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

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

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

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

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

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


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

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


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

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

itunes quantified body

What You’ll Learn

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

Thank Andrew Scarborough on Twitter for this interview.
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Andrew Scarborough

Tools & Tactics

Interventions

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

Supplementation

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

Diet & Nutrition

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

Tracking

Biomarkers

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

Lab Tests, Devices and Apps

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

Other People, Books & Resources

People

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

Organizations

Books

Other

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

Full Interview Transcript

Click Here to Read Transcript

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

[Andrew Scarborough]: Thank you for having me.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Andrew Scarborough]: Yes, sorry.

[Damien Blenkinsopp]: Okay.

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

[Damien Blenkinsopp]: Is that a straight MRI?

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: So roughly 28 or 27.

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

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

I thought I was healthy.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Andrew Scarborough]: Yeah.

[Damien Blenkinsopp]: Okay.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Andrew Scarborough]: Yep.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: You just eat them straight?

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Which medication where you on?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Okay.

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

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

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

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

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

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

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

[Andrew Scarborough]: Yeah.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Thank you very much for being on the show.

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

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

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

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

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

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

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

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

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

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

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

itunes quantified body

What You’ll Learn

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

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

Michael Nova, Pathway Genomics

Tools & Tactics

Diet & Nutrition

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

Tracking

Biomarkers

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

Lab Tests, Devices and Apps

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

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

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

Other People, Books & Resources

People

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

Organizations

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

Other


Full Interview Transcript

Click Here to Read Transcript

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[DAMIEN BLENKINSOPP]: Oh sorry.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[MICHAEL NOVA]: There might be.

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

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

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

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

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

[MICHAEL NOVA]: Yeah, it could be.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[MICHAEL NOVA]: Yes.

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

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

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

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

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

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

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

[MICHAEL NOVA]: Sure.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[MICHAEL NOVA]: Right.

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

[MICHAEL NOVA]: My pleasure.

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

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

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

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

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

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

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

itunes quantified body

What You’ll Learn

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

Eugene J. Fine, MD

Tools & Tactics

Drugs & Supplements

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

Diet & Nutrition

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

Tracking

Biomarkers

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

Lab Tests, Devices and Apps

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

Other People, Books & Resources

People

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


Full Interview Transcript

Click Here to Read Transcript

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Gene Fine]: Yes.

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

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

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

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

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

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

[Gene Fine]: Yeah, sure.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Gene Fine]: Yes, true.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Great, great.

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

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

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

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

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

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

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

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

[Gene Fine]: Yes.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Were you measuring blood levels?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Gene Fine]: Fasting levels, right.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Damien Blenkinsopp]: Great, great.

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

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

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

[Damien Blenkinsopp]: Right, you’re right. The question is the protein. That’s the missing…

[Gene Fine]: Right. And as I say, I haven’t tested the protein values. We didn’t restrict protein in our group. I think we could have.

We were dealing with patients who, as I say, had advanced cancers, and we were getting them as through referrals from their oncologists as volunteers, and we really didn’t want to give them something too complicated to do, so we just tried to [simplify it]. But yes, protein, certainly restriction might have had further benefit.

But as far as inducing ketosis with medium chain triglycerides, coconut oils and the like, ketone esters, I think these are interesting approaches. They can certainly, possibly offer more convenience, rather than going through a low-carb diet. And that I think has value.

The other thing to note is that they don’t actually mimic the full effects of a low-carb diet because they don’t inhibit insulin. So, there is that aspect of it. While there may be value, I’m not sure that they’ll produce the full effect.

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

Now the other thing I wanted to just bring up was metformin, I don’t know if you’ve looked at all at that.

[Gene Fine]: Well, yeah. I mean, I’m aware that this is being used, at least in trials, as another potential mimicker. And it has it’s own value. I think what it does for me is it illustrates the value of low-carb diets, because what it really does, metformin, is it limits glucose and thereby insulin secretion. So, it’s fine. To me it’s major mechanism is the same mechanism as a low-carb diet.

It has some independent mechanisms. It seems to up-regulate AMP kinase, which happens also to be done by low-carb diets. So metformin may have some advantages. It’s a drug. It’s a very well tolerated drug, but it’s not a universally well tolerated drug.

There are some side effects that have been reported. Not frequently, but some patients develop lactic acidosis, which can be very serious. And some patients develop hypoglycemia. So, I think overall it would be considered a very safe approach, it just has to be tested, like everything else.

[Damien Blenkinsopp]: Great. Thank you.

I was wondering if you had any opinion on calorie deficit versus high intake of calories. I could be on a high fat diet, or a low carbohydrate diet, and still have a surplus of calories versus a deficit. Do you think that’s anything that could be either affecting your results, or something to look at?

[Gene Fine]: Yes, it is something, definitely, to look at. The calorie restricted approach has been advocated…well, it’s just been advocated. I can’t say exactly whether the mechanism is the same, overlapping, or somewhat different.

But I can just say this, that in our study we actually wanted patients to not lose weight. We encouraged them to overeat. Overeat a low-carb diet, but overeat. So to eat as many calories as they needed to sustain their weight.

So the only comment I can make about this is that all the patients lost weight. We did not intend for them to lose weight, that was not our goal. We encouraged them, we would be weighing them weekly and we’d tell them, “Eat more, eat more. You’re making these shakes, add more cream to it. Add more oil to your foods. Put butter on everything.”

Well anyway, whatever it is that we encouraged them to do, all 10 of them lost weight. They lost on average about four percent of their initial body weight. The interesting thing about that, I just suppose that this is why these diets are effective as weight loss diets.

No one knows exactly why they work, but you certainly can speculate some pretty plausible mechanisms. One is that ketosis may inhibit appetite. Another is that your inhibiting insulin, and insulin, as I say, under the influence of carbohydrate makes you fat and keeps you fat. The absence of insulin does the opposite. It releases lipids from your fat cells, and metabolizes them in the liver. So the fact is that low-carb diets intrinsically may be weight loss diets.

We believed in our study that it’s possibly to defeat this. That there’s such a thing as overfeeding, and maybe if one is particularly conscious about this, one can do this. But the other interesting factor is that seven out of the 10 patients were above a body mass index of 25, which is to say they were overweight. Only three of them were in the normal weight range, between 20 and 25.

And as it happens, the patients who lost the most weight were the heaviest. Frankly they were delighted with their weight loss, even though we were trying to maintain weight just for the principles of our study.

The patients who were in the normal weight range, the two who were the higher two in the normal weight range — I should say, the heaviest patients lost about five to six percent of their body weight. The patients who were in the normal weight range, the two heavier of them — 25 BMI and 23 — lost about three percent of their body weight. And the patient who was 20 lost no body weight at all.

So what this tells us is something we all know also, which is that the closer we approach our ideal body weight, the harder it is to lose weight. I don’t know whether you’ve observed that yourself, whether you have gained, lost or are stable in terms of your body weight, but I believe that high fat diets do not necessarily cause weight loss, particularly in people who are approaching their ideal lean body weight.

[Damien Blenkinsopp]: I’ve been on this diet for many years, just as an n=1 experiment. I think I lost a bit of weight when it first started, but ever since I’ve been really stable, ever since. And I’ve never paid attention to the number of calories. Sometimes I’m sure I’m eating a lot of calories, and sometime I’m not eating so many, for whatever it’s worth.

[Gene Fine]: I should also mention one other thing, which is that in our study, when we calculated what the calorie intake was on the basis this is of course on the patients self-reports, that all the patients reduced their calorie intake as well. Now, we didn’t want them to, but the measured calorie intake on the basis of their self reports was reduced, in fact by about one third.

The other interesting thing though is that the stable disease effect and partial remission, those patients who showed stable disease or partial remission had three times the ketosis. But the degree of weight loss in the two groups was the same. They both lost about four percent. So although there was weight loss in all the patients, weight loss, or calorie deficit, did not appear to correlate with the effects that we saw.

[Damien Blenkinsopp]: Well that’s a great point then.

I think the other point you illustrated, if we’re talking about your studies, is how difficult it is to set a good cancer study up, given the situation with the patients and you’re trying to control for a lot of things. So, as you say, it took you four years to recruit the patients for the last study. So I think it gives us a much better appreciation of how difficult it is to do these types of studies.

[Gene Fine]: Yeah. I think it is the fact that physicians are trained to treat with drugs and that’s very understandable. Drugs generally work well. And in cancer, it would be naive to start off with the assumption that diet is going to be a successful therapy. It has to be tested.

And so, whereas there was some reluctance, there wasn’t entirely, and many of the oncologists were very helpful and cooperative and referred patients when they were on a chemo holiday, or chemo break. That’s what was needed to get this study done. And also the fact that I didn’t want patients who were too thin and too sick.

But I think going forward, I think that we can count on, perhaps, some additional support. And we are actually aiming for human studies going forward as well. Right now, as I say, we’re also trying to couple diet with drugs in animal studies. So this combination, we hope, will lead us somewhere.

[Damien Blenkinsopp]: Yeah, Great. So is it the first time someone’s been trying to couple chemotherapy with diet? Or are there existing studies that you’re basing your current work on?

[Gene Fine]: Coupling a low carbohydrate diet with other therapies has been done. I know that Colin Champ and Doug Spitz, I believe, have coupled low-carb diets with radiation therapy. As far as coupling with drugs, I’m not actually immediately aware that anyone has done that. I think that we may be the ones who are looking at that right now.

[Damien Blenkinsopp]: Great. Wrapping up a bit, thanks so much for your time today.

Where could we learn more about this subject? Are there other people you would look to to learn more about this? Perhaps people you’ve worked for who are doing a lot of studies in this area. You mentioned Valter Longo, of course who was mentioned in Dr. Seyfried’s as well. Or are there any books or presentations on the subject that are good?

[Gene Fine]: I’m trying to think, other presentations. I know that there are some other people working in the area that I know have been doing good work.

Dominic D’Agostino in Florida. I think he has a website, and it would be interesting to look at some of the work that he’s done. A somewhat, I hope, accessible discussion of what we’ve talked about.

I have a couple of guest blog posts that I wrote. My colleague Richard Feinman has a generalized biochemistry and metabolism web blog, and he invited me to write some guest blog posts for his web blog. So I wrote two.

One which is on the general hypothesis, which I didn’t even discuss today. I mean, I discussed it in the broadest forms, but I didn’t discuss some of the details. And the other one is more on the clinical trial, on the recharge trial. So it gives more detail on that.

And I think Colin Champ has an interesting website as well, Caveman Doctor. I think I’d look at that. These are other resources. I think I’ve mentioned most of those that I know.

[Damien Blenkinsopp]: Great, great. So, we’ll put links to all of that in the show notes, thank for those.

Well how about you? What are the best ways for people to connect with you? I mean you mentioned the blog posts, which we’ll put in. Is there anything else? Do you have a website, or are you on Twitter? Is there anywhere you are active where people could learn more about what you’re up to?

[Gene Fine]: Let’s see. The website that I have is my website at Albert Einstein. You can also, through the blog posts that I mentioned it gives other links to papers that I’ve written as well as to my website. So I think that probably the most complete portal, you can look me up just at Albert Einstein and find my website there. And that will also link me to the dietary studies and the blog posts and the papers. They all connect to each other.

[Damien Blenkinsopp]: Great, great. We’ll put those on the show notes.

Something we spoke about just before the interview, your perspectives are a little bit different to Dr. Thomas Seyfried that we’ve already had on the show. Could you briefly summarize where you think you might have a different opinion?

[Gene Fine]: Well, I just think that we really are in the same camp. I think that we both believe in metabolic therapy, as do the other people that I’ve mentioned. I think that he believes that when he describes cancer as a metabolic disease, he believes that the fundamental problem is it starts as a metabolic disease in abnormal mitochondria. That may be true.

The only thing that I think that I would differ is that that abnormality in the mitochondria, I believe, is a genetic abnormality, even in the mitochondria. That you still have, what’s happening in the mitochondria is that, to me the fundamental problem in cancer is actually a genetic mutation that leads the cells to increased proliferation and growth and unlimited growth and immortality, and so forth.

The source of these mutations, I believe, could certainly be in the mitochondria, but in fact if it is, and that would make sense to me, it would be increased reactive oxygen species. And increased reactive oxygen species can cause mutations in the genetic portions of the mitochondria, and that would cause abnormal mitochondria. Or it could cause mutations in the DNA of the cell. Certainly hydrogen peroxide, peroxide can migrate over distances and can migrate into the nucleus.

So, I actually believe that the fundamental problem that leads to the cancer may initiate in the mitochondria with reactive oxygen species, but nonetheless results in the fundamental change of cancer is in a mutation. So I think that [in a] certain sense we’re describing the same phenomenon, but we have a different emphasis on which syllable we’re emphasizing.

[Damien Blenkinsopp]: Right. Potentially where it starts and where it finishes, and so on.

[Gene Fine]: Yeah, yeah.

[Damien Blenkinsopp]: Great. Great, thanks for that clarification.

Before you go, I just wanted to look at a bit of what you do on a personal level with your body data. I was just wondering if you track any metrics at all for your own health, biomarkers, or anything like that on a routine basis. Maybe yearly, or more so?

[Gene Fine]: When I started studying this in, around 2003, and I got interested in it, by the way, from my friend and colleague Richard Feinman. He’s a biochemist, and he’s been interested in this principally from the point of view of the effects on metabolic syndrome, diabetes, lipid disorders, and so forth.

However, I came in from the nuclear medicine background, and PET scanning and Warburg effect, and hypoxic cells. For me it was attractive for the possibility that this may have some effect, low-carb diets in inhibiting glycolosis, and as I mentioned earlier through the uncoupling protein 2 having a unique inhibitory effect on cancers while sparing normal cells.

So in 2003 when I got interested in this, and I decided that — you know, I never really had a weight problem, but I had gradually put on a few pounds over the years. And I have a small frame, so I’m about five foot nine, and 165 pounds. For me that was carrying excess fat.

So I figured well, you know, if I’m going to study this in others I might as well experience what it’s like for myself. And maybe I’ll even have some benefit in terms of overall body composition.

To make a long story short, I’ve been on a low-carb diet of various degrees of strictness over the years. In some cases I’ve been ketogenic, I’ve been very strict. In other cases, I’ve just been low-carb, but not likely ketogenic. I haven’t been under 50 grams a day, I’m not quite sure.

But the short story is that over a period of now, what 2003, really 2004, about 11 to 12 years, I’ve lost 33 pounds. Sometimes it’s been in fits and starts, but I’m very, very happy and comfortable with my weight right now. I like myself at 132. I have a small frame. I feel that for me I am lean and fit, and that’s a good thing.

There’s that aspect of it. In terms of other biomarkers, the numbers that I like to look at, in particular, are those that have risk profiles for, well my glucose and my hemoglobin A1C has dropped. In addition, my fasting blood glucose.

[Damien Blenkinsopp]: So if you remember, where did they start and where are you at now? And are you happy with the numbers now?

[Gene Fine]: Well yeah. I mean, I think I’ve been stricter lately and more consistent, so I’ve only been monitoring them really. I don’t think I’ve really been taking very close watch of them.

But I think over the past year or two my blood glucose, a couple of years ago had actually been at 100, and my hemoglobin A1C I think at one time was around 5.7. I’m sorry, this was only about one year ago.

The hemoglobin A1C changes slowly, but in two successive measurements, I’m about to come up with a third, it’s dropped to 5.7 to 5.6 now to 5.5, and I’m expecting it will continue to be going down because I’m doing this. And my fasting blood glucose is now about 94. So it’s dropping, and I’m satisfied with that.

I used to eat what was recommended. I used to eat a low fat diet, which of course means a high-carb diet, and I think I suffered the consequences. But little by little that has been reversing.

From the point of view of my lipid profile, the things that I’m most interested in are those that are atherogenic, that contribute to risk of cardiovascular disease. And I think the current thinking, which makes some sense to me, is that it’s not so much LDL which is targeted by the cardiologist, because LDL is a mixed bag.

Low density lipoproteins really consist of two major fractions. One of the light, buoyant LDL, which is really not harmful, and the other is the small dense LDL, which is. And what happens on a low-carb diet is you reverse the ratio. You reduce the amount of small dense LDL.

And the good measure of that, because it’s hard to get that measurement directly. There are only a few labs in the world that actually measure small dense LDL directly. You have to send away to specialized testing for them. However, there’s a good index of it and it’s the ratio of your triglycerides over your HDL.

[Damien Blenkinsopp]: So there’s a proxy?

[Gene Fine]: There’s a proxy for small dense LDL, yeah.

[Damien Blenkinsopp]: Oh, great.

[Gene Fine]: And so when I started, I guess when I first measured my triglycerides to small dense LDL when I had been not very compliant at all, my triglycerides at one point were about 150, and my HDL was about 50. So the ratio was about three. And since going on a low-carb diet, my triglycerides fell in half, to 74, and my HDL went from 50 to 75. So basically my ratio is now one.

[Damien Blenkinsopp]: That’s pretty high.

[Gene Fine]: So all the things went in the right direction. I’m very pleased that the HDL went up, without any major increase in exercise, just the diet alone. And my triglycerides fell in half. So those are both just exactly what you would expect on a low-carb diet, and what you want.

[Damien Blenkinsopp]: Great, thanks for those.

They’re very useful, especially the triglyceride HDL ratio. Because it is difficult to get the, I guess you were talking about the NMR, nuclear magnetic resonance. We spoke about that in a previous episode. And then there’s the LDLP to get the number of particles. But as you say, there’s only a few specialized labs, so it’s not as accessible. So it’s great to know that there’s a proxy to use also.

Last question here. What would be your number one recommendation to someone trying to use some kind of data to track, whether it’s biomarkers or something else, to make better decisions about their own health?

[Gene Fine]: Yes, well I mean it depends on what aspect of the health you’re talking about. But I don’t know if ketosis is necessary.

As I mentioned, any change of diet can be difficult to sustain over the long term. I don’t even know what it takes. Willpower is something that, what is it. So, it’s hard to know how to do that.

And by and large the reason I would say it’s hard to change diet is people eat what they like. And you want to eat what you like, and so changing your diet means you’re, by definition, changing it to something that you didn’t prefer. So it seems as though there’s a fundamental issue there.

On the other hand, I think that if you have a weight issue that you’re not happy with, or your doctor reports blood lipid markers or glucose markers that you’re not happy with and evidence of pre-diabetes or diabetes, and you’re on meds, so forth — let’s not consider meds yet. Let’s just talk about without being on meds. Because low-carb diets, if you can actually go on them and you’re also on meds, you have to do that under supervision because you might actually become hypoglycemic, and you have to be careful about that.

But without considering meds if you just want to, say, improve your health in terms of obesity or aspects of metabolic syndrome, lipid disorders, blood glucose levels, pre-diabetes. Without going on a strict low-carb ketogenic diet it’s not as hard, I think anyway, to reduce the quantity of carbohydrates that you eat.

You can have a breakfast where, you can cut out, well cut in half the size of the desserts that you eat. You can cut in half the amount of mashed potatoes that you eat. You can eat one slice of bread instead of two, or you can not eat bread. Although that sometimes is hard for people, but if you eat the bread and don’t eat the mashed potatoes, you’ve reduced the number of carbs that you eat.

So if you just start by reducing certain portions of carbohydrates. And I actually found I still have carbohydrates a little bit now. I have a sort of modified Atkins Plus, I call it, or South Beach Plus. I have a little ice cream at night. It’s my treat.

Overall, I probably eat about 60 grams of carbs a day. But, I treat myself to a little bit of ice cream at night. I’ll find out what that’s done to my lipid profile, by the way. But I don’t think it’s going to have a major effect. I think that overall it’s going to be still pretty good.

So the idea of reducing the overall quantity of carbs, I think, is actually important. I think that with the average American diet, I don’t know if the same is true in UK but probably, that overall consumption of carbs is 300 to 400 grams a day. And that’s really quite a lot. And if that could be cut in half to 150, that would be a big improvement.

So, I think that that would be lower stimulation of insulin secretion. Yeah, I think that that would be my principle recommendation in terms of health.

Now as far as exercise is concerned, exercise is also something that many people do but can’t stick to an exercise regime. And overall, I think that even if you look at the overall impact on insulin sensitivity and improving metabolic profile, there’s no question that exercise helps. But it really comes a distant second to diet in terms of having a dramatic impact on insulin sensitivity and these other biomarkers of lipids and glucose and so forth.

So that, while you’ll never hear me discourage anyone from wanting to do exercise, I think that if you want to have an immediate and more dramatic effect, the thing to do would be to reduce carbohydrates in the diet somehow.

And that’s probably the best I can say at the present time, because as I say, I don’t think anyone has a magic bullet as to how to help someone go on a diet. It’s never easy, but if you can find a way to reduce carbohydrates, you’re off to a start.

And if you feel encouraged by the results that you see, you tend to continue it.

[Damien Blenkinsopp]: Absolutely. Thank you for bringing that up, because we’re introducing changes here, new habits. And as you say, it’s super difficult.

I feel one of the things that helps people is making it clearer how helpful it can be in different areas of their life. Once you’ve heard it 10, 20 times from different people who are studying these things, like yourself, in different areas. I think it makes it easier for people, just because of the repetition, for the clarity in their heads.

I think part of the problem is the mystery and the misunderstanding, especially in the media and the press. The more times you’ve heard five different stories, the less you feel like taking action against any one of them, because you’re just not sure, you’re hesitant.

So thank you for your time today, because it’s certainly helping with these type of things.

[Gene Fine]: Thank you. I’m glad that you have this program, really, to spread the word through interviewing people who are active in the field.

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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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