94: Cancer as a Metabolic Disease with Dr. Thomas Seyfried

Transcript of Episode 94: Cancer as a Metabolic Disease with Dr. Thomas Seyfried

With Dr. Daniel Pompa, Meredith Dykstra, and special guest Dr. Thomas Seyfried, Ph.D.

Meredith:
Welcome to Cellular Healing TV, Episode 94.  We have a very special guest joining Dr. Pompa and I on the call today.  We have Dr. Thomas Seyfried.  I’d like to start off by sharing a little bit about Dr. Seyfried, and then I will introduce him and then we’ll get started with the interview.

I’m so excited to have Professor and Dr. Seyfried on the call.  He’s an expert and pioneer in the field of cancer research.  He’s a professor of biology at Boston College and one of the leading academic researchers in promoting how to treat cancer nutritionally.  He's been teaching neurogenetics and neurochemistry as it relates to cancer treatment at Yale University and Boston College for the past 25 years.

He's written many, many peer-reviewed scientific articles and book chapters, and has also published a book called, Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer, which we’ll be discussing today.  The book provides extensive information showing that cancer can be best defined as a mitochondrial, metabolic disease rather than a genetic disease, which is an exciting concept and has implications for developing new, nontoxic cancer therapies, including a ketogenic diet, which we talk about a lot on this show.

Experts in the research field have praised this comprehensive study as one of science’s most cutting-edge topics.  I know your work has really impacted Dr.  Pompa and his approach in supporting his clientele, so we’re so excited to have you on the show.  Welcome Dr. Seyfried.

Dr. Seyfried:
Thank you very much.

Dr. Pompa:
I would love to say this up front.  Here’s the book if everyone can see it.  I tore this book apart, Professor, and loved every page of it.  I really did.  Some people might not appreciate the biochemistry, but I can say that I absolutely loved it.Cancer is a disease today that I believe many are taking a wrong approach to.  I want to say this at the top of the show; we’re not claiming to treat cancer.  We’re not claiming to treat any disease, but I believe the research in this book really shows that where the billions of dollars are being spent is absolutely being misdirected.  I believe science shows that if we put these dollars in a different direction that you talk about in this book we would see the statistics changing.

Doc, I don’t know where it was in your book, but you talked about the number of cancer cases per year and the number of deaths per year either not changing or, in fact, going up on a yearly basis.  Let’s start there, because your theory here runs contrary to what’s being done.  In cancer, we’re not winning the war.  We’re losing the war.  What about that?

Dr. Seyfried:
The death rate in the last 25 years is about a 37% increase in new cases and about a 3½ to 4% increase in deaths per year.  If you look at the trajectory of the two paths, you’d say we’re winning the war on cancer, because the number of deaths per year is not increasing at the same rate as the number of new cases.  However, the number of deaths per year continues in its relentless increase year after year after year.  If you have something that’s going to be effective, you should see a very sharp drop in the number of deaths per year, not a lower rate of increase because the lower rate of increase could be due to a lot of different kinds of things, but if you have something that really works, you’re going to see a significant drop in the number of deaths per year.

Dr. Pompa:
You and I would therefore agree then with the argument that the money, because billions are being given to cancer research, is being spent on an approach that is simply not working.  You and I agree that those statistics are showing that, so where the money is being spent is genomic research, right?  Most people out there, I think, in the public anyway would say they’re doctors and they’ve heard, “Hey, you get cancer it’s because you’re unlucky, right?  You’ve got the gene,” yet I know and I’ve read in other studies and yours that there are at least 700 gene-targeted therapies out there and yet none of them have been shown to reduce tumors.  What’s going on with that?

Dr. Seyfried:
I think the conception is that’s it’s a disease of unbridled cell proliferation.  Most of the therapies that are being used to treat the disease are focusing on the proliferation of the cells.  These toxic chemicals, various chemos, are designed to block the cell cycle in various respects, damage the DNA so that the cells can’t divide. Irradiate this.  This is all based on breaking DNA to try to stop the uncontrolled growth of the cells, so we subject ourselves to a whole range of different toxic drugs and different kinds of therapies.

The genomic approach is now into checkpoint inhibitors based on the mutations that exist in the various cells.  Not as many people are getting drugs based on the genomic research as are getting the standards of care which have been in the field for quite some time, mainly because a lot of those drugs, the new drugs based on so-called “immunotherapy” are extremely costly.  What’s more important is they don’t work for the majority of people, and they can also have very significant side effects and toxic effects.  They can be equally as troubling as these standard toxic drugs that work that we’re currently using.

We persist with radiation and chemo because the checkpoint inhibitor drugs have not led to the kinds of drop in disease that we would like to see.  If those checkpoint inhibitor drugs for the new fad that is currently in place, which are immunotherapies that many drug companies and institutions are actively investigating or implementing these kinds of things, if these really worked as well as they should then we should see an precipitous drop in the number of deaths per year and we’re not seeing that.  We have to rely on the tried and true toxic therapies that have been in existence for the last 50-75 years.  These are very horrifically toxic kinds of therapies, so we’re working on areas of research that will reduce some of the toxicities, things that are not quite relevant to the nature of the disease, but trying to take the edge off the toxicity from some of the drugs that are being currently used.

If people realize that cancer is a mitochondrial metabolic disease and therefore all of the cells are fermenting to one degree or another, they have to use those fuels that are available in sufficient quantities that allow the cell to grow by using fermentation, which is a primitive form of energy metabolism.  It’s very clear to those of us who work in the field that the two primary fuels that are driving these cells to grow are glucose and glutamine.  These are the fuels that are present in our body in sufficient quantities logistically to allow cells to proliferate and have the fuels available that can allow them to proliferate.   The simplistic way to manage the disease is to simply restrict the availability of those fuels that are driving the fermentation metabolism, because you have to realize that every cell genetically is a different entity, so no two cells in the tumor will have the same genetic mutations, but all of the cells in the tumor are fermenting to one degree or another.

Why are we focusing on the unique aspects of every different cell in the tumor when we can focus on the malady that’s common to every cell in the tumor?  This is the conundrum.  This is the puzzle.

Dr. Pompa:
Absolutely, and let me back up for our watchers and listeners.  You threw out some good biochemistry there, but I’m going to back up and make it as simple as possible, and tell me where I go wrong if I do.

According to the Warburg Theory – I read his stuff some years ago from the early 1900s – he said, based on his theory, cancer cells have one thing in common.  Something gets damaged in the mitochondria.  There’s damage there.  For folks listening, that’s where we produce cellular energy.  If you remember back in biochemistry, I’m stretching some of you, there’s a process called oxidative phosphorylation where we make most of the ATP, which is the cell energy.  Something gets damaged, and now the cell can’t make that same amount of energy.  Am I good so far?

Dr. Seyfried:
Yes.

Dr. Pompa:
In that process, the cell then can turn on a gene, some adaptation occurs, and it up regulates a less effective form of cell energy production called glycolysis, which means without oxygen.  It’s a different, less efficient way of making cell energy, the use of glucose for energy.  That’s what Professor was saying.  Therefore, it up regulates that to make up that energy difference.  Now we have these cells that have adapted to damage, probably turning on a gene, so according to your research, the gene doesn’t come first, because that’s what research is saying; we have bad genes, and then that causes a cellular problem.  You’re saying no.  The damage happens first, and the adaptation then perhaps can trigger the gene, which is the secondary thing.  Then, we have this adaptation where the cancer cells are utilizing glucose as an energy source.

Dr. Seyfried:
Yes, but there’s a confusion that exists over the term aerobic glycolysis and aerobic fermentation.  You’re right.  All of our cells use the glycolytic pathway, glycolysis, converting glucose to pyruvate. Under normal, aerobic conditions, our bodies are well oxygenated, so all of our cells take in glucose.  We break food down.  Glucose is a prime fuel for the brain, and many other organ systems take in glucose.  The glucose is metabolized to pyruvate, and then in normal cells, the pyruvate enters into the mitochondria for full oxidation, with the waste products being CO2 and water.  This is the standard respiration in our body.  It’s called aerobic glycolysis.

Many people use the same term, aerobic glycolysis, to reflect the abnormal energy metabolism in a tumor.  The tumor cell is using aerobic fermentation because it produces lactic acid.  The pyruvate, rather than going into the mitochondria, which can be defective in many ways – there’s not just one way.  There’s many different ways in which tumor cell mitochondria can be abnormal.  If pyruvate can’t be fully oxidized, it’s rapidly reduced to lactic acid or lactate which is then dumped outside the cell, leading to an extracellular acidification of the micro environment leading to a wounded microenvironment leading to the inflammation and progression in a lot of the other things.

Now, the mutations – if the respiration is not affected yet some oxygen can still get into the cell, they form reactive oxygen species because the respiratory system of the cell is not completely efficient.  ROS, reactive oxygen species, are known to be carcinogenic and mutagenic.  These reactive species coming out of defective mitochondria then damage the nuclear genome and cause mutations as a downstream effect of the damage to the respiration.

Dr. Pompa
It’s turned on secondary to the–.  The damage happens first, the gene gets turned on, secondary to the metabolic shift.

Dr. Seyfried:
You have to be careful about the gene that gets turned on, because what’s happening is the ROS damaged the nuclear DNA.  If the mitochondria do not produce sufficient energy through respiration, the cell naturally detects this and begins to ferment.  The genes that control fermentation are often the oncogenes.  They are transcription factors that up regulate fermentation when respiration becomes insufficient.

Oncogene turn-on is a response to the damage to the respiration.  The oncogenes are needed to up regulate the primitive form of energy metabolism to a greater extent, because all of our cells are producing pyruvate through glycolysis because our energy through respiration is so efficient, so streamlined.  Now, if that doesn’t work, in order for the cell to remain alive and not have a massive energy failure, the cell has to gradually increase the capacity to produce ATP through an alternative system, which is this primitive form of energy called fermentation that existed on the planet before oxygen came into the atmosphere.

For the cells, this is a relic of the past.  That pathway of glycolysis is one of the most ancient pathways that we know of in metabolism, and that pathway is the first step in normal energy metabolism, but becomes the dominant form of energy when the respiration becomes defective.

Dr. Pompa:
We have something very odd going on.  We have the production of energy via oxidative phosphorylation and that’s that very efficient aerobic pathway, the use of oxygen, and this fermented glycolysis process going on, or utilization of glucose.  I’m trying to make it simple for our people to understand, which is less efficient.  Both of them are going on at the same time, which I think Warburg refers to as respiratory fermentation, which is almost contrary in itself where you have these two things going on at the same time that typically aren’t because these certain genes get triggered through this.

Dr. Seyfried:
I think the idea of the fermentation – fermentation happens in muscle.  You get lactic acid fermentation when oxygen becomes insufficient to generate the energy so the muscles begin to ferment.  They produce lactic acid.  If we go into a room with very low oxygen levels, we get lactic acid increase in our body because our cells begin to transition naturally to the primitive pathway.  We end up with lactic acidosis as the result of going into hypoxic environments.  During epileptic seizures, the body will stop breathing and you get a tremendous increase in lactic acid as the result of this.

Fermentation is the production of lactic acid.  Pyruvate is at the fork of this.  Under aerobic conditions, pyruvate is normally fully oxidized in the mitochondria, but under hypoxic conditions, pyruvate then generates lactic acid very highly.  The strange thing about the tumor cell is that it continues to produce lactic acid even when oxygen levels are sufficient for respiration.  That’s happening because the mitochondria are deficient.  Those cells behave as if they’re in a hypoxic environment, despite the fact that they look like they have respiration, but they don’t.

Dr. Pompa:
Warburg’s theory years ago and yours today is okay, great, so we have this cell that has adapted to this damage and now functioning with this very uncommon, odd energy pathway combination here.  We know that this is common in all cancer cells, unlike the gene theory that’s trying to find specific genes common to each cancer, which they have not been successful, but yet we know that this is common to the majority of tumor formation cancer cell formation.

Your theory then is, if we can stop this fuel, the glucose – we’ll get to the use of amino acid in this process of energy as well, but let’s focus on the glucose for now.  If we can get the cell to not use glucose, then we can either kill these cells through apoptosis, where the cell kills itself, and fix and even diminish tumors.

Dr. Seyfried:
This is has been tried many times and it’s been unsuccessful throughout a number of different drugs they’ve used to stop glycolysis.  The problem, of course, is when you do that you stop that glycolytic pathway in every cell of the body.  This now becomes a real problem because every normal cell is using the same pathway; it’s just that the tumor cell happens to be using it to a much greater extent than the normal cells.

By using an indiscriminate inhibitor of glycolysis, yes, you will kill some of the tumor cells, but you’ll also damage the functionality of the normal cells.  This is why when we do therapeutic fasting or ketogenic diets you lower the glucose in the body for the tumor and you transition all of the cells of the body over to ketones, which we evolve to use when we didn’t have access to food.

The tumor cells, because they have defective respiration in mitochondria, cannot use the ketone bodies.  This is an elegant, nontoxic way to metabolically marginalize the tumor cells while enhancing the health and vitality of the normal cells.  It’s not just targeting the glucose availability to the tumor cell, you have to offer the rest of the cells in the body an alternative fuel that can be metabolized to the glucose that you’re taking away from them.  The tumor cells, because they have defective respiration and mitochondria in a number of different ways, are less able to use the alternative fuel than the normal cells so they become marginalized.  They become more vulnerable to die as the result of these energetic transitions.  It’s a very simple and nontoxic way.

People say, “Will it cure cancer?” but we never use the term cure, but say “Can it be used to manage cancer?”  Yes, it can be used to manage cancer and slow the degree of growth down then offering the opportunity to mix and match a number of diets and drugs in a nontoxic series of approaches to finish off the surviving tumor cells.

Many of the surviving tumor cells, whatever they happen to be, will likely have some characteristic in common if they can still survive the metabolic transitions.  These cells now become potentially targets for immunotherapies and these other kinds of therapies because now you’re dealing with a population of cells that have something all in common.  Rather than at the beginning when they are all genetically different from each other, the survivors from metabolic therapies could be very vulnerable to the kinds of approaches that the industry is now using to target the tumor at the very beginning of its existence.  We’re doing a lot of things right, but we’re just doing them in the wrong way.

Dr. Pompa:
I remember listening to something or perhaps I read about it.  You said if you take the nucleus of a cancer cell and put it into the cytoplasm of a normal metabolism cell, what happens is all of the phenotypes, all of the genetic problems go away, but this isn’t a genetic issue.  This is a cell metabolism issue, and if we can change the cell metabolism then we can surely change it in the body.

Dr. Seyfried:
Those experiments were done primarily to test the hypothesis as to whether cancer was a nuclear genetic disease or a mitochondrial metabolic disease.  This is very important, because as long as the cancer industry and the academic cancer industry consider that cancer is a nuclear genetic disease, we will not shift the paradigm and approach the disease in an altogether different way.

Those experiments were designed and done by a variety of exceptionally talented developmental biologists over many, many years.  What I did simply was to bundle those experiments into one group and present them for the first time as a bundled group.  When you look at all these different experiments done by a number of different people using a number of different types of tumors in different systems, the conclusion was very much the same.  The nucleus of the tumor cell is not capable of driving the disease period.  It’s the mitochondria that are driving the disease.  Once this becomes more widely recognized, it becomes very difficult to support the idea that cancer is a genetic disease therefore warranting the billions of dollars we’re spending on approaches that are based on that theory.

Once the theory is undermined, shown by hard, scientific facts that it cannot be the true explanation for the disease, only then will the field begin to recognize that we should look in a different direction.  As long as people are considering that, we’re still going to persist with the situation that we have today.

Dr. Pompa:
That was my argument at the top of the show.  We’re spending billions in the wrong direction.  If we get people to understand that it’s not a genetic disorder, that’s secondary, then we can actually make some headway.

I believe in my work that this mitochondrial damage, this mitochondrial issue is leading to not just cancer but a multitude of other things that we’re seeing from chronic fatigue to fibromyalgia, and many unexplainable illnesses, even hormone conditions such as diabetes and thyroid.  I believe it’s there.  I have something Doc that I call my five R’s of cellular healing, and R number three is restoring normal cellular energy.  It’s absolutely vital.

In this, look, you mentioned, to go back here a second, something that’s near and dear to my heart, utilizing a state of restriction, if you will, via either fasting or ketosis in using them together.  Meredith, how many shows have we done on the benefits of fasting?  We even move people in and out of these states, which I call diet variation.

Let’s talk about that, because that is a solution to – we’re discussing cancer here, but we’re talking about people who benefit with multiple conditions.  I’m putting them in these restricted states of ketosis where, by the way folks listening for the first time, I have many articles and past shows on ketosis.  That just means that your cells can use sugar or fat for energy.  We’re forcing the cell to use fat and make ketones.  He brought that up.  We even use these ketones in healthy people to make healthier, because they turn off bad genes.

Amazing things happen when ketones are produced, obviously, and cancer cells can’t use them.  That was Doc’s point here.  We utilize this state of making the cell make these ketones to actually make people healthier.  You’re saying, “Hey, this can also cause these cancer cells to become weaker and now our immune system actually has a chance to get rid of them.

Talk a little bit about restriction, because one thing that we’ve found with ketosis, Doc, is some people don’t lose weight in ketosis.  Some people even have even getting into ketosis, and typically these are the people who need it the most, but you say ketosis without some form of restriction in your studies doesn’t work.  Explain that.

Dr. Seyfried:
Keto-adaptation that my colleague, Dominic D’Agostino from the University of South Florida –

Dr. Pompa:
We’re interviewing him in some coming up shows.

Dr. Seyfried:
He’s big into keto-adaptation, which is a form of therapeutic ketosis as opposed to ketoacidosis, which is the pathological state that is experienced by some type II diabetics  When one stops eating, blood sugar goes down and eventually glycogen reserves in the liver and muscles are used up, and then the body has to turn to fat.  The fat is mobilized out of fat stores.  The liver is the organ that primarily makes ketones from fat, so the fat is then metabolized in the liver and the liver makes water soluble byproducts, little energy ketone bodies, which then can be used by the brain, heart, and other organs, to become energy efficient.  They contribute to mitochondrial biogenesis.

Dr. Pompa:
They help you make more mitochondria.

Dr. Seyfried:
Yes, they can help you make more mitochondria and healthier mitochondria, producing very few reactive oxygen species or wasteful energy.  You want to consider reactive oxygen species as kind of a spark that can be damaging, like a wire that has poor insulation and it starts to spark and it damages the area.  That goes down substantially when you’re burning ketones.  The energy is primarily used for the energy resources within the cell without making any wasteful or harmful products.

Dr. Pompa:
I always say it’s like burning natural gas with wood in the fireplace.

Dr. Seyfried:
Right, you produce very little products that would be considered wasteful or potentially harmful to the body.

Dr. Pompa:
You’ve got to regulate cellular inflammation just by burning leaner fuels.

Dr. Seyfried:
We clearly showed that calorie restriction down regulates the inflammatory cyto cascades contributing to tumor cell inflammation and a variety of other things.  The tumor cells can’t use the ketones, but the normal cells can.  The normal cells get very healthy under these keto-adapted states, but you raise a very important question that has been perplexing the field for a long period of time.  How do people know if they do fasting, they do ketogenic diets, or they do this or they do that, how do they know whether or not they’re really in the zone of keto-adaptation?  We published a paper earlier this year on the glucose ketone index calculator that was designed primarily for cancer patients but could be used for any person who would like to know whether or not they’re in a therapeutically ketotic state.

Dr. Pompa:
We use it for all of our patients.

Dr. Seyfried:
You have a little meter that can measure both blood glucose and blood ketones.  That’s the key.  You have to measure both of them.  You get the ratio in millimolar for glucose to ketone and you get a number, which is a singular number which is the index.   If you can get numbers close to 1.0 or below, then you’re using ketones maximally efficiently.  Healthy people who don’t have cancer are able to get into these metabolic zones much easier than cancer patients are.

One of the things we’re realizing with respect to cancer is that cancer produces a lot of anxiety among the sufferers.  Anxiety can lead to elevated blood sugar levels, because the patient understands that they may have a life-threatening disease, which brings a lot of stress and anxiety.  We find that those cancer patients that are able to handle stress can get into these therapeutic zones easier than the cancer patients who can’t handle the stress.  It’s a global, physiological treatment of the body to allow the cancer patient to get into these very healthy states.  They can get in, but it’s more difficult for the cancer patient than it is for the healthy patient.

Dr. Pompa:
Absolutely, and by the way, it’s more difficult for my very unhealthy patients than it is for somebody healthy to get into this target zone.  The ratio you talked about is glucose divided by ketones.  We use a precision extra meter.  If you have a target zone of glucose between 55 and 65 and ketones between 3 and 7, then that’s going to put you in that 1 range somewhere.

Dr. Seyfried:
It’ll put you below.

Dr. Pompa:
Yeah, and that’s where I like to get people in that range as well, because magic happens there, right?  You have autophagy going on and autolytic where the body is eating stuff, and you’re producing enough ketones to make more healthy mitochondria and turn off the bad genes; all that happens in that zone.

Dr. Seyfried:
The issue is you can hit those zones by just water only fasting for four to seven days.  That’s very hard to do for a lot of people, so water only therapeutic fasting, believe me, it’s not easy.  You’re tried it; I’ve tried it, and it’s not easy.  For a lot of people who keto-adapt, but ketogenic diets restrict it, allow the blood sugar to go down and the ketones to go higher than if you did pure therapeutic fasting.  However, many people think that if I eat all this fat this now becomes an Atkins’ diet.

The Atkins’ diet is very different from a ketogenic diet.  Atkins’ diet has no restriction on proteins and fat, and also the types of fat are very different.  If you eat a lot of protein, that’s going to be converted to glucose.  It’s going to be harder to get into the metabolic zone on an Atkins’ diet than it will on a ketogenic diet.  All of these things have to be understood by people who want to engage in these kinds of activities.

For cancer management, a ketogenic diet is part of what we call metabolic therapy.  This is an alternative to chemotherapy and radiation therapy, but we think that the outcomes can be the same.  In other words, we think that we can get every bit as good of effective therapy without the toxicity.  This is the key thing.  We’re trying to manage cancer without toxicity.

People have this mindset that you can’t do this unless the patient is subjected to these horrifically toxic approaches.  We’re under the impression that if we understand the metabolism of the body and you’re able to tweak the pathways in different directions, we can achieve management of these very difficult diseases without using toxic drugs or drugs that can be used in such low quantities that they’re no longer toxic but now very therapeutic effective.

All of this becomes a reality once people realize that cancer is not a genetic disease, but you raise another very important point.  Many other diseases that predispose people to cancer are also metabolic problems.   Diabetes, for example, puts you at risk for cancer, because you have dis-regulated blood glucose control.  If you can manage type II diabetes, you can effectively reduce the risk significantly for a number of different cancers.

Type II diabetes leads to systemic inflammation because of elevated blood glucose.  Ketogenic diets are effective at lowering all of this, reducing the body, and as a matter of fact, ketogenic diets can cure type II diabetes in many patients, so in that respect, you can do this.

The food industry is now becoming very interested in these kinds of approaches, because there’s a void here.  We have the pharmaceutical companies on the one hand that are pushing these various different kinds of expensive drugs to manage these diseases and we have this void in the middle, and some of the food companies are now moving into this void realizing that they can produce foods that could potentially put people in keto-adaptation, ketotic states, that would reduce their risk for type II diabetes and cancer.  I see a major shift coming in how we deal with a lot of these diseases.  It’s not necessary to use expensive drugs that could be potentially toxic to manage things that we can do by knowing how to manage the metabolic systems of the body and the cells.

Dr. Pompa:
Listen, all the crazy things that we see with unexplainable illnesses, none of them would get well if we didn’t utilize these diet variations, shifting people in and out of ketosis, or utilizing fasts of some sort.  You know, Doc, a lot of times just with beef stock alone we can hit certain people in these target ranges, but I want to go back to this point.  The word restriction – we’re talking about some type of restriction in food, whether it’s via a fast that we do for a period of time, whether it’s four days to a week, or something that I do, I combine ketosis with daily intermittent fasting where I fast from 18-24 hours before eating the next meal and doing it daily.

Look, I remember reading in your work and others, and even in my own experiences, some people go into ketosis and they’re just simply consuming, even if it’s not a lot of protein, a lot of fat and a lot of food.  They’re still consuming a lot of food, and if they don’t fall into that target range, we don’t see the results.  We don’t even see weight loss, and some of them struggle to get into ketosis, because they’re still consuming a lot, so we utilize restriction with fasting with ketosis, or daily, intermittent fasting where at the end of the day, they simply take in less calories.  Talk a little bit about that, because you found that mice and people didn’t lose weight unless there was some form of restriction.

Dr. Seyfried:
That’s a very important point.  A lot of people use ketone sticks, the urine sticks, to measure ketosis, and that’s inaccurate because if you do take a lot of fat in your body, yes, you will produce more ketones and you’ll see it on the urine stick; however, the blood will not have the elevated levels because you’re peeing out the ketones as fast as you’re making them.  Friction allows the ketones to replace the lost glucose, so the ketones then, if you restrict a little bit, then you’re getting the full benefit of the ketones.  The body will retain them and use them for energy metabolism, so you’re absolutely right.

We showed, and others have shown, that if we allow the animals to eat all the fat they want, in other words, an unrestricted ketogenic diet, this can lead to insulin insensitivity and dyslipidemia, which is very pathological.  This is not healthy.  People say, “Oh, I’m going to go on a ketogenic diet and eat all the fat I want.”  You could put yourself into harm doing that, because your blood sugar doesn’t go down.  Your insulin goes up, and the next thing you know you have very high triglycerides.

A ketogenic diet is a medical therapy.  It must be administered usually under the supervision of a trained person, or people who do this have to be aware of all of the potential risks using this.  It’s a medical therapy like any medical therapy.  It’s like a drug.  Drugs can be good in one concentration and toxic in another concentration.  Metabolic therapy using ketogenic diets is a powerful tool to enhance physiological health, but it can also be very hazardous if it’s not done right.  You can’t overemphasize this point.

Dr. Pompa:
Some people that we know say, “I’m not getting into ketosis.”  I have them looking at their glucose and invariably their glucose is still too high.  That means they have to be restricted more somehow some way, or their carbohydrate intake is too much.

Dr. Seyfried:
You have to also be careful of some people who have these rare, inherited diseases like carnitine deficiency and certain inborn errors in metabolism where they can’t make fat, they can’t make ketones, or they can’t use the fat, this and that.  There’s a variety of things where a rare person may come out and say, “Oh my god!”  This person could potentially be harmed by this type of therapy.

Dr. Pompa:
That’s why measuring glucose and ketones is important.  In review, someone may be taking in too much protein, an Atkins’ type of diet.  Someone could just be taking in too much caloric intake totally via fat even, and someone also could just simply be having too many carbohydrates.

Genetically, some people have to reduce carbohydrates more than others.  That could be stopping you from getting into ketosis.  That could also be stopping you from hitting this target range that we’re talking about.  It can even stop you from losing weight.  Some people say, “I’m in ketosis, but I’m not losing weight.”  You could still be consuming and not restricting enough.

One way I make sure that people – I’m not a believer in just pushing food away and saying I’m not going to eat any more.  I’m a believer in restricting because you are less hungry.  You’re just simply not hungry so you don’t eat.  Daily intermittent fasting people where we skip breakfast in ketosis is a way to get them to restrict, and eventually, they’re like, “Yeah, I’m not even hungry anymore.”  Sometimes it takes a little while to get there until their ketones rise up, of course.

Dr. Seyfried:
It does.  You’re absolutely right, and also the kinds of fats are different.  Atkins’ diet fats is where you take in much fat, but ketogenic diets are heavier in to the medium-chain triglyceride oils like coconut oils, avocados, and things like this.  You don’t want to use too many long-chain fatty acids.  Some of this is good.  A little bit of fish oil is fine, this kind of polyunsaturated fatty acids, but the bulk of the ketogenic diet is shorter-chain, saturated fatty acids.  This plays a very important role in how high you can get your ketones as well.  There are certain foods that are more prone to producing a better state of ketosis than other foods, and it could differ from one person to the next, so everybody is their own experimental system.

Dr. Pompa:
I find that to be true.  You brought up an interesting point with the fats that people are eating.  I find that today people are taking in too much fish oil, too much rancid fish oil, but even when it’s not rancid, because it’s a very fragile oil, there is simply a lot of healthy people who are taking in too much and are ending up in an omega-3 dominance.  I remember years ago showing that omega-3, when taken too much, can displace cardiolipin out of the mitochondrial membrane, and it creates actually a metabolic problem.  I think everybody right now overloading on fish oil can actually be a dangerous thing.  I’m obviously in agreement with that.   This is great.

Meredith, I don’t know if we’ve got any other questions.  I know some of our doctors had questions.  I think we answered most of those, but you always have some great questions, so let me fire at you.

Meredith:
Thank you.  This is just such empowering information too, I think, for anyone watching who has been touched by cancer, which we all have or been diagnosed with cancer.  This gives you the power back, not just relying on a lot of the conventional treatments, but taking charge and experimenting with the ketogenic diet, and these other nontoxic, nutritional therapies.  I’m wondering, Dr. Seyfried, what do you think of the use of exogenous ketones?

Dr. Seyfried:
I think that’s important.  The body makes d-beta-hydroxybutyrate.  There are different forms.  There’s a D and an L form, and the L form is metabolized as if it were a fatty acid whereas the D form goes through the full ketotic mechanism within the liver.  However, my colleague, Dom D’Agostino, gets some pretty good results with exogenous ketones.  I think we need to recognize that.  We haven’t fully explored all of this.  This is an avenue of great interest and future research.  Is it possible that we can even further exploit keto-adaptation using exogenous ketones?  Right now, they’re not easy to make.  The natural ones are not easy to make.

Dr. Richard Veech at the NIH has been working on this area for many, many years.  He is probably one of the world’s authorities on the knowledge of making natural kinds of ketones and how they influence the mitochondrial function, enhancing the redox potential of the mitochondria and the coenzyme Q couple.  He is the ultimate knowledge base for really understanding this, but I think the world of exogenous ketones is an emerging field that’s going to receive tremendous attention from the food industry and the academic community as we move forward in understanding how we can manage cancer using metabolic approaches.

Dr. Pompa:
I have to ask this question, and I’m going to ask Dominic as well.  If we know that ketones are a byproduct of breaking fat down, fat metabolism, so by taking exogenous ketones, by taking ketones, are we going to slow down the fat metabolism somehow?  Are we not going to get the benefits of actually getting our body to burn fat to actually make ketones?

Dr. Seyfried:
I don’t know.  I think that’s a good question.  We need to do a lot more basic research on that fact.  These are things that we will need to vet in the future.  I can’t really say, because most of the stuff that we work with has been with naturally produced ketones through ketogenic diets or therapeutic fasting where the body is making the ketones naturally in tune.  How can we supplement this?  Is it possible to supplement this? Will we get the same level of therapeutic benefit without any toxic issues?  This all has to be explained.

I do want to mention one more point about how we can better implement these kinds of approaches, and I think it has to do – it can have a lot to do with how we pay or how we finance these kinds of things.  One thing I put in a recent paper is the issue of global budgeting.  There are certain hospitals in the country that receive a certain amount of money to handle the various health issues that they have in their population.  If they can use therapies that keep people healthy and out of the hospital and manage disease as outpatient, the finances can be better distributed within the hospital.

This is an opposite view to fee-for-service.  Fee-for-service is where each aspect of the treatment is paid for as a fee-for-service.  If global budgeting becomes a way to reduce the incidents of cancer, the hospital staff and physicians could better justify why they’re more interested in keeping people healthy using these kinds of things, then it becomes financially feasible to do something like this as opposed to fee-for-service, which is going to be – the hospitals need to balance their budgets.

It’s very hard to balance a budget on a therapy that doesn’t generate revenue.  Medical therapy does not generate the revenue as toxic drugs and these other things do.  The pharmaceutical companies and the hospitals make a lot of money on these kinds of therapies.  Radiation therapy generates tremendous revenue.  These cancer drugs generate tremendous revenue.  If you come in with an alternative therapy that contributes to health and wellbeing, where is the revenue generation going to come from if you’re going to transition away?  It has to come from a different form of payment.  Global budgeting becomes a potential way to achieve both goals – the health of the patient and the health of the hospital.

Dr. Pompa:
I’ll tell you what, without that right there, we’re dead in the water, because you’re right.  It always comes down to finances.  If we’re going to change this paradigm, that absolutely has to be at the forefront; otherwise, you’re never ever going to change what people are doing.  That’s great.  I love that approach.

We talk about fasting, and we talk about ketosis.  I believe the magic happens with that combination of utilizing fasting, whether it’s daily or whether it’s what I call block fasting for four days, ten days, or whatever it is of restriction – water, beef stock, whatever gets you into that target glucose and ketone range.  Magic happens there.  We’re about doing shorter, because we see major benefits.  When we do shorter, four-day fasts, multiple, every other month or things like that.  We think there’s hope in that.

Dr. Seyfried:
Absolutely; some people who may not be able to do a seven-day fast, which is the majority of people, could certainly benefit from a three- to a four-day fast done a few times a year.  The benefits to your body are enormous just from these shorter periods of inanition, which is the cessation of eating, and just drinking water or green tea.  You can have these kinds of things.

Also, a lot of people should feel that if you’re going to do a ketogenic diet say for a couple or three weeks or a month, or whatever, we’re learning from a lot of the cancer patients and people who are doing this about the kinds of foods or drink that you can take without spiking glucose or altering the glucose ketone index.  We found that some dark red wine can be taken.  People who have done three-day fasts – a cup of wine – you can look at your GKI and not see it spike, but if you take white wine or beer it spikes, so everybody can then develop diets and therapies that can meet at least keep them as part of the society that we’re in so you don’t have to feel so alone when you go and embark on these kinds of things.  This is a new area of health.

Dr. Pompa:
I find that exactly.  That’s why we measure the glucose and the ketones to see where people are, because it’s a little different for everybody.  Some people can have their morning coffee with fat and not go out of that target glucose range and still be in that fasting mode.  For some people, the beef stock fasting keeps them in the range, and other people do better with other things.  It is varied, but that’s why you have to measure that glucose and the ketones to see if you’re in that target range.  I guess there’s three factors there – too much protein, too many carbs perhaps, or simply not enough restriction, where you’re literally eating too much food.  The fasting is a remarkable thing.

Years ago I was inspired by Warburg’s work, and my wife was diagnosed with some cervical pre-cancer and cancer, and we put her on a fast, she says 12 days or whatever it was, but I thought it was 13, but she water fasted for 12 days.  She went back some months later and there was no more cancer, to their surprise, but they said that that basically would never happen.  That started me years ago into fasting, and just looking at the benefits of it, we’ve been utilizing it ever since.

I talk about diet variation.  I learned this by accident.  People that were having trouble getting into ketosis and having some difficulty, after three or four months I would move them back into what I call my cellular healing diet.  It’s still a low-carb diet, but it’s not ketosis.  Something would happen.  They would all of a sudden lose some weight when they shifted back into that diet.  Then I would say, “Okay, let’s keep them there for three months.”  I would move them back into ketosis, and I would see this remarkable thing happen where this time it was easier to get in it.  Shifting people in and out of these restricted phases – ketosis, diversion – you can see there’s benefit somehow to that adaptation.

Dr. Seyfried:
Yes, absolutely, and this is what we think to manage cancer, because we think the shifting back and forth from these different diets is going to be exactly what you need to eliminate the tumor cells.  You have to realize that the tumor cells have a lot of mutations.  Nobody denies that they are loaded with mutations for the reasons as secondary consequences of respiration – a defect to respiration, but the issue is those cells have all these kinds of mutations that make them less adaptable to the shifts in these dietary therapies.

The normal cells of our body evolved over millions of years to make these adaptations under these dramatic shifts that you just mentioned.  If you have a cell that has all kinds of broken chromosomes and deletions and duplications, those cells cannot make those kinds of shift.  They end up getting eliminated.  They are eventually gone because they can’t make those shifts, so we can then exploit the genetic defects in the tumor cells by forcing the body to make these dramatic shifts in one direction or the other.  This is part of the metabolic therapy.  What you just mentioned is the strategy that we think can work.

Dr. Pompa:
I learned it by accident just this metabolic stress is caused by these dietary shifts.  When you look at the Hunza people who live disease free and these cultures that are really successful in their health and live very long but live long healthy, they’re forced into diet shifts, which today with refrigeration and being able to eat whatever we want any time we’re not, but the Hunza people, we thought they were vegetarians because the British would go there in the summer and they were eating mostly vegetables, fruits, and things, very light foods.  In the wintertime, what they didn’t see was they were surviving on fatty foods.  They were in complete ketosis.  Then spring came, and they call it in their culture starvation spring when they literally went weeks or months without food.

Dr. Seyfried:
A lot of animals are the same way.  They eat different kinds of foods at different periods of the year that was available at that time.  Again, these are the kinds of shifts you’re speaking about.  These are all very important points that are now just being realized for the first time.

Dr. Pompa:
It’s that adaptation from that stress in the shift that we can recreate in our laboratories and clinics these metabolic shifts utilizing the body’s innate intelligent through adaptation to shift the hormones and to create this metabolic thing.  I have to read this quote from you.  This was out of your book and I love it.

If all cancers arise from metabolic dysfunction then replacement of damaged mitochondria with normal mitochondria should prevent cancer.  In other words, mitochondria producing sufficient respiration, meaning energy, should suppress tumor growth regardless of the numbers and types of mutations.

That was from your book.  What you talk about, I love it.  You utilize the term mitochondrial – I forget the term –

Dr. Seyfried:
Mitochondrial enhancement therapy.

Dr. Pompa:
Yes, mitochondrial – MET, mitochondrial enhancement therapy.  These shifts that we’re talking about – utilizing diet, utilizing fasts, varying the diet, and putting people in and out of these restricted times, is what you’re talking about with MET, correct?

Dr. Seyfried:
Yes, and that’s the way to prevent cancer.  If cancer is a mitochondrial metabolic disease and you protect your mitochondria from damage, you don’t get cancer.  A lot of these preventive – what you talked about – you’re not going to get cancer as long as mitochondrial cells are healthy.

Even if you inherit a gene like a BRCA1 mutation or a P53 for many, those genes damage the mitochondria.  There are ways to enhance mitochondrial function to reduce the risk of having cancer, even if you inherit a gene, so this idea of going out and getting prophylactic mastectomies or oophorectomies or this kind of stuff is a naïve way to deal with this issue.  If you know that if you protect your mitochondria from damage with these metabolic therapies, the risk of developing these diseases is significantly reduced.

Dr. Pompa:
What do you think if you just did maybe two fasts a year?  Just two fasts a year, right?  What do you think it would reduce your risk of cancer?

Dr. Seyfried:
I mean, this would only be speculative, because we don’t have any data to support that, but I think you have to look at those guys in the calorie restriction society of America.  I’ve spoken to those folks.  They’re in ketosis all the time essentially.  They’re always on a restricted diet.  Paul McGlothin and his wife are in this group, so I asked them, “How many people in your organization have cancer?” and they said, “Almost nobody.”  They remembered one guy from 1980 that got cancer, but cancer is extremely rare in those guys who practice calorie restriction.

It’s supportive evidence to say that if you were to do fasts once, twice, or three times a year, the risk of cancer would be probably reduced.  We see that.  That’s why when they want to manage type II diabetes with ketogenic diets to reduce glucose and weight, the risk of cancer in all likelihood will go down.  It’s just that we don’t have enough data yet to support that.

Dr. Pompa:
You brought up diabetes and diabetes rolls into thyroid and all the weight loss resistance and I have really found those conditions impossible to completely resolve without these types of therapies that we’re talking about.  People think, “I’m diabetic; I can’t fast.”  Oh no, quite the contrary.

Dr. Seyfried:
It’s hard.  You have to realize it is not easy.

Dr. Pompa:
Yeah, and that’s why, again, to those folks listening, we have doctors we’re training and practitioners we’re training around the country in coaching people in these types of therapies, so I want to emphasize that as well.  I think you made that point too.  People really need supervision with people who know what they’re doing with this.  It’s important to note that.

I think when we put these things together, ketosis, fasting, or intermittent daily fasting, we really have something that is needed today to fix this metabolic problem.  It is leading to not just cancer but leading to diabetes, thyroid, or why people can’t lose weight, this is an answer.

I want to be clear about one thing.  We’re talking about caloric restriction, and all studies show that really the only way to live longer healthy, to extend your life – life extension if you will – is to eat less, caloric restriction, but I don’t want people to think that we’re just talking about saying, “I’m going to eat half of my meal and put it away,” because that, in America, is what caloric restriction is.  You and I aren’t talking about that.  We’re talking about, at the end of the day, I don’t eat clearly as many calories as most people.  It’s not because I’m pushing food away, but because I’m very efficient in my cells at utilizing fat and, I’m simply not as hungry.

I’ve watched my clients and others get very proficient at fat burning at the cellular level, and they simply just don’t need as much food.  They eat less.  When we’re putting people in these forced times like a fast, eventually the mitochondria gets more efficient, you develop better mitochondria, and guess what folks?  You automatically eat less.  Would you agree with that?

Dr. Seyfried:
Yes, I agree with that.  I also feel that moderate exercise is also an important contribution, together with what you just mentioned.

Dr. Pompa:
Absolutely.

Dr. Seyfried:
Moderate, I like to say the word moderate, because if you exercise at marathon running or extreme sports, that damages the immune system and creates inflammatory conditions that can actually provoke the onset of cancer in some people, not all people.

Dr. Pompa:
We like short, high-intensity.

Dr. Seyfried:
I don’t think you have to do this prolonged damage to your body in any sense, so I think moderate – it also depends on your age and physiological state.  Some people put themselves – they’re being tortured from all this exercise.  Moderate exercise is an important component for enhancing mitochondrial function under the right kind of diet conditions, so you put all that together, and the probability of having chronic disease is significantly reduced.  Unfortunately in our society, we don’t.  It’s hard.  It’s hard.

Dr. Pompa:
Hey, Meredith, he said something really cool there.  He said, “Putting it all together,” right?  I teach something I call a multi-therapeutic approach where we put all this together.  I have my five R’s of how we fix a cell, and we do this cellular detox and removing these things that create the damage in the first place of the mitochondria, and then we utilize these ancient healing strategies, fasting and putting people in and out of ketosis.  These, we put all together and the right form of moderate exercise that you’re talking about.  We put it all together and we call that a multi-therapeutic approach.

You know, Professor, we have more and more practitioners around the country that I’ve been teaching this multi-therapeutic approach to and this is the future in essence and your work really – I said this off air here that your work really just proved text exactly what we’ve been doing for so long.

We are so appreciative of the work and studies you have done.  I can’t be more appreciative of your work.   Is there somewhere that people can go and donate to your work?  Where do you want to lead people more about your work?  Here’s the book.  You can buy it on Amazon, but where else would you like us to lead people?

Dr. Seyfried:
We have a cancer fund here at Boston College.  There’s a Facebook page for my book, Cancer as a Metabolic Disease, and there is a site there for people who want to make contributions.  I can guarantee you that 100% of the money that we get goes right into the research.  It doesn’t go anywhere else.  As I said, a lot of the work that we do –

Dr. Pompa:
Research in the right area; it’s not going to the genomic research folks.

Dr. Seyfried:
Yeah, I think it’s used to enhance the concepts of the book and eventually to come with a reasonable therapy for managing cancer without toxicity that can give people empowerment and have them be participatory in their own healthcare.  Our goal is to have people finish the cancer therapy healthier than when they started the cancer therapy, not looking like they’ve been half starved and beat up by the system.

This can happen more as people become more understanding of what the nature of the disease is, and believe me; I don’t have a cure for cancer.  What I have is a strategy for long-term, nontoxic management of the disease.  There’s a big difference here.  I tell people that we don’t know if you’re cured from cancer unless you die in old age from something other than cancer, and only then would you know you were cured from cancer.  Other than that, we try to manage the disease, and we try to keep people in a very high state of health, and we know we need diet, metabolic therapy, and certain drugs that work synergistically with the diet.  That can really play a very powerful role in managing the disease.  People do donate to our research and it’s very appreciative for anything.  Every penny – no contribution is too small or too large.

Dr. Pompa:
Where do they go?

Dr. Seyfried:
It’s on my book, Cancer as a Metabolic Disease Facebook page.  There’s a Facebook page associated with that and it tells people how they can donate.

Dr. Pompa:
Okay, great.  Get a picture of that.  There it is, Cancer as a Metabolic Disease and there’s your name, Thomas N. Seyfried.  I love your work Doc and I’ll tell you it’s really an answer to a growing epidemic, even beyond cancer I want to say.  This is why so many people don’t feel well.  It is a mitochondrial problem.  It is a cellular energy problem, and again, our number three is restoring cellular energy.  We just appreciate you, and we’d love to have you on in the future and promote, again, more of these concepts.  Thank you so much for being on the call.  Meredith, is there anything else in finishing?

Meredith:
I’d just like to thank you as well.  This has been such an information-packed interview.  I’m definitely going to have to re-watch this episode myself and I’m sure many viewers will as well.  There’s so much incredible information.  We would love to have you back in the future.  I’m sure we’re going to generate a lot of questions from this show.

Dr. Pompa:
Meredith, with that said, I do want to say this.  There are articles written on diet variation.  There are shows here at Cellular Healing TV about diet variation, ketosis, and different types of fasting.  We have shows and articles on all that if you’re new to watching it.  We have all that information because we may have lost you in some of those conversations, so watch the past shows.  Thanks, Doc.  Thank you very much.

Dr. Seyfried:
Thank you very much.

Meredith:
Thank you to everyone, and we’ll see you next time.  Tune in next week.  In Episode 95, we’re going to have Dr. Stephanie Senna from MIT and we’re going to be discussing GMOs, so thanks for watching everyone.  We’ll see you next time.