • Ketones: Ketone concentrations can be tested in blood, breath and urine samples to determine if you are in ketosis (burning ketones for fuel) and to what extent. We covered these markers extensively in episode 7 – how to measure ketones.
  • Creatinine and Blood Urea Nitrogen: These two biomarkers are often elevated above normal levels in endurance athletes, without being indicative of a health risk. In endurance training, creatinine levels lower than about 1.1 mg/dl do not pose a health risk. It is also relatively normal to have BUN levels over 20mg/dL.
  • Liver Function Tests: When excessive exercise is present, the blood levels of liver enzymes Alanine Transaminase (ALT), Aspartate Transaminase (AST), and Alkaline Phosphatase (ALP) are elevated above normal.
  • The 25-hydroxy Vitamin D Blood Test: The most accurate way to measure how much vitamin D is bioavailable to be used by your body is the 25-hydroxy vitamin D blood test. Optimum vitamin D levels range between 50-70 ng/ml.
  • Salivary cortisol to Dehydroepiandrosterone (DHEA) ratio: An increase in DHEA levels is highly suggestive of adrenal dysfunction because DHEA is produced exclusively by the adrenal glands. Excessive exercise stresses the body to produce very high levels of cortisol, which causes a depletion of endogenous DHEA. This results in an elevated cortisol to DHEA ratio. Testing for this ratio several times per day provides a more complete image of adrenal function, compared to a snapshot provided by simple monitoring of blood cortisol levels. A normal cortisol : DHEA ratio is approximately 5:1 to 6:1.
  • Thyroid Functional Test Panel: A TFT panel typically includes thyroid hormones such as Thyroid Stimulating Hormone as well as the thyroid hormones triiodothyronine (T3) and thyroxine (T4). Excessive exercise can stress the body to produce high-levels of cortisol (the stress hormone) which inhibits the conversion of thyroid hormone from inactive (T4) to biologically active (T3). This can result in lower levels of active thyroid hormone despite normal or up-regulated levels of TSH. Thus, testing for (active) T3 hormone concentrations is more relevant for endurance athletes self-tracking. Optimal reference ranges for TSH are 0.4 – 2.5 milliunits per liter (mU/L). Optimal reference ranges for free (bioavailable) T3 range between 350 – 780 pg/dL.
  • Sex Hormone Binding Globulin (SHBG) and free testosterone: The standard reference ranges for SHBG are 0.2-1.6 mg/dL for non-pregnant adult females and 0.1-0.6 mg/dL for adult males. Changes in SHBG levels affect the amount of free hormone that is available to be used by tissues, including the levels of free testosterone. In case SHBG levels are in abnormal ranges, then free (bioavailable) testosterone should be tested (reference ranges 1.0-8.5 pg/mL for females and 50.2-210.3 pg/mL for males).
  • Tests for detecting adrenal fatigue and thyroid system insufficiency

  • Iris Contraction Test: This test consists of you looking at the pupil of your eye in a mirror while shining a bright light at your eye. The light should cause the pupil (center black spot of your eye) to contract or become more narrow. The contraction should be sustained for longer than 20 seconds before the pupil starts to flicker or dilate. Otherwise, if the pupil starts to flicker immediately upon shining light, this is a good indication that you have adrenal fatigue – mainly because your adrenal gland is functioning properly in managing blood pressure.
  • Dizziness Test: If you lay down or you sit down and you stand up quickly and you get dizzy, then this is a sign of blood pressure mismanagement. Importantly, problems with blood pressure often accompany adrenal fatigue because one of the main functions of the kidneys is to regulate blood pressure via production of hormones in the adrenal gland.
  • Broda Barnes, MD Temperature Test: This test was developed by Dr. Broda Otto Barnes, who was best known for developing novel perspectives on hypothyroidism – a type of thyroid system disease. In essence, you do oral and armpit measurements every morning in bed upon waking up and keep a graph of the results. If your temperature is consistently low, then this is an indication that your thyroid system is dysfunctional even in the absence of a blood thyroid test.

Lab Tests, Devices and Apps

Other People, Books & Resources

People

  • Dr. Terry Wahls: Dr. Terry Wahls is a a clinical professor of medicine at the University of Iowa. Previously, Dr. Wahls was kind to participate in the third episode of our show, where we focused on linking mitochondrial health to autoimmune and chronic disease.
  • Alan Cash: Alan Cash is the CEO of Terra Biological. Previously, he has been a guest on our podcast in Episode 30, where we discussed the potential for using oxaloacetate as an anti-aging supplement.
  • Joe Friel: Joe Friel holds a masters degree in exercise science and is a USA Triathlon and USA Cycling certified elite-level coach. For Joe’s blog click here. For his Twitter click here.
  • Sami Inkinen: Sami Inkinen is a balanced person. He is a successful businessman and a top-age Ironman competitor. For his Twitter click here.
  • Dr. Peter Attia: Dr. Peter Attia is a scientist who is knowledgeable in healthy endurance exercise and self-quantification. For Dr. Attia’s Eating Academy Blog click here. For his Twitter click here.

Books

Other


Full Interview Transcript

Click Here to Read Transcript
[04:46] [Damien Blenkinsopp]: Ben, welcome to the podcast.

[Ben Greenfield]: Hey, thanks for having me on man. And I’ve got to ask you, is it Damien, or Damion? Or Dami-something else?

[Damien Blenkinsopp]: Or Damian? It depends where you come from, I guess.

[Ben Greenfield]: Okay. Just checking. I don’t want to stick my foot in my mouth.

[Damien Blenkinsopp]: Yeah. You can call me Dam. I tell people to call me Dam, just to avoid all those questions.

[Ben Greenfield]: There we go. I want to sound like I’m cursing the entire episode.

[Damien Blenkinsopp]: Yeah. But it even works in Asia, tried and tested.

[Ben Greenfield]: Nice.

[Damien Blenkinsopp]: I mean you’ve got a three letter name. That works well.

[Ben Greenfield]: Yeah, totally. Ben.

(05:12) [Damien Blenkinsopp]: So, Ben, you’re into triathletes, Ironman, and basically the way I look at you is you go around searching for tactics and tools to give you an edge in these areas that you’re interested in. Is that a fair kind of back story to who you are and what you’re doing?

[Ben Greenfield]: Yeah, I do a lot of that I guess n=1 guinea-piging myself. Going out and doing crazy things like training with the Navy SEALS or doing these Spartan Races or Ironman triathlons, things like that.

But then I also think I learn just as much via a lot of the coaching and consulting that I do, just because people typically come to me for one of two reasons.

They either want to do some crazy feat that’s completely unnatural for the human body to do, like they want to go run 100 miles in the wilderness or something like that, and figure out how to do it without destroying themselves. So my job is to figure out how to do that from a nutrition and a physiology and an exercise standpoint.

Or they come to me because they basically want to live as long as freaking humanly possible, and want me to manage how do you sleep when you want to do something like that, how do you exercise, what do you measure, what do you pay attention to in your blood and your gut. And so there’s that kind of biohackiness that I get into.

And I’ve got to admit, for me personally it’s a little bit of both, really. I certainly do want to live as long as possible. I also want to do as many crazy events as I can during the process, see as much of the world as I can at the fastest pace possible. And so for myself, personally, I’m doing a little bit of both.

But sometimes people come to me and want to do something that I know nothing about, so I’ve got to go and learn it. So part of it is that, too. That, or if it’s not coaching someone it’s writing about that. Because I’ve done a lot of writing recently. This morning [I] published a big article on my website about how to use marijuana to get performance enhancing gains.

And I never really would have delved into that if I hadn’t been asked by so many people, especially here in the US with the growing legality. It’s like, can I use this while I’m exercising? That type of thing. So it’s a little bit of everything.

[07:12] [Damien Blenkinsopp]:Yeah, great. So [what was] the event that started the whole Ben Greenfield fitness podcast, and the blog and everything? How’d you get involved in that? Because you’re obviously very passionate about it.

[Ben Greenfield]: Yeah. Well there’s, I mean I get that question a lot, and frankly – nothing against you – but it annoys me, because I hate when people go, “When did you decide to do this? When did you decide to do that?” I never make decisions. I don’t have a 10 year business plan. I don’t have some ‘Come to Jesus’ moment where I said, “Oh hey, I want to learn how to exercise.”

It’s just that I live my life. I do things that I’m passionate about, or that other people who I’m helping are passionate about and tend to fall into whatever I might fall into based on that. I’m getting into hunting right now – well specifically bow hunting and hunting competitions – before that obstacle racing, before that Ironman Triathlon, before that water polo, before that body-building, before that I was a collegiate tennis player.

It’s just like life is a series of chapters and moving targets. It’s never just like one commitment to do one thing. But I would say, to give you a rough answer to your question, the very first time I decided to something a little bit more endurance orientated – which I would define as something that has a nutrition rate.

You don’t see people dropping out of baseball or cricket games because of fatigue and heat stroke and lack of nutrition. That’s very rare, but you see it all the time in marathons and Ironman triathlons and things like that. So I would say the first time I started to get into that side of sports would have been my first Ironman Triathlon that I did back in the city of Portalane, Idaho in 2007.

And up until that point I’d been primarily an explosive power athlete. Like body-building and tennis and stuff like that. But my girlfriend, who is now my wife, was a runner. She ran cross-country for University of Idaho. So I kind of had to take up running, to a certain extent, just to be able to woo her.

And she dragged me to a triathlon one day and she actually had me run the running leg of the triathlon, which hurt like hell. I was a body builder; my boobs were bouncing up and down and my lower back was locking up and it was horrible. But it kind of got me interested in this high that you can get from endurance sports.

And so I wound up doing a few triathlons and doing, what I would say, is the biggest mistake for anyone who wants to avoid getting into endurance, that is I went and watched an Ironman Triathlon. And after watching Ironman and watching these intense feats of physical performance and the huge feeling of satisfaction and self-completion that these people were experiencing as they threw up their arms when they crossed the finish line I was like, I want that. I want to experience that.

And so I signed up for an Ironman and began taking everything I had been studying. At that point I had a Master’s Degree in Exercise Physiology and Nutrition and I was able to start applying that stuff to my training, and experimenting with a lot of what I was finding in research and sports science and seeing what worked and what doesn’t.

For example, all laboratory studies, or most of them, done by the white coats in their little labs will tell you that the body can take on about 200 to 250 calories of fuel during exercise. You can oxidize 200, 250 calories of carbohydrates while you are exercising. But for anyone, especially anyone who’s above about 150 pounds who has tried to go out and do an Ironman Triathlon, you completely bonk after about five hours on that number of calories, and you technically need about twice that in order to be able to get by in an Ironman race in most cases.

So, it’s a situation where what they’re saying in the lab and textbooks actually doesn’t work once you get out in real life and you try this stuff in the streets, in the trenches. So, that’s been kind of fun too, figuring out from research what works, and what doesn’t.

[Damien Blenkinsopp]: Right. Yeah, we often talk on here about n=1 experiments are often going to be different to the research, for a variety of reasons like the ones you brought up, and the use of averages, and other things like that.

[11:24] So, anyway, in terms of endurance training, since we’re there, what kind of biomarkers have you found to be the most useful to track your performance? Or what do you track around your capabilities for endurance training, and see as important?

[Ben Greenfield]: Oh, for endurance specifically?

[Damien Blenkinsopp]: Yeah.

[Ben Greenfield]: So for endurance specifically, that’s a great question. So one would be your level of HSCRP, which really that’s just for exercise in general. Or high sensitivity C-reative protein, just to make sure that your levels aren’t straying too high above 0.5. And the reason for that…

[Damien Blenkinsopp]: So that’s kind of your benchmark? You try to keep them under there? Where do yours tend to hover around?

[Ben Greenfield]: I actually fall below 0.2 now for HSCRP, probably because I eat a very anti-inflammatory diet, very clean. And I won’t insult your listeners’ intelligence by defining what a clean diet or an anti-inflammatory diet is, because it’s pretty easy to go out and figure that out with Dr. Google.

But I eat very clean. I also use a lot of anti-inflammatories. Like I make ginger tea, and I use a ton of turmeric, usually combined with black pepper to increase the efficacy of it, and I use percumin and I consume a lot of very dark and colorful vegetables with very limited amounts of dark and colorful fruits, and wild caught fish, and fats, and things that really help with inflammation.

And I’m also very careful with my training, where I do extremely focused and intense, but short, bouts of training with a specific purpose. I never go out and just pound the pavement for the hell of it, which is a great way to build up a lot of voluminous training based inflammation.

And so I have a very precise, dialed in training program that also includes things that help to mitigate inflammation, like foam rolling, and cold soaking, and these things that can help to remove a lot of these byproducts of metabolism that can create inflammation. So, inflammation is a biggie. Honestly, it doesn’t take a rocket scientist to figure out that if you keep your inflammation controlled, it’s a good thing.

So, a few others that I’ll pay attention to for endurance. When we’re talking about labs, as far as blood goes, TSH, preferably a full thyroid panel, is pretty prudent to pay attention to simply because high level endurance training can inhibit conversion of inactive to active thyroid hormone.

And because of the high amounts of cortisol that can potentially be produced through an improper training program can stress the body out enough to where you experience some hypothalamic pituitary adrenal axis insufficiencies, particularly high cortisol, creating a feedback loop that reduces the conversion of inactive to active thyroid hormone and thus an increase in thyroid stimulating hormone. So your body turns out a bunch more thyroid stimulating hormone to try and get more T4 present, even though a lot of that T4 isn’’t getting converted into T3.

And by monitoring TSH, if you see a pattern or a rise in TSH many times it’s concomitant with an increase in cortisol and stress, and often also accompanies a not enough eating period. Sometimes not enough carbohydrates is the biggest culprit, but in many cases just not enough damn calories, period. Damn, not referring to your first name but to the curse word. Just so we’re clear.

That’s another one is TSH. Cortisol, I alluded to, but when we’re looking at a hormonal panel, I also like to pay attention to sex hormone binding globulin. Because the body has this interesting mechanism where when it’s stressed out, when it’s in a time of famine, in a time of need, under high amounts of stress, doing a lot of migrating, a lot of moving with low amount of calorie intake, the last thing you want the body to do is produce a bunch of babies at that point.

And so sex hormone binding globulin often rises simultaneous to cortisol to keep total testosterone bound, and keep it from being available as free testosterone. So even if your testes are working just fine, or your pituitary gland is working just fine, –obviously talking about the males more than the females now– and even the leydig cells in your testes are producing testosterone just fine, if sex hormone binding globulin levels are really, really high that’s all for naught. And so that’s another really, really important one to keep an eye on. And that’s typically addressed by addressing cortisol.

[15:50][Damien Blenkinsopp]: Right. So, why would you look at SHBG versus free testosterone, or that marker? The [unclear 15:56]?

[Ben Greenfield]: Well, because if free testosterone is low, but if you look upstream perhaps it’s because total testosterone is low because the leydig cells in your testes are not producing enough hormone because you’ve got low levels of luteinizing hormone. In contrast to that, perhaps your luteinizing hormone production is fine, your leydig cells are producing enough testosterone just fine, your total testosterone is high, but it’s more of a cortisol issue than it is a central nervous system issue or a glandular issue.

So that’s why you test that versus just looking at free testosterone.

[Damien Blenkinsopp]: So basically, free testosterone could be many, there’s more reasons behind it, but the SHBG is more specific to endurance and specific dynamic.

[Ben Greenfield]: Yeah. Really, two reasons behind it. Either you aren’t producing enough total testosterone, or you are producing enough total testosterone but it’s not getting converted. So those are really the two main things to look at.

[16:48] [Damien Blenkinsopp]: So, are you looking at the standard reference ranges for that, or do you look for something a bit more precise?

[Ben Greenfield]: A lot of times you have to look at symptoms synonymous, because standard reference ranges are going to vary widely.

I’ve worked with a lot of endurance athletes who have very high libido levels, show no signs of over-training, have very robust nervous systems, high heart rate variability, low cortisol, and even low sex hormone binding globulin, but their total testosterone is in like the high 300s. Which, for a body builder they would scoff at that and say, oh that’s rock bottom low. Even though a lot of times hypogonadism is levels below 100.

And you’ll get many people who just feel like fricking crap at 300, and some people will be closer to 500, and some people will need levels of 700, 800, or even 1000. So it kind of depends. It varies widely, I suspect based on genetics as a big part of it.

So ultimately it’s really tough to hold things up to reference ranges. I mean, you can ballpark it. You can say well if total testosterone is starting to get below 300, that’s where we would really start to get a little bit concerned. But it really is kind of tough. A lot of times it’s a moving target based off of a cluster of other symptoms.

If someone’s complaining of low libido and low motivation, and lack of energy, etc, and their testosterone is at 400, well that’s a pretty good sign that 400 is not going to be adequate for them. So I know that’s one of those deals where it’s total soft science, but it does really depend. That’s one of those ‘it depends’ answers, but that is definitely a variable that I will look at.

[18:20] Liver enzymes is another one, like alkaline phosphatase, aspartate aminotransferase, the ALT, the AST, some of these liver markers just because a lot of times they can be elevated when excessive exercise is present. And so that’s another one to pay attention to. It doesn’t have to be excessive exercise; sometimes it can be alcohol, pharmaceutical intake, things of that nature. But liver enzymes are the one that I’ll look at.

Kidneys, a lot of people say to look at kidneys, but frankly it’s very rare for me to see an athlete who doesn’t have slightly elevate creatinine and blood urea nitrogen levels, which are two common markers in the kidneys that a physician will get concerned about if they see elevated, but that are very common to see elevated if an athlete is exercising anywhere in the 48 hours leading up to a blood panel.

So, as long as creatinine levels aren’t much higher than about 1.1, and as long as blood urea nitrogen isn’t through the roof and – I apologize, but off the top of my head I don’t remember the lab reference ranges for blood urea nitrogen. The reason being that I do most of my coaching for blood panels with a company called WellnessFX. It’s basically more like a dashboard with graphs, more than it is hard numbers, so occasionally I’m looking at graphs more than I am numbers.

[Damien Blenkinsopp]: And they just have those red zones.

[Ben Greenfield]: Yeah, exactly. They’ve got red, yellow, green, which actually annoys me some of the time. Because they’ll flag high LDL as red when I purposefully try to get my LDL high. So there’s some issues with the whole red yellow green type of quantification. But anyways, blood urea nitrogen and creatinine, even though a lot of people talk about those, they’re not super duper important in my opinion, because they’re always going to be a little bit elevated.

Vitamin D, that’s another one that I’ll look at just because of it’s importance. As you can suspect, a lot of these aren’t just specific to endurance, they’re specific to exercising period. Just as a hormone and a steroid, vitamin D is another important one that I’ll look at.

And then as far as other things, I typically will have most of the athletes I work with or the people I advise do at least once a year a full gut panel. You know, a comprehensive gut panel that includes parasitology, measurement of pancreatic enzyme production, measurement of yeast and fungus and any type of bacterial overgrowth in the digestive tract because I find that, especially when you’re jogging your body up and down for 10 plus hours while racing, having a really, really good gut and GI system and very efficient digestion is incredibly important.

And so I will look at things like presence of yeast or fungus, like Candida Albicans, or the presence of H pylori, or absence of hydrochloric acid, or absence of pancreatic enzymes, or overgrowth of specific bacteria, or lack of short chain fatty acids in the digestive tract, in the colon, and a lot of those things that tend to influence an athlete’s performance or their feelings of well-being. So that’s another thing I’ll pay attention to.

[21:18][Damien Blenkinsopp]: Right. A lot of people wouldn’t think of that as something performance related, more like a chronic issue related.

Have you got any case studies where you saw people, basically not performing but not having any negative symptoms in terms of GI distress or anything that they would have noticed, but when you put through these tests some negative results came?

[Ben Greenfield]: Sure. Now we’re delving a little bit more deeply. And I mean, obviously explosive diarrhea halfway through a marathon can be a good sign of digestive enzyme insufficiency, but so can, for example, vitamin B12 or vitamin D deficiencies, or even if you go more advanced and run like an organic acids profile, or an amino acid profile, severe imbalances of a lot of micro-nutrients.

Well if you’re not digesting your food efficiently, for example, if you’re not producing adequate hydrochloric acid, you’re not activating pepsin to break down proteins, beginning in the stomach an moving on to the small intestine, then you’re going to: a. have undigested protein fragments winding up in the bloodstream causing some auto-immune issues, and that can include fuzzy thinking, which no athlete wants.

But then you also can get amino acid deficiencies, like deficiency in the ability to create neurotransmitters, and also deficiencies in the ability to repair and regenerate skeletal muscle tissue, because you aren’t breaking down the proteins that you’re eating.

And the same could be said for something like inflammation in the digestive tract from wearing down of the microvilli. So perhaps you’re not producing adequate levels of lactase, so you’ve got some lactose issues and bloating and gas. Or you’ve got inflammation that is resulting in malabsorption of fat-soluble vitamins, so vitamins A, D, E, and K aren’t getting absorbed properly, or bacteria aren’t helping you to produce those, and so you experience hormonal deficiencies, or steroid deficiencies.

And so, yeah the gut is incredibly important, and that’s one of the things I’ve been kind of getting on companies like WellnessFX, for example, to do is to not just use the strategy of blood testing but also really pay attention to the gut. I mean, in an ideal scenario, what I would like to see is a done-for-you system.

And for me right now, what I do is just kind of string this together for the athletes who I work with. But a done-for-you system where you get your blood testing, you get your gut testing, and you get your genetic testing so we can look at everything from genetic snips to bacterial imbalances in the gut to all the blood and biomarkers, and have all of that done with either one panel or one service.

That would be really nice, because right now you’ve got to go to typically three different places. You’ve got to go to whatever DNAFit, or 23andMe, and you’ve got to go to DirectLabs, or Metametrix for GI affects, and then you’ve got to go to WellnessFX for whatever else. And then if you want to do food allergy testing, well then you’ve got to throw in a Cyrex panel, or something like that.

So maybe it’s a first world problem to want all this stuff to be available in one central location, but it certainly would be nice.

[Damien Blenkinsopp]: Yeah. It’s so near the early days from that perspective. There’s a lot of specialized, it’s still kind of specialized in terms of the labs. Each is in their little separate box and everything.

[Ben Greenfield]: Yeah.

[24:17] [Damien Blenkinsopp]: So, in terms of the kinds of decisions you’ve made, or you’ve advised a client based on some of these values, some of this data that’s come back, what have been the biggest changes that you’ve implemented to optimize training?

[Ben Greenfield]: You mean as far as training?

[Damien Blenkinsopp]: So, say the TSH came up too high, what would you do about that?

[Ben Greenfield]: Oh okay, so for high TSH, obviously it’s never a shotgun approach. It’s never a multivitamin. So for high TSH it may be looking at your carbohydrate intake. That’s the first thing that I’ll look at.

Even before you look at total amount of calories, you just make sure nobody is on some low, like 40 gram per day carbohydrate diet, because frankly a lot of the ‘low carb’ or ‘ketosis’ based diets that are out there were created for sedentary people. Even the bulletproof diet. I love the whole bulletproof philosophy, but it was written by a computer programmer, not by an athlete.

And so the levels of carbohydrate, and even the levels of calories in that diet, have to be adjusted and modified for a hard-charging athlete, especially an endurance athlete. So, otherwise with caloric depletion and carbohydrate depletion, you basically lose a lot of your ability to convert inactive to active thyroid hormone.

And in the case of calories, as you would deduce through common sense, when you send your body a message that calories are insufficient but you’re still requiring it to move a lot, your body down regulates metabolism. And one of the main ways it does that is by down regulating thyroid.

So, I look at carbohydrates, I look at calories, and then I also look at dietary intake of organ meats and fat soluble vitamins, which can also assist with thyroid health. So in my case, because I did an n=1 experiment about a year and a half ago where I did 12 months of ketosis.

Not cyclic ketosis, not cycling carbohydrates in and out throughout the day, but full on eating only 5-10 percent of my total daily intake from carbohydrates. Very low carbohydrate diet. Too low, in my opinion, for most endurance athletes who want to maintain optimal levels of health elsewhere.

[26:10] [Damien Blenkinsopp]: Did you see negative effects from that over the 12 months?

[Ben Greenfield]: Yeah, and that’s what I’m getting at with the thyroid. I started taking thyroid glandular extract. I took one called Thryo-Gold, which is made from New Zealand cows, that are like an A2 cattle.

A lot of A1 cattle has proteins in it that cause an immune reaction within the human body, but cattle that are breed via A2 are cattle that contain this A2 genetic profile that is more bio-compatible with the human body. And so I basically took a T1, T2, T3, and T4 combo, and that seemed to turn my thyroid around. But that was after I had already done a number on it.

So for thyroid, that would be an example of what I would do with something like thyroid, would be increase calories, increase carbohydrates, increase intake of organ meats and fat soluble vitamins. And then for a really hard-charging athlete who insists upon doing something like restricting carbohydrates to tap into the performance enhancing effects of ketosis, understand that you’ve got to get on extra help from the thyroid.

Since your body isn’t going to make T3, dump it into the body. And preferably get it from a whole source, like levothyroxine or synthroid. But a source that contains other elements of thyroid in addition to just T3, so you’re not creating an imbalance.

[27:22] [Damien Blenkinsopp]: Great. Well, connected with the thyroid issues, I was wondering if you’ve come across adrenal fatigue also. If that’s every come up with you or with anyone else.

[Ben Greenfield]: Absolutely. Adrenal fatigue, gosh. There’s like four chapters of my book on that alone. But adrenal fatigue, well what do you want to know about it?

[Damien Blenkinsopp]: Well first of all, have you looked at some of the tests? I’ve done some of the salivary tests.

[Ben Greenfield]: Oh yeah. Yeah, like an adrenal stress index is kind of gold standard, cortisol DHA. If you look at the cortisol DHA curve, that’s much, much better when you’re addressing something like adrenal fatigue versus a blood cortisol measurement, which is just a snapshot. You want to see a moving target of salivary cortisol levels, preferably matched to salivary DHEA levels, throughout the day.

[28:03][Damien Blenkinsopp]: I was just thinking, based on it’s endurance exercise, and it has this tendency to raise cortisol, that that would be more of an issue and something that you would keep an eye on. Or by monitoring TSH, does that kind of take care of itself? If the TSH is alright then you tend not to have an adrenal issue as well?

[Ben Greenfield]: No, not necessarily.

You can still have adrenal fatigue and have a thyroid that’s managed properly. Because what you would typically see in that case is someone is eating boatloads of calories and taking care of themselves from an energetic standpoint, but simply outputting too much energy. They’re just training way too much. Even though they’re supplying their thyroid with what it needs, there’s just too much training still.

And a lot of times you’ll see inflammation high, but yeah. Cortisol DHEA, and that adrenal stress index can be a good measurement. And there are less quantitative measurements. You could do a pulst test, where you look in a mirror and you shine a bright light at your eyes, and your pupils should stay dilated. But if it stays dilated and then just starts flickering rapidly.

[Damien Blenkinsopp]: Have you tried that one?

[Ben Greenfield]: I have, yeah.

[Damien Blenkinsopp]: Because I was just wondering. I did try it and I find it a little bit difficult to judge.

[Ben Greenfield]: Yeah, it’s certainly not as precise as a salivary measurement, but once you’ve done it a few times you can definitely see the pupil, and whether or not it’s actually flickering versus staying dilated. If you look at if for long enough, it’s just going to start flickering period, but if it starts flickering after just a few seconds, that’s typically a sign that your kidneys are not producing enough aldosterone, which is synonymous, or can accompany, adrenal fatigue.

The other one is just the dizziness test. If you lay down or you sit down and you stand up quickly and you get dizzy, that can be a sign of blood pressure mismanagement that often goes hand-in-hand with adrenal fatigue. And again, these are the super cheapo poor man’s methods, but it can give you clues.

And then there’s temperature tests for thyroid, the Broda Barnes Temperature Test, where you do oral and axillary measurements of your temperature in bed every morning, and keep a running graph. And if it’s consistently low, that can be a pretty good indication that even if you haven’t done a blood thyroid test that your thyroid might be having issues.

So, there are a lot of things. One of the best ones I like though is just pure heart-rate variability. Testing the interplay between your sympathetic and your parasympathetic nervous system by using something like a Bluetooth enabled heart rate monitor and one of these heart rate variability apps, and simply paying attention to whether heart rate variability is high or low on any given day.

And if it’s consistently low, and you see consistent suppression of both sympathetic and parasympathetic nervous system feedback, then that can be a pretty good sign that you’re on the cusp of adrenal fatigue illness or injury, and so that’s another really good one to pay attention to. And I do that one every day myself.

[Damien Blenkinsopp]: Do you do it in the morning as soon as you wake up?

[Ben Greenfield]: Yes, that’s gold standard, because that’s where most of the studies have been done on heart rate variability were five minutes resting in the morning.

[30:45] [Damien Blenkinsopp]: Right, right. I believe you use the HR…what’s the name of the company?

[Ben Greenfield]: SweetBeat?

[Damien Blenkinsopp]: Yeah, SweetBeat.

[Ben Greenfield]: Yeah, but because I want to build up that technology and add some features and stuff like that, I’ve actually white labeled their technology. And so I use the app called NatureBeat now, but it’s the SweetBeat technology.

[Damien Blenkinsopp]: Great, great. Yeah, she’s been on the show.

[Ben Greenfield]: Yeah.

[Damien Blenkinsopp]: So I was using that for a long time, and then I just recently started using iFleet, because I also talked to the guys at iFleet, and it does have this other thing that they just added recently. You might just want to check out.

It’s kind of interesting. It shows how high your energy levels are on a given day, so it kind of does this matrix thing. So it shows you if your in the bottom right corner, it means something a little bit different. So I’ve been checking it out. I’m still trying to understand what it means each day. But I do find that when I’m at the bottom, low energy, those days tend not to be good. Even if I have a high HRV.

[31:39] So anyway, out of interest, what is your HRV levels? Because you think normally endurance athletes have higher HRV, right?

[Ben Greenfield]: Yeah. Usually higher HRV, which isn’’t necessarily a good thing if you’ve got what are called HF to LF ratio imbalances.

You want your HF to LF ratio to be pretty close to one. That’s sympathetic and parasympathetic nervous system feedback. And if parasympathetic nervous system feedback, which would be your high frequency number, if that’s super duper depressed, and your LF is really high that can be an indication of aerobic based over-training, or vice versa.

So ideally you’ve got high HRV and a pretty close to a 1-1 ration between HF and LF. That’s what you want to go to. And you want both HF and LF to be up in the thousands. That’s a sign of a really robust nervous system.

So, my values tend to be between about 92 and 98, with HF and LF values that vary between about 4,000 to 8,000, around in there. Generally with a 1-1 ratio, depending on what my previous day’s training had looked like.

And I would expect, for example, this Tuesday I’ll do a CrossFit’s Murph and I’ll do that with a 20 pound weighted vest on, and just crush myself. And that will take me about an hour to do, and I guarantee my LF value will be tanked the next day. But I also won’t be doing any sympathetic nervous system training for like 48 hours afterward.

[Damien Blenkinsopp]: So you recover within 48 hours?

[Ben Greenfield]: 48 to 72 hours, depending.

[Damien Blenkinsopp]: These scores recover for you pretty quickly?

[Ben Greenfield]: Yeah, but I mean, if I were to do something epic, right? Like, usually something that gets you to the state of glycogen depletion. Or let’s say instead of Murph, I do double Murph, or I do a Murph with a 5k sandwiched on either end rather than just a mile, then it can take me several days to recover, for sure.

[33:23] [Damien Blenkinsopp]: If you had to pick one marker to optimize your endurance training by and make decisions on, which one of the ones we’ve talked about would it be?

[Ben Greenfield]: HRV.

[Damien Blenkinsopp]: Okay, great.

[Ben Greenfield]: Just because it’s easy, right? You don’t have to give blood.

And maybe at some point, once we’ve got the lab and chip technology finalized, and I can put a drop of blood onto a little dongle that will plug into my iPhone and I can measure, let’s say, testosterone cortisol ratios, maybe that will become a more valuable metric for me. But at this point, I would have to say something simple and easy to utilize and relatively inexpensive, the HRV would be the one that I’d choose.

If I had to choose an actual blood biomarker, tough to say. Tough to say. I guess I’d probably have to go with HSCRP, again. Just because inflammation is generally going to be high when cortisol is high. It’s generally going to be high when diet is crappy, it’s going to be high when triglycerides are high, it’s going to be high when omega-3 fatty acids are low. So, that’s a pretty good one to measure.

[Damien Blenkinsopp]: Yeah. So it catches a lot of things. Mainly whenever something starts going wrong.

[Ben Greenfield]: Yeah.

[34:29] [Damien Blenkinsopp]: Well so you’ve referred to over training quite a bit over this as something that you’d have to change. So HRV would be one of the first places you’d see over training.

Are there any other tell-tale markers, and what do you suggest, more to the point, because you mentioned earlier that you do very – is it short, intense kind of endurance exercises. And I think a lot of people when they’re thinking about endurance, they’re thinking about very high-volume, kind of long duration activity.

So how do you approach it, and avoid over training? What are the top things you’ve taken in over time?

[Ben Greenfield]: First of all, one of the common pitfalls that people fall into with endurance training is doing the long voluminous training every weekend. It’s very stereotypical that you’ll see in a lot of athletes these Saturday long bike rides and then Sunday long run, for example. Or in a marathon, the Saturday long run.

I’ve found that in most cases, you can maintain endurance really, really well. Unless you’re a professional athlete trying to perform at the peak of performance, most people can perform just fine. With doing digging into the well like that, really, really, deep for like a death march, a really long ride or something like that, you typically only need to do that one to two times a month. Not every weekend.

I’m a bigger fan of using shorter, very temporal based intervals. So to give you an example, for the Ironman triathletes that I work with, while their peers are out doing a five hour ride followed by an hour long run, my athletes will be doing two hours of 20 minutes at race pace followed by 5 minutes recovery. So a very focused activity with a specific goal in mind. And then they’ll finish that up with a 15 minute tempo run at a cadence of 90 plus.

So it’s all extremely high quality. And then once a month they’ll go out and do something big, something long, something voluminous that builds the mental tolerance to training, but that doesn’t dig so deep into the well as doing it every week.

And the reason for that is based off of the human body’s natural slow twitch muscle fibers. The human body’s ability to cool because we’re upright and not covered in fur and hair. Our ability to sweat, rather than pant, to reduce heat. And a cluster of other factors.

We’re pretty good at going for long periods of time. And when training for endurance, bigger limiters are things like power, speed, cadence, strength, the integrity of the fascia connective tissue, the intelligence to be able to use nutrients and calories properly.

And really pointing in one direction, and going for long periods of time is not that much of a weakness for the human body, but the problem is that it’s easy. And people take pride in it. They’re like, “Oh I persevered today. I did my three hour run.”

And my question to you is well yea, but what did you accomplish side from being on your feet for long periods of time? Which frankly I could stand up at my standing workstation and write an article for three hours and get the same amount of time on my feet as you just did out pounding the pavement. So it would be better in that case to do something with intervals at race pace for a shorter period of time.

Focus on cadence. Allow enough time before and after for a good warmup. Maybe some meditation and breath work. Some good recovery. And so that’s where the more intense, more quality, lower volume approach nine times out of ten trumps the voluminous approach.

The exception to that fact would be the person who has a lot of time on their hands to train: the professional athlete. Professional athletes, assuming they’re using this 80-20 approach, it’s called polarized training. 80 percent of your training is done aerobically, with about 20 percent done high intensity.

That approach works very well, and it is what a lot of the elite cross-country skiers and marathoners and cyclists etc. will use, but what is important to understand about that approach is it requires many, many hours per day.

That approach can require two to four hours per day of training, and even more than that, on weekends, for example. And the majority of folks simply don’t have the luxury of time available to utilize that approach effectively. That in a nut shell is my approach to training.

I’ve got a couple of athletes who I work with who are more, what I would consider to be on the professional level, who have that luxury of time. And I do train them with that aerobic approach, where they’re out doing long voluminous sets of training at a controlled heart rate aerobically, putting lots of time in the saddle or time on the pavement. But its very few and far between that I’ll recommend an athlete to train like that.

[Damien Blenkinsopp]: Great, great, thanks. That’s a great summary of it.

[39:01] I wanted to move on to, because I know you did this 12 months of ketogenic dieting. Could you talk a little bit about that? Give us an overview. What was your approach to that, what were you actually eating, and was there any specific goals to track over the year?

[Ben Greenfield]: Well yeah, for that specific diet, that was for a study at University of Connecticut that was done on, basically, a group of athletes who followed a high-carb/low-fat diet, versus a group of athletes who followed a high-fat/low-carb diet.

And it was basically a measurement of fat oxidation during exercise. And they also did muscle biopsies before and after exercise to see the rate of glycogen use as well as the rate of glycogen replenishment following the post work out meal to just see if the body does a better job at oxidizing fat, or at sparing glycogen during exercise when you’ve eaten a high-fat diet.

And it did turn out in that study that the athletes who followed the high-fat diet were oxidizing a lot of fat. The textbooks tell you that you can burn about 1.0 grams of fat per minute, and the group of athletes who followed the high-fat diet were burning 1.5, 1.6, 1.7 grams of fat per minute. Literally rewriting the textbooks when it comes to how much fat you can burn during exercise.

I haven’t seen the muscle biopsy data yet to see how much glycogen conservation actually took place, or whether or not the body became more glycogen depleted when using primarily fatty acids as a fuel. But ultimately, what that diet consisted of was really controlling carbohydrates.

Whereas I would normally – and this is what I do now – I would carb-cycle, or I would do cyclic-ketogensis or cyclic-ketosis, where I don’t eat carbohydrates all day long and at the very end of the day, typically in the post-workout scenario, with dinner I’ll eat anywhere from 75 to 200 grams of white rice, red wine, sweet potatoes, sourdough bread. You know, safe starches, not like pizza and ice cream, but good carbohydrates. And then the rest of the day just high fat and moderate protein.

Whereas on this full on ketosis diet, it was pretty much just things like bulletproof coffee, and high fat shakes and lots of coconut milk and coconut oil, and heavy cream and MCT oil and seeds and nuts, and just fats, fat, fats. Bone broth and avocados, and olives, and you name it.

And frankly, in my opinion, it wasn’t that enjoyable to have to not have sweet potato fries, and not have, even coconut ice cream has cane sugar in it. So you have to make your own with chocolate stevia. And so it’s a little bit laborious and a little bit tough, but I mean at the same time the endurance payoff was huge.

The amount of focus that I had for long periods of time. My ability to just hop on a bike and ride for hours with no fuel at all, with just water. It was pretty profound, because you produce all these ketones as a bi-product of fatty acid oxidation, and they’re used as the preferred fuel by the brain, by the heart, by the liver, by the diaphragm while you’re out exercising. And that’s a huge boon to an endurance athlete.

And like I mentioned, there’s some blow-back. Like the TSH could take a hit, the testosterone could take a hit. But ultimately, it’s a cool little bio-hack. If I could go back and do it over again, I would definitely start taking thyroid glandular earlier to stave off some of those thyroid issues.

I would,– it’s not legal – but I would really encourage folks to pay attention to testosterone. And I mean like, you can’t use testosterone in a WADA, or a USADA or like an NCAA sanctioned event, but my testosterone dropped so much during that experiment with ketosis, I would say if you’re not competing, use AndroGel or just some kind of testosterone support because your testosterone is going to fall to pieces.

And then the question becomes well is it really worth it to you if you’re doing this thing and you’re not even competing.

[Damien Blenkinsopp]: Yeah. Did you feel different?

[Ben Greenfield]: Oh, yeah.

[Damien Blenkinsopp]: Because we talk about testosterone with things like anxiety, your drive, your libido, of course. And so did you get any kind of low testosterone symptoms?

[Ben Greenfield]: Oh yeah. Absolutely. I mean even something as simple as only having to shave every four or five days, whereas normally I would just shave every one to two days.

[Damien Blenkinsopp]: That’s a benefit.

[Ben Greenfield]: I mean, little things like that, but you notice. Yeah, potentially. You save money on razors.

Yeah, the libido, sex drive, number of times having sex per week, desire to have sex, quality of the erection, all of those kind of things certainly they took a hit during ketosis. They weren’t good. But that was, mind you, ketosis in the presence of high amounts of physical activity. Even doing the ‘low volume approach’ it’s still a massive amount of work, right?

[Damien Blenkinsopp]: Right.

[Ben Greenfield]: You’re still working out 60 to 90 plus minutes every day, and longer than that on the weekends.

And you look at something like Dr. Terry Wahls and her ketosis approach for managing MS. Well sure. I mean, that’s going to work just fine for managing MS. I mean, going on a walk with your dog every morning, and maybe lifting easy weights, three sets of 10 for 20 minutes twice a week.

But once you jump into hard exercise, it’s a whole different type of ketosis.

[Damien Blenkinsopp]: Right, right. Just to be clear, were you getting better times? Did you feel like you were competing better?

[Ben Greenfield]: Oh, I was competing way better. Yeah. Absolutely.

[Damien Blenkinsopp]: Right. But it’s just the downsides to your lifestyle, to all the other things, were too great to do this on a constant basis.

[Ben Greenfield]: In my opinion, yes, because I don’t like being cold all the time, I don’t like not having libido. So again, I’m not saying you can’t do it properly, even though it’s way, way tougher once you get into training, but I think that you basically have to use supplementation pretty intensively.

[44:34] [Damien Blenkinsopp]: Did you kind of see the benefits evolve and get much better as the months passed, or is this something someone could do on a month basis, one month on and one month off?

[Ben Greenfield]: For exercise, you barely even see any benefits until you’ve been doing it consistently for about six months, and the real benefits start to manifest after one to two years.

But the other thing to realize is that right about the time I finished up the experiment, companies like KetoForce started coming out with beta hydroxybutyrate salts that could be consumed to elevate your ketone bodies, even in the presence of a lot of carbohydrates or glucose. And so it’s possible that now, since the experiment that I did, you could get the best of both worlds.

And I actually have some bottles of the beta hydroxybutyrate salts and the resistance starches, and a lot of the things that, if I had to go back and do it all over again, I would try to get the best of both worlds. I would eat more carbohydrates, but then I would also hack myself into ketosis by consuming actual ketones bodies.

The question there becomes a matter of long term health and gut health and how that actually manifests in terms of actual symptoms or the way you felt, or even I would definitely pay close attention to blood and biomarkers.

Were I to delve into that type of bio-hack? I potentially may. I could see myself, and obviously I’m at a point in my athletic career where I’ve still got a good eight years of hardcore performance left in my body, and I could see one of those years being spent utilizing a ketonic approach again, but with the incorporation of beta hydroxybutyrate salts, resistance starches, even higher amounts of MCT oils, particularly like the C8s and the C10s. And a little bit more attention paid to ways to get into ketosis that go above and beyond just carbohydrate restriction and exercise.

[Damien Blenkinsopp]: This is great Ben, this is a wealth of information.

[46:20] In terms of the biomarkers you would track, you said you would track some biomarkers if you were going to do this again what kinds of ones that we haven’t spoken about already would you look at? Did you track your blood ketones?

[Ben Greenfield]: Yeah. Breath ketones. I mean, urinary ketones become, many times, absent after a few weeks in ketosis just because you’re utilizing your ketones. Blood ketones are accurate but expensive and invasive to test, and breath ketones are pretty [easy].

There are breath testing monitors like the Ketonix device that, one breath and you know your ketones, and you’re good. So breath testing is a really good way to go as far as measurement of ketones. You look for values anywhere from 1.0 up to 3.0 millimolars. You’ll finish exercise as high as 7.0 millimolars.

You’ll rarely see ketoacidosis, which would be like 10 plus millimolars. It is a non-issue. I have yet to see any athlete I work with go under ketoacidosis, which would be an actual deleterious biological state. Not something you need to worry about unless you are letting yourself become severely hypoglycemic.

[47:20] [Damien Blenkinsopp]: So again, is that something you saw evolve over the months? Like your ketones ratings would get higher.

[Ben Greenfield]: Yeah. You get to the point where it’s just super duper easy to get into ketosis. Yeah. And your ability to go for long periods of time without eating just goes through the roof.

So ultimately, the biomarker I would say, in addition to what we’ve already talked about, would be breath ketones. And then pay attention to triglycerides too, because they’ve shown that compared to total cholesterol values, a better predictor of your coronary disease risk factors is your triglyceride to HDL ratio, specifically keeping that at one or lower in terms of your number of triglycerides versus HDL.

But I’ve found that some people will switch to a high-fat diet and have such a high intake of vegetable oils, and even an imbalanced high intake of animal based oils, like butter for example, versus olive oil and avocados. Their triglycerides go through the roof.

Pay attention to that HDL ratio. That’s my advice is make sure that that thing isn’t getting much above one, that would be another important thing to pay attention to, especially on a higher fat intake.

[Damien Blenkinsopp]: Great, great. Excellent points.

[48:25] So there are a couple of other things I’ve noticed you’ve done in your experiment. I read your book of course. One of the things that we’ve come across before – I spoke to Alan Cash from benaGene –oxaloacetate, and I was wondering what you’ve done with that and if you’ve tracked anything or learned anything about that.

[Ben Greenfield]: Yeah, obviously if you talked to Alan Cash your listeners can go back and listen to that to learn more about what oxaloacetate is. But in a nutshell, the reason that I used it was because it can increase the turnover rate of lactic acid into pyruvate, and increase the rate at which lactic acid is shuttled back up into the liver to be reconverted into glucose.

And so if you are eating a low-carbohydrate diet anyways, that by nature means you might not be taking as much exogenous glucose in, or might not even have as high a level of glycogen stores, but you can still take the lactic acid that you’re producing as a byproduct of metabolic activity anyways and have that reconverted into usable glucose sources to have a glycogen sparing effect and to get a little bit more intensity. And so the way that would be achieved if you’re going to increase the rate of that cycle, which is called the Cori cycle, would be via the use of oxaloacetate.

And so, I actually did use that. I don’t use it right now. It’s one of those things where it’s just like, I would benefit from it its just one more supplement to remember to take. But I certainly used it through that entire ketotic experiment with the oxaloacetate just to increase the conversion of lactic acid into glucose.

[Damien Blenkinsopp]: Right, it sounds like it would help specifically in that ketogenic diet state when you’re exercising.

[Ben Greenfield]: Exactly.

[Damien Blenkinsopp]: So you designed it that way? You decided to take it before, or was it something you came up with afterward to help?

[Ben Greenfield]: I talked to Alan at one of the Bulletproof bio-hacking conferences. We talked about the physiology of oxaloacetate, and then based on that I just kind of had a little light bulb moment, where I realized that if I was restricting carbohydrates anyway, that this was one more way that I could create endogenous glucose more quickly.

[Damien Blenkinsopp]: Great, great.

[50:27] Cold thermogenesis. Do you still play around with that? Is there anything like, for instance, have you seen your HSCRP any time, potentially when you first started it or did it a bit more intensively, change with that?

[Ben Greenfield]: Yes. I have not done a dedicated experiment with cold water exposure, cold temperature exposure, or the use of ice baths or cold showers to see the direct effects on HSCRP, although reduction of inflammatory cytokines has been observed in literature when it comes to cold thermogenesis and inflammation.

What I use cold thermogenesis for is increased conversion of white adipose tissue to brown adipose tissue. Simply because it’s very difficult to kill fat cells, but you can convert fat cells into energy utilizing and heat producing tissue. And that’s one thing that cold thermogenesis is good for. That would mean cold baths, cold showers, cold soaks, etc.

Also very useful for increased production of endothelial nitric oxide synthase, which can cause your blood vessels to dilate much more readily, which is good for everything from exercise to sex to heating your body when it needs to be heated. And then there’s also increased tolerance to the mammalian dive reflex, which is that activation of our sympathetic fight-or-light nervous system in response to stress.

And when you are able to withstand cold stress without taking that sharp influx of breath, that means that you have become more resilient and more resistant to subconscious activation of that fight-or-flight nervous system. You’re better at controlling stressful events that happen.

And so, what I do is I never take a warm shower. I do a cold shower in the morning, cold shower in the evening. I do once per week a 30 minute cold soak that gets me up to shivering level, typically needing to shiver for one to two hours afterward in order to regain warmth. And those are the ways that I use cold thermogenesis. I also keep my house relatively cold. My office is at about 55 degrees. In my home, typically I’ll sleep at 60 to 65 degrees.

It’s just a really, really good way to make yourself tough, to burn fat, and to increase blood vessel health. And it’s just super simple. And frankly, the other cool thing is when I go hunting or when I have long periods of time outdoors or when I’m at the beach and evening comes and I forgot my coat, I don’t get as bothered, which is just kind of nice. You’re just more tough.

[Damien Blenkinsopp]: It sounds like the only time it was an issue when you were doing you ketogenic thing. What was the issue there? Were you getting a lot colder, or?

[Ben Greenfield]: Yeah, but that was because of the thyroid. If you have hypothyroidism, cold thermogenesis is going to be very uncomfortable. Heck, even normal temperatures you’re colder during. So I was still doing cold thermogenesis then but it was quite unpleasant. It was hard for the body to get warm again.

[Damien Blenkinsopp]: Okay. Right, great.

[53:17] Some quick fly questions that I have just to finish off here.

First of all, if people want to connect with you and learn more about you and what you’re up to, where is the best place? Twitter, your website?

[Ben Greenfield]: Bengreenfieldfitness.com, because if you go there, you’ll find links to my Twitter, Facebook, Instagram, my blog, my podcast, etc. So that’s a good place to go as a portal.

[Damien Blenkinsopp]: Great, great. And who besides yourself would you recommend to learn more about endurance training, or some of the other topics we spoke about today? Ketogenic diets and so on?

[Ben Greenfield]: As far as people who have their head screwed on straight who are paying attention to the research, I’d say three people come to mind.

Number one would be Joe Friel. He’s coached a lot of professional cyclists, but also has just been in the sport a long time and pays attention to the science and the research and has a pretty good unbiased view of things.

Sami Inkinen, who is a top age group for Ironman competitor. He’s a higher fat diet, pays attention to quantified data, and is a smart, well spoken person who performs well.

And then Dr. Peter Attia, who I would not say is on the pointy edge of physical performance, even though he’s in much better shape than the average, general population. He’s not out doing Ironman triathlons or anything. But, as far as the science goes, he probably knows the science better than just about anybody else when it comes to being able to speak to these things, and he also does quite a bit of self-quantification himself.

So, those would be three people that would be good resources for this.

[Damien Blenkinsopp]: Great, thanks so much for that.

[54:48] Beyond everything, like all the biomarkers we’ve spoken about today, are there any other biomarkers you pay specific attention [to] on a routine basis, I don’t know whether it’s monthly –that you feel are important that we haven’t spoken about?

[Ben Greenfield]: I’ll finish with this because it’s important. And many times in our type of circles it’s not talked about, and it’s not quantifiable to a great degree, as far as I know. And that would be simply paying attention to your levels of gratitude every single day, and multiple times per day.

For me, I guess you could kind of quantify it – at least six times per day I’m grateful. Because I’m journaling, and at the beginning of the day I journal three things I’m grateful for, and at the end of the day I journal three amazing things that happened to me that day. So there’s at least six times per day that I’m being grateful for things.

And then I practice quick coherence technique, which is something you can read about at heartmath.org, which increases heart rate variability and decreases stress. And that’s where you simply think of something that you love or someone you hold dear, and you imagine intense feelings of gratefulness washing over your body and going into your heart after you feel those feelings of gratefulness.

Saying thank you to people, saying I love you to people, randomly calling up people and telling them how much you appreciate them. If you listen to my voicemail, I ask people to end their voice message by telling me one thing that they’re grateful for that day.

It’s certainly something that’s not super duper quantifiable, again, but it is one thing, not a biomarker, but certainly something I pay attention to every day is gratefulness for being alive, for the people in my life, for the experiences that I’ve had, and for simply being able to take one more breath.

[Damien Blenkinsopp]: Excellent. Thanks for that, that’s not the typical, but definitely something really important. So I can see how that would be useful. I do a meditation gratitude every morning too, and I find that really, really useful.

So Ben, thanks so much for your time today. It’s been really stock full of biomarkers and hacks and everything, so it’s really been a great episode. Thank you for your time.

[Ben Greenfield]: Awesome. Well thanks for having me on, Dam.

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

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

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

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

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

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

What is the Fast Mimicking Diet?

Prolon l-nutra
Photo: L-Nutra

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

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

The nutrition rules established for the Fast Mimicking Diet are:

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

In practice this translates to:

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

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

Fast Mimicking Diet Recipes

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

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

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

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

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

So your day ends up looking like this.

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

That takes all of the thought out of it.

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

itunes quantified body

The Fast Mimicking Diet Experiment

The Specific Fast Mimicking Diet Variation Tested

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

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

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

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

Biomarkers Tracked to Understand Benefits/ Risks

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

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

Biomarkers Tracked by Area

the-tracking-fmd

5 Day Fast Mimicking Diet Results

Metabolic Switch to Ketones a Day Earlier than Fast #1

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

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

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

Metabolism: Blood Glucose and Ketones

Ketones and Glucose Fast Mimicking Diet

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

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

Metabolism: Seyfried’s Glucose Ketone Index

Glucose Ketone Index Fast Mii

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

Does the Fast Mimicking Diet = Lean Gains?

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

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

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

Weight (Kg) via Omron Home Scales

Weight-gain-fast-mimicking-diet

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

Body Composition (Kg) via BodPod

fast-mimicking-diet-lean-gains

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

Regeneration & the Immune System Reset

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

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

IGF-1 (Insulin-like Growth Factor 1)

igf-1-fast-mimicking-diet

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

White Blood Cell and Lymphocyte Counts

white-blood-cells-fast-mimicking-diet

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

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

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

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

The Opposition: Adrenal Fatigue

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

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

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

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

adrenal-function-panel-fasting

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

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

Potential Confounders for these Results

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

    Metabolic Switch

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

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

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

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

The 5-Day Fast Mimicking Experience

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

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

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

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

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

Next Steps – A Change of Plan

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

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

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

What I’d Like to Explore Next

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

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

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

Tracking

Biomarkers

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

Lab Tests, Devices and Apps

Lab Tests

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

Devices

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

Tools & Tactics

Diet & Nutrition

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

Supplements

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

Other People, Books & Resources

People

Additional Charts and Data

Click Here for Additional Charts

Inflammation (hs-CRP)

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

hs-CRP (C-Reactive Protein)

hs-crp-fast-mimicking-diet

References:

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

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

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

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

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

Fasting for Reasons Beyond Cancer

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

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

What does this have to do with fasting?

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

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

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

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

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

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

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

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

The Upside: Reasons to Do a 5 Day Water Fast

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

    First, the health benefits:

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

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

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

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

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

itunes quantified body

The 5 Day Water Fast Results

Big Metabolic Changes Kick Start on Day 3

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

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

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

fast-glucose-ketones

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

67 hours into the fast my index dove below 1, and it bottomed out around 90 hours, from then on hovering between 0.5 to 0.6. So I was in the therapeutic zone for all of days 4 and 5.

fast-gki

Exactly on plan: My blood glucose, ketone and GKIC markers settled into the expected ranges Seyfried outlines in his book for the fast. That’s between 50 to 60mg/dL for blood glucose, and between 6 and 7 mmol/L for ketones.

Lagging Metabolism Adjustment at End of Fast

When I hit the 120 hour (end of 5 day) mark I dug into a couple of big bowls of bone broth. Quickly full and satisfied seemingly as if the fast had never taken place.

The next day I had a higher carb than usual breakfast. We’re not talking crazy, just some blueberries and yacon syrup (for the gut, will talk about this soon in another episode) with bulletproof coffee (ghee, MCT oil and coffee). Despite this my ketones stayed high and actually hit their peak of the whole experiment (6.8 mmol/L) nearly 24 hours after the fast had ended.

This makes sense. It’s normal to see a lag of response of the blood readings the first 3 days of the fast while you adapt to ketones/ fatty acid metabolism. So it follows that there would be a lag in the switch back to primarily glucose metabolism.

Was Weight Loss Permanent? or Just Momentary?

Interested in the fast to lose weight also?

Cycling into 5 day fasts say once per month, could be quite effect based on my data (~loss of 1 lb per day in terms of permanent weight loss, not just momentary during the fast).

If weight loss isn’t desirable, which is my case, you’ll need to compensate to regain lost muscle weight post fast.

Within a few days I had recovered one third (3 lbs) of the 9 lbs I’d lost during the fast. I consciously made an effort to eat as per usual to see if it the weight would naturally come back on. Two weeks later after the end of the fast (day 19) it’s still stabilized at 6 lbs down. Actively compensating for this in between future fasts will require consciously eating to gain weight.

fast-weight

HRV, Muse Calm and Mental Performance

I also tracked my HRV with the ithlete app, my daily meditation sessions with the Muse Calm and my mental performance via reaction tests at Quantifed Mind.

These weren’t my main focus for this fast, so the data isn’t extensive enough to make any big conclusions. However, looking at what I collected, I plan to take a closer look at mental performance and HRV in future fasts.

First thing in the morning HRV dipped at the start of the fast (day 1 and 2) and go back to my normal range from then on. This is a pretty good fit with how I felt during the fast. The first two days were a little rough as I had a headache, but from then on I felt more ‘euphoric’ and productive than usual.

This time round I haven’t seen any noticeable increase in HRV post-fast (potentially a bit more of the opposite) whereas intermittent fasting typically raises HRV. Something to keep an eye on for future fasts especially as I have to deal with my own personal variable – adrenal fatigue.

Adrenal Fatigue Confounder? I have documented adrenal fatigue currently (low cortisol output as a knock on effect of the chronic stress from lyme disease and babesiosis infections). I suspect the adrenal fatigue would be the cause of any negative HRV impact, and would be personal to me (if you’ve tracked HRV during a fast let me know your experience in the comments).

This may have been behind or contributed to my less consistent sleep and shorter duration sleep as noted before.

It is very common (even fashionable) to fast on meditation retreats. The idea the retreats promote is that fasting helps to calm the mind.

Although I got my best Muse Calm score to date on one morning (80% calm), I didn’t notice any real difference between fasting and my normal scores.

The 5-Day Fast Experience

Two of my fellow entrepreneur buddies (Patrick Stiles and Patrick Kelly (@pjkmedia)) recently also did the 5 day water fast so we caught up to share notes on our experiences. Our experiences turned out to be pretty different in some areas. You can listen to our full note swapping discussion in this episode.

Here’s the brief highlights of my experience from the discussion:

  • Day 1 and day 2 were a little challenging in terms of hunger but not that noticeably (I put this down to my previous experience with intermittent fasting and ketogenic diets)
  • A headache from the end of day 1 to the beginning of day 3 (potentially linked to the switch in brain from glucose to ketone use)
  • On day 4 and 5 the physical weakness was a lot more noticeable and there was some slight dizzyness when standing up at times.
  • Undercover bad breath: I wasn’t actually aware of this during the fast. My sister mentioned afterwards that she feared for her 1 year old son’s wellbeing when I was playing up close with him towards the end of the fast. Given the high ketone levels, this would mostly be due to high acetone levels in the breath.
  • Rash of spots on chest: I believe this is very much personal to me and my current situation. Fasting tends to lead to detoxification, and potentially stress your detoxification system, as you break down body fat including accumulated fat-soluble toxins and process them. While dealing with lyme these have occurred from time to time (added lyme biotoxin burden causing overload), so it’s unsurprising that adding broken down fat-soluble toxins would lead to this currently. I took activated charcoal daily to help bind and clear any toxins from my system.
  • After a couple of nights of good sleep at beginning of the fast it got progressively less deep as the fast went on whereby I was sleeping between 4 and 6 hours compared to a normal 6.5 to 7.5.

What’s Next? Fasting as a Routine Tool.

The experience during and after the fast has been so positive that I’m planning to do this on a once per month or once per quarter basis. Which one I go with will depend on how my body responds.

As more research comes out on the specifics of Fast Mimicking Diets (FMDs) I’ll also want to test that out, to see if the same benefits can be achieved (or better) with less discomfort.

Immune System Reboot – Any Evidence?

It’s only 2 weeks since the end of the fast so it’s early to tell just through tracking symptoms of my chronic infections (lyme, babesiosis). Nonetheless it’s looking positive from that anecdotal basis. After a first rough work post-fast, it’s been up and up. Meaning more exercise, more activity and generally feeling better with less symptoms.

I’m cautiously positive because lyme and babesiosis are both cyclical in symptoms presentation. I’ll update this section at a later date. The real solution to understand the immune reboot potential or impact of course is more data…

What I’ll Track Next Time

I’ve already begun contacting labs and working out how to dig deeper into the fast on a few levels:

  • Further validating the immune system reboot side by tracking IGF-1 which is one of the main markers used in Longo’s paper.
  • Is this sustainable for me? Is it beneficial as a monthly routine or would that have some negative blowback? I’m looking into tracking Cortisol vis-a-vis monitoring my adrenal fatigue status, and will track weight with future fasts.
  • What’s the downside in terms of productivity for the 5 days fasted? While I didn’t feel like there was much negative impact this time (it felt more positive) it’s something that I’d like to confirm with some short mental performance tests done during next fasting round.

In Practice: How to Do this at Home

For my tracking I took readings 4 times per day for my blood glucose and ketones.

However, I recommend to reduce cost (ketone strips are expensive) and to make it more convenient, you can simply track your blood ketones and glucose once per day in the morning. This will give you meaningful results, and tell you if you’re hitting the same milestones based on Seyfried’s work like I did.

Tracking this way, for a ten day tracking (5 days as control, 5 days of fast) you’ll be looking at a budget of around $80 to $100 all in (versus the ~$500 I spent).

Step 1: Get Your Tracking Gear

  • Combined glucose/ ketone monitor: Abbott is behind the best value for money units, the Precision Xtra Blood Glucose and Ketone Monitoring System in the U.S. and the Freestyle Optium Neo Glucose & Ketone meter in the UK (the one I used).
  • Glucose strips: the latest format that work with Precision Xtra and Freestyle Optium devices.
  • Ketone strips: Purple colored strips for measuring blood ketones (Beta-hydroxybutyrate). These work with both Precision Xtra and Freestyle Optium (Ketone Strips – Note: These are ~$4.50/ unit, I managed to get these at a lower cost per unit in the UK of $1.97. If you know where to source these cheaper let us know in the comments)
  • Lancets: It’s good practice to use a new lancet each day to prick your finger with. These Lancets are the latest format and work with Precision Xtra and Freestyle Optium devices, but are cheaper.

Note: Make sure to buy adequate strip and lancet supplies. I ran out of ketone strips the day after my fast otherwise I would’ve tracked more post-fast data. You lose some strips unavoidably in my experience through a bad reading on the device where for instance you didn’t provide insufficient blood. Make sure to have a buffer of 10% or so to account for this.

Step 2: Track Some Control Data & Learn to Take Readings

This is one of those situations where a video walkthrough is better than 1000s of words. This walkthrough is with the Freestyle Optium Neo, which is identical in use to the Precision Xtra).

I used my control data week (charts in appendix here) to work through any slip ups in taking readings.

You’ll want to get some control days where you take some baseline data eating your standard diet so that you can compare it to your fast. Blood sugar and ketosis metabolism are very personal aspects of our biology as we learned from Jimmy Moore in episode 7.

So the relative change in your measurements (normal diet, fasted states) could be as insightful as the absolute numbers.

Step 3: Schedule in Your Fast

The experience of a fast is highly variable depending on your personal situation as you’ll have noticed from the discussion in this episode with the two Patricks.

There is a risk that you’ll feel pretty rough and weak, and may be a danger to yourself and others (e.g. no driving or other similar ‘responsible’ activities please).

So I recommend you plan ahead and schedule it in for a time when you can quietly do some mental type work, study or rest at home. If you’re able to do more, so much the better, but plan for not being able to do anything.

Step 4: The Fast

Pretty straightforward. Stop eating at your scheduled time (after an evening meal is when most people do it) and start taking readings as set time intervals.

I used a standard iPhone timer alarm to notify me to take readings every 4 hours while awake. If you’re just taking one reading per day, it’s simple enough to make it part of your first thing in the morning routine.

It’s also useful to keep a diary of anything interesting or unusual you notice during the fast. Items I found useful to note down were hours sleep and sleep quality, physical weakness, any fatigue, mood, and other symptoms like headaches or dizzyness. This way you can relate them back to the data afterwards for more insights.

Step 5: Finishing the Fast Points

Boom, you’re done! You’ll be feeling great if it was anything like my fast. There are a few things you may want to keep in mind at this point.

I was advised by friends, and some long term ‘fasting experimenters’ to reintroduce food slowly. The idea behind this is that your body needs a little time to restart enzyme and stomach acid production. Some people experience gut symptoms or/ and bouts of ‘disaster pants’ if they jump straight back into their usual diet (or a ravenous version of this).

In my case, I prepared a bone broth ahead of time so that my first meal was mostly liquid and ate as normal from the next meal onwards. No discomfort or adverse gut symptoms. Straight back to business as usual as if the fast had never happened.

In future I’ll be tracking data for a few days post-fast since this experiment showed that my metabolism took a while to return to normal despite refeeding with a vengence!

Tracking

Biomarkers

  • Blood Ketones (Beta-Hydroxybutyrate / β-hydroxybutyrate): Blood ketones are the gold standard for measuring your state of ketosis. During the fast, ketones are expected to peak in the range of between 6 and 7 mmol/L based on Seyfried’s work and experience. In episode 7 Jimmy Moore notes that values over 1.0 on your blood ketone monitor give you the benefits of ketosis, and there is no need to go over 2.0. Tim Ferriss also prefers this range, noting that his best mental performance is typically with values between 1.1 and 1.7 mmol/L.
  • Blood Glucose (mg/dl): A measure of the level of glucose in the blood at one point in time. Dr. Seyfried’s therapies target reduction of blood glucose levels to limit cancer cell growth, and according to his theories high blood glucose is a biomarker of increased cancer risk. For the fast he notes values between 50mg/dL to 60mg/dL are standard. Non-fasting values should be below 80mg/dL ideally, and at least 92mg/dL.
  • Glucose-Ketone Index (GKI): The ratio between the concentration of glucose in the blood to ketone bodies in the blood. The calculation is Glucose (mmol)/ Ketone (mmol). Dr. Seyfried created the index as a better way to assess metabolic status. Therapeutic efficacy is considered best with index values approaching 1.0 or below. Patients with chronic disease like cancer have consistent index values of 50 or more.
  • Weight (lbs): Standard scales measurement of weight in morning without clothes (to avoid biases).

Lab Tests, Devices and Apps

  • Blood Ketone/ Glucose Monitors: The Precision Xtra in the U.S. or Freestyle Optium Neo in the UK are the current recommended monitors. You’ll need lancets, ketone strips and glucose strips also.
  • Damien’s Routine Tracking Devices : Some of Damien’s daily use apps featured in this experiment including the Muse Calm for meditation, the iThlete Pro app for HRV, and Quantified Mind for mental performance.
  • Healbe GoBe: Damien mentioned that he’s been testing this device, and that the tracking of hours slept works quite well – but that other functions of the device make it hard to use consistently.
  • uBiome: Damien mentioned as a side note on another experiment he’s working on to shift his whole biome to a more positive balance of bacteria.
  • Functional Adrenal Stress Profile (BioHealth): Mentioned by Damien in relation to testing for adrenal fatigue.

Tools & Tactics

Interventions

  • 3 to 5 day Water Fast: The fast featured in this episode. Recommended by Dr. Seyfried as a potential tactic against cancer (reduce risk, or fight cancer disease). More details in Seyfried’s interview. Also used to promote stem cell regeneration of the immune system as per Valter Longo’s work. These fasts are often referred to as Prolonged Fasts in the literature.
  • Ketogenic Diet: The term given to low carb-high fat diets that put your metabolism into a state of ketosis (using ketones for fuel). Damien’s day to day diet shown in the baseline results is at times ketogenic.
  • Fast Mimicking Diet (FMD): FMDs have been covered increasingly in the research and there are two papers covering human clinical trials expected to be published on them in 2015 by Valter Longo’s group. With the FMD you fast 5 days each month by restricting certain proteins and keeping calories below a specific range each day. The goal is to reduce fasting discomfort and downsides while accessing the same upsides as the fast.
  • Intermittent Fasting: A form of fasting where you fast for part of or full days. The most popular formats are using eating windows of 4 to 8 hours each day. Bob Troia discussed his results from intermittent fasting in episode 22.
  • Slow Carb Diet: Patrick 1 mentioned that he’s primarily on this diet from Ferriss’ The 4-Hour Body.

Supplements

  • Activated Charcoal: The only thing I did beyond restricting myself to filtered water and black coffee (total of 3 cups in whole fast), was to take activated charcoal once a day to aid in clearing toxins from my system. I took a handful, around 8 to 10 capsules per day.
  • Brain Octane: Damien takes brain octane every morning in coffee to help raise his ketones.

Other People, Books & Resources

People

Books

  • The 4-Hour Body: Contains a once per week intermittent fasting format that got Damien started with fasting in 2010.

Additional Charts and Data

Click Here for Additional Charts

Pre-Fast Control Data Eating My Standard Diet

Blood Glucose & Ketone Levels at Different Times of Day

control-glucose-ketones

Glucose-Ketone Index at Different Times of Day

Control-GKI

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Is some aspect of mitochondrial damage behind cancer? If so, can this theory help us take control of cancer via tactics such as yearly or more frequent “7 day water fasts”.

When we think about death, cancer is often what we think of first. If you’re like me, most, if not all, of the deaths affecting you personally in your life may have been due to cancer.

Part of what makes a cancer diagnosis so devastating is that it’s mechanisms – how it works, where it comes from, how we can treat it effectively, how we can track it’s development, assess our risk and avoid it – continue to allude us. That makes us feel powerless against it.

Today’s episode is about the theory that mitochondrial damage is behind cancer, and how this theory may let us take control of cancer. We also hear our guest discuss the power of “water fasts” as a potential tactic to beat cancer.

If that’s true then tools that we have today such as ketogenic diets, fasting, lipid replacement therapy and other approaches to mitochondrial repair may help reduce or eliminate the risk of cancer, and even treat it when we have it.

We’ve already seen how important our mitochondria, and keeping them healthy, is in previous episodes, looking at longevity and aging with Aubrey de Grey, and autoimmune diseases with Terry Wahls. Today we add to that list the role they may be playing in the cancer diseases process.

“All cancers can be linked to impaired mitochondrial function and energy metabolism. It’s not a nuclear genetic disease. It’s a mitochondrial metabolic disease… therapeutic ketosis can enhance mitochondrial function for some conditions, and can kill tumor cells.”
– Dr. Thomas Seyfried

Today’s guest, Dr. Thomas Seyfried, is Professor of Biology at Boston College, where he leads a research program focused on the mechanisms by which metabolic therapies such as ketogenic diets and fasting can manage chronic disease and cancer. He sits on the editorial boards of four research journals, and has over 60 published papers on cancer and metabolism.

He is the author of the review paper Cancer as a Metabolic Disease, appearing in the Journal of Nutrition and Metabolism in 2010, and of the textbook in 2012 entitled Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer.

He’s a frequent lecturer and speaker at conferences on the topic of cancer, impaired mitochondrial function, and using ketogenic diets and fasting tactics as therapy to treat and avoid cancer.

This was personally an important episode for me. I hope you feel more in control of your cancer risk after listening to it, as I do having followed Dr. Seyfried’s work.

The show notes, biomarkers, and links to the apps, devices and labs and everything else mentioned are below. Enjoy the show and let me know what you think in the comments!

itunes quantified body

Show Notes

  • How the idea that a change in mitochondrial function is behind cancer started in the 1920s (4:10).
  • The ancient energy mechanism through which cancer cells can bypass the mitochondria through fermentation instead of normal mitochondrial respiration (7:20).
  • The part of mitochondrial function that seems to be compromised in cancer – oxidative phosphorylation (8:15).
  • Different types of cancer cells and tumors have varying damage to their mitochondria. The worst and most aggressive cancers have the least mitochondrial function (9:00).
  • The oncogenic paradox (9:00).
  • Lipids such as Cardiolipins in the inner membrane of mitochondria are the part responsible for respiration (15:10).
  • How Dr. Seyfried pooled research from over 50 years together to develop his conclusions on cancer and the mitochondria (18:00).
  • Therapeutic ketosis and fasting can enhance mitochondria (23:00).
  • Ketone bodies produce cleaner energy, with less oxidative stress (ROS) than glucose molecules, when used for fuel in the mitochondria (27:00).
  • Nuclear genetic mutations prevent cancer cells from adapting to use ketone bodies as their energy source (29:30).
  • Which biomarkers could be indicative of cancer risk? (33:10).
  • Using therapeutic fasting of several days to improve your metabolism (36:00).
  • Using combined blood glucose – ketone meters to take readings and using Dr. Seyfried’s calculator to calculate Glucose – Ketone Indices (38:00).
  • It requires 3 to 4 days of fasting to get into the therapeutic glucose – ketone index zone (42:00).
  • “Autolytic cannibalism” to improve overall mitochondrial function – the mitochondria can either be rescued, enhanced or consumed (47:30).
  • The difficulties with directly measuring mitochondrial respiration vs. anaerobic fermentation and lactic acid to assess cancer status (49:50).
  • Weight loss can come in two types, pathological and therapeutic. The weight loss via fasting is therapeutic and healthy (52:00).
  • Cancer patients do better with chemotherapy, with less symptoms, when they are in a fasted state (52:00).
  • Cancer centers currently do not offer mitochondrial based therapies, only chemo or immuno therapies (57:40).
  • The biomarkers Dr. Thomas Seyfried tracks on a routine basis and his use of the ‘fasting’ tool (101:40).
  • What Dr. Seyfried would do if he had cancer (102:30)
  • Should you remove organs if you discover you have a high genetic risk for cancer? (E.g. BRCA1 as with Angelina Jolie) (103:30)

Dr. Thomas Seyfried

The Tracking

Biomarkers

  • Blood Glucose: A measure of the level of glucose in the blood at one point in time. Dr. Seyfried’s therapies target reduction of blood glucose levels to limit cancer cell growth, and according to his theories high blood glucose is a biomarker of increased cancer risk.
  • Glucose – Ketone Index (GKI): The ratio between the concentration of glucose in the blood to ketone bodies in the blood. The calculation is Glucose (mmol)/ Ketone (mmol). Dr. Seyfried created the index as a better way to assess metabolic status. Therapeutic efficacy is considered best with index values approaching 1.0 or below. Patients with chronic disease like cancer have index values of 50 or more. Thomas’ paper on the use of GKI for cancer patients has just been accepted for publishing: The Glucose Ketone Index Calculator: A Simple Tool to Monitor Therapeutic Efficacy for Metabolic Management of Brain Cancer. It is on Nutrition & Metabolism journal here and you can download an excel sheet to calculate the Glucose Ketone index here.
    Glucose Ketone Index - Thomas Seyfried

    Glucose Ketone Index Tracking of a Water Fast as Therapy for Brain Tumors Trial – Thomas Seyfried

Lab Tests, Devices and Apps

The Tactics

Treatments

  • 3 – 5 Day Water Only Fasts: A water-only fast of at least 3 days and preferably 5 days is recommended by Dr. Seyfried as a tool to reduce cancer risk and to lower your glucose – ketone index to 1.0. He recommends doing this twice yearly. For cancer patients he recommends much more intensive use of the water fast.
  • Ketogenic Diets: The ketogenic diet is a low carb diet which also raises the level of ketone bodies in the blood. We discussed this in depth, as well as the Ketone biomarkers and devices in episode 7 with Jimmy Moore on Ketosis.
  • Intermittent Fasting: An approach to fasting where you fast for part of the day or certain days per week. There are many approaches to this, however in Dr. Seyfried’s research he has found this doesn’t have a significant enough impact on raising ketone bodies to be therapeutic. He has only seen this via the water-fast.
  • Hyperbaric Oxygen Therapy (HBOT): Another therapy Dr. Seyfried believes may be beneficial to fight cancer but is relatively non-toxic in comparison to current treatment modalities (chemo and immunotherapies), and would like to trial in conjunction with fasting protocols.

Supplements

  • Oxaloacetate: A support for the mitochondria, also dubbed as an anti-aging supplement as it has caloric restriction mimicking effects. It is sold by Dave Asprey in his “Upgraded Aging” formula.
  • 3-Bromopyruvate (3BP): Dr. Seyfried would like to incorporate this non-toxic molecule in combination with fasting therapies to treat cancer patients.
  • PQQ (Pyrroloquinoline Quinone): Mentioned by Damien as a potential tool for mitochondrial biogenesis.

Other People, Resources and Books

People

  • Otto Warburg: A well known scientist who worked on cancer in the 1920s and 30s and discovered that cancer cells have different metabolism to normal cells.
  • Albert Szent-Györgyi: The oncogenic paradox was first coined by this nobel prize winner for his work with vitamin C and energy metabolism.
  • Valter Longo PhD.: Dr. Seyfried referred to Valter Longo’s work at the University of Southern California on the impacts of fasting on patients undergoing chemotherapy.
  • Angelina Jolie: The actress recently had her breast’s removed when she discovered she has the BRCA1 genetic mutation, that predisposes women to breast cancer.

Organizations

Books


Full Interview Transcript

Transcript - Click Here to Read

[Damien Blenkinsopp]: Thomas, thank you so much for joining us today.

[Dr. Thomas Seyfried]: Thank you.

[Damien Blenkinsopp]: I’d like to start off with basically kind of an overview, because you are putting for a different theory of cancer compared to that that’s been the reigning theory for a very, very long time now. Could you describe the differences between the two theories, and what is the basis for your new theory?

[Dr. Thomas Seyfried]: Well, it’s not that my theory is new. The theory was initiated in the early part of the last century, in the 1920’s through the 30s and 40s, by Otto Warburg, the distinguished German scientists and biochemist. It was Warburg who found that all tumor cells continue to ferment glucose in the presence of oxygen. Put it this way, lactic acid fermentation.

This is a very unusual condition that usually happens only when oxygen is not present. But to ferment in the presence of oxygen is a very, very unusual biochemical condition. Warburg said, with his extensive amounts of data, that the reason why tumor cells do this is because their respiration is defective. So, in our normal bodies, most of our cells generate energy through respiration, which is oxidative phosphorylation. And we generate ATP this way.

But cancer cells, of all types of tumors and all cells within tumors, generally have a much higher level of fermentation than the normal cells. And this then became the signature biochemical defect in tumor cells. And Warburg wrote extensively on this phenomenon, and presented massive amounts of data – he and a number of other investigators.

But what happened after Watson and Crick’s discovery of the structure of DNA, and the findings that genetic mutations and DNA damage were in tumor cells, and the enormous implications of understanding DNA as the genetic material, this just sent the whole field off into a quest to understand the genetic damage in tumor cells. And it gradually became clear to many people that cancer was a genetic disease, rather than a mitochondrial metabolic disease as Warburg had originally showed.

[Damien Blenkinsopp]: Right, so when you were talking about the energy and respiration of the cells, just a minute ago, that was actually in fact the mitochondrial respiration, and energy generation from mitochondria within cells.

[Dr. Thomas Seyfried]: That’s correct. That’s correct, it’s mitochondrial. It’s an organelle within all of our cells, the majority of our cells – erythrocytes have no mitochondria, so they ferment. But the mitochondria are the organelle that dictates cellular homeostasis and functionality, and provides health and vitality to cells in our organisms, and ultimately our entire body.

And when these organelles become damaged, defective, or insufficient in some way, cells will normally die. But if the damage or insufficiency is a gradual chronic problem, the cells will resort to a primitive form of energy metabolism, which is fermentation. Which is the type of energy that all cells had, all organisms had before oxygen came onto the planet, which was like a billion years ago.

So what these cells are doing then is essentially going back to a very primitive state of energy metabolism, which was linked to rapid proliferation. Cells would divide rapidly and grow widely before oxygen came onto the planet. So what these cancer cells are doing is just falling back on the type of energy metabolism that existed for all organisms before oxygen came on the planet.

[Damien Blenkinsopp]: Does that type of fermentation type of respiration, metabolic activity, is that originating from the mitochondria, or from the cell itself?

[Dr. Thomas Seyfried]: No, there was no mitochondria before oxygen came on the planet. So this was purely a reductive activity within cells. It doesn’t require mitochondria, it’s a purely cytoplasmic form of energy. Glucose is taken in, and rapidly metabolized to pyruvate through cytoplasmic in the cytoplasm, and then the pyruvate is reduced to lactic acid or lactide, which is called lactic acid fermentation.

And this then could drive energy metabolism, and the processes that can emerge from this type of energy metabolism. But it’s a very inefficient form of energy generation, and it’s often associated with rapid proliferation.

[Damien Blenkinsopp]: Right, thank you very much. So, in very simple terms it seems like, basically what you’re saying is, as the mitochondria get damaged they stop functioning, and then the cell goes back to the original form of energy generation, and it’s as if the mitochondria weren’t there any more.

[Dr. Thomas Seyfried]: Well it’s not that they’re not there. They are there, and they can also participate in certain kinds of amino acid fermentations. They still play a role in generating energy and nutrients for the cell, but it’s not through the sophisticated aspect of energy generation through oxidative phosphoryation. That part of their function seems to be compromised, but other parts of their function can take place. But they’re not generating energy through what most cells would generate energy through, which is respiration or oxidative phosphorylation.

And I also want to point out, it’s not a complete shut down of oxidative phosphorylation. Tumor cells, depending on the grade, and how fast they grow, and how aggressive the tumor is. It is true that some very, very aggressive tumors have very few, if any, mitochondria. So these cells are primarily massive fermenters.

But some tumor cells still have some residual function of their respiration, and they grow much more slowly than those tumor cells that have no function, or very little function, of their respiration. So it’s a graded effect, but the bottom line is the cells continue to grow, but they’re dysregulated. Because the mitochondria do more than just provide efficient energy. They are the regulators of the differentiated state of the cell. They control the entire fiber network in the cell. They control the homeostatic state of that cell.

So these organelles play such an important role in maintaining energy efficiency. And when they become defective, the nuclear genome turns on these oncogenes, that are basically transcription factors that drive fermentation pathways. So the cells are able to survive, but they’re dysregulated.

[Damien Blenkinsopp]: Right, which becomes cancer.

So, in what ways are the mitochondria getting damaged. What is the context for this kind of damage that takes place today? Is this a modern phenomenon, because, obviously cancer has become a bigger and bigger target of medicine over the years, and, potentially, it’s been growing. I’d like to hear your view on that.

Is cancer something that’s always been around, or is it something that affects us more today, and how is it that the mitochondria are getting damaged?

[Dr. Thomas Seyfried]: Yeah, what you said there is referred to as the Oncogenic Paradox, which has been discussed by Albert Szent-Gyorgyi, who received a Novel Prize for his work on Vitamin C and energy metabolism and these things, and John Cohn from England. These people had referred to this phenomenon as the called the Onogenic Paradox. How is it possible that so many disparate events in the environment could cause cancer through a common mechanism?

And when we think of what causes cancer, we think of carcinogens. And these are chemical compounds in the environment that are known to be linked to the formation of cancer. So there’s a whole array of these kinds of chemicals that we call carcinogens. Then there’s radiation can cause cancer. Hypoxia, the blocking of oxygen into cells, can be linked to the formation of cancer.

A common phenomenon and finding is inflammation. Chronic inflammation that leads to wounds that don’t heal. This is another provocative agent for the initiation of cancer. Rare germline mutations, such as the mutations in the BRCA1 gene that a lot of people hear about because of Angelina Jolie bringing attention to that area. Viruses, Hepatitis virus, papillomaviruses. And there’s a variety of viruses that can be linked to cancer. Age. The older people get, the greater the risk of cancer.

All these provocative agents all damage respiration. Their common link to the origin of cancer is damage to the mitochondria, and damage to the respiratory capacity of the cell. So the paradox is solved once people realize that these disparate, provocative agents work all through a common mechanism, which is basically damage to the cellular respiration.

Now, but people say, “Well what about all the genome mutations? What about all these mutations?” Which is a major focus in the field right now, is that cancer is a nuclear genetic disease. Now what happens is the integrity of the nucleus and the genetic stability of the nucleus becomes unstable once energy from respiration becomes defective.

Now it’s very interesting. All of the so-called provocative agents that are known to cause cancer through damage to respiration release these toxic reactive oxygen species, which then cause nuclear genetic mutations. And this is what most people are focusing on. The nuclear genetic mutations in the tumor cells are the targets and focal point of the majority of the cancer industry. Now, when you look at the disease as a mitochondrial metabolic disease, the nuclear genetic mutations arise as secondary downstream epiphenomena of damage to the respiration. So what most people are focusing on is the downstream effect, rather than the cause of the disease.

[Damien Blenkinsopp]: You’re saying that because mitochondria are damaged and energy output is damaged, that causes the cell to lose it’s integrity?

[Dr. Thomas Seyfried]: Lose the genomic integrity.

[Damien Blenkinsopp]: Ah, genomic integrity.

[Dr. Thomas Seyfried]: Yeah. Most people you talk to about this, they say “Oh, cancer’s a genetic disease. We’re trying to talk all these genetic mutations. Every kind of tumor has all kinds of mutations. We need personalized therapies because the mutations are different in all the different cells, and the different types of cancer.” And that’s true, but all of that is a downstream effect of the damage to the respiration.

So, people are focusing on red-herrings. They’re not focusing on the core issue of the problem, which is stabilized energy metabolism. And this underlies the reason for why we’re making so little progress in managing the disease.

[Damien Blenkinsopp]: So, I don’t know if you can break it down into a bit more detail. The mitochondria are made up of several parts: the outer membrane, the inner membrane, and so on. Is it certain parts, or is it any part of the mitochondria that’s getting damaged?

[Dr. Thomas Seyfried]: Yeah, it’s very interesting. It seems to be we’ve defined the lipid abnormalities, the lipid components of the inner membrane of the mitochondria. So there’s certain types of lipids that are enriched primarily in the inner membrane of the mitochondria. This lipid called cardiolipin. It’s an ancient lipid that’s present in bacteria and in mitochondria, but it plays a very important role in maintaining the integrity of the inner membrane, which is ultimately the origin of our respiratory energy, which is that inner membrane.

And many of the proteins that participate in the electron transport chain depend, or are dependent under interaction in the lipid environment in which they sit. So, lipids can be changed dramatically from the environment, which then alter the function of the proteins of the electron transport chain, effecting the ability of that organelle now to generate energy.

This is a real issue, and that inner membrane can be effected by all these carcinogens, radiation, hypoxia, viruses. The viruses themselves, or the products of the virus, will enter into the mitochondria and take up residence, thereby altering the energy efficiency of the infected cell.

And most of the cells die. When you interfere with respiration, most cells die. But in some cells of our body that have the capacity to up-regulate fermentation, these primitive energy pathways, they survive, and they go on to become the cells of the tumor.

[Damien Blenkinsopp]: Great, thank you for that. So, this is a very different theory to that which most people have come across, which, of course, you just outlined with the DNA mutations. Which bits of research have you pulled together in your book, and in your presentations, that you feel like present this view of the world the most strongly. Are there key research elements, researchers that have gone on, and maybe it comes down to four pieces that you feel strongly support this versus the other argument?

[Dr. Thomas Seyfried]: I think that’s an extremely important point. What is the strongest evidence to support what I’ve just said? And what I did in my book in evaluating the therapeutic benefits that we’ve seen in managing cancer by targeting fermentation energy. How is it possible that we overlooked this information? It’s very interesting.

Over the last 50 years, various sporadic reports had been published in the literature showing that if the nucleus of the tumor cell is placed in a new cytoplasm, a cytoplasm that has normal mitochondria – and this is cytoplasm either from a newly fertilized egg, or an embryonic stem cell. Because now we have this technology where we can do these kinds of nuclear transplantations. And this ultimately was what lead to the cloning of Dolly the sheep, and these kinds of experiments. These had been done many, many years earlier in frogs, and in mice, before we moved on to the larger mammals and things like this.

But it became clear that when the nucleus of the tumor cell was placed into the normal cytoplasm, sometimes normal cells would form, and sometimes you could clone a frog, or a mouse, from the nucleus of the tumor cell. Now this was quite astonishing. Because people were thinking you would get cancer cells, because the mutations in the nucleus, if the hypothesis is correct that this is a nuclear genetic disease and the gene drivers are in the nucleus, then how is it possible that you could generate normal tissues without abnormal proliferation. In other words, normal, differentiated tissues from the nucleus of a tumor cell.

I was able to pull together a variety of these reports that had been sporadic in the literature over 50 years. And when these reports came out, it was considered kind of an oddball report that didn’t support the gene theory, but most people discounted it, because it was one singular report. But every four or five years, another report. Eight years would go by, another kind of report. And some of these studies were done by the leaders of the field, the key developmental biologists, the best there were. These people were heavy-weights in the field.

And they were coming to the same conclusions. That we were not getting tumors from transplanting the cancer nucleus into a normal cytoplasm. We were cloning mice, we were cloning frogs. We were seeing normal regulated cell grow. Now how can this happen, if the nucleus is supposed to be driving the disease?

So what I did was, I put all these reports together in a singular group. And I distilled it down to what the ultimate results showed. And then when you look at the whole group of papers, together for the first time, and the conclusions are consistent from one study to the other, using totally different organisms, totally different experimental systems, the results are all the same. The nuclear mutations are not driving the cancer disease.

And then if you take the normal nucleus and put it into a tumor cytoplasm, you either get tumor cells or dead cells. You never get normal cells. So this was clear. It became very clear to me, and when people look at these kinds of observations in their group and their totality, it’s a devastating statement on the nature of the disease. It’s not a nuclear genetic disease, it’s a mitochondrial metabolic disease. And the field has not yet come to grips with this new reality.

[Damien Blenkinsopp]: Just on that point, quickly, if you were to predict the future, do you think that this view of cancer metabolism is going to get traction in the near future? Say the next five years, next ten years, and what will it take to make that happen?

[Dr. Thomas Seyfried]: Well, it’s already gaining a lot of traction. People are now coming to realize that metabolism is a major aspect of cancer. But, unfortunately, what the field has done, there’s still links to the gene theory. So, the top papers come out and they say, “Oh, the abnormal metabolism in cancer cells is due to the nuclear gene mutations. Therefore, we still must be on the quest to find out what these mutations do.”

They have not evaluated in the depth of the information that I’ve presented. It becomes clear that this is not a nuclear genetic disease. So the mutations are not driving the disease, they’re the effects of the abnormal metabolism.

Now, there’s a groundswell of new interests in this. Now this opens up a totally different way to approach cancer. Once you realize it’s not a nuclear genetic disease, but it’s a mitochondrial metabolic disease, you have to then target those fuels that the tumor cell is using to stay alive. These amino acids and glucose, which can be fermented. Those molecules that can be fermented through these primitive pathways now become the focal point of stopping the disease.

So it becomes a much, much more manageable and approachable disease once you realize that if you take the fuel away from these tumor cells, they don’t survive. They become very indolent, they stop growing, they die. And now this gives you an opportunity to come in and target and destroy these cells, using more natural, non-toxic approaches.

[Damien Blenkinsopp]: Right. If you could reinforce that a little bit, because as I understand it, the current approach, which is pushed the most, is to target all of the different nuclear genetic mutations – and there’s many, many thousands of them, you can’t really count how many there are, because it’s constantly developing – versus, with mitochondria, as I understand it, mitochondria are all the same. So it’s a completely different problem when you look at it from that respective. Am I summarizing it correctly?

[Dr. Thomas Seyfried]: Yes, I think you’re absolutely right. I mean, it’s a completely different problem. It now becomes a problem of energy metabolism. And the nucleus becomes a secondary peripheral issue.

[Damien Blenkinsopp]: Right. And the fact becomes much simpler, because you’re targeting the same problem versus thousands of different problems.

[Dr. Thomas Seyfried]: Absolutely.

[Damien Blenkinsopp]: And then therapy is… Today we’re developing thousands of hundreds of different drugs to target different types of cancer.

[Dr. Thomas Seyfried]: Yeah, it makes no sense. And the issue is every single cell in the tumor suffers from the same metabolic problem. But every single cell in the tumor has a totally different genetic entity. And we’re focusing on the very different aspects of every cell, rather than the common aspects of every cell.

The problem becomes a much more solvable problem once you target the commonality. The common defect expressed in all cells, rather than the defects that are expressed in only a few of the cells. You would not do that until you came to the realization, and saw the data, that this is a disease of energy metabolism, not nuclear genetic defects. It’s a totally different way of viewing the disease.

[Damien Blenkinsopp]: Right. Thank you.

This may be kind of off subject for you, let me know if it is. But, I understand it, there’s also, more and more people are starting to link other types of diseases – say multiple sclerosis, Parkinson’s, and some of the other chronic diseases that we have and are not very solvable today – to mitochondrial disease. So I’m wondering if in any way you link that to the same origin of cancer, here. That we’re discussing.

[Dr. Thomas Seyfried]: Well, those diseases, that’s true. There are mitochondrial abnormalities in Parkinson’s disease, Alzheimer’s disease, epilepsy, and Type 2 diabetes. I mean, you can go right down the list and find a mitochondrial connection to a lot of these different diseases. But the mitochondria can be damaged, and insufficient, and influenced in many different kinds of ways. So, only cells that can up-regulate, significantly up-regulate fermentation, can go on to form tumor cells.

But many of our cells are not killed outright, and they struggle. For example, the brain. We rarely get tumors of the neurons in the brain, because if you damage the respiration of the neuron, the neuron will die.

Many of the tumors in the brain come from the glial cells. These are supportive cells of the brain, they play an extremely important role in the homeostasis of brain function. But those cells have a greater capacity to ferment than do the neurons. So when mitochondria are damaged in neurons, the neurons usually die. You can never get a tumor cell from a dead cell.

Now Parkinson’s disease and Alzheimer’s disease, these are situations where populations of neurons die from reactive oxygen species. So these reactive oxygen species, which are produced by inefficient mitochondria, kill the cell. And the cells never form tumors, they just die. So you have populations of cells in the Substantia nigra in Parkinson’s disease, or in the hippocampus in Alzheimer’s disease, where the neurons are dying. And they’re dying from mitochondrial energy inefficiencies.

And the idea then, is can we enhance neuronal function by using therapies that will strengthen mitochondrial function. And the answer is, yes. And this is why these ketogenic diets are showing therapeutic benefit for a variety of different ailments, a very broad range of ailments. But the diets and these approaches – what we can therapeutic ketosis – can enhance mitochondrial function for some conditions, and can kill tumor cells in other conditions.

So one now has to appreciate a new approach to managing a variety of diseases that may have a linkage through inefficient mitochondrial metabolism.

[Damien Blenkinsopp]: Could you talk about – we’re coming into treatment here a little bit now, based on your theory. There’s the difference between ketone, or like, fat versus glucose metabolism in the mitochondria. And you were just talking about efficiencies. Could you go over that? What is the difference there? Why is it that glucose metabolism is different that of fats and the production of ketones?

[Dr. Thomas Seyfried]: Yeah, well the body is very flexible. It can burn energy from carbohydrates, which is glucose, or it can burn energy from fatty acids. Or it can burn energy from ketones. And we evolved as a species to survive for considerable periods of time without food. It’s amazing how people don’t understand this. They think if they don’t eat food in a week or less, they’re going to drop dead. This is nonsense.

We evolved as a species to function for long periods of time. As long as we have adequate fluids, water, the human body can sustain functionality for extended periods of time without eating. Now, you say to yourself, well where are we getting our energy. We evolved to store energy in the form of triglycerides, which are fat. And many of our organs store fats to various degree, and we have fat cells that store fat.

Now, when we stop eating, the fats are mobilized out of these storage vacuoles in the cells. And the fats go to the liver, and our liver breaks these fats down, like a wood chipper, to these small little ketone bodies, which now circulate through the bloodstream, and they can serve as an alternative fuel to glucose. So we can sustain, because the brain has a huge demand for glucose, but the human brain can transition to these fat breakdown products called ketone bodies.

So this all comes from storage fat, and our brains can get tremendous energy from these ketones. The energy in food comes from hydrogen carbon bonds that were produced during the production of the food. Ultimately from planets and the sunlight. But the energy in the bonds is ultimately derived from the energy of the sun. Now, our bodies break down these bonds, and recapture that energy. What we’re doing then is just recapturing this energy.

Now ketone bodies, when they’re burned in cells, they have a higher number of carbon oxygen bonds. They produce more intrinsic energy than does a glucose molecule, which is broken down to pyruvate, which is a glucose breakdown product. And when ketones are metabolized, they produce fewer of these reactive oxygen species. They work on the coenzyme Q couple within the mitochondria to produce clean energy, energy without breakdown products. It’s a very efficient form of energy.

[Damien Blenkinsopp]: I like that analogy there, because people could relate to how we had lead gas before, and we cleaned it up a bit, and now we’ve got less waste products in the environment.

[Dr. Thomas Seyfried]: Yeah!

[Damien Blenkinsopp]: It’s a little bit similar.

[Dr. Thomas Seyfried]: It’s the same thing. I mean, our bodies are so super energy efficient when we begin to force them into a situation. In the past, this was done all the time, because in the past the humans almost were extinct a number of geological epochs, for the ice ages, lacks of food and all. And I mean, we have a very energy efficient machine in our bodies that can generate this energy from within. Clean, powerful, efficient energy that allows us to sustain our mental and physiological functions for extended periods of time.

And this comes from the genome. Our genome has a remembrance and a knowledge to do this. It evolved over millions of years to do this. The problem today is that this capability is suppressed by the large amounts of high energy foods that are in our environment. And what happens, this then creates inflammation and the kinds of conditions that allow inefficiencies, and eventually inflammation and the onset of cancer.

So, returning to the more primitive states allows our bodies to reheal themselves. And, as I said, here’s the issue. The nuclear genetic mutations that collect in these cancer cells prevent those cells from making the adaptations to these food restrictive conditions. So, because the mutations are there, the cells are no longer flexible. They can’t move from one energy state to the other, like the normal cells can, which have integrated genomes.

So, the mutations can be used to kill these tumor cells, but by forcing the body into these different energy states in a non-toxic way. It’s not necessary to have to poison people, nuke people, surgically mutilate people to make them healthy. There’s natural ways we can do this, if we understand the differences in metabolism between normal cells and cancer cells.

[Damien Blenkinsopp]: So, from your perspective, anything that would help to repair mitochondria, would that be helpful against cancer?

[Dr. Thomas Seyfried]: Oh, absolutely. Absolutely. You’re not going to get cancer in cells that have very healthy mitochondria. If mitochondrial damage is the origin of cancer, and the cells have very high efficient mitochondria, it’s very unlikely. The risk of developing cancer in those situations is remarkably low.

There are groups of people that we have in the United States, the Calorie Restriction Society of America. It exists in other areas throughout the world. These people have a very low incidence of cancer. They’re in a constant state of ketosis, and the incidence of cancer in these people is very, very low.

Now, I have to admit. This is not an easy lifestyle. People don’t want to be restricting themselves all the time, and doing this stuff. This is the issue. We live in an industrialized society that has come a long way to create an environment that is free of the massive kinds of starvations, and these things that existed in the past. So it’s hard to take your body and go back into these primitive states to do this kind of thing.

[Damien Blenkinsopp]: Right. So, there’s [unclear 31:58] a really big focus on what you’ve been saying on reactive oxygen species, which is kind of like the mini explosion that takes place inside a car when it’s running. And I think people can relate to the fact that all engines are causing damage while they’re running, because they’re producing heat, and so on.

So, with the mitochondria, it’s basically the same. And you’re saying that when we’re on a ketogenic diet, or where we’re fasting and we’re producing this more efficient type of fuel, it reduces our assets [unclear 32:23] causing less damage. And it’s an important type of the damage that is caused to mitochondria.

And this is why eventually it helps with the status of the mitochondria, to heal them and repair them, or to limit the additional damage that goes on which would help to promote the cancer. Is that a good summary, or have I got some things wrong?

[Dr. Thomas Seyfried]: It’s a very close analogy. I would say this is exactly what it is. We damage our body by the kinds of foods we eat, the kinds of environments we’re exposed to. And the mitochondria in certain cells just get damaged, and these cells then revert back to a more primitive form of energy, which is fermentation, which then leads to a total dysregulation of the growth of the cell. Collects these mutations that come as a secondary downstream epiphenomena of this.

And the thing of it is is, how do you target and eliminate those kinds of cells. And cancer, people must realize, this is systemic disease, rather than a focal disease. People say, “Oh, what does he study? He’s a liver cancer, breast cancer.”

These cancers are all the same. They’re metabolically all the same. You need to treat cancer in a singular global systemic way, and this then will marginalize and reduce the growth of these cells. And you have to be able to do it non-toxically.

And these ketogenic diets, or therapeutic ketosis, is just one way to enhance the overall health and well-being of the body while targeting and eliminating these inefficient cells. And this can be done if people do it the right away.

[Damien Blenkinsopp]: Great, great. Thank you very much.

So, based on this theory, what kind of biomarkers would give us insights into someone’s potential to develop cancer? Because today we look at 23andMe data, for example, genetics to kind of asses our risks of future cancer. For instance, on mine it says my highest potential cancer is lung cancer. And that’s pretty much the only markers that we’re given. Are there markers related to mitochondrial function, or damage, that you would feel that would be relevant to estimating a future potential risk of cancer?

[Dr. Thomas Seyfried]: Yeah, well I think one of the risks of cancer is high blood sugar, blood glucose levels. I mean this creates systemic inflammation, which underlies a lot of the so-called chronic diseases that we have, including heart disease, and Type 2 diabetes, and Alzheimer’s disease, and cancer. These are just the predominant number of chronic diseases that we’re confronted with.

So, if we know that high blood sugar is a provocative agent that increases the risk for cancer, then making sure your blood sugar levels are low. And the other thing too is elevation of ketones. So we developed what they call a glucose-keton index that can be used for people to prevent cancer, as well as managing the disease.

So if the glucose-ketone index, which we have defined as the ratio between the concentration of glucose in the blood to the concentration of ketone bodies in the blood. If this index can be maintained as close to 1.0 or below, the body is in a very high state of therapeutic energy efficiency. Which is then going to reduce the risk for all of these different kinds of chronic diseases. So, and if you look at most people with chronic disease, their index is about 50 or 100, rather than 1 or below 1.

We’ve just developed this, and we’re working on a paper. It’s called the Glucose-Ketone Index. It was designed basically for managing cancer, because patients who have cancer, if they want to know what these therapies are doing, how they’re working, you look at your index.

Now, people who don’t have cancer, who would like to do something to reduce their risk, they would do the same thing. And people would say, “What’s your index today?” “My index is 1.2.” You’re in a very good state of health.

And if most people – I can guarantee – people who eat regular foods, their indexes are about 60 or 70, not 1.2 below. Because what you do is when you have a lot of carbohydrate in your bloodstream, the ketones are very, very low. They’re like 0.2, 0.1. And you’re blood sugar is like 4 or 5 millimolar, and your blood ketones are 0.1 millimolar. Well what do you think your index is going to be? It’s going to be huge.

But then if you increase your ketones, if you can bring the ketones bodies up to the same level as glucose, then I have a 1.0.

[Damien Blenkinsopp]: Is this sensitive enough to manage potential? You made a very clear scenario of 60, where that’s a very dangerous situation to be in.

[Dr. Thomas Seyfried]: Oh no, no. I don’t want to say it’s dangerous. I want to say it’s the norm.

[Damien Blenkinsopp]: Oh, okay. Great.

[Dr. Thomas Seyfried]: It’s not dangerous. When you take somebody who has Type 2 diabetes, and his blood sugar is like 300 milligrams per deciliter – and you have to divide that by the number 18 to bring it down to millimolar – and his ketones, you can’t even measure them. I mean, these guys are inflamed. Their bodies are in an inflamed state. And inflammation will cause all kinds of effects.

So, you want to bring people down. How do you get these low numbers? Well, you can either go on these calorie restrictive ketogenic diets, or you can do therapeutic fasting, which is water only fasting, for several days. You’ll bring those numbers right down. You’ll get into an extremely healthy state. Because the ketones go up naturally when you don’t eat, and blood sugar goes down naturally when you don’t eat.

So then you enter into these states, it’s called therapeutic ketosis. The problem is it’s very, very difficult for most people in our society to do this, because our brains are addicted to glucose. If you take somebody who stopped eating for 24, 36 hours, this guy thinks he’s going to go crazy. It’s almost like trying to break the addictions to cigarettes, alcohol, drugs. It’s not easy. It’s very, very difficult to break the glucose addiction.

[Damien Blenkinsopp]: Absolutely. It takes a little bit of time to change your metabolism.

[Dr. Thomas Seyfried]: Yeah.

[Damien Blenkinsopp]: So we spoke to Jimmy Moore before. I don’t know if you connected with him before, and his book…

[Dr. Thomas Seyfried]: Yeah, I know Jimmy.

[Damien Blenkinsopp]: Right, right. So we spoke about some of the different ways to measure ketones. We had the blood test, the blood-prick test with the precision, which is a little bit expensive today. And you have the breath test, the Ketonics, which has just come out. With that index, are you using the blood-prick test, or are you using maybe blood labs, or something a bit more complicated?

[Dr. Thomas Seyfried]: There’s a couple of companies that use the blood test, the most accurate. It’s more accurate than the breath, blowing into a ketosis meter. Or you do urine sticks. So the most important measure, of course, is blood. So you have to take a blood stick. There’s only a few meters that can do both ketones and glucose, using the same meter.

You have to use different sticks. There’s a ketone stick, and a glucose stick. So from the same drop of blood, you can get your blood sugar, and then you can put a new stick into the machine, which is a ketone stick, and then you can take the same drop of blood and get your ketones.

Now what we did was we developed a calculator so that all the person would have to do is to push the button on the meter, and it would calculate already your glucose-ketone index. This would give you a singular number from a drop of blood.

[Damien Blenkinsopp]: So you’ve developed your own device, you’re saying, which does that calculation?

[Dr. Thomas Seyfried]: We developed the calculation. It’s called the Ketone Index Calculator. And because you have to convert everything back to millimolar. Because many of the ketone meters give you blood sugar in milligrams per deciliter, and ketones in millimolar. So we have to convert. You can do all this by hand, you just have to do the divisions and all of this stuff.

[Damien Blenkinsopp]: So you’ve got an online calculator where people can put their values in and it will give them the index?

[Dr. Thomas Seyfried]: Well, we don’t have that yet. What we did was develop the calculator that could be incorporated into these meters.

[Damien Blenkinsopp]: I see.

[Dr. Thomas Seyfried]: This is the thing. So people, regardless of whether you’re a cancer patient and you want to manage your disease, or you’re a person who wants to prevent cancer, or you’re an athlete who wants to know what his physiological status is, or you’re someone who wants to lose weight. All of these issues, you can get a sense, a good solid biomarker sense, by looking at your glucose-ketone index.

And everybody can do that from these meters that are capable. But the meters right now are not designed to give you glucose-ketone indexes. And this is what we’re saying; it’s the index that will tell you your overall status, your health status.

[Damien Blenkinsopp]: Right. So I imagine, right now, you’re approaching the providers of these tools to see if they can incorporate this calculation into their devices?

[Dr. Thomas Seyfried]: Yes. Exactly. They don’t have it yet. They’re not even aware yet of the potential market, or interests, among the general population. Not only for people that are afflicted with various diseases, but people who are healthy and don’t want to get those diseases.

So this is a very simple tool. The only drawback from it is you have to stick your finger with a little prick to get a little bit of a drop of blood. The people with Type 1 diabetes do this regularly. This is not an issue. But for those people who are into this, and they want to do it the right way, and they want to get accurate biomarker measurements, then they would do this. For those people who are interested in this.

This is invasive in the sense that you have to prick your finger to get a drop of blood, but it’s not invasive in the sense that you have to take tissue samples, or any of this kind of thing.

[Damien Blenkinsopp]: And so this is something that people could do on an on-going basis? So I’m guessing for someone with cancer – I don’t know if this would be something you would say – they’d probably want to look at daily, or every few days, or something like that. And someone else, maybe it’s just something they need to do a lot less intensive routine, in terms to just monitor the levels of their general ketogenesis.

[Dr. Thomas Seyfried]: Yes. You’re absolutely right about this. People who are trying to manage their diseases thoroughly might want to do this maybe once or twice a day. Just like someone who might have Type 1 diabetes. They measure their blood sugar several times a day.

The issue right now is the glucose strips are relatively cheap – they’re like 50 cents a piece – but the ketone strips are much more expensive. They can range from anywhere from $2 to $5 a stick.

[Damien Blenkinsopp]: Do you know if that’s due to economies of scale? Or if it’s simply because not enough people are using them yet?

[Dr. Thomas Seyfried]: Yes, it’s an economy of scale, absolutely. Because very few people measure their ketone levels. But now, linking those ketones to your overall general health, a lot of people would be interested in this.

And people in general like numbers. They want to know, and especially a singular number that would dictate your state of health. If you can say to somebody, “Listen. My index is between 1.1 and 0.9,” people would automatically know this guy is in a tremendous state of health.

People like to know that. You say, “Where is your number?” And people like to keep log books. They like to record these numbers. And they also link this to a greater sense of well-being. People who have their numbers down in these ranges, they tell me – and I’ve done it. Some people get into a state of euphoria. It’s like unbelievable.

When your body starts burning these ketones, it’s like you enter a new physiological state. And athletes are doing this sometimes. So it’s a whole new realm of how to monitor your own health with accurate biomarkers that give you an indication of your health status.

[Damien Blenkinsopp]: So do you follow a similar prescription to Jimmy Moore? I believe you understand his approach, where he’s eating a high fat diet, or sometimes he’s fasting. Kind of like intermittent fasting, which has become pretty popular these days.

[Dr. Thomas Seyfried]: Well intermittent fasting is, from what we’ve seen in our work, you don’t get the health benefits, the power of the health benefit, until you’ve gone three to four days without any food. Just drinking water. And then those who can go a week, like a seven day period, this is really when you start to see your blood sugars going down and your ketones going up.

But once you can get into this zone – we call it the zone of therapeutic management – where now you know your in the zone, this is where the health really comes in. And when you say periodic fasting, now there’s a lot of people that I know – numbers of people – who have a rather restrictive diet for the week, and then one day a week they’ll not eat anything. So, it’s one day off on food, like a 24 hour period where they’ll just have maybe a green tea, no calories, or just pure water.

[Damien Blenkinsopp]: Some of the intermittent fasting regimes propose that approach, a 24 hour fast every two days.

[Dr. Thomas Seyfried]: Yeah, but then you’ve got to know, okay what did that do to my index? How effective was the 24 hour fast on my index? And you look down, you say, “Well, I didn’t get my ketones up very far. They went from 0.1 to say, 0.5.” Okay, but if I go four or five days, it goes from 0.1 to 3.0. Oh wow, this is the magnitude difference.

[Damien Blenkinsopp]: Yeah. So have you looked at different people, because when we were talking to Jimmy, he was saying that different people have different responses. It’s based on their current state of metabolism. They’ll have to be more extreme in their approach to get the same level of ketones, and the same impact on an index, depending on, potentially, how damaged their mitochondria are. I don’t know how you look at it.

[Dr. Thomas Seyfried]: Yeah, no, that’s a really important point. It’s certain people. It’s also certain sexes. Women can get into these ketone states much easier than men. And young people can get into these zones much, much easier than can older people.

So it’s an age issue, it’s a gender issue. We’ve seen some of our students get down their blood sugars down into the low 30s, which people would say would be a crisis situation, you’d have to go to the hospital. But their ketones are elevated, and when the ketones are elevated, you have no crisis situation. It’s only when you lower blood sugar and don’t elevate ketones that you have this situation.

Males have a lot more muscle, they tend to burn protein, which can be converted to glucose. So their blood glucose doesn’t go down as sharply as women, the blood glucose of females goes down. Females can get their blood sugars down and their ketones elevated – from all the data that we’ve seen for several years on different gender – and this is what we see.

And older people are simply locked into a much longer lifestyle of high glucose. And for them to get their blood sugar down, it’s a real struggle. And also their muscle mass over the age. They have a lot of other issues that play into this whole thing.

And you’re absolutely right, it’s an individual thing. Some people can’t tolerate this. They get really sick, they get light-headed. Where other people make the adaptations much more quickly. So again, people have to know their own physiology.

But they have to have the biomarkers that let them know. They need to see these numbers, and once they see these numbers they’ll know that they’re on the right path, and they probably can do this if they persist a little bit longer. Rather than throwing their hands up, not knowing what’s going on, being very frustrated. And as I said, once you have this information and knowledge, that these kinds of things become much easier.

[Damien Blenkinsopp]: Yeah. It definitely helps with your confidence in something if you can see that, maybe you don’t feel better, or you don’t feel a difference yet, but if you see the numbers starting to move then it gives you that sense of accountability, and motivation also. I think that’s one of the very helpful aspects of these kind of indexes that you’re talking about.

[Dr. Thomas Seyfried]: Absolutely. This is a very important point, you’re absolutely right about this. Because when you see that you’re killing yourself, and nothing’s happening, or you don’t feel anything, but when you see numbers starting to change in the direction you know your hard work is starting to pay off. And then you get motivated, and you want to see then how far you can push these numbers.

Now this is not going to hurt anybody. You’re just lowering blood sugar and elevating ketones, and your body gets into a new state of health. And people feel it, believe me. You can feel this stuff happening. But there’s a rocky road going from the high glucose state to the high ketone state. And that rocky road can be more rocky for some than others.

[Damien Blenkinsopp]: Absolutely. So there are other aspects to mitochondrial health that certain people are looking at at the moment. I don’t know if you’ve come across any of these, but I thought I’d just throw them out in case you had some comments on them.

Some people are talking about mitochondrial repair, in terms of repairing the membranes with specific lipids, by providing those lipids to help reinforce the mitochondria. Other people talk about things like PQQ to help stimulate biogenesis of new mitochondria. I don’t know if you’ve heard about these things, or have any ideas or opinions on them.

[Dr. Thomas Seyfried]: Well, in my book I called it autolytic cannibalism. And this is basically, the mitochondria can either be rescued, enhanced, or consumed through an autophagy mechanism. And when you stop eating, now every cell in the body must operate at its maximal energy efficiency. That means that the mitochondria in those cells must be operational at their highest level of energetic efficiency. Otherwise the cell will die, and the molecules of that cell will be consumed, and redistributed to the rest of the body.

Now, in cells that have some mitochondria effective, or more efficient than other mitochondria within the same cell, the inefficient mitochondria can be incorporated into the lysosome. The parts of that mitochondria can then be redistributed to the healthy mitochondria within the cell. And this way you eliminate internal energy inefficiencies, but without having to kill the cell, because the cell is able to repair itself.

Whereas those cells that can’t repair themselves die, and their molecules are then consumed by macrophages, excreted back into the blood stream, and the nutrients now are used to support the health and vitality of those cells in the body that have this higher energy efficiency. It’s a remarkable state of efficiency. So it works both with individual cells, and throughout the whole entire physiological system.

[Damien Blenkinsopp]: Great, great. Thank you. I’m just thinking, you’ve spoken about fermentation versus respiration. Is there any way to measure that, that you know of? Is that being done in studies? So are the studies coming out are comparing the state of fermentation versus respiration taking place in people’s bodies, and correlating that to cancers, or anything like that?

[Dr. Thomas Seyfried]: Yeah, that’s kind of hard to do, because we all have lactate in our bloodstream, and the lactate comes from erythrocytes, our blood cells. The blood cells have a shorter half-life than many of the other cells in our body, and those cells have no mitochondria. They have no nucleus. So they’re little cytoplasms that primarily ferment.

But they don’t use a lot of energy, because the role of that cell is simply to exchange gases. So it floats around in our tissues, it deposits it’s oxygen and picks up CO2, as more or less a little mailman running around, picking up this and dropping that off. And they have a shorter half-life. But they have lactate.

Now if you have a tumor, or if you’re under hypoxic stress, lactic acid will go up in your bloodstream. But it’s hard to know if a tumor will do that. Sometimes what tumors will do, they have a phenomena called cachexia. This is where the tumor cells will send out molecules that will digest proteins, or dissolve proteins in our muscles and other proteins. And these proteins then go to the liver, and are broken down into amino acids, and the amino acids are conjugated into glucose.

So the glucose goes now into the tumor cell, and some of the proteins and the amino acids go to the tumor cell after being broken down. So the tumor is essentially causing our body to starve to death. We might be eating, but it looks like we’re not gaining any weight, and we’re becoming moribund and looking like we’re starving to death. This is an effect of the tumor,.

Sometimes you don’t see that. Sometimes lactic acid will go up, and sometimes it won’t. So there’s a lot of ambiguity of looking at a good biomarker to assess the state of what level of tumor growth you might have, other than the fact that you’re losing weight even though you’re eating. Which is the cachexic state; you’re kind of wasting from within. This is the whole thing.

And this is one of the fears that the medical profession has with cancer patients, because they say these poor people are losing weight through this cachexic mechanism, and then you come along with a metabolic therapy, and they say, “Oh, this can’t work.” But the issue, of course, is that there’s two types of weight loss. One is a pathological weight loss, and the other is therapeutic weight loss.

Pathological weight loss is cachexia, and of course if you treat it with toxic chemicals and radiation, you get so sick with fatigue, nausea, diarrhea, vomiting. I mean, this is pathological weight loss. Therapeutic weight loss is you’re losing weight, but your body is getting extremely healthy, and killing cancer cells at the same time.

So weight loss can come in two different varieties: pathological and therapeutic. And people have a tremendous difficulty in understanding the differences between these kinds of weight loss.

[Damien Blenkinsopp]: I think we’ve mentioned on a podcast before that when people are fasting in this state, they actually feel better, even if they have, for instance, chemotherapy. They tend to do better in chemotherapy when they have been fasting.

[Dr. Thomas Seyfried]: Yes, because it reduces inflammation. We published a number of papers showing how therapeutic fasting reduces systemic inflammation. Systemic inflammation contributes to a pathological state, and facilitates tumor growth.

So therapeutic fasting, while at the same time you’re taking a toxic drug, it’s like what are you doing here. But it does take the sting out of that toxic drug. People feel better when they’re therapeutically fasting. I think Longo’s group down at University of Southern California has clearly shown that some of these cancer patients can do a lot better, and feel better, when they’re fasting while they’re taking chemotherapy.

But you’re absolutely right about that.

[Damien Blenkinsopp]: Thank you so much for this interview[unclear 53:08] Thomas. I want to ask you just a few more questions to round off now.

What do you think will happen in the next five or 10 years, or hope? What are your visions for this area, in terms of biomarkers, like testing devices, or change in the way we approach this? Do you think there’s specific opportunities ahead, are there specific questions you’re looking at at the moment to resolve, in research, or so on?

[Dr. Thomas Seyfried]: Yeah, well I think the people themselves are demanding a change. The issue is that they haven’t been shown other alternatives, other than the standards of care, which are conducted by the major medical schools: Dana Farber Cancer Center, MD Anderson, John Hopkins, Yale Cancer Centers, Sloan Kettering, UCSF. The major industries of cancer and academics are closely aligned in how to do this.

And it’s not working. We’re having about 1,600 people a day are dying from cancer in this country. And the statistics in other countries in Europe, and China, and Japan, are not far off of this. And if we had Ebola outbreak in this country, where 1,600 people were dying a day, this would be of the greatest catastrophe that people can imagine.

But for cancer, it seems to be okay. This is the norm. Well it doesn’t have to be this way. It doesn’t have to be this way. And the issue here is that the people see that we have more, and more survivors, and people doing pretty well on these metabolic therapies. Why are we not doing this as more of a general treatment as opposed to these toxic approaches to manage the disease?

So I think the change will come from the grassroots. I don’t see it coming from the top medical schools, because these people are not trained. They’re medical education doesn’t give them the training to identify these approaches to therapy. It’s not part of the medical training.

There are a number of physicians that are recognizing this now, and they want to become part of this new approach to cancer management. Now, you have to realize that we’re just beginning. This is just a new field, it’s a beginning field. Even though the science is well, well established, the implementation of this science for patient health is just at the beginning. It can be refined, it can be modified.

A lot of this now we’re talking about, the potential for managing cancer in a non-toxic way with greater therapeutic efficacy, is just beginning. So, I think that we need more trained people. We have to have people that understand this. Eventually, these kinds of approaches will be more and more recognized, and more and more implemented in the overall society.

The problem is people have not yet found a way to make a large profit on this kind of an approach as you can with certain drugs, and immunotherapies, and these kinds of things. But that will probably come in time, once people understand what the best approaches and techniques are.

[Damien Blenkinsopp]: Another aspect I wanted is there’s more research being undertaken on mitochondria over time. Do you think that will help, in any way?

[Dr. Thomas Seyfried]: Yeah, I think it will help a lot, like you said, with the lipids. And we’re looking into this ourselves. I think there’s ways that we can enhance mitochondrial energy efficiency through various diets and supplements, and things like this.

And there will be a real quantitative measures that can assess this, for people to recognize what works and what doesn’t. So I think it’s just that it’s an area that has been not well appreciated, and not well recognized.

And as long as people think that cancer is a nuclear genetic disease, the focus on the mitochondria hasn’t been there. People have known the importance of mitochondria, and it’s been a very major area of scientific research. But it’s not recognized as the solution to the problem. It’s kind of a side effect.

What we’re looking at is understanding mitochondrial functions, and it’s interaction with the nucleus and other parts of the cell to maintain a healthy cell – a healthy society of cells – and a healthy overall physiology. All linked to the mitochondrial energy metabolism. This is going to be a very exciting new development.

[Damien Blenkinsopp]: Yeah, I agree. There’s not a day that goes past that I don’t think about mitochondria these days. And hear someone talk about it. It happens a lot on this show, also.

If someone wants to learn more about your work, and this theory of cancer, and the index you were talking about, where should they go?

[Dr. Thomas Seyfried]: Well, I wrote the book On Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of the Disease. That’s published by John Wiley Press. Unfortunately, it’s a science book and it’s not cheap, like you’d find most of the Amazon books, but it gives you the literature, it gives you the science. It gives you the hard evidence to support everything that I’ve said.

Another book that’s just appeared is Tripping Over the Truth: The Metabolic Theory of Cancer, by Travis Christofferson, who’s written a book for the layperson, where he actually read my book and went back to test all the things that I was saying, and actually talking and visiting and interviewing those scientists who work in the gene theory, and work in the metabolic theory, and get the word directly from them. It reads like a novel, and it’s much less scientifically intimidating than what I wrote.

I wrote this book to convince my peers, and people in the cancer and scientific field, the evidence that supports what I’m saying. This sometimes can be intimidating to the layperson. Whereas Travis went out and actually interviewed those scientists, and asked them the specific questions. And now it becomes a very intriguing story; I mean, how did this cancer thing get so far out of whack with what we know about it. People like to see this, and read it.

So that is another book that’s generating… If you go on Amazon, you’ll see the reviews. They’re all quite outstanding for Travis’ book. And I’ve been privy to a number of other books that will be coming out over the next year, which are harping on the same general theme, that cancer is a metabolic disease, and it can be beaten by metabolic solutions. Totally different than what’s been going on in the main focus.

And this is kind of shocking, because you go to the top cancer centers, and they don’t speak anything about this. They’re still talking about the standards of care as they have been done, or they’re talking about immunotherapies, which is the new buzzword for the cancer field, where you’re going to identify all the mutations, and then make anti-bodies to the defective proteins, and then treat people. And they show a few survivors on the cover of the Wall Street Journal saying how wonderful this works. But they don’t show you the other evidence showing how many people are dying from this.

All this will change, because the people in this society, the public, is going to be fed up with the lack of progress, and what we have is a new way to approach this problem based on solid scientific fact. It’s just that these facts are not well understood or recognized at this point.

[Damien Blenkinsopp]: Great. Thank you very much, and we’ll put all of this in the show notes, so people will find these links easy. Also the index you spoke about, I’m guessing there’s nothing really published about that. If people go to your website in the future, will you have something on there which will talk about that in more detail?

[Dr. Thomas Seyfried]: Yeah. We have a paper that’s under review right now, where we’ve submitted a paper for the index, and we’re in the process of making some revisions on the index. And the index was, in this paper, was mostly focused on managing brain cancer, but we also noted that this index could have a broad applicability to a whole range of different diseases.

And in the Journal of Lipid Research, which is the top journal in the field of lipid biochemistry, I edited one of the issues that was entitled Ketone Strong: Emerging Evidence for the Role of Ketones and Calorie Restriction for the Management of a Broad Range of Diseases. So, more and more scientists are getting involved in this, and more and more information will be coming out. Both in the professional scientific journals as well as in the public interests articles in journals, and magazines, and radio shows.

More and more people will be coming to know this, and I think the field is going to have to deal with it. And I think in the long run, we’ll emerge into a new way to manage these chronic diseases with a lot less toxicity, and greater efficacy.

[Damien Blenkinsopp]: Great, great. Thank you. Now, just two more questions, personal questions for you.

What data metrics do you track for your own body on a routine basis, if any?

[Dr. Thomas Seyfried]: Well, basically I try to get on a scale and see how much I weigh. Obviously, if you can keep your body weight at a stable level for a period of time, this is certainly one way to maintain homeostasis.

I’ve done the three day fast, but as I said, when you’re older like myself, it’s very uncomfortable, but it’s certainly doable. It’s like training exercise. You’d have to do it probably a couple of times a year to get into the state. I think every time you do this, you become more confident in your ability to do it again.

There is a state of uncertainty and discomfort, like, “Oh my god, I’m not eating any food. How can I go, and I feel uncomfortable, and a little light-headed.” And you try to drink water to say, “Maybe I can fill my stomach up with water and I won’t feel as hungry.” And then you start getting water intoxication. And eventually you realize that you really don’t need to drink a lot of water, and you just have to bite the bullet.

But as I said, as we begin to do this, we realize that it’s not so life-threatening as everybody would think it would be. So I think I try to do that. But as I said to a lot of people, they said, “Oh, you must do this all the time.” No, I don’t do it all the time. But if I had cancer, I’d know exactly what I would do.

[Damien Blenkinsopp]: What would you do? Just to speak it out clearly.

[Dr. Thomas Seyfried]: I would stop eating.

[Damien Blenkinsopp]: Completely?

[Dr. Thomas Seyfried]: I’d get my index down below 1, that’s for sure. And then I would transition off to these high-fat, nutritious kinds of diets, ketogenic diets, and maintain my index. And then of course, we’re investigating – it’s very hard to get funds to do this kind of stuff too, because it’s not considered sexy science – what is the best combinatorial therapy that would work with therapeutic fasting and ketogenic diets, that would put the greatest amount of pressure.

And most of it has to do with what kind of non-toxic drugs would you dovetail in with therapeutic fasting and ketogenic diets? And like hypobaric oxygen therapy, 2-deoxyglucose, 3-bromopyruvate, oxaloacetate. I mean, we can go down these lists. Most of these are non-patentable drugs, but they have tremendous power when used together with these other therapies. And most of this stuff is just trying to figure out the dosages, the timing.

These kinds of issues, it’s just like perfecting the engine. How did the car engine become so efficient today from the way it was in 1900?

[Damien Blenkinsopp]: Right. So the things you just mentioned either stress the cancer cells specifically, like hypobaric oxygen, or they support the mitochondria, oxaloacetate, right?

[Dr. Thomas Seyfried]: Yes! Exactly. What you’re doing is you’re enhancing mitochondrial function in normal cells, and you’re putting maximal metabolic stress on the tumor cells. For the first time, we’re using our normal cells to directly combat and battle the cancer cells, while enhancing their health and efficiency.

[Damien Blenkinsopp]: So for someone who has, say we do a 23andMe test – like a lot of people on this podcast do their 23andMe test – and it comes out with some DNA, and it says, maybe you have a pretty high chance of cancer in your lifetime – and it could be lung cancer or whatever. Lung cancer’s not a good one, because often it’s smoking. So, one of the other more general ones, like breast cancer.

What would you basically say that they should be fasting once per month for three days, or twice per year for seven days, and maybe looking at those therapies you just outlined.

[Dr. Thomas Seyfried]: Yeah. People who have Li-Fraumeni syndrome, which is an inherited germline mutation in the gene for P53 which encodes a protein in the electron transport train, or BRCA1. Product of the BRCA1 gene has been found in mitochondria. We look at a number of these so-called inherited genes that increase your risk for cancer. But as I told you, everything passes through the mitochondria The mitochondria are the origin of the disease.

So, the inherited mutations simply make that organelle slightly less efficient in certain cells of our body. Not all cells, but only certain cells, like the breast, the uterine, or these kinds of things. And we know that there are people, like if you inherit the BRCA1 mutation, your risk of cancer goes up significantly. But not everybody who has BRCA1 mutation develops cancer.

So clearly the environment can play a huge role in determining whether that gene will be expressed or not. You can do prophylactic removal of organs, and things like this, to reduce your risk. But it would be just as effective in my mind to transition the body to a metabolic state that would minimize the problem of that gene influencing the mitochondrial function. It seems a lot less draconian than doing these massive surgical mutilations.

Or you can do both. The idea is some of these inherited mutations, they might have a preferred organ – like a breast, or a uterus, or ovary – but you’re not going to remove all your organs. You’re not going to remove brain. You’re at a higher risk, so what can you do to lower your risk? As I said, if you keep your mitochondria healthy, the risk is going to be significantly reduced.

People need to know this so they can make choices that would be best suitable for them.

[Damien Blenkinsopp]: Thank you so much for the information today. This is really an information packed episode. It’s got this great new take on cancer, which I think is very positive, because it’s talking about something which people can have more control about. So it’s not just that this is a new approach, and the older approach has been struggling for quite a while, it’s become very expensive, and so on, with not so much success, but also that this is an approach which is within people’s own manners, sphere of management.

A lot easier to start having an impact on their own lives. So it’s very positive from that perspective also.

[Dr. Thomas Seyfried]: Yeah, I agree. Absolutely.

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The problem with diets is that we think that one diet should be good for everyone. But research and N=1 experiments show that’s not the case. Learn about measuring ketones and ketosis to understand how your low carb or high fat diet is really affecting you.

If there is one area of our bodies that is debated to extremes, with literally hundreds of differing strong opinions on it, it’s nutrition. For many, beliefs about nutrition and diet are tribal. We put ourselves in different camps and we war agains the other camps. Whether it be paleo, low fat, low carb, Atkins, high fat, low protein, vegan, raw vegan and so on.

It’s exactly this sort of area where I see data as essential. Without data we have no hope of cutting through the maze of opinions to get to what really works.

Part of the problem with nutrition and diets is that we tend to think that one diet should be good for everyone. But increasingly, research and N=1 experiments, are showing that that isn’t the case. And this is exactly why you should pay attention to today’s show.

Today, we’re looking at what has relatively recently become the fastest growing nutrition or diet trend. The high fat diet. Also known in different guises as the ketogenic diet, or the low carb diet. And specifically how this can affect our different individual biochemistries, how we can measure “Ketosis” and other biomarkers to understand how our specific biology is reacting to it… and allowing us to troubleshoot and course correct when it isn’t getting the desired results we’re looking for from it.

Today’s guest is Jimmy Moore. In 2004, Jimmy, at 32 years, weighed 410 pounds. Since then he has transformed his own biology, shedding all that additional weight with low carb and ketogenic diets. He has also interviewed nearly 900 people on his “living the Vida low carb show” podcast, discussing every aspect and detail of ketogenic diets you could think up.

Most recently he pulled together the best information, in collaboration with the top experts he has found in the field, into a book “Keto Clarity: Your Definitive Guide to the Benefits of a Low-Carb, High-Fat Diet“. It’s extremely detailed, and I’d recommend that anyone on or interested in high fat, ketogenic or low carb diets read it. You’ll definitely learn more no matter your existing knowledge.

The show notes, biomarkers, and links to the apps and devices and everything else mentioned are below. Enjoy the show and let me know what you think in the comments!

itunes quantified body

Show Notes

  • The benefits of getting your body into the state of ketosis.
  • The wide range of biomarkers a high fat, low carbohydrate and low protein diet can impact positively.
  • Why we can’t just assume we are getting into ketosis and staying there as was originally thought and assumed with low carb diets such as Atkins and other ketogenic diets.
  • How cholesterol markers typically said to be predictive of cardiovascular health have been superseded by more accurate lipoprotein particle biomarkers.
  • How to interpret your blood glucose numbers and why it’s the most important marker of your metabolic health.
  • When protein is not a healthy macronutrient and how to use ketone measurements to understand your protein tolerance.
  • How to measure ketones in blood (beta hydroxy butyrate), in urine (acetoacetate) and in breath (acetone) and the differing accuracy, cost and convenience of each approach.
  • How to measure ketones with The Ketonix while avoiding some of the confounders that can affect its accuracy.
  • Jimmy Moore’s suggested ketone body testing strategy to minimize costs and maximize convenience and accuracy.
  • What Jimmy Moore routinely tracks for his own body and who he recommends to learn more about the subject of ketosis from.
  • Using the hs-CRP to monitor body inflammation from diet and being aware of big confounders to its reading such as exercise, injuries and illness.

Give some love to Jimmy on Twitter to thank him for the advice in this interview.
Click Here to let him know you enjoyed the show!

The Tracking

Biomarkers

Lipids and Cardiovascular Risk Markers

  • Cholesterol Panel: The cholesterol panel covers a number of markers related to lipoproteins 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.
  • Triglycerides: Below 100, optimally under 70. Jimmy’s are at around the 40 mg/dl mark now.
  • HDL: The traditional measure of ‘good cholesterol’ used by doctors and healthcare. Jimmy mentioned that on a true ketogenic diet people can measure up to 80 mg/dL which is very high. Levels are consider protective of cardiovascular disease over 60 mg/dL. Damien’s levels were 72 mg/dL at last test.
  • LDL (Low Density Lipoprotein): The traditional measure of ‘bad cholesterol’ that many doctors still use, but that research has now determined not to be the best predictor of cardiovascular risk.
  • LDL-P: Measures the density of your LDL particles. Research shows that small LDL particles are the ones that play a role in cardiovascular disease. This test is not yet routine.
  • hs-CRP (high sensitivity C-Reactive Protein: The inflammation marker that is used to track amongst other things cardiovascular risk. Below 1, you do not have a cardiovascular disease risk. As examples, Jimmy’s is at 0.55 mg/dL when he last checked and Damien’s hovers between 0.1 and 0.2 mg/dL.

Blood Sugar Regulation

  • Fasting Blood Sugar: Typically taken first thing in the morning after an 8 hour fasting period. Should be in the 80s, and definitely below 92 mg/dL.
  • Post-Meal Blood Sugar: You can test your blood sugar response after meals with a standard glucometer available in pharmacies. 1 hour after a meal your blood sugar should be below 140 mg/dL and after 2 hours it should be back to your baseline (in the 80s ideally).
  • HbA1c (Hemoglobin A1c): This is a proxy biomarker for your average blood glucose level over the lifetime of red blood cells. Doctor’s tend to use a reference range where anything below 6% is fine, however this already represents blood sugar disregulation. You should be aiming for less than 5.3%. Jimmy noted that his is now around 4.3%.

Ketones and Ketosis

  • Beta-Hydroxybutyrate / β-hydroxybutyrate (Ketones in Blood): Blood ketones are the gold standard for measuring your state of ketosis. Jimmy finds that over 1.0 on your blood ketone monitor gives you the good benefits, and there is no need to go over 2.0. Stephen Phinney and Jeff Volek (from the Art and Science of Low Carb) recommend between 0.5 and 3.0.
  • Acetoacetate (Ketones in Urine): Measuring urine ketones is the easiest way to get started, however for some people this measure will not reflect blood ketone levels once they have become fat adapted, start to mobilize ketones routinely in their blood.
  • Acetone (Ketones in Breath): Measuring breath ketones is the latest method for monitoring ketone levels. Research studies show that there is good correlation between breath acetone levels and blood ketone levels (β-hydroxybutyrate).

Devices and Lab Tests

The Tools

  • Ketogenic Diets: The main tool discussed in this episode were low carb-high fat diets that put your metabolism in a state of ketosis. Jimmy outlined how easily your body switches to making ketones depends on the state of your metabolism with factors such as your weight and diet history and your genetics. Jimmy is releasing a book with recipes for ketogenic diets in 2015: The Ketogenic Cook Book.
  • The Atkins Diet: The popular Dr. Atkins’ diet is a low carb, high fat and high protein diet. We discussed in this episode how it’s not well designed to put you in a state of ketosis, however it may work for some people – results depend on your metabolism. For Jimmy limiting protein is a requirement to put his metabolism in a state of ketosis.

Jimmy Moore & Livin La Vida Low Carb

Other People, Resources and Books

Full Interview Transcript

Transcript - Click Here to Read

[Damien Blenkinsopp]: Hey Jimmy, thank you very much for making time to come on the podcast today.

[Jimmy Moore]: Hey man, what’s going on, Damien?

[Damien Blenkinsopp]: It is going good. So I have been wanting to get you on because you have spoken to a lot of people about one specific topic. How long have you been working in the area of ketosis?

[Jimmy Moore]: Well, ketosis and low-carb diets – I have been doing this for about the past decade since I lost pretty famously 180 pounds on Atkins diet back in 2004. But really hot and heavy looking into ketosis and what we call nutritional ketosis in my new book probably since 2012.

[Damien Blenkinsopp]: Great, so you got into this and it was more focused on the low-carb approach and you weren’t really considering getting into ketosis and all of these aspects.

[Jimmy Moore]: Well, I assumed that being low-carb was ketosis when I first started this because a lot of Dr. Atkins’ teaching talked about ketogenic diets and getting into a state of ketosis. At the time i thought it was all predicated just on limiting your carbohydrates but I have since learned in my own testing on myself and then interviewing literally all the experts in the world on this topic that is just one element that it takes to get into a state of nutritional ketosis. There is really a whole lot more involved with it, which is why we wrote Keto Clarity.

[Damien Blenkinsopp]: Great, and I understand it is a very individual kind of thing that people weren’t expecting, especially ten years ago when you got started and so everyone is kind of saying if everyone will just follow the same diet plan it is all going to be fine and the same.

[Jimmy Moore]: How is that working for you? Not very well.

[Damien Blenkinsopp]: I find the same, that you kind of have to test yourself. This podcast is all about testing or making sure that you are doing whatever is right for your body so it is fantastic to have you on to talk about this topic. So how many people, just as a quick background, how many people have you interviewed on this topic over the years?

[Jimmy Moore]: On the specific topic of ketosis? Is that what you are asking?

[Damien Blenkinsopp]: Yeah, if you know a rough idea.

[Jimmy Moore]: We hit on ketosis here and there with different people. I would say at least a couple hundred of the almost 1,000 interviews that I have done, and at least a couple of hundred have shared some pretty good nuggets of truth that didn’t end up in my vernacular in thinking when it came to wanting to write a book about this. But yeah, I have interviewed literally 1,000 people on all kinds of topics over the years, not just ketosis. But obviously ketogenic diets are a huge passion of mine.

[Damien Blenkinsopp]: Yeah, so what are the benefits people are looking for? This is a very quick broadstroke, if one of the listeners at home hasn’t gotten into ketosis and why to do it, on one hand what are the benefits people are looking for when they are trying to get into the state of ketosis?

[Jimmy Moore]: Oh man, do you have all day? That is the great thing about this, Damien, is there is a lot of great science that we have, both solid, good, and emerging science that we have put in the back 16, 17, and 18 chapters that talk about all of the great health issues that can be improved with a ketogenic diet. But just for people that are wanting to maybe make their day-to-day quality of life better, check out this list of things that you have to look forward to if you get into a state of ketosis.

How about this? Natural hunger and appetite control, effortless weight loss and maintenance, mental clarity like you have never had before because your brain just loves ketone bodies, sounder sleep, normalized metabolism, your blood sugar gets stabilized, your insulin sensitivity is restored, inflammation levels, which we know is the real cause of heart disease as one of the themes that we talked about in my last book, Cholesterol Clarity. It is not high cholesterol that is causing heart disease, it really is inflammation and this diet lowers it. A feeling of happiness and general well-being.

Your blood pressure comes down, your HDL (good) cholesterol goes up, your triglycerides come down, you have less of those small, dense LDL particles. You can fast spontaneously between meals upwards of 12 to 24 hours because you just aren’t hungry. You use your stored body fat as fuel, you have energy beyond belief. I am in a ketogenic state and have lots of energy. Heartburn goes down, you improve your fertility and sex drive, it helps with traumatic brain injury, your immune system is improved – I could go on and on and on. But there are so many great benefits, even if you don’t have some dastardly disease just these day-to-day quality of life improvements that happen from a ketogenic diet make it all worth it.

[Damien Blenkinsopp]: Great, and you rattled out a whole bunch of markers when you were talking about this too so these are things people can then track. What are the main things, when you have been talking to either interviewers or you have been seeing with people you are consulting with, their numbers. What are the main things that you have kind of rattled out there that change quickly and maybe change over the long term in terms of markers?

[Jimmy Moore]: Yeah, oh my gosh – immediately when you start reducing carbohydrates and replacing those carbs with more fat and getting into a state of ketosis, let’s go to your cholesterol panel since I wrote a whole book about that one last year. Here are the things that are almost instantly going to happen within a couple of weeks to a couple of months. Your triglycerides will fall like a rock. You will see those go down below 100 and optimally under 70 and my personal level right now is in the 40s. Then your HDL cholesterol will respond very well to the increase in saturated and mono and saturated fats that you consume and those are the raw materials that help you make HDL cholesterol and it will go way up. Mine is currently around 80-something.

[Damien Blenkinsopp]: Wow.

[Jimmy Moore]: And then the small LDL particles, and these are the truly atherogenic particles of your LDL that will penetrate the arterial wall – a lot of people will be like, ‘What do you mean, LDL particles?’ Yeah, there is more than one LDL. LDL is not just one number, it is actually two major numbers. One is large, fluffy LDL particles which really are not atherogeneic and are benign when it comes to heart disease but it is those small, dense LDL particles that are the real problem and how do you get small, dense LDL particles?

It is two things. You have too many carbohydrates in your diet and that shifts your LDL to the small kind and you are consuming vegetable oils which pretty much leaves your body devoid of all of the large, fluffy – that’s why vegetable oils are promoted, because it does reduce your LDL cholesterol but it reduces all the good ones and leaves you will all the bad ones and then does this nice little thing called oxidation to those LDL particles, which makes them inflammatory, which we just said is the real cause in heart disease. So those are some blood markers that we see change immediately. Now, you might see your total cholesterol go up and you might see your LDL-C number go up, but those aren’t a big deal in the context of all these other numbers getting better.

Now, we mentioned inflammation. There is a great marker and if you haven’t had it run before this is one I love having run, because especially all these people that think my high cholesterol is going to kill me, I point to the HSCRP number, that is the C-reactive protein and is the key inflammatory marker in the body. If that number is below 1.0 you have nothing to worry about when it comes to inflammation and without that inflammation you can’t have heart disease. So i think my level when I last checked it was 0.55, which is really, really good.

Another one at home I think people could have run, and this is one when I did a whole year and I did an online experiment that I talked about in Keto Clarity of this nutritional ketosis. What i did was i quantifiably measured weight just because people think that’s interesting. I don’t but people do. Blood sugar levels and then blood ketone levels. So let’s go to blood sugar. Blood sugar is a huge marker of where you stand in your metabolic health. If you have got fasting blood glucose levels that are in the triple digits you need to get that under control and a ketogenic diet does that for in spades. Now, it doesn’t do it immediately in a lot of people. Some people say, ‘I have been eating low-carb, high-fat for a week. I have got great ketone levels but my blood sugar is still elevated.’ I am like, ‘Come on, you have got to give it a little bit of time but over time as blood ketone levels go up your blood sugar levels will come down.’ And they will even come down to levels that some might say are too low and we can talk about this in a minute if you want to, but when you have higher levels of blood ketones they step in the place of the blood sugars so you could have a lower blood sugar that would look like hypoglycemia to most medical doctors and yet you’re completely fine. And again, we can get into that in a second.

Then the last thing I wanted to mention was the blood ketones and this is kind of technology that has been out there. I had never heard of it before 2012 when I read the art and science of low carbohydrate performance by Dr. Stephen Phinney and Dr. Jeff Volek and he talked about measuring blood ketones. And I am like, ‘What’s that?’ The ketones are what you pee on a stick and you see a urine test and those are great and all for when you first start but when you want to see how you are doing in nutritional ketosis once you become keto-adapted and started using that fat for fuel. Then you need to be testing for blood ketones. I did that for a whole year and it is exactly like a glucometer. It takes a little bit more blood than a glucometer, and yes I prick my finger every morning and night. That is probably no strange thing for your listeners to do that, and sometimes I did it every hour on the hour all day long.

[Damien Blenkinsopp]: There are a couple of things you mentioned in there that I just wanted to clarify. First of all, you were talking about the LDL and the particle size. Is that the LDL-A test? Could you specify because I know that most people are going to walk into their doctors or most labs and get a straightforward LDL test and what you are given even when you ask for it, you have to really know what you are asking for in these cases because you are going to get the standard, which isn’t what we are looking for here.

[Jimmy Moore]: Yeah, the test that you mentioned, I am not familiar with it. Is there a name for that test or is it just called the LDL-A test?

[Damien Blenkinsopp]: Well I know on my one that [inaudible 00:13:28] chart, they have LDL bracket A.

[Jimmy Moore]: Oh, Wellness FX. That is what I was getting at. Where are you running that, dude? No, where are you located?

[Damien Blenkinsopp]: I am in Spain right now.

[Jimmy Moore]: So in America you can actually run a test that will test for the particles and you can actually go to your doctor and ask for the particle size test – even Dr. Oz did a big show on this asking patients to go to their doctor and asking for the particle size tests. But there are so major ones that are out there that measure for the particle size. There is one I am not a big fan of but I know people love because it does show you the breakdown of the particles. It is called the VAP test. But there is another one that I am a big fan of because it shows you the number of particles that you have in your LDL and then it gives you the breakdown and it specifically gives you a number of the small, dense LDL particles. That test is called the NMR lipoprofile test and it is run in Raleigh, NC. And they are basically the only lab in the whole world that does this specific test. And again they will spit out the total number of LDL particles that you have and then the small ones. And again the way you get more small is you eat more carbohydrates and you consume vegetable oils.

If you do those two things you are going to have a lot more small. So that is why a low-carb, high-fat of saturated and monounsaturated fats, a ketogenic diet helps with that because it helps to eliminate and greatly bring down the number of small LDL particles but the way you test for it – I am not sure how you can do it overseas but in America you have got the VAP test, you have got the NMR profile test and there is one other that is kind of coming on in the recent years called the HDL labs test, which also shows you your particle size breakdown.

[Damien Blenkinsopp]: Great. So with those people can get a much clearer idea and they can order that test from any doctor, like the ones that you were talking about with One Lab.

[Jimmy Moore]: Yeah, literally any doctor in America that uses Lab Corp, which is what every doctor uses, they can run it. They can run this test but they may give you pushback. That is kind of the frustrating part about all of this, patients are trying to do the right thing to get the tests run and to see where they stand, see how they are doing in their health. And yet doctors are like, ‘Whoa, that is unnecessary because you don’t have a family history of heart disease and that is only for the people with the greatest risk.’ But then they will turn right around and say, ‘Oh, you’re total cholesterol is 230 so that is way too high and we need to put you on a statin drug.’ And that is when I would push back as a patient and say, ‘Wait, I want to have this run because this will tell me whether my LDL cholesterol is really the bad kind or if I am okay despite having a higher level of total cholesterol.’

[Damien Blenkinsopp]: The other test I wanted to just touch on that you mentioned was the glucometer, your blood sugar. You didn’t talk about the context and I know this can vary a lot. So are you talking about fasting blood sugar there?

[Jimmy Moore]: When you do a blood sugar reading it almost always needs to be in a fasted state – and we can talk about postprandial state, but when we are talking about where you are in your blood sugar, when you wake up in the morning after an overnight fast and you haven’t eaten all night, your morning blood sugar reading should be pretty steady in the 80s. That is a normal reading, definitely below 92 and you’re going to be okay.

Now, we can talk about post-prandial and how it should be after you eat something, but you test it fasting and then you can test for a couple of hours every 30 minutes after you eat – at the one-hour mark you definitely should not be over 140 and after the two-hour mark you should be back to baseline. So if you started at 85, two hours later you should be pretty darn close to 85. If you’re not, guess what? You probably ate too many carbohydrates or maybe just a tad too much protein in that meal with just keeping your blood sugar elevated. Fat is benign when it comes to your blood sugar and it will not raise your blood sugar unless you are gorging yourselff on it. Then that gorging will extend the gut and make your insulin and blood sugar go crazy. But if you are eating normal amounts of those things it should not impact it at all.

[Damien Blenkinsopp]: Great, and the other one I don’t think you mentioned is HBA1C – is that something you look at too?

[Jimmy Moore]: Yeah, I did not mention that one but that is an ancillary one to the blood sugar one we were just talking about, absolutely that is a great marker. Most medical doctors say, ‘Well, get it below 6.’ And I am going, ‘5.9 is still severe insulin resistance.’ Why don’t we aim for a much better one of how about below 5.0? I had mine measured in the midst of my nutritional ketosis experiment and i came in at 4.3, which is really good.

[Damien Blenkinsopp]: Yeah that is really. My understanding is that some of these tests can have confounders because when you change to a low-carb diet, like some of them will change. I think HBA1C is one of them where your red blood cells will start living longer so the values don’t kind of matchup. Some of these tests have confounders. Are there a lot of these tests that have confounders that you have to watch for and maybe it takes longer – like you were saying there is a longer period that you need to look at it. Or is it just a few of them?

[Jimmy Moore]: I think it is just smart to remember all of these tests are simply tools. don’t rely on them as gospel truth. I get well over 500 emails a day and people write to me and say, ‘Oh I just went to my doctor and I got this one test and it said this. And so now the doctors want to put me on some medication or have some surgery,’ and I am going, ‘One test, really? How about you ask for a few more months and run that same darn test again.’ Why are we making treatment based on one test that could be flawed?

[Damien Blenkinsopp]: In terms of flawed to you mean not accurate, a bad reading?

[Jimmy Moore]: It could be a very bad reason and yet they want to make changes. I will give you a hard example of this. My wife, Christine went to see her general practitioner in November last year and her total cholesterol came in at 240, which they think is high – anything over 200 is high. The doctor said, well – and he knows better than to bring up the statin drug thing to me. So i was sitting in there and he said, ‘Christine, I think you need to cut your saturated fat.’ Because he thought that was what it was going to take to improve her numbers and she said, ‘No, I am going to keep eating saturated fat.

That is what helped me to get these numbers to begin with.’ She had great HDL, incredibly triglycerides numbers, and lower inflammation than she would if she was eating a standard American diet. so she said no. And he had read my book Cholesterol Clarity and he said, ‘Well, maybe Jimmy can fix your numbers.’ Challenge accepted.

So I go home and guess what we do, Damien? I don’t cut her saturated fat. We doubled her saturated fat. So whatever she was eating before, I had her eat twice as much saturated fat and we went back for the six-month checkup, her total cholesterol? 200. It had gone down by 40 points and it was all in the LDL. So what she did was she shifted the small, dense LDL particles over to more of the large, fluffy LDL particles and her HDL stayed the same, her triglycerides stayed the same, and don’t you know he didn’t say a damn thing about it.

[Damien Blenkinsopp]: Yeah, that’s amazing. there are tons of stories. And you made some important points about the tests here. Now, you have just given us a whole slew of tests and I am sure for some people that is a real maze. How do you typically suggest – when someone is coming and saying they are thinking of doing a low-carb or ketogenic diet, what is the obvious place to test in order to understand if it –

[Jimmy Moore]: If it is working?

[Damien Blenkinsopp]: So that they know they are getting the benefits they want. Are there the main areas like – my concern is diabetes, my concern is – I don’t know, the top three concerns and there are a couple of tests for each one that they should focus on or something like that?

[Jimmy Moore]: I think what everybody should pay attention to, probably more than anything else, is that blood sugar level. If your blood sugar is elevated, regardless of what you think your current state of health is, you should know your blood sugar level and it is not just for people with diabetes. This is one that frustrates me, Damien, and maybe our next book will be Blood Sugar Clarity, because I think people are confused about what do you mean, I have to test my blood sugar? I am not diabetic.

People think it is all about diabetes but it is not. Having a normalized blood sugar level is a sign of great metabolic health. So getting that blood sugar level down and by extension your insulin levels down, unfortunately you can’t test your insulin at home but you can test your blood sugar all day, every day. Test, test, test and see where you stand in that blood sugar.

That is a great marker to know where you stand in your metabolic health. So that is one that absolutely everybody should go down to their pharmacy, pick up a glucometer and start testing your blood sugar to see where you are. If it is in that 80s range when you wake up in the morning, great. If not then you need to start making some tweaks to your diet and supplementation and there are things that we have talked about actually in Keto Clarity that can help with that because that is a biggie.

[Damien Blenkinsopp]: So is it between 70 and 90, is that what they are kind of aiming for?

[Jimmy Moore]: Yeah, 70 to 90 is probably pretty good but in the context of Keto, which I was alluding to earlier, sometimes it might even go lower than 70 and it doesn’t mean that you are outside the range within context if you have higher levels of blood ketones, you could have lower levels of blood sugar because the ketones kind of step into the place of where that blood sugar would be. So I wouldn’t even put it in that low range of 70 to 90 because it could be below 70 and still be normal.

[Damien Blenkinsopp]: So you really need to focus on not having over 90 and that is more the emphasis?

[Jimmy Moore]: Yeah, that is probably a good thing to shoot for. Now, postprandial, after you have eaten something it will go up somewhat. I will have a breakfast of eggs cooked in some butter and some sausage and my blood sugar will be 85 before and then after an hour it might have gone up to like 95. Then by the end of two hours it is back to 85 or 86. That’s perfect.

[Damien Blenkinsopp]: Great. So, you have been doing this for a long time. Now, take someone who has still been eating donuts and stuff – because I guess you never eat donuts these days.

[Jimmy Moore]: No, not unless they are made of bacon.

[Damien Blenkinsopp]: Do you know what would happen to your numbers if you had a donut. You gave us an example where it shoots up really high still, or obviously maybe you don’t know but do you have an idea of what would happen now? Would it be the same as it was 10 years ago?

[Jimmy Moore]: I have no idea. That might be a fun N=1 experiment although I wouldn’t look forward to eating a donut. My wife might like that. But to be honest I have no idea. I would assume that because I had this problem before where that would spike my blood sugar that it would still act the same way now. I don’t want the way I would feel after eating that. Forget what happens to blood sugar, I don’t want to feel like crap and I definitely would eating that, just based on past experience.

[Damien Blenkinsopp]: Great, so if everyone focused on the blood sugar that is a pretty good area to focus on no matter where you are coming from for this ketogenic diet?

[Jimmy Moore]: Yes, correct. And I think that one we mentioned earlier about the CRP level, that HSCRP. Everybody needs to know your level of inflammation. If you are above 2.0 on that, you probably need to do something to bring down the inflammation in your life and for a lot of people it is those processed and refined carbohydrates that are primarily doing that and even the so-called healthy whole grains are also causing that inflammation to go up, and the vegetable oils. Eliminating those from your diet, your inflammation should come way down and you can see that in your HSCRP.

Now, there is more that impacts that inflammation than just those two food items. If you are highly stressed that is also going to show up on your HSCRP so run that number. Optimally you want it under 1.0 and definitely under 2.0 and anything above that shows that you have problems. And that is an easy test to run too. I think it is like 60 bucks if you run it on your own or your doctor can run it for you.

[Damien Blenkinsopp]: Right, I am glad you brought up that test because that is the test I have been running for the longest, probably about since 2004 or something, when I first learned about it. And it is has been interesting to see how mine has changed over time. I think mine is 0.1 these days and sometimes it is 0.0 or something. It depends on the lab because I don’t think all the labs actually have the high sensitivity to the actual [inaudible 00:26:21] like less than 0.1.

[Jimmy Moore]: Yeah, you definitely need to have the HSCRP.

[Damien Blenkinsopp]: Yeah, and that is the point I wanted to make because there are a lot of the CRP tests still out there and maybe not so much in the US. I haven’t had so many problems when I test in the US, but when I test abroad they will sometimes give the C-reactive protein, which only measures down to 1 so you don’t have any idea of how good you are or if you are doing well. You can just say, ‘Oh, I am doing bad because I am over 1,’ which isn’t that helpful.

[Jimmy Moore]: Now, you mentioned you wanted a third test. And the third one I think besides blood sugar and CRP is absolutely your triglycerides. If your triglycerides are over 100 and we mentioned this in Keto Clarity, if your triglycerides are over 100, that means you are eating too many carbohydrates in your diet. So that is one way you can figure out how sensitive you are to carbohydrates, by looking at that triglycerides number. Get it below 100 and you’re in nirvana.

That’s where you want to be, optimally under 70 but definitely under 100. Your doctor might say, ‘Well, 140, oh that’s normal,’ and he won’t even bat an eye. But 140 is, again, showing signs of insulin resistance. So you have got to get that number down, down, down and the way you do that is cut the carbs. So that is a great trifecta of tests where if you wanted to kind of track your progress to see how you are doing in your whole health, those three are probably the standard bearers.

[Damien Blenkinsopp]: Great, thank you for clearing that up. That makes it a lot simpler to follow. So we’re trying to get into ketosis. And the people will say that you are becoming a fat burner and I think that can be a little bit confusing for some people. They say a sugar burner, a fat burner, and this is some of the terminology that is used. Is that what is actually happening in your body? How do you look at the mechanism for this when you start eating less carbs and you start increasing the fat? What is going on in your body here, the main metabolic change? What is happening here?

[Jimmy Moore]: Yeah, I think it is a great imagery for people to realize that the body can be fueled by fat. That is going to be a new concept to a lot of people because if you ask people what is it that fuels the body most people are going to say that you drink Gatorade and that replenishes your body with electrolytes and gives you energy, blah, blah, blah, and that is when you are a sugar burner. So I think it is easy for people to understand that a lot of people are sugar burners. But when we start talking ketosis we want to change the terminology to make people realize sugar is not the only way you can fuel your body. So saying that you’re a fat burner kind of gives it – and yes it is very layman’s terms and that is kind of my style of writing and my style of educating, to make it a little simpler.

But here is what happens – you are shifting your body from using glucose as the primary fuel source over t using fat as the primary fuel source. So when you cut off the carbohydrate content of your diet and limit that so that you are not raising your blood glucose levels and then you are limiting your protein and we can talk about why you do that here in a minute. But you limit your protein also so that you are limiting the glucose effect and then you are eating more fat and the body has to do something. It has to switch from being a sugar burner to one that burns fat and then the resulting ketone bodies that come from that as fuel. So yeah, I think it is a great way for people to understand that sugar is not the only way to feed your body and fuel your body, you actually can make that switch over to being mostly a fat burner.

[Damien Blenkinsopp]: So are you saying that any fat we eat will turn into ketones that we are going to burn? Or is it a bit more complicated, like you are saying?

[Jimmy Moore]: Certainly you want to try to find the best quality fats and you can certainly drink vegetable oils and produce ketones. I wouldn’t recommend that, by the way, if you want to keep your inflammation levels down. So yeah, I mean, they are the raw materials by which ketones are made. So cutting your carbs is definitely a huge must and we talked about this at the very beginning. I used to think just because I cut my carbs on my Atkins diet that it was producing ketones.

Well, that is only one thing that you do. You cut carbs to your personal tolerance level, you moderate down the proteins to your individualized protein threshold and we can talk about that if you want. And then you eat fat to satiety, the saturated and monounsaturated fats that are primarily what we are talking about. Of course, the omega-3 fats are in there as well. And when you do that those things are the raw materials that make switch over from sugar burner to fat burner and it is that burning of fat that results in the production of ketones.

[Damien Blenkinsopp]: Okay, and then you can test for ketone levels to see if you are actually in the fat-burning mode or not. Is that the idea?

[Jimmy Moore]: Absolutely. And currently there are three different ways that you could measure for ketone levels – one that I really hate, one that is the gold standard, and one that is the future of testing. So do you want to talk about that?

[Damien Blenkinsopp]: Yeah. First of all, you kept on bringing up the confounder of the proteins so I would like to kind of get that out of the way before we jump into that.

[Jimmy Moore]: There is so much to say.

[Damien Blenkinsopp]: Right, there are a lot of confounders, basically. It is not easy stuff. So if I am eating a ton of protein every day what is happening? Why is that not going to put me in ketosis?

[Jimmy Moore]: Yeah, this is the big confounder and this is probably arguably the biggest mistake people have been making in their low-carb diet when they say, ‘Well, I have tried that low-carb thing and my blood sugar never came down and I gained weight and I could never get my hunger under control and blah, blah, blah.’ This is why. When you consume protein in excess there is this real long G-word that we talk about in Keto Clarity called gluconeogenesis. Now, don’t let that long word scare you. All it means is when you consume more protein than your body can use the liver has to convert that protein into sugar. SO while that is not a one-for-one thing like you would be eating carbohydrates and raising your blood sugar, it is still producing sugar in the body and when there is glucose present, sugar present in the blood, guess what that does to ketone levels? It kills them.

They are gone. And so that is why moderating down on the protein is so critical. Don’t fall for the media headlines that say that low-carb, high-protein diet – now. It is a low-carb, moderated protein to your individualized threshold level, high-fat diet and that is what will get you into ketosis. People eat chicken breasts every day, Damien, and they are like, ‘It’s low-carb.’ Yeah, it is low-carb but it is loaded with a lot of protein and that is not a health food. Even if you drench it in butter in the pan it is still giving you a huge, big bolus of protein. Moderate down the protein and either use less of it or choose the fattiest cuts of it.

[Damien Blenkinsopp]: That’s great, so that is one mechanism. Is that very individual, like the carbs? Do people have different protein tolerances as well?

[Jimmy Moore]: Absolutely. And think about it this way. If you are really sensitive to carbohydrates like I am – I used to weight 400-plus pounds, so I have a little bit of a problem with carbohydrates. I have often joked that I have already eaten all the carbs that I am allowed to have my entire life in the first 32 years of my life so I have to keep them low the rest of my life. That is probably not true, but anyway – yeah, if you are sensitive to carbohydrates you are going to be sensitive to the protein as well because of that gluconeogenesis.

When you have a low sensitivity to carbs it means your body very quickly starts making this glucose and wants to become a sugar burner again. So that will happen with the protein if you start eating it in excess and having a chicken breast, blah, blah. Then that is going to convert to sugar and very quickly your body will be like, ooh, you are giving us glucose. Let’s use that for energy and it will get away from being a fat burner, which is counterproductive for what you are trying to do with being in a state of ketosis.

[Damien Blenkinsopp]: Great, so the other mechanism I just wanted to look at before we look at how you measure ketosis and know that you are actually getting into this state. People talk about also taking fats to push you into ketosis, so actually consuming more. People talk about this in the context of taking some MCT oil or some other specific fats. Could you talk a little bit about how that works? If I am eating some regular diet in the morning and then maybe I test and I am not in ketosis and I have some fats, how does that work?

[Jimmy Moore]: There are definitely supplements out there that you can take that will temporarily boost your ketone levels. So you mentioned one of them, MCT oil, Medium Chain Triglycerides. These are readily made into ketone bodies. So if you take some of this, and be careful not to take too much of it because it will give you a stomach upset in excess but if you take some MCT oil within like 30 minutes you can test your blood ketones and you are going to have really high levels of ketones. You might think, wow, this is easy, why am I cutting my carbs? The only problem with that is it temporarily raises blood ketone levels. It is just a transient thing. So it could be helpful for people that are using it for – I know some athletes that get into ketosis and like to be fat burners and use ketones for fuel.

This is a great thing for an athlete to use maybe before an athletic performance. It is great to do that. Or if they are doing it for therapeutic purposes, let’s say you are an Alzheimer’s patient and you are trying to get more ketones in there for the therapeutic effects from that I think MCT oil is a perfect thing for people like that. But for the average, everyday person that is probably listening to your podcast right now it is best to do it nutritionally by getting your carbs to that personal tolerance level, moderating down that protein like we just talked about, and eating more real food-based fats like butter, coconut oil, lard, full-fat meats and cheeses, cream, and that kind of thing. That is going to give you the therapeutic effects fo real nutritional ketosis without artificially raising them with these supplements.

[Damien Blenkinsopp]: And the idea behind that is that you are saying it is temporary and it is not going to last very long whereas –

[Jimmy Moore]: Very transient, yeah. It doesn’t give you a true, accurate picture.

[Damien Blenkinsopp]: Are you aiming to stay in ketosis the most amount of time or are you aiming for the highest levels? Or is it a combination of both. Maybe this hasn’t been discovered yet but what is the ideal that we should be aiming for?

[Jimmy Moore]: There really aren’t any studies that have been done on a long term of doing this. I try to stay in it all the time because I feel best when I am in a state of nutritional ketosis pretty much as much as I can. It is very easy because of my tolerance levels being so low. It is easy for me to be out of it so I don’t want to be out of it. So I have to work really hard to make sure that I am in it. Now, you asked about trying to get levels higher and higher. Your goal is not necessarily super, duper high. Optimally what you are trying to do is get over 1.0 on that blood ketone monitor and if you’re over 1.0 that is the level that I feel the most benefit starting to really kick in.

Now, Volek and Phinny in their book talked about between 0.5 and 3.0 kind of being the range, but I found anything over 1.0 probably is going to give you the most therapeutic bang for your buck and I didn’t really see any reason to go too much over 2.0. Now, you can go over 2.0 and I have – in fact, the highest reading I ever had was 6.7 on the blood ketone monitor. My blood sugar at the time was 62 and I felt completely fine. But the goal is not necessarily higher or being better, just steady within a good range of somewhere between 1 to 3.

[Damien Blenkinsopp]: Right. As with most things it is probably some kind of U-curve where you get benefits in a certain area but if you are going to push it to crazy heights something else could go wrong that we don’t understand yet.

[Jimmy Moore]: And there is no need to do that if you don’t have to. The only thing I can think of is if you get your levels to higher amounts like that it gives you a little more wiggle room to maybe have a few more carbohydrates or a few more grains of protein than you otherwise would because it is going to knock it down a little bit and that may not be a bad thing.

[Damien Blenkinsopp]: Right, so it is literally like a ratio in your blood when there is more ketones it is hard for the blood sugar to get raised.

[Jimmy Moore]: Correct.

[Damien Blenkinsopp]: I guess this is what people are sometimes are using the MCT as well to help them along, great.

[Jimmy Moore]: Yeah, and unfortunately the MCT oil doesn’t necessarily bring down the blood sugar though because people are like, ‘Well, my ketones are 4.5 and yet my blood sugar is 105.’ And I am like, ‘Well, did you take MCT oil?’ They are like, ‘Of course.’ And I am like, ‘Well, of course your body hasn’t really adapted to using those ketones and making those ketones, and you just basically infused ketones into your body. That doesn’t mean that your blood sugar levels are going to just automatically come down.’ That is why I believe doing it nutritionally is going to give you the best benefits because you will eventually see that blood sugar go down as you nutritionally raise your blood ketones.

[Damien Blenkinsopp]: Right, so what you are saying is you have to get the blood sugar down because that is causing damage and that is a negative. And until you get rid of the negative you are not going to get all of these benefits, although you might feel a bit better if you have got more ketones running in terms of energy.

[Jimmy Moore]: And I think it takes time in a lot of people. When I first started doing this I had been low-carb for a while but not purposely ketogenic so during my experiment, that year that I did the experiment, it took probably three to four months before my blood sugar came to a level where it was naturally in the 80s range in the fasted state. It took some time to be able to get that under control and that is okay. I think that is part of the healing process.

[Damien Blenkinsopp]: Yeah, nothing is going to be achieved in one day, especially if you have been going for 20 years.

[Jimmy Moore]: Exactly.

[Damien Blenkinsopp]: Okay great, so I understand that it is a little bit complicated and there are a few different measures with different accuracy and that is one of the things you go through in Keto Clarity trying to get to the bottom of it. First of all it would be great to have a bit of background on what you achieved now – like, do you know how much time you spend in ketosis? Do you see that as the most important – 90% of the time when you test are you in ketosis? And when you slip out what is the kind of standard after you been on a ketogenic diet for like a year, or I think it is three months, is it relatively easy to be in that zone for 90% of the time?

[Jimmy Moore]: Yeah, people ask that question all the time – oh my gosh, if i have one carb-based meal is it going to knock me out of ketosis and I have to go through this all over again? One thing I have found, Damien, is that once you are in ketosis and then you have some indiscretion that knocks you out of it you can get back into it really quick. So I know that sometimes I will be in a situation where maybe I have a little more protein than I typically do and that will completely kill the ketones. Well, it takes about two to three days and I am right back into ketosis again.

So no, it doesn’t take long. I think that initial period where people try to get adapted is going to depend on their carb intake before starting. So when I started this I was already pretty low-carb, having been low-carb for a long time and just not ketogenic. So all I did was up the fat more and moderate the protein and within four days I was in nutritional ketosis. For somebody like the old Jimmy MOore who used to eat 16 cans of Coca-Cola a day and two boxes of Little Debbie snack cakes a day and was a carbohydrate-addicted mess, that man might take two or three months before he got into a state of ketosis because his body would have to deal with all that first. So yeah, I think it is going to depend very highly on the individual.

[Damien Blenkinsopp]: All right, great. So why should we test for ketosis? We just spoke about the important thing as reducing the blood sugar to make sure that is in line. Why do you see it as important also to test for ketosis?

[Jimmy Moore]: You are flying blind if you don’t. You will have assumed, like Jimmy Moore did in 2012, where I thought I was being ketogenic simply because my carbs were low. You can’t assume anything. You have to test to know where you stand so when I tested that first time, Damien, and I pricked my finger and got the blood reading that said 0.3 and Volek and Phinney said it needed to be between 0.5 and 3.0, I went, ‘Ah, crap.’ Now I see why I am having some issues going on here so without testing you are just simply guessing whether you are actually in ketosis or not. Now, you can be super, duper strict in your carbohydrates and get your protein down to some arbitrary number and eating more fat and probably most people that would make them ketogenic but unless you are testing, you have no earthly idea.

And when you first start there is probably – the easiest way when you first start, only for the first couple of weeks – I think if you want to see where you are in your ketosis go buy those urine strips. They are called keto sticks and they are about $15 for a little thing of 50 of them and you can actually test to see how you’re doing spilling a ketone body that is known as acetoacetate. So you measure for that acetoacetate and it will turn pink to purple on the pee stick and if you show any color change then you are producing ketones. So that is a great kind of reinforcement for a lot of people when they first get started. Unfortunately, they don’t always stay in the urine.

So that acetoacetate actually gets converted over into the blood ketone body and that one is called – that ketone is called beta hydroxybutyrate. And so that is the one that is free flowing in the body and when we say your body is running on ketones that is the one we are talking about, beta hydroxybutyrate. So measuring directly for that with the ketone meter – one that I love that I think is just the best one in the whole world is called precision extra. Now, the strips are extremely expensive and we talk about this in the book, how you can get them on the cheap and where to get them, but man oh man, that gives you great information.

[Damien Blenkinsopp]: What kind of price are we talking, just to give people a rough –

[Jimmy Moore]: The meter itself is about $15 to $20 but the strips in the States can cost as much as $3 to $5 apiece.

[Damien Blenkinsopp]: And how many do you use? You said before you were testing every morning and every evening.

[Jimmy Moore]: Yeah, during my experiment I tested morning and evening and sometimes every hour on the hour. So yes, it got quite expensive and I will tell you about a cheaper alternative that may be pretty good here in a second. But you can go to Google and type in ‘Canadian Pharmacy.’ And some of those Canadian pharmacies have the strips for about $2 apiece. I did see down in Australia they sell them very cheaply but there is no online place for people to buy them. I think they are like $0.70 apiece there.

[Damien Blenkinsopp]: And just to be clear you use one strip every time. So you are saying it is $2 a piece, that is pretty expensive and it is going to add up quickly.

[Jimmy Moore]: But if you are a quantified selfer and you want to see where you are going with this, that is worth it. And keep in mind you are not doing this forever. I think if you did it for a morning and night for two to three weeks just to see what it takes I think after a while you kind of know and you can kind of feel okay, I am in a state of ketosis or not.

[Damien Blenkinsopp]: That is an interesting point. Are you able now to associate with the way you are feeling or certain aspects of your being now that you have been measuring for a while?

[Jimmy Moore]: Yeah, let me answer the ketone story and then I will answer that one. So that is blood and I think blood is probably still the very best way that you can test. The third ketone body, though, this is the one that is coming in the future and it is called acetone. It is the one in the breath and that is the ketone body in the breath. They are actually coming out with these things that you can blow into so people are a little squeamish about pricking their finger and you can just blow into these devices and it will give you your ketone reading of acetone.

Now, acetone unlike acetoacetate which gets converted over to beta hydroxybutyrate and some people lose acetone on the urine, breath ketones actually correlate pretty darn well and a couple of good studies with the beta hydroxybutyrate levels in the blood. So if you are testing for breath it is not a one-for-one thing because all these ketone bodies have different mechanisms and different times that they are operating in the body but it is pretty close and people that don’t like the prick, it is good, and it is less expensive. Right now there is one meter on the market called Ketonix – this guy with epilepsy in Sweden that developed this and it is pretty darn close.

I actually tested it side by side with blood ketones and urine ketones for about six or eight months. And I found for about 80% of the time the Ketonix was spot on. Now, I did find that it was much more accurate in the morning after an overnight fast. Don’t eat or drink anything within four hours of blowing into it because apparently drinking and eating washes out some of the breath ketones out of the mouth. So you want to make sure that you are not skewing the results by eating or drinking but that is technology that is definitely developing and there are a lot more companies that are working on meters.

[Damien Blenkinsopp]: Are there slips with that? Are there variable costs involved or is it the one-off meter cost and you can use that indefinitely.

[Jimmy Moore]: The Ketonix one is a little device that you just blow into and yeah, you can blow into it thousands of times so it is not a one-off. Some of the ones that I know are in development are disposable but they are a lot more accurate apparently. We will know when they come out.

[Damien Blenkinsopp]: Yeah, are these coming out really quickly? Are you expecting over the next year a lot of different ones to come out?

[Jimmy Moore]: Well, so the one that I am aware of in Arizona is a company called InVoid Technologies and they are actually going through the FDA approval process right now and as soon as the FDA gives them the go ahead they will be ready to roll. They are hoping by this fall and I know Japanese researchers are working on an iPhone app that would be this apparatus that you plug into your iPhone and then you blow into it and it gives you a reading on your iPhone. So I don’t know when that one will be developed but I know in the next couple of years we are going to be seeing a lot more acetone readers come on the market.

[Damien Blenkinsopp]: That’s great news because a lot of people don’t like the finger pricking all the time and the pretty high cost. I don’t the glucometer all that much because of that. One thing I wanted to clear up for the audience is that you have got the ketones coming out of your breath and out of your urine – is this your body throwing these away? So we are using the proxies of something that is throwing away and it is why it is not working over time in the urine? What is the mechanism here? Ideally we definitely want to know what the blood level is because that’s the end result.

[Jimmy Moore]: Right, and so when you are using ketones in your body yeah, absolutely that is a great point. I am really glad you brought that up. When you are spilling them over into your urine, that is what the body is kind of saying okay, we don’t need these, and it is getting rid of them. So it is very transient and that is why that acetoacetate is getting converted into beta hydroxybutyrate after a while you don’t see the acetoacetate anymore because the ketones have made that shift.

You have gone from sugar burner to fat burner. When you are still making that transition the body is like, ‘Oh, it is giving me what I want to be able to convert these ketones in the urine and acetoacetate over to beta hydroxybutyrate in the blood.’ So yeah, absolutely they are a waste product but it is a transitionary type of thing.

[Damien Blenkinsopp]: So that sounds like a positive thing. If your urine stops producing these it actually means that you have adapted metabolically to burning ketones properly?

[Jimmy Moore]: That is exactly right and that is why testing blood is so critical because you could pee on a urine stick and see no ketones. That can mean one of two things – one very bad thing or one very good thing. The very bad thing is you are still not in ketosis and you are not making ketones in the blood or you are in great ketosis and you have become fully keto-adapted and you have now shifted all of your acetoacetate over into beta hydroxybutyrate and that is a very good thing.

Now, the problem with this Damien is it only happens in some people. Others, myself included, show ketones on the pee sticks basically all the time. I don’t ever not show it. So I am one of those people who shows both acetoacetate in the urine and blood ketones and that is okay too. I think it is more important to know what your level of ketones are in the blood because that is the one that actually matters.

[Damien Blenkinsopp]: Is that exactly the same measure? Like, you gave us the 1.0 reference there. Do they give you the correlated or do they give you another measure that you then have to kind of map?

[Jimmy Moore]: Unfortunately it doesn’t work that way because it is not the same ketone body. There is just a correlation there so when they have done the studies they showed that when your level of blood ketones are at a certain level the acetoacetate is also at a corresponding level. Unfortunately those levels aren’t spot on perfect but they are pretty darn close and from a cost-effectiveness I would rather blow into this device that costs $100 a be kind of close 80% of the time than to necessarily break the bank testing blood. But if you can afford it definitely do the blood more than anything.

[Damien Blenkinsopp]: Yeah, so it sounds like the testing strategy would be like as soon as you want to do this for the first month you can probably do the urine one without any concern or do some people adapt quickly?

[Jimmy Moore]: My strategy would be yeah, use the urine test for the first week and see if you are even producing ketones and if you start to see color change on there then go grab you a blood ketone monitor. Then if you want to do it on the cheap you can use 8 total strips within a month and here is how you do it. Sometime during the week measure in the morning, so when you wake up in the morning before you drink or eat or do anything – well, you can go to the bathroom but before you do anything that you would ingest, prick your finger and see what your blood ketone level is. It is probably going to be lowest in the morning, highest in the evening, but test that one time in the morning and sometime during the week. So let’s say you choose Tuesday morning to test, so test it and write that down.

Then some other time during the week test at night. So let’s say you choose Saturday night, so you do a test on Saturday night at night at least four hours after eating or drinking anything and test and see it again and that number should be higher at night than it was in the morning. It is not always true with everybody but that is the general correlation. And then do the same thing again the next week, the next week, and the next week. So over a month period you get to see the trend of how you are doing in the morning, how you are doing in the evening, and over time you will be able to see how you are doing in your state of nutritional ketosis. That is 8 strips and even if you paid $4 a piece for those that is still about $32, not as bad as pricking your finger every single day morning and night and breaking the bank.

[Damien Blenkinsopp]: Great, thank you so much for that. It is very valuable. Then would you move over to –

[Jimmy Moore]: Acetone in the breath, yeah, as a maintenance strategy once you kind of get going with this blood ketone thing for a while and you are like me and you can kind of sense where you are, I can almost within a few tenths of a [inaudible 00:53:35] pretty much tell you what my level of ketosis is on a blood ketone meter now, just by how I feel.

[Damien Blenkinsopp]: In terms of that feeling, what is it? Is it like an energy feeling? Or is it something else?

[Jimmy Moore]: Well the energy you are going to have being in a state of ketosis. That definitely is a big one, the mental clarity, the hunger control. That is a big one. But I am talking about just kind of intangible type of feelings like in my mouth. When I wake up in the morning I can almost tell just by – it is not really a film or anything but just kind of the feeling on my tongue and I can just feel that I have got a lot of ketones going on. And it is a beautiful thing and I have been doing this a while, Damien. It is kind of cool that I really have to prick, but then I do prick my finger and it is 1.4, and I am going wow, okay yeah. I felt it right.

[Damien Blenkinsopp]: I was interested if you have looked into fasting and intermittent fasting and any kind of impacts that has on ketosis?

[Jimmy Moore]: Yeah, we did a whole chapter on just this topic in Keto Clarity because it is the other F-word because people don’t like the word fasting and yet this is one thing that I have found doesn’t have to be forced. In fact when I first started doing my testing my wife Christine looked over at me one day and she said, ‘When is the last time you ate?’ So I looked up at the clock and I noticed it had been 24 hours since my last meal. And I went, ‘Oh, it was yesterday. I guess I could eat something.’ You totally forget to eat because is it is so satisfying and the hunger is under control.

So I have never been a fan of intermittent fasting before I started doing this nutritional ketosis thing but what I found is if you allow your body to do it naturally in response to your satiety signals, being under control, not having hunger to me, Damien, is a great sign of metabolic health. I think if you are doing it naturally, don’t starve yourself. People say, ‘I could never do intermittent fasting because I don’t like being hungry.’ It’s not about being hungry. It’s about allowing your body to kind of basically use your fat for fuel. So you do that by allowing your body to eat the fat that is on your body and the way you do that is not giving it more energy to deal with in the interim. So that is why intermittent fasting is so incredibly important.

[Damien Blenkinsopp]: Have you seen anything interesting from the measurements of the ketosis when you were fasting? Is there any difference that you see or in typical scenarios of fasting which compares to when you are eating fats on a typical diet?

[Jimmy Moore]: Yeah, one thing you will see is that is a great way to raise your ketone levels. The reason why is people are eating so often because they are just eating by the clock. So it is 7 o’clock in the morning, oh, it is breakfast time, so they eat. And then noon comes around and oh it is noon, so it is lunch time. So then they eat. And then supper comes at 5:30 or 6 o’clock and it is supper time, so they eat.

So they are constantly eating and they are never allowing their body to really tap into those energy stores that are on their body – even if you are eating low-carb, high-fat, you need to give your body some of those times between the meals to be able to make the ketones and utilize the ketones and one thing to remember is if you are getting hungry that quick after eating, so like you ate at 7 and the you have to eat again at noon, five hours later, you didn’t eat enough fat or enough fat in that earlier meal. So try bumping up the fat and making sure the carbs and protein are where they need to be but try bumping up the fat earlier in that meal or earlier in that day and then maybe skip that lean meal and then eat again at 6 o’clock. Now that is a great sign of metabolic health.

[Damien Blenkinsopp]: Right, so would you say most people could eat twice per day and that would be –

[Jimmy Moore]: Once or twice a day is about the pattern that I fall into most days.

[Damien Blenkinsopp]: Once per day?

[Jimmy Moore]: Once or twice per day.

[Damien Blenkinsopp]: That is great to hear. I know I have been doing this for a while too and I forget to eat a lot and I find that I get a lot of work done.

[Jimmy Moore]: Yeah, absolutely. You become more productive and me, that’s money. Time is money they say but that really does make you much more productive in your day if you don’t have to sit there and constantly think about food. Think about all these people, Damien, when they go eat. What is the thing they talk about when they are done eating? Gee, I wonder what I am going to have for lunch after they had breakfast. Gee, I wonder what I am going to have for dinner when they are just done with lunch – so people are always thinking about food, let’s get away from thinking about food and go into more important things.

[Damien Blenkinsopp]: For sure, it is very distracting. So when you fast and you take fat – some people talk about you are fasting and then you have some fat while you are in that fast and they kind of count that still within the fast. Is that how you look at it?

[Jimmy Moore]: No, because technically a fast is going without food. So if you are giving your body nutrition – I assume you are referring to bulletproof coffee for example. Some people actually write to me and in fact I just got an email from a lady, ‘So if I still in a fast if I am having bulletproof coffee?’ And technically a fast is no nutrition at all, no food or anything, so no, but I don’t think you will necessarily lose your ketones doing that because like we said earlier carbohydrates will raise blood glucose which would kill your ketones and protein in excess will raise your glucose, which will kill your ketones, but fat is pretty much benign on blood glucose levels and so you should not lose your ketones.

So it is a good strategy, especially if you think you are going to feel a little bit peckish and need to eat a little something – definitely have that and I am personally no fan, Damien, of coffee in general. So I don’t do that and I would much rather have the butter straight up.

[Damien Blenkinsopp]: Yeah, that is good to hear. Butter has a bit of protein in it. Do you make the difference between like [gui 00:59:25] and other pure sources of fat versus the one that has a little bit of protein in it? Is this something you think about when you are eating or would advise certain people, maybe those with more difficulty that others, who should think about that sort of thing?

[Jimmy Moore]: If people are sensitive to dairy in general I think they should be very careful with that. That is where foods like [gui 00:59:43] and coconut oil step in to help those people. But if you don’t have a sensitivity to dairy certainly butter is okay. I have never thought about the protein content of butter because it is so overwhelmingly high in fat, especially saturated fat, which is what I want.

[Damien Blenkinsopp]: Great. I am just wanting to look at some very typical scenarios of when people are doing this and what kind of challenges they have come across. You have kind of gone for the typical one where it is pretty straightforward to getting ketosis, but what are the common troubleshooting that might come up where they are not getting into ketosis based on the measurements we have just been talking about. What are the biggest things that they should be looking for that might be getting in the way?

[Jimmy Moore]: They are doing it all wrong and we kind of touched on this already that one of the big ones that we talked about in the book that I think bears repeating over and over and over again is that protein thing. Don’t overdo it on the protein. And some people are like, ‘Well, I am only eating 150 grams of protein and I heard that one gram per kilogram of body weight or 1 gram per pound or whatever the different calculations they have,’ and that is a big one. Maybe you are using too much protein in your diet and that is going challenge you and you are going to be like, ‘Well, dang, I can’t get into ketosis because it is always low.’ It is probably that protein.

[Damien Blenkinsopp]: So that is the biggest one? That is the number one?

[Jimmy Moore]: That is the biggest one. I think if people, whatever amount of protein they are having, and they are not seeing ketones, obviously make sure your carbs are dialed in because that is an obvious choice and obvious thing to look at, but the protein and dialing it in, that has helped so many people.

I have already gotten this book that has been out a couple of weeks and I have gotten more emails from people that said, ‘Thank you, thank you, thank you for telling me about the protein moderation. I have been stuck for 2.5 years, I have been stuck forever.’ This was kind of a cool one – ‘My fasting blood sugar was between 98 and 105. All I did was moderate down my protein by about 15 to 20 grams from what I was eating and now it is 85.’ It made all the difference in the world. So don’t neglect that one.

Then we also talked about how people are using urine ketones to test and we have already explained why that is a bad thing and you might want to take another look at the blood ketones. Saturated fat and monounsaturated fat I think we have become so fat-phobic in our culture that even people that know those things aren’t harmful to their health, maybe in the back of their mind they go, ‘Well, if low carb is good maybe I should back up a little bit on my fats.’ No, you need to probably eat more fat than you have ever eaten in your entire life.

[Damien Blenkinsopp]: Could you give us an example just to make it kind of concrete, like five sticks of butter or to put it into terms so people can get it because I know that not eating enough fat is one of the issues, which I think is what you are pointing out.

[Jimmy Moore]: Well, and again it is going to go back to the individual. So for me I have to keep my carbs very low, so that is around 30 grams a day, and I have to keep my protein moderated at a pretty low level of around 80 grams a day. So everything else in my diet has to be comprised of fat and depending on how many times I eat in a day, if I am eating twice in a day obviously it is not going to be as much in that one meal as it would be in two meals so one meal a day – you need to get all of your calories in that one meal.

And I think when you skimp on the fat you do several things and you don’t give your body enough of the materials that would keep you satiated so you don’t have to eat again and then you are not able to produce the ketones that you would want to produce as well and then you get into a hypocaloric state, which brings on some of the negative side effects that people say about ketosis – that it damages your thyroid and all this other nonsense that is put out there.

All that is is you are not eating enough calories and that goes back to the fat thing. So for me if I am making a meal, let’s go back to that egg meal I was talking about earlier. I would cook say, four eggs cooked in butter. I would put cheese on top of that and then I would have an avocado on the side of that. I would have sour cream and maybe some sausage. Now, that is a whole lot of fat.

[Damien Blenkinsopp]: That is mostly fat right there.

[Jimmy Moore]: And it is a moderated amount of protein and very few carbohydrates. Most of the carbs are from the avocado but that is what I know I need to do in order to produce the ketones to feel satisfied and have all those benefits that we talked about in the beginning of the podcast and all those benefits come because I eat that kind of a meal.

[Damien Blenkinsopp]: Great, I think that is eye-opening for a lot of people who haven’t been doing this for a while. You have a lot that you have to get through. Have you ever seen any negatives from consuming this much fat? Like people’s measurements or biomarkers or anything that goes wrong in some areas? Is there anything to look out for on the negative side?

[Jimmy Moore]: Well the doctor will think it is wrong but your LDL will probably go up, the LDL-C number we were talking about earlier and your total cholesterol will also possibly go up, not in everybody but definitely in a certain segment of the population and keep in mind that when you are still losing weight, don’t be doing any testing because your body is in a transient position at that point. You will have some levels of cholesterol and different other markers that may, in that interim while you are losing weight, while fat is being mobilized in the body – it may show up on these tests as a false negative.

So if you are losing weight get weight stable for a few months and then go get tested and you will have a much more accurate picture so yeah, your doctor may see some funky things on your panel and say, ‘Oh, you have a statin drug deficiency. Let’s give you Lipitor for that high cholesterol.’ No, that is not necessarily true. Definitely read my book, Cholesterol Clarity, if you want to know the whole story about that. but yeah, that is definitely a very good point, thank you for bringing this up.

[Damien Blenkinsopp]: Thank you, I just wanted to make sure we covered any of those downsides. I had very high LDL and I got told the same story by a doctor. So I think it is not uncommon. I think a lot of people have walked into doctors with high LDL and they start eating differently like this. So they expect it, basically. I just want to ask you a few rounding off questions now and thank you for the review of all the ins and outs. Who would you look at besides yourself to talk about these types of topics or other health-related topics in terms of who have good data vision on it? Are there people that you have learned from or that you respect or that you look at?

[Jimmy Moore]: I am going to turn to my co-author first because I think he is one of the leading voices on behalf of ketogenic diets, his name is Dr. Eric Westman. he is a researcher at Duke University in Durham, North Carolina and has been using this in research and practically with patients for over a decade and a half now. He has been doing some really great work over the years and I am very honored that he decided to join little ol me in writing books about these subjects but he is a great one that I think more people should know about.

But he is not alone and I mentioned earlier that there were two other researchers that had written some books as well, the art and science of low carbohydrate living, low carbohydrate performance and they also co-wrote the book with my co-author, Dr. Eric Westman and the New Atkins for a New You. They are the low-carb researchers, Dr. Steve Phinney and Dr. Jeff Volek doing some really fantastic work. Keep an eye on them in the coming years because they are doing a lot of work with ketogenic diets and athletic performance. You might have heard about Labron James cutting his carbs and getting in better shape since the end of the NBA season and that’s huge. Guess how he did it? A ketogenic diet.

So we are seeing more and more of these things happening in our mainstream culture and it is the influence of these researchers like this now. Besides the United States you can go around the world. In Sweden you have got Dr. Annika Dahlqvist, Dr. Andreas Eenfeldt down in South Africa. You have got professor Tim Noakes who is doing some really good work. Over in the UK you have got Dr. John Briffa and Zoey Harcombe, all kinds of people literally around the world who are using this approach to help improve the health of their patients and of their clients and it really is catching on like fire and I am really privileged to kind of be on the forefront of this ketogenic diet movement.

[Damien Blenkinsopp]: Great, thanks for that. That is a great list and we will make sure to have all of those in the show notes. What would be your number one recommendation of one piece of data someone should track in this area if they want to keep an eye on it?

[Jimmy Moore]: Blood sugar. You knew that was what I was going to say. Blood sugar.

[Damien Blenkinsopp]: Well it is good for reinforcement.

[Jimmy Moore]: Absolutely, I can’t emphasize blood sugar enough. I think everybody right here right now listening to your podcast, if you do not own a glucometer go to the store and get one. Measure your blood sugar. Do it when you wake up in the morning and if it is over that 90, 92 level you probably need to make a few changes to something and definitely a ketogenic diet will help you get it lower and into that better range.

[Damien Blenkinsopp]: Great, thanks very much. So are there any other data metrics that you track? What do you track currently, routinely? Once a month? Once a week? Once every day? What is your ongoing measurement cycle?

[Jimmy Moore]: Because I did that test for a whole year I don’t really like to test too often unless I am actively doing an experiment. I know I do test blood sugar pretty often and I also test ketones with that breath meter I was telling you about. I do that every single day now. I do step on the scale – not because I think there is any inherent good or bad that comes from seeing what your weight is, but I think it is a good marker to keep an eye on.

So I do this very easily where we step on the scale and you can see where you stand. I don’t let it mess with me psychologically. If it is up, okay, whatever, and if it is down okay, whatever. It doesn’t really mean anything but it does kind of let you know okay, something is going on in the body that might be making weight fluctuate. And then when I do blood tests I do like to run that CRP to know where I sand. I do like to run triglycerides, like we mentioned earlier.

But I am one of those people where I have done so much testing I almost know where I stand and I don’t get so obsessive about it that I feel like I have to do it all the time. I think if you do a once or twice a year whole body analysis that is probably going to be enough for most people.

[Damien Blenkinsopp]: Right, that is great. It sounds like mostly the blood tests, right, and you are doing them once every six months?

[Jimmy Moore]: Yeah, like thyroid, cholesterol.

[Damien Blenkinsopp]: LIke you said, the things like CRP and these other things, you don’t see them vary that much if you have been living the same kind of lifestyle and it shouldn’t really be jumping around or doing anything anyway.

[Jimmy Moore]: But it could be a precursor of something happening so that is why it is important to run it and to kind of see if anything is off the charts. Now, that doesn’t mean one reading should make you upset but that one reading if something is off then okay, get that same reading within six months and let’s see how you’re doing.

[Damien Blenkinsopp]: Yeah, and I just remembered a confounder we didn’t talk about, and this happened to me. I fell on my ass and broke my coccyx and then unfortunately one of my first CRP tests was pretty soon after that. It was high because I had a lot of information going on in my body because of broken bones rather than anything else going on. So then obviously it covers all sorts of information from beyond this and broken parts of the body. And also overtraining is I think an obvious one, like a lot of crossfitters would have that a bit higher than me or other people.

Well, Jimmy, this has been great and there are tons of metrics. This has been such a full episode and thank you very much for your time and going through the ketosis topic so comprehensively. It is a great map.

[Jimmy Moore]: Thank you man and I really appreciate that podcasts are out there because I think this whole quantified self movement and trying to make yourself into a great, quantified body – this is the future of medicine so you are really leading the charge with this podcast and I just wish you well as you continue on.

[Damien Blenkinsopp]: Thank you so much. I am really happy that you are doing your work as well because we can learn from you.

[Jimmy Moore]: I have done a couple.

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