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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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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