The Dr. Hyman Show - A Radical New Dietary Approach To Cancer Treatment with Dr. Thomas Seyfried

Episode Date: June 21, 2023

This episode is brought to you by Cozy Earth, Rupa Health, Apollo, and Wonderfeel. Over the years, it has become a widely held belief that cancer is predominately a genetic disease or simply the consequence of bad luck. An empowering evolution in cancer research, however, suggests we have far more control over our risk than previously thought.  I’m excited to talk to Dr. Thomas Seyfried about the underlying causes of cancer and why addressing metabolic dysfunction is a very important and often overlooked area of its prevention and treatment.  Dr. Thomas Seyfried is an American professor of biology, genetics, and biochemistry at Boston College. He received his Ph.D. from the University of Illinois Urbana-Champaign in 1976 and did his postdoctoral fellowship at the Yale University School of Medicine. Dr. Seyfried has over 150 peer-reviewed publications, and his research focuses primarily on the mechanisms driving cancer, epilepsy, and neurodegenerative diseases and calorie-restricted ketogenic diets in their prevention and treatment. He is the author of Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer and presently serves on the Nutrition & Metabolism, Neurochemical Research, Journal of Lipid Research, and ASN Neuro editorial boards. This episode is brought to you by Cozy Earth, Rupa Health, Apollo, and Wonderfeel. Get 40% off your Cozy Earth sheet at cozyearth.com and use code MARK40. Rupa Health is a place where Functional Medicine practitioners can access more than 3,000 specialty lab tests. Check out a free, live demo with a Q&A or create an account at RupaHealth.com. Apollo was designed by neuroscientists and physicians to tap into your body's natural rhythms to bring calm and focus and restore equilibrium to your nervous system. Check out the Apollo wearable and save $40 at apolloneuro.com/drhyman. Wonderfeel Youngr NMN works by increasing your levels of NAD, a critical molecule our bodies produce that we literally need to survive. Feel the wonder of innovation at getwonderfeel.com. Here are more details from our interview (audio version / Apple Subscriber version): How Dr. Seyfried’s work on treating epilepsy with a ketogenic diet informed his understanding of cancer (6:57 / 3:14)  Mitochondrial damage and cancer (16:58 / 14:44)  Glucose fermentation and oxidative stress and their links to cancer (25:52 / 24:47)  Our current misunderstanding of the cause of cancer (32:19 / 29:54)  Current cancer treatments vs metabolic oncology (38:31 / 36:50)  Populations without cancer incidence (56:10 / 51:55)  Metabolic cancer treatment for dogs (1:09:27 / 1:05:11)  Using a ketogenic diet with current cancer treatments (1:12:56 / 1:08:50)  Learn more at tomseyfried.com and at the Foundation for Metabolic Cancer Therapies.

Coming up on this episode of The Doctor's Pharmacy. Cancer is a disease of Western diets and lifestyles because it never existed, nor does it exist in our closest primate relatives, the chimpanzee, which is about 98.5% similar to us in gene and protein sequence. Hey everyone, it's Dr. Mark. I don't think there's anything better than waking up feeling super rested, relaxed, and energized. When we get high quality sleep, that's the norm. Without it, our simple day-to-day tasks can seem impossible and our health suffers. That's why I'm always looking for ways to upgrade my sleep routine and bamboo sheet sets from Cozy Earth is my new favorite way to get an amazing

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conversations that matter. And if you've had cancer or anyone you've known or loved has had cancer, I think this is going to be an important podcast because we're going to talk about a very radically different view of how to approach cancer treatment beyond the usual slash burn and poison. Cancer is one of those diseases that is on the rise, not on the decline. And we're really not that far ahead of where we were 50 or 100 years ago. We have some good treatments like immunotherapy, CAR T therapy, checkpoint inhibitors, which are great advance, but we're going to talk about something quite different, which is

the approach of using metabolic therapy or metabolic oncology today with one of the world's experts in this field. And we're going to talk about all about metabolic health, metabolic treatment of cancer, what that means, and how we can really potentially get a leg up on this horrible condition that is affecting so, so many people. So today we have as our guest, an incredible scientist, Dr. Thomas Seyfried. He's an American professor of biology, genetics, and biochemistry at Boston College. He received his PhD from the University of Illinois, Urbana-Champaign, in 1976, and he did his postdoc fellow at Yale University School of Medicine. He's written over 150 peer-reviewed publications, and his research focuses pretty

much on the mechanisms, the underlying mechanisms driving cancer, as well as things like epilepsy and neurodegenerative diseases, and how we may be able to use food, believe it or not, calorie-restricted ketogenic diets to prevent and treat cancer. He's the author of an incredible textbook. It's not a light read, so it's not a book you want to get unless you're really willing to go into the science. It's called Cancer as a Metabolic Disease on the Origin, Management, and Prevention of Cancer. And he's currently on editorial boards of many journals, including Neurochemical Research, Nutrition and Metabolism, the Journal of Lipid Research, and ASN Neuro. And welcome, Dr. Seyfried. Well, thank you very much, Mark. It's a real pleasure to be here and

have this opportunity to discuss some of our views on the origin of cancer with you. Thank you. Well, you know, my father died of cancer. My sister died of cancer and had cancer twice. So I'm very interested in this subject. I see so many patients with cancer. So many of my friends and colleagues reach out to me, you know, looking for a Hail Mary on cancer treatment. And it's one of those horrible, horrible conditions that we haven't made a whole lot of progress on. And we think we're a little bit better at early detection. We're a little bit better at some of the chemo regimens. We've gotten advances in certain areas like immunotherapy and CAR T cells and things like that, but

they don't work universally. And we still have a lot to learn about how to use those therapies. So the question is, you know, is there a different way of thinking about cancer? Is there a different way of looking at how to understand the origins of cancer and cancer metabolism as a way of coming up with a radically different approach to treating cancer? And you've been doing this work for 30 years. Now it's pretty much an accepted form of research and thinking. But when you start, it was kind of heresy. And I remember not too long ago, I was with Siddhartha Mukherjee, who is an oncologist who wrote The Emperor of All Maladies,

won the Pulitzer Prize for that, is a leading cancer oncologist, researcher, and thinker. And he now is doing his work really primarily on using ketogenic diets to treat cancer. And when I saw him once at a conference, he says, Mark, I think we finally figured out what's the problem causing so much cancer. I'm like, what's that? And he's like, sugar. And I'm like, oh, yeah, of course. And we know that people who are overweight have a higher risk of cancer. People with diabetes have a higher risk of cancer.

And so this is actually something you've been working on for 30 years. And I'd love to sort of walk back to the origins of this idea, which arose early in the 1900s from a scientist named Otto Warburg, who talked about the Warburg effect. And he was a guy who was theory caught hold a little bit, but was mostly discredited and ignored and still sort of on the peripheral of medicine. But you've taken his work to the next level. And I'd love you to sort of talk about what is the metabolic theory of cancer and how did Otto Warburg come across this and where we come since then? And let's sort of have you unpack some of that. Yeah. Okay, great. Well, thank you very much. Yeah, these are really important points in our understanding of cancer, you know, where we've

been and where we are and where we need to go, actually. Yeah, well, you know, in my science training over the years, the word Otto Warburg really was mostly in the background. I didn't really know what he had done in any meaningful way as trained geneticists and biochemists. And when we started our work in epilepsy at Yale University, we were working predominantly on biochemistry of epilepsy. I even tried to write a grant on ketogenic diet for epilepsy at Yale back in the 1970s, an internal grant. And they basically said, forget about it. Nobody cares about ketogenic diets for epilepsy. It was Jim Abrams from

Hollywood, whose son Charlie almost died from standard treatments for his epilepsy. And Jim started the Charlie Foundation using ketogenic diets. And one of my students at that time, that was late in the mid-1990s, said, oh, you know, there's a real excitement about this ketogenic diet. I said, forget about it. Nobody's interested in ketogenic diet. I mean, how could food have anything to do with disease, right? Yeah, right. After my experience at Yale, I said, wow, these guys down here, they don't care about. So anyway, she went out there, came back. Oh, man, everybody's excited about this ketogenic diet. So we had developed really some excellent models of epilepsy in our lab.

We were trying to figure out mapping genes for epilepsy and doing all this kind of stuff. And we came back. She came back, Mariana Trotov, and said, let's try ketogenic diets on epileptic mice. And at the same time, we had been doing a lot of work in cancer, but it was mostly biochemistry. It wasn't. It was like traditional biochemistry. It was no translational benefit to the clinic about most of what we were doing, other than trying to figure. So we had two parallel projects.

One was epilepsy. One was cancer biochemistry. And then we started treating our really good model of epilepsy with calorie restriction and restricted ketogenic diets. It all came down to the lower the glucose, the better the seizure management was on this. So some guy came in, a company that was interested in a drug, 6-Deoxy, it was NBDNJ. It's a kind of a drug. And we found out that if you feed it to the mice, their seizures went away and say, wow, this is really exciting. But we fed it to the mice with cancer and all of a sudden the tumors went down as well.

Wow. So we said, what's going on with this drug? This is a drug also known as DON, right? D-O-N. No, no, no. That wasn't DON. This was noradromicin. It's a kind of a glucose analog of some sort. And it was having an effect on epilepsy, at least in preclinical models. But we tried that drug on

some of our T, our, our, our cancer mice. And we found also that it, it seemed to reduce tumors. The same drug that we had for epilepsy. So what's going on here with this? And it turns out that the drug blocked sucrases in the gut. So the animals would eat the food, but they couldn't digest the food and their blood sugar went down. So the drug company at that time thought we had a blockbuster drug for cancer because it was shrinking tumors. But the mechanism wasn't known about how that worked. Then when we found out that, well, the animals were eating food, but they were losing body weight and the tumors were shrinking. So we said, what the hell is going on with that? So then when I put in a control group of mice, feed them until their body

works, cut their calories down until the body weight of the control mice not getting the drug and the mice getting the drug were the same. And we found that the tumor shrunk just as well in the control guys as it did in the drug-treated guys. And the drug was simply preventing the mouse from eating the food and digesting the food. And the blood sugar went down. So when I told the company that this drug was working through calorie restriction, they dropped the project immediately. They didn't want any part of this. So they want to move on now. We want drugs that are going to, I says, yeah, you can get the same effect if you restrict calories. So then, so you'll find out how fast people are.

They're all excited until you realize what the mechanism is. And then when you realize all you have to do is just cut calories and get the same effect. That wasn't exciting. But we were excited about it. And we thought, what is the mechanism by which calorie restriction is have such a powerful effect on reducing cancer, brain cancer in particular? And then we started to hear about Warburg. And he was saying the tumor cells are dependent on glucose, and these drugs block glucose, and the calorie restriction blocks glucose. So we started to then bring in what Otto Warburg was saying for a long time. And then, you know, we started to do the mechanism of action. And what we found was calorie-restricted diets that

would reduce blood sugar and elevate ketone bodies, which is an evolutionarily conserved adaptation to food restriction. We all go into ketosis if we stop eating food for a long enough period of time. You know, our brains have to have some level of energy. And what happens is the blood sugar goes down, you start mobilizing fats, they go to liver, and you make water-soluble ketone bodies that go to the brain and allow the brain to burn energy in the presence of low glucose and other tissues, the heart as well. So we were looking into all of this stuff, and we found that calorie restriction is powerfully

anti-angiogenic, which means the abnormal blood vessels and tumors are really hammered. And at that time, early 2000s- And the tumor cells need the blood flow and the blood vessels to go there. Yeah, they're abnormal too. The blood vessels are leaky, they're abnormal, and that was thought to be provocative to the growth of the tumor. And as you know, during the early 2000s, they were coming out with all these anti-angiogenic therapies from the pharmaceutical industry, many of them which don't work. And we found out why they don't work for the most part. But at that time, it was a hot area. Anti-angiogenic therapy was like

Judah Volkman and a lot of well-known people were saying how powerful these anti-angiogenic therapies. Napoleon Ferrara, who later came out and said most of them don't work. A lot of them were pulled off the market for all these adverse effects. Some of them are still on the market, which to me makes no sense at all. But in any event, it was a hot area. And we showed the calorie restriction could be as powerful or more powerful than anti-angiogenic. And then we did some really good mechanistic work on inflammation. NF-kappa B inflammation was targeted by calorie restriction. And then the cells were dying through a variety of mechanisms.

Tumor cells were dying. The microenvironment was becoming much, much less inflamed. Angiogenesis was going away. And I'm saying, what the hell? You know, this stuff is, this calorie restriction is really powerful. And we were doing it in the mouse. And then we realized, you know, what does calorie restriction mean in the mouse to a human? And then when we compared the base differences in basal metabolic rate between the mouse and the human, we realized that the human could get the same effects as this calorie restricted mouse, only if they did water-only therapeutic fasting. Well, nobody wants

to hear about that. You know, let's be honest. I mean, oh, well, you know, who's going to go out and do all that stuff? But we started to look more and more into the mechanisms of action by which calorie restriction. And then with our knowledge of ketogenic diets, I said, why don't we consider shifting just water-only fasting to calorie? Because that's ultimately what Wilder found in the 1920s for managing epilepsy. He said people with epilepsy who went on water-only fasting, invariably their seizures would go away. But it wasn't a sustained way to treat epilepsy. So he developed the ketogenic diet as a prolonged way of treating epileptic seizures. So I said-

Because it mimics calorie restriction, right? When you're fasting, your body starts to burn fat from your fat stores. So it's a survival mechanism. And we end up having the ability to actually burn fat, which mimics calorie restriction. That's right. And what you do is when you water only fast, your blood sugar goes down and your ketones go up. And then Wilder said, why don't we get a diet that will make blood sugar go down and ketones go up? And that was a ketogenic diet, but it was quite unpalatable at the time. But I said, let's try that same concept with cancer. And some people

had dabbled with that in the past, but not in a serious way. Uh, so we kind of launched a much more aggressive and serious evaluation of how we can, uh, move someone from water only fasting into another therapy that would, that would have a similar, uh, benefit. And then of course, Otto Warburg's concepts came in and I looked at what Warburg had said, and we started getting his his papers, some of his German papers translated into English. I read all of his major papers. And his argument was that in cancer, there is some defect in the ability of the mitochondrion in the cell to produce energy, which is the way most of our cells get energy. We breathe oxygen, and oxygen is a form of – serves as the final common acceptor of electrons in our mitochondria

to generate energy through oxidative phosphorylation. And he said that's broken in cancer. Wait, wait, wait. Just to slow that down for a second. What he basically said was in order for us to produce energy in our cells, most of us combine oxygen with sugar in this kind of chemical reaction down an assembly line called oxidative phosphorylation. It's kind of the normal way you produce energy from food. And it's through glucose primarily and oxygen.

So that's what you're talking about. Yeah. Yeah, yeah, yeah. So we bring glucose into the cell or other foods that would be broken down either into glucose or acetyl-CoA, which is the end product of the glycolytic pathway. So the cell brings in glucose. There's a 10-step pathway called glycolysis, the old Emden-Meierhoff-Parnes pathway. And then the pyruvate, which is a three-carbon derivative of glucose, then enters into the mitochondria and is fully oxidized to produce significant amounts of energy with the key waste products being water and CO2.

So every time we exhale, we're exhaling the waste products of food metabolism, which is CO2 and the moisture water. We can develop urine from combining with amino acid breakdown products. So it's a very highly efficient, highly energy efficient system. But Warburg was saying that cancer cells have a defect in their mitochondria, and that defect is compensated for by an upregulation of these ancient glycolytic fermentation patterns. So glycolysis is present in all of our cells. The problem is when the mitochondria become defective, the end product of glycolysis, pyruvic acid, is no longer entering the mitochondria,

but is being diverted to lactic acid, a waste product of the glycolytic pathway, and that acidifies the cancer microenvironment. So cancer then becomes a disease of cells that proliferate with, instead of producing oxygen, CO2 and water, they're producing lactic acid as a waste product. So, and Warburg noticed that all the major cancers that he studied were all blowing out large amounts of this lactic acid. And he said- Which is kind of what accumulates in your muscles when you over exercise it causes exactly exactly but they but then that deficit is made up as soon as the oxygen can be the muscles can be re-oxygenated they go back to respiring so the muscles have a capacity that when oxygen

becomes deficient from overuse of muscles the muscle will then use the local glucose to produce massive amounts of quick energy with the waste product of lactic acid, which goes back into the bloodstream in exercised folks. And the lactic acid goes to the liver and is created back to glucose. And that's the Cori cycle. And Saul and Gertie Cori received the Nobel Prize for their recognition of how lactic acid from muscles can be reconverted back into glucose for the body. Okay, hold on one sec, hold on one sec. I think that what you just said was so important. I want to make sure everybody gets it, and then we can kind of continue on how this relates to cancer. So everybody, basically, from my understanding is that when we eat, our food is primarily turned into glucose.

Glucose then has to go through this process of breakdown into byproducts we call pyruvate. And there's a whole bunch of steps that then turns that into energy in the body. With cancer cells, that basically process is kind of defective. And so it turns, instead of turning into easy form energy from glucose, it creates lactic acid, which changes the whole environment itself. And basically, the other sort of point I think it's important people realize is that your body is like a hybrid car. It can run on gas or electric. Your cancer cells, and the gas is sugar, and the electric is fat. In cancer cells, they don't run well on fat and it basically starves them. They only can run on sugar, which is gas. So it's kind of the

dirty burning fuel. And that ends up with all this linkage of cancer to things like diabetes and insulin resistance and all these various factors. So that's all how it ties together. Hey everyone, it's Dr. Mark. We all know that getting quality sleep and enough of it is one of the most important components of optimizing health and wellness. But sleeping well can be incredibly difficult thanks to our modern stressful environment. And that's why I'm so excited to tell you about Apollo Wearable. Harnessing the power of soothing vibrations, this wearable helps you achieve deep rejuvenating sleep. The groundbreaking Apollo Wearable was designed by neuroscientists and physicians to tap into your body's natural rhythms to bring calm,

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So get ready to feel the wonder of innovation at getwonderfeel.com. It's more wonderful, it's Wonderfeel. And now let's get back to this week's episode of The Doctor's Pharmacy. Now, take us down to this process of the secondary pathway, which is fermentation, instead of what we call the primary pathway of burning energy, which is oxidative phosphorylation, essentially the Krebs cycle. It's how we break down sugar into energy. So I think that I just sort of want to reinforce that because there was a lot in there. No, no, you're 100% correct, Mark.

This sometimes can be a little overwhelming. I mean, even most doctors, by the way, like, you know, we remember biochemistry for just enough for our exams, then we forget it all, including the Krebs cycle, which is what you're talking about, which is how we turn food and oxygen into energy. But it's one of the most important things we do. You know, it's really interesting thing because, you know, most of us, when we had to study the Krebs cycle as a requirement, only because it was tortuous to try to memorize all this stuff. And it was no pleasure in doing that other than the fact that you say, oh, if you memorize it, you regurgitate it on a test, and then you wouldn't have to worry about it again. But when we are in a different sphere now, where we really need to understand that in order to manage a very devastating disease. So I took a completely different view of these tortuous biochemical pathways when I said I needed to know this in order to manage the cancer,

in order to have an effective non-toxic management of the tumor. So now it becomes a process. It becomes part of your soul to understand these processes because you're going to be able to wield the power of your knowledge to manage a disease because you finally understand what all this crap meant. And so now we realize that, as Warburg said, cancer cells don't need oxygen for their growth. And he showed data that he can take all the oxygen out of the system, and these tumor cells were still growing fine. And his argument was they replaced their oxidative phosphorylation or energy through respiration with energy through fermentation. Fermentation is energy without oxygen. And he said that they were getting their 18-

That's how you make wine or beer, right? Yeah. Yeah. Yeah. Well, the byproduct, that's alcoholic fermentation, rather than both lactic acid fermentation. There's an extra step that the yeast use to convert the lactate into ethanol. So, but that's another step. Our muscles and our cancer cells are producing lactic acid as a waste product of the fermentation process. So, as a result, but Warburg was saying that you have to replace energy. So, without energy, nothing will grow, period. That's the key basis of all of our life existence.

Without energy, we die real quick. And you want to know how fast we can die? If people drink cyanide, you die real, real fast. As I said, that is the mitochondria. Yeah, it poisons complex four in the mitochondria, shuts down electron transport, prevents oxygen from binding to electrons, and your whole body just shuts down instantly. So you can't make energy if you drink cyanide. You just can't make energy and then you die. You can't make energy. Your brain dies,

your heart dies, everything dies. Anything that's linked to oxidative phosphorylation dies real quick, except the cancer cell. So Warburg said, cancer cells are resistant to cyanide. I said, whoa, this is, so they don't need, they don't need oxygen and they can live in cyanide. And I said, whoa, what the hell is this? But he said a long time ago in the 1920s, they were showing this kind of thing. They would take a rat that had a tumor and they would inject the rat with cyanide and the rat would die instantly, but not the tumor. It could take the tumor out and grow the cells and culture was fine. The tumor was resistant to the cyanide.

And he said, that's because they're oxidative phosphorylation. They have replaced oxidative phosphorylation with fermentation, which is energy without oxygen. So that became very clear from his hundreds and hundreds of scientific papers and analyses. And so I went back and I looked at all that stuff really, really carefully and confirmed in no uncertain terms that Otto Warburg was 100% correct in his knowledge of the origin of cancer. He was not correct in the readouts, and I'll explain that in a minute because we've cleared that all up, the misinformation regarding the readouts of dysfunctional respiration. But he claimed that cancer starts with a chronic disruption of oxidative phosphor

energy through oxidative respiration. Then the cell will gradually over time transition to this ancient process of fermentation. And he also clearly said that if you damage respiration too acutely, the cell will die, and you will not get a cancer cell from a dead cell. And that's exactly what happens with the cyanide. You can never get, if the whole body is dead, there's no way you're going to get a cancer cell. But if you have a cancer cell in there, it's not going to die from cyanide. So as I said, so people with cancer drink cyanide to kill themselves. Well, they'll kill

their body, but the tumor cells in their body will still remain alive. So as long as they have the fermentable fuels in the microenvironment. And at that time, Warburg figured that the major fermentable fuel was the sugar glucose. So glucose can either be completely respired in the mitochondria of the cell, or it can be fermented if the mitochondria are not functional or the individual would be in a low oxygen environment. So it became clear to Warburg that the release of large amounts of lactic acid from tumor cells was the result of a defect in oxidative phosphorylation. And this then could explain the origin of cancer. Problem is, in the 1950s, Sidney Winehouse and others, who was the head of the National Cancer Institute, and rightly so, reported that there were some cancer cells that took in as much oxygen as some normal cells. So he said,

Warburg must be wrong because the oxygen consumption, we're seeing cancer cells that are taking in oxygen as avidly as normal cells, and yet the cancer cell is still blowing out lactic acid. What's going on with this? So they said then, oh, the cancer cell needs so much energy, it both respires and produces lactic acid at the same time. So this major controversy and battle went on for years and is still going on for many people today in the papers that they publish showing that cancer cells consume oxygen just as readily as normal cells in culture, and therefore, cancer cells are using oxidative phosphorylation. Wrong. We've shown that's not the case. It turns out that the tumor cells do, in fact, consume oxygen, but they're not using it for ATP

synthesis. They're not using the consumed oxygen for generating energy through oxidative phosphorylation. They are using it to produce reactive oxygen species, ROS. ROS are carcinogenic and mutagenic. These radicals, oxygen radicals, damage DNA, RNA, and proteins. They cause the mutations that you see in the nucleus of the tumor cells. So the oxygen consumed by cancer cells is producing DNA damage as a downstream epiphenomenon of the damage to oxidative phosphorylation. So the cancer field today is focusing on mutations and targeting mutations. These are all effects. They're not the cause of cancer. And this goes back to the argument with Sidney Winehouse and Warburg in the 1950s. Except the folks today absolutely do not understand, do not appreciate, or cannot accept

the fact that the oxygen consumption in cancer cell is not used for oxidative phosphorylation. It's used for reactive oxygen species and other reactions not involving ATP. So you have to put the story together. So when you mentioned CAR-T immunotherapy, all these immunotherapies, they're based on the somatic mutation theory. So now Warburg was the initiator of the mitochondrial metabolic theory of cancer. I will explain more because he did not know about glutamine fermentation, which we now know about. He also assumed that the oxygen consumed by cancer cells, even though it was low, was still linked to oxfoc.

Okay, that's a misunderstanding on Warburg's part. You're giving him credit. That was over 100 years ago. Yeah, it was 100 years ago. And because the pathway for glutamine fermentation was not yet developed. So he did not know about the second major fermentable fuel. So he was absolutely right on the origin of cancer. He was incorrect on assuming that lactic acid production equaled a certain amount of ATP. We now know that that calculation is somewhat in error. We also know that oxygen consumption is in error. So we can put it all together. Warburg was 100% correct in the knowledge of how cancer started. His readouts were incorrect. And we're polishing

it all up. So the mitochondrial Let me take a pause there for a second. So basically what you're saying is that most oncology today is focused on the idea that cancer results from genetic mutations in the cancer. However, what we're learning at the same time is that you can take 100 cases of breast cancer and they may be all genetically very different, or colon cancer, or prostate cancer, or pancreatic cancer. And so even though they have the same name, the same pathology on a microscope, the underlying genetics are quite different. And so we're playing a little bit of whack-a-mole. Now, there may be some ways of improving cancer response to chemotherapy by

identifying which genetic mutations there are and which drugs work better for which ones. And it's sort of an incremental improvement. But it's not a kind of cataclysmic shift in our thinking around cancer, which is moving from a genetic theory to a metabolic theory. And I think the metabolic theory is quite interesting. I think it clearly needs to be fleshed out more, but it looks like it's holding promise to deal with things like stage four melanoma, stage four pancreatic cancer, stage four breast cancer, cancers that are really death sentences are responding, even glioblastoma, which is brain cancer, very well to ketogenic diets. So you kind of have to be able to sort of navigate this new landscape where certain cancers are really responding to a metabolic approach. And so we can't just sort of relegate it to some crazy whack job theory. This is actually now becoming

more mainstream thinking. Well, going back to what you said about the breast cancer, you know, when you look at individual breast tumors, you know, they have different stage ones for, you know, all the different kinds of, you know, HER2 and... Yeah, the staging and the typing, which actually may be less important. Yeah, yeah. So, but you're 100% correct when you look at the genetic profiles of all these different tumors. They're all essentially different from each other. I mean, there's some commonalities in mutations, of course, but many of them, many studies have shown if we take all the individual cell, many individual cells out of a tumor and do a full genomic sequence, no two cells in the tumor

have the exact same kinds of mutations. Yet, every cell in that breast tumor has dependency on fermentation as a source of energy. So the common metabolic problem, all the cells have one major common problem or phenotype or observation. They're all fermenting, regardless of what their mutations are. So the common pathological phenotype is fermentation. Okay. So then the simple question is, how do they get their energy from fermentation? And the two fuels that drive fermentation are glucose, the sugar, and what we have shown is the amino acid glutamine. Now, glutamine for the cancer field, people will say, oh, we all knew glutamine was a big, big role in cancer. You guys in the field thought it was

being respired. No, because the oxygen the field thought it was being respired. No, because the oxygen, no, it's not respired. It's fermented just like the glucose. But it's also fermented in the mitochondria. So the mitochondria, the pathway is called glutaminolysis, and it's a fermentation pathway in the mitochondria. So you have a fermentation pathway in the cytoplasm, and you have a fermentation pathway in the mitochondria. So you have a fermentation pathway in the cytoplasm, and you have a fermentation pathway in the mitochondria, which makes it look like the mitochondria are respiring, especially when they're taken in oxygen. So we had to parse out all this stuff and clearly define what the actual biochemical mechanisms are that are driving the beast. And the beast is driven by fermentation. And you're right, Mark, the cells in the glioblastoma, the cells in colon, lung,

they're all fermenters. So they all have different, that's why when you take CAR T immunotherapy, if you're not hitting the fermentation pathway, you're essentially missing the target. So nothing could be like when you say, oh, we have a targeted therapies, precision medicine. These targets, I mean, they're missing the target. And you pay a lot of money for a missed target. And then you say, oh, we're going to use precision medicine. Well, if it's so precise, how come you blew out my liver when you were trying to cure my lung cancer? Exactly. I mean, that's the problem.

You know, most of the treatments we have now are really toxic. Radiation, chemotherapy, surgery is a bit crude. And what's amazing about metabolic oncology is the therapy is diet and maybe some other compounds that block some of these fermentation pathways that really have not only no side effects, but have a ton of beneficial effects in terms of overall metabolic health, in terms of reducing inflammation, improving stem cell function, causing DNA repair, and helping you deal with oxidative stress. I mean, it's just the list goes on about how this works. It's quite amazing. No, it is. It's remarkable. And because we're going back to the origin of many of the diseases that we have. And a lot of this is

systemic inflammation, chronic exposure to different chemicals. You put all that together and you end up with diabetes, cardiovascular disease, cancer, dementia. You end up with all these kinds of chronic diseases. And a lot of it has to do with disturbed energy. Metabolic homeostasis is disturbed in many of these chronic diseases. The issue for us, though, is ferreting out the mechanisms of how cells grow, cancer cells grow in a dysregulated way. And I think, you know, I don't want to become too diffuse and say, okay, let me jump now into Alzheimer's and show you how this works. Let me jump into type 2 diabetes and show you how that works. Let me jump into type 2 diabetes and show you how that

works. The major focus we have right now is correcting massive misinformation on how cancer cells express this dysregulated growth, because ultimately that's what the disease is. It's cell division out of control. And these cells are dividing out of control because they have lost their ability to use energy through respiration, have fallen back on ancient fermentation pathways. And the organelle inside the cell that controls the cell cycle and regulated growth is the mitochondrion. And Warburg clearly showed many years ago, and I have in my own work validated everything that Warburg said with respect to mitochondrial dysfunction,

that the organelle controlling the differentiated state and regulated growth is dysfunctional. And therefore, the cells are falling back on ancient fermentation pathways and are dysregulated in their cell growth. So, you know, so what's the best way to manage cancer is pull the plug on their fermentation fuels. And there's only two fuels that can drive this beast, and it's glucose and glutamine. So, and then they can't, as you mentioned earlier, they can't burn fats or ketone bodies because you need a good mitochondria oxidative phosphorylation system to generate energy from fats and ketone bodies. So the fats and ketone bodies, though, help the heart, help the brain, especially for

ketone bodies. So you mentioned, as you said, all of these different chronic diseases can be improved significantly by this metabolic approach because when you burn ketones, you essentially increase the metabolic homeostasis of normal cells. And the cancer cell is marginalized. It can't use the ketone body or the fat. So you really put them in a very compromised position, and they will gradually be eliminated. And not only that, in our paper, in my book, and in the paper we just showed for managing cancer in the dog using purely metabolic therapy,

when you cut the calories down, we have this process called autolytic cannibalism. It's very interesting. So all cells in the body must carry their weight when food restriction. So there has to be a coordinated interaction among all the cells in our body. And when you have a cancer, a group of cells that are using energy in a very inefficient way and not contributing to the society of the cells, the body will turn on those cancer cells and use them as fuel, eat them, and supply their metabolites for the rest, called autolytic cannibalism. And in order to get into that stage, you have to lower blood sugars, and you have to increase ketones, and then the body starts turning on these cancer cells and dissolving them.

So does it have to be both calorie-restricted and ketogenic? Because ketogenic diets aren't necessarily calorie-restricted, although people might want to eat less because they're not as hungry because fat inhibits appetite. Yeah. In humans, the ketogenic diet, high-fat diet impacts the hormone cholecystokinin, which shuts down appetites. It impacts on the 10th cranial nerve. But you don't have to deliberately restrict calories for the ketogenic diet to get cancer? Well, most people do because their appetite is turned off. So it's an indirect calorie restriction. Nobody sits down and eats a whole, you know, let's eat a pound of butter. You know,

nobody's going to do that. And as a matter of fact, we are learning now from a lot of our colleagues, there are many palatable types of ketogenic diets. And we developed the glucose ketone index calculator to allow the cancer. I did it mostly for cancer patients, but it seems like people just want to get healthy. They use the GKI. It's the ratio of blood sugar to blood ketones using a finger prick, you use keto mojos or these different instruments to measure this. And, you know, regardless of what you're eating, if you can keep your GKI levels to 2.0 or below, I mean, you're going to put significant metabolic pressure on these tumor cells.

So, you know, people say, oh, this ketogenic diet is unpalatable. Well, you can develop a Mediterranean diet that will do the same thing. Just got to use the GKI to let you know what you can eat and what you can't eat. So people are learning now, hey, you know, I'm a vegan. I can get my GKI down and I feel pretty good about the whole thing. And this other guy, I'm a carnivore and I can do the same thing and the pescatarian and whoever the hell else you want to be. You know, the bottom line is if you have an instrument now and a ratio to put pressure on your cancer cell and you can build

your own diets for this. So that's a nice tool that allows the physician or the patient to know when they're in this zone. And then when they're in this zone of low glucose ketone index, that's when you bring in the drugs like glutamine inhibitors and other glucose inhibitors to fully target and eliminate these tumor cells in a non-toxic way. So it's a strategy. Yeah, you have to be aware of how to do this. You just can't all of a sudden go into a clinic at the top medical school and say, man, I'd like to have metabolic therapy instead of CAR T immunotherapy. Oh, we don't

know how to do this. This doesn't work. There's no evidence. You got to read the scientific literature. My favorite thing is that there's no evidence. It means, translates as, I haven't read the evidence or looked for the evidence. You know, this is another thing. Sometimes I do these podcasts and people say, well, who's this guy pulling this crap out of his assay and all this kind of stuff? And I say, well, why don't you read my papers? I mean, I open access. I mean, it's not like I'm making this stuff up.

I mean, we've been spending 25 years doing the research and we publish the research. It just so happens you don't read the research. I mean, what am I supposed to say? You know, so everyone says, oh, where's this guy getting all this information? You see it. I did the damn experiments for crazy. You know? It's like I know what I'm talking about.

And then I published them. Oh, I wasn't aware of that. Well, what do I do? What more do you want me to do? Write it in crayon and put a big sign on the side of the road? There's only about nine million papers in the National Library of Medicine. So, you know, I think most doctors haven't read a fraction of that. And it's true. And I blame them. They're overwhelmed with their cancer patients

and trying to do the best they can. But what bothers me is the absolute resistance on the part of the medical establishment to might even consider what we're saying. And as a matter of fact, as I said, you only have two major theories to describe the origin of cancer. And that is the somatic mutation theory, which is advocated by the National Cancer Institute. If you go to the National Cancer Institute, the thing you say about cancer, cancer is a genetic disease. So this drives the grant support from the National Cancer Society and the NIH are all supporting gene approaches, which then involves the immunotherapies and all this crazy stuff that you hear on television every night. And it's all driven by the somatic mutation theory of cancer. And the alternative and the correct theory is that cancer is a mitochondrial

metabolic disease. So it's the mitochondrial metabolic theory. So when patients go into the clinic, they should ask their oncologist, is the treatment you're giving me based on the somatic mutation theory or on the mitochondrial metabolic theory? Of course, it's like a deer looking into the headlights. Most of them just don't know anything about what I just said. But the tragic thing is that the National Cancer Institute itself is pushing misinformation on this incorrect theory. The theory cannot, is no longer, we've presented so much evidence that the only way you can say cancer is a genetic disease is through ideological dogma. It can no longer be rational thinking. It's ideological dogma is maintaining the status quo in managing cancer. So you have to realize that dogma is an extremely powerful force on the brain. It underlies religion, it underlies political affiliations, and it also

underlies the somatic mutation theory of cancer. So when you put all that together, you can see why we're not making the kind of advances that we should be making. It's due mostly to a dogmatic view that cancer is something other than what it actually is. Talk a little bit more about the glutamine because it seems like we can restrict sugar pretty easily through a ketogenic diet and reduce our carbohydrate intake and switch to mostly fat. And also we have to limit protein because protein can turn into sugar in the body. So be careful. It's not a high protein diet. But what about glutamine? Because glutamine is an essential amino acid. It's involved in the found production. It's found in many healthful foods, such as fish and dark green leafy vegetables, which we think we should eat, you know, when we're,

you know, eggs, nuts and seeds, soybeans, seaweed, meat. So, you know, wow, what are we going to do? How are we going to get away with limiting glutamine? Yeah, yeah. No, this is so, so important because I don't know what it is. People from all the other podcasts that I've done, they all rush out and say, well, what can I eat to reduce glutamine? Nothing.

There's no diet that can reduce glutamine. Now, what we did find, the work done by George Cahill and others, prolonged water-only fasting will reduce glutamine. But glutamine, as you said, is a non-essential amino acid because we can make it predominantly from glucose, actually. But there's no diet by itself that can reduce glutamine. So therefore, we need drugs to target the glutamine. I want to say it again. There is no diet that can effectively reduce the availability of glutamine in our body, okay? So that's why we need drugs. And the drugs are designed to further put the pressure on glutamine. And as you said, this is an incredible amino acid. It may not be considered an essential amino acid, but it is essential for the immune system, for our gut, and for the urea cycle. So that's why the glutamine issue allowed me and my colleagues to develop the press pulse strategy for managing cancer.

You can press glucose, as you said, Mark. We don't need glucose. We can replace glucose with fats and ketone bodies that the tumor cells can't use for energy. So we can push glucose levels down pretty low. And then the rest of the normal cells, when they're deprived of glucose, will compete directly with the tumor cell for any available glucose in the body. So we're really, we got the glucose thing under control. The glutamine issue now requires kid gloves because we know how important that molecule is for the normal physiological health of our body. So when I say press pulse, we press glucose chronically.

Stress, just diet and some small amounts of other drugs can press glucose without harming the body. But we pulse glutamine. We can't chronically deprive our bodies of glutamine because it's an essential amino acid. So we put a drug like 6-deoxynorleucine, which is DON, which has been a known glutamine inhibitor. It shuts down the glutaminolysis pathway. So you can't metabolize glutamine to glutamate. But we can't be too aggressive with that because if we're too aggressive with it, we're going to damage our immune system. We're going to damage our gut. We can damage things. So we just put it in there for a short period of time at a particular

dosage, slaughter a whole bunch of tumor cells, and then pull it away. And then we need our immune cells to come in and pick up the corpses. So our immune cells, our immune system, and the tumor are both utilizers of glutamine. So yeah, you can kill tumor cells because they're absolutely dependent on glutamine, but we can also paralyze the function of our normal immune system if we keep glutamine targeting too aggressive on there. So we have to pull it back, allow our indolent immune system to become aggressive again, pick up the dead corpses of the cells that we just killed, and then hit them again with a small dose of glutamine. So you press the glucose, hold that down with diet, and then you pulse the glutamine,

and eventually you gradually degrade the tumor while enhancing at the same time, enhancing the health and vitality of all of the normal cells in the body, including the immune system. So you have to know biology. You have to understand the biology of the different systems that you're working with, because you can play off one biological system off of another. It's a beautiful, elegant system. Well, once people understand how to do this, it's going to be the paradigm shift. It's going to be the way we're going to manage all these differences. So you have to do both, right? You have to do both the glucose restriction and you have to inhibit glutamine pathways through a drug or a compound, which is not actually an approved drug. It's some research compound right now. Well, it was approved. I mean, they did phase two trials with this drug. I mean, it was

used in little kids with leukemia. It's just that they never targeted the glucose when they used it, and they didn't know the dosages. So it's like anything, you know, if you don't know how to use the tool, it's never going to give you the outcome that you would have expected. Does it have side effects? Well, what we showed, yes, of course it has, like any drug. I mean, radiation has side effects. You know, CAR-T, all this stuff has side effects. But what we showed is that when you administer Dawn with the ketogenic diet, you use much

lower dosages and you pulse the system. You don't press the system. And therefore, you eliminate the toxicity while at the same time improving therapeutic efficacy. So therefore, you learned how to use the tool. If you don't use the tool, that's what they said, we can't use Don because it was too toxic. We didn't know how to use it. You got to use it. You got to know how to use this drug. And believe me- Have there been clinical trials in humans on this? Well, of course, they're doing it now at Johns Hopkins. They took that drug gone and they put a little tail on it, made it like a new drug. There's two ways to make a new drug.

One, you can take an already existing drug, modify it slightly, and then say, oh, we're going to make a billion dollars on this. The other way to do it is like we did. We have a drug that we knew worked, but we didn't know how to use it in the correct context. We changed the context, and the drug now becomes super powerful. So it's like a new drug, but you put it into a different environment, you get the same effect. So my goal is to save lives and improve quality of life. Other people may want to make billions of dollars on this stuff. But either way, the bottom line is that if you use the drug from Johns Hopkins, or you use the regular drug in a different context in a different way, the outcome is going to be

similar. But now the problem, of course, is if you use Dawn by itself, you're never going to get the complete therapeutic benefit unless you target the glucose. You got to target the glucose with it. And we also found that in administration of DON to brain cancer in a ketogenic diet, the ketogenic diet facilitates delivery of the drug through the blood-brain barrier onto the target. So clearly, you're going to get much more bang for your buck by administering the drug in a ketogenic diet than if you administered in a high carbohydrate diet. We published beautiful papers, beautiful papers on this. Now, what about the data around the Inuit? Because they were populations that lived in the Arctic Circle who ate primarily fat, whale

blubber, seal, you know, and they essentially were on ketogenic diets. And they had very few cancers, right? I mean, what did we learn from those populations? Well, we have a book coming out from Tim Noakes' group, and it's a big book on ketogenic diets used for everything. And they talked about the Inuits in that book. When they were first evaluated, they were considered to be resistant to cancer and some of the other chronic diseases. And they ate very little vegetables, of course, seasonal. Everything had to be seasonal. But yeah, they were in nutritional ketosis probably for the majority of their lives. And they didn't have

any cancer. I visited the medical hospital. Is that because we just didn't diagnose it or because they actually didn't have it? Well, you know, it's a combination of both probably. I mean, who would know whether some guy might've had some problem? I mean, there wasn't a lot of medical evaluations, but the Western physicians, I think mostly from England, I have to go back and double check on that. But they did some evaluations. I mean, just overall, any kind of chronic diseases. And the bottom line was cancer was not recognized as being any concern in these folks. But when I visited the medical school at Thunder Bay, Canada, I gave a lecture there. And that medical school predominantly focuses on the health of Inuits because a large population of Inuits are in the Canadian provinces in the northern Arctic Circle.

And these folks were just decimated by type 2 diabetes, cancer, dementia, all kinds of things that they never had or were afflicted with until Western diets and lifestyles came into their environment. And, you know, the Inuits are just one example. The other example is Albert Schweitzer's evaluation of the African tribes in various countries of Africa and the African tribes that lived according to traditional ways. And he actually was looking for cancer. And he looked at almost 40,000 Africans and found not one single case of cancer in tribes that were following traditional ways. So clearly, cancer is a disease of Western diets and lifestyles because it never existed. And nor does it exist in our closest primate relatives, the chimpanzee, which is about 98.5% similar to us in gene and protein sequence. And these animals are under constant veterinary surveillance at the major zoos.

And there's never been a documented case of breast cancer in a female chimpanzee, despite the fact that they have the same very similar, if not identical, genes and proteins that we have. So what is it about a chimpanzee that, or Inuits, or African tribes living according to traditional ways, that makes cancer an extremely rare event in their environment. And clearly, it's the environment that we live in that's putting us at risk for all these chronic diseases, including cancer. And we know how it arises. We know that you cannot get cancer if you maintain healthy mitochondria. So it starts, as Warburg said, with mitochondrial disruption. So then the question is, well, how do I prevent

cancer? Well, if you can keep your mitochondria healthy. Well, how do you keep your mitochondria healthy? Avoid highly processed carbohydrate foods, do exercise, this kind of thing. In other words, now that we know the plan, who is willing to adapt the plan, adapt the plan to their lifestyle. And it's hard because every corner we have a fast foods, we have fast food. So, and we can't do the kind of experiment that would show the evidence. Like if we took chimpanzees and gave them an American diet and lifestyle in the zoo, jelly donuts, pizzas, and, you know, big hero sandwiches. They said, I asked the zookeeper at the San Diego zoo. I said, can you, why don't you, I said, how would these bonobos, they have some bonobo.

Oh, they would eat those donuts like there'd be no tomorrow. I said, but I said, why don't you give them go down to the Dunkin' Donuts and bring them in a box of jelly fills? They said, we had animal cruelty. That's right. They said it would be animal cruelty so i said what about us oh no you know so um but any event i i've i've always asked that to the uh the veterinarians at the zoos with their primate i said why don't you guys go down again you think this guy would love a big pizza you know margar Oh, they'd be all over it.

But they can't do that because it would be a cruel thing to do to them. You know, and I say, well, we're doing it to ourselves. And now we're suffering from all the consequences of this action. And consequently, we have all these chronic diseases. And then we can manage them all very effectively. If you listen to the TV coming out with all these wonderful ways. And then we can manage them all very effectively. If you listen to the TV coming out with all these wonderful ways that take this drug, that drug, do this, and then you got a thousand side effects that'll kill you before the disease will.

You know, it's really crazy, man. I don't know what to say. I want to ask you about a couple more things I think are interesting in your work. One is the, you know, use of hyperbaric oxygen therapy as an adjunct to what you're talking about in combination with interrupting the glucose pathways and the glutamine pathways. And by the way, just so everybody knows, the way we detect cancer in screening for recurrence or looking at someone's overall status is we use a PET scan, which is basically a special type of scan where we give people a radioactively labeled sugar, like basically sugar, it's radioactive sugar, and it goes back to the cancer. And that's how we tell what the cancer is. It doesn't work for the glutamine pathways, but it actually is how we detect metastatic cancer. So

it's weird, the doctors say to patients, oh, don't worry about what you eat. Why don't you eat ice cream and milkshakes? And I'm like, what are you doing? You know, this doesn't make any sense, right? And especially in the context of knowing just from pure, you know, well-established research that insulin resistance and prediabetes and the whole phenomena of too much sugar in our diet is driving so many cancers. The major cancers, colon, breast, prostate, even some lung cancers, pancreatic cancers are driven by sugar. Yeah, and you're right about that. I mean, we use fluorodeoxyglucose. It's an analog of glucose that can't be metabolized,

so it collects in the tissue and it lights up. And you say, oh, there's your cancer right there. It's sucking down the glucose. And then on the same breath, you're going to have a drink infimel to help you. And then you take a guy and they're so fearful of weight loss in a cancer patient. You take a guy who weighs 350 pounds, and you say, now, you got to keep your weight up. You know, we don't want you to lose any weight. I mean, you got to be nuts to say something like that, right? So, but, you know, the whole thing here is getting back to hyperbaric oxygen, which was your original question.

Dom D'Agostino and I, Dom is a guy who's constantly in nutritional ketosis. He had done some studies in his lab showing that in hyperbaric pressure, the cancer cells were exploding. And they would create a tremendous amount of reactive oxygen species. Furthermore, from not only the fact that they produce ROS, but the oxygen under pressure enhances the killing effect of the ROS. So what we did in our PressPulse big paper that we wrote, the PressPulse strategy for managing cancer, hyperbaric oxygen was part of the pulse strategy. So if the patient can get into therapeutic ketosis with a glucose ketone index of 2.0 or below, we would then 2.5 atmospheres

for about 90 minutes. You could put that patient in hyperbaric oxygen. And hyperbaric oxygen would essentially facilitate the killing of the tumor cell through oxidative stress. And it's important to remember that radiation and some of the toxic drugs that we use for cancer management in the clinic also kill cancer cells through oxidative stress. But the key is with hyperbaric oxygen, you're killing the cancer cell with oxidative stress without causing collateral toxicity to the rest of the body. So it beautifully dovetails in with the overall concept of metabolic therapy. And that becomes another arm of treatment is hyperbaric oxygen once the patient is in therapeutic ketosis.

Because we know that that's when hyperbaric oxygen will have its greatest therapeutic benefit, is when that patient has the glucose ketone index value, which could change during the course of the day. So he or she would know when to go into the chamber for oxygen therapy when their GKI would be at the lowest point during the day. And then they would schedule treatments that would be based around those values. So clearly, it becomes an arm of the therapeutic strategy called mitochondrial metabolic therapy is the whole concept for this new treatment strategy. So hyperbaric oxygen, ketogenic diet. Now, let's talk about phenyl butyrate and glutamine,

because this is a compound that's been around for a long time, and it seems to bind to glutamate, and it causes excretion in the urine. Is that a reasonable approach, and is that available as a drug still? Or what do you think about that? Well, I think for blood cancers, it could be very effective. I haven't tested it yet, because in the mouse, we do most of our work in the mouse. And the way it works in humans is phenylbutyrate is metabolized to phenylacetate. And phenylacetate then binds with glutamine, and you kind of flush it out of your body. The mouse doesn't have that enzyme. So we're never able to test phenylbutyrate in a full effective way in the

preclinical system. But I certainly think it could be effective for, because glutamine is the most abundant amino acid in our blood, in the blood of a normal person. It's about five milligram, five millimolar. I guess it's about five millimolar constant. It's the most abundant amino acid because it plays such a vital role in so many of our physiological processes. But phenylbutyrate could be an effective way to reduce levels, especially under calorie restriction and ketogenic diets, could be further a very powerful way to kill blood cancers. And blood cancers like brain cancer, colon cancer, they all have damaged oxidative phosphorylation. So they're all fermenting. So they're using glucose and glutamine, and they would be even more vulnerable to, I think. I don't want to say that with any level of certainty until I actually do the experiments myself.

Most of the knowledge that I provide or tell is because I've done the experiments and I've looked at different things. But I think for humans, it could be a real value to try to reduce, especially for blood cancers. Whether it works for solid tumors, it's hard to say because the microenvironment of the solid tumor may not be permeable to phenylbutyrate or phenylacetate. And therefore, I cannot speak to that. A lot of your work has been done in animal models, in lab data. Can you talk about some of the clinical human trials that are happening now and ones that have been done? What have we learned and where is this being effective? I've seen some pretty remarkable things happening in colioblastoma and other cancers. So can you talk about what we know right now in humans and where do you think

we're going to be in three, five, 10 years with cancer treatment? Well, we're developing a treatment protocol right now as we speak, a comprehensive treatment protocol for humans, so that we bring together all of the things that I was saying in a kind of how-to manual and strategy. So once the medical professionals read this, they'll know what to do and how to do it. And I am working with folks in different countries right now where there's a little bit more flexibility in what we're able to do. And to be honest with you, Mark, I'll tell you, the mouse basal metabolic rate is seven to eight times faster than that of a human. So everything happens in a kind of a split second timeframe. Whereas in humans, we have so much more flexibility to really max out these therapies.

And what we're seeing in humans, we're seeing therapeutic benefits in humans, we have so much more flexibility to really max out these therapies. And what we're seeing in humans, we're seeing therapeutic benefits in humans that we never could see in a mouse. So, you know, we have not cured any mice with advanced metastatic cancer. We've managed it certainly massively better than if we didn't do the right things. But in humans, we're seeing much, much greater therapeutic benefit and dogs too. I want to emphasize that cancer is the number one killer of domestic dogs, and we're starting to see tremendous therapeutic benefit in dogs because their basal metabolic rate is closer to that of a human than it is of a mouse. It's interesting. I had a lab with sort of widespread metastatic lymphoma who was given like a few weeks to live. And I basically put him on a ketogenic diet.

And he lived for at least a year when he stopped eating the food. And then I said, all right, I'll just give him the food he likes again. And then he died within a few weeks. It was quite amazing. Yeah, no, it's unbelievable. As a matter of fact, we published the papers, Open Access in Frontiers in Nutrition, on the complete resolution of mast cell cancer in a dog with no radiation, chemo, steroids, or anything, just metabolic therapy. And we published the recipe in there. So if anyone has a dog with cancer, the recipe for managing the cancer without toxicity is present in that paper. And,

you know, it works in dogs really well. And I think we're going to be able to manage the cancer in the dogs. So the dogs become now a really good tool to test out all these things that we want to plant to put into humans. But what I do in my preclinical mouse models is we can troubleshoot all the different strategies, doses, timing, and scheduling that will be necessary for the eventual long-term management and possible resolution of the majority of human cancers. And that's how the funding for our research comes predominantly from private foundations and philanthropy. And because there are folks out there that know we are on the right track. And as you said, when will this become a reality is not clear to me. Because I mean, you have an institute powerful institutions that have built

up around the somatic mutation theory of cancer. So you get this dogmatic ideology that keeps the status quo. But you have to break that down. Yeah, basically the Earth is flat and the Earth is round, right? Yeah. Well, no, the center of the Earth – the center of the solar system is the Earth, not the sun. Right. So this was the heliocentric, you know, geocentric theory that was broken down. And the Catholic Church adhered very strongly to keeping the earth in the center of the solar system until Galileo, Copernicus, and Kepler came along to prove that it could not be. So we have absolutely shown that cancer cannot be a

genetic disease, absolutely cannot be a genetic disease. And I have written all these papers, and people say, oh, I don't believe you, I don't believe you. Well, read the damn papers, will you? And then you'll come to the realization that this is what it is. So once you realize it's not a genetic disease and it is a mitochondrial metabolic disease, the field will shift over. And it will shift over because people want to live. I mean, you have a very anxious population of suffering people that would like to have their disease managed in a more logical way, not through some medieval kind of stuff that we're doing to these folks today. So clearly, it's going to happen. It has to happen, and it will happen, because what we're doing today is not working. Cancer is going to overtake heart disease soon, and that's only

because we're locked into the somatic mutation theory of cancer. And once you realize the sun is the center of the solar system, you're going to start to see advances real fast, really effective. Amazing. But it's not necessarily just something we have to do alone. And I've seen data, for example, from Walter Longo, who uses calorie restriction diets as an adjunct of therapy for chemo and radiation. It seems that ketogenic diets can be used along with chemo and radiation to actually improve their effectiveness. And I have a very close friend who had, you know, throat cancer, basically, and had neck cancer and was, you know, very poor diagnosis. And he decided to go on a ketogenic diet and get chemo and radiation. And not only did he do great, but there's been no cancer three years out.

And he's also actually had no side effects from the treatment because of the way that the ketogenic diet protected him against the chemo and radiation side effects. Yeah. Yeah. Yeah. Well, I think that's important because we're going to go through a hybrid system because you can't dramatically change one series of treatments over to another overnight. So you're going to have to gradually go through this kind of a hybrid system where some level of radiation or some level of chemotherapy or even immunotherapies may be enhanced in their action when combined together with metabolic therapy. So there's going to be that hybrid transition. And that might be essential because, you know, some of the strategies for the complete resolution of cancer using metabolic

approaches alone are not yet completely developed and validated in clinical trials. So you will have this interim hybrid approach. Like all major technologies that go from one paradigm to another, there's always this hybrid, a transitory hybrid system. And I think we're going to realize that extremely, and this is what some of our clinics are doing, extremely low doses of chemo managed together with metabolic therapy seem to be far more effective with significantly lower toxicity. So whether that's radiation or chemo, you can significantly improve the outcome by using much lower doses and these kinds of things. So I think that until we come up with the most

elegant and complete way of managing cancer with metabolic therapy alone, I think we're going to have this hybrid transition period. And what is your conversation with oncologists? Do you get invited to the oncology meetings? Do you talk to them? What do they say? Well, it's a variation of things. I think some of them feel threatened sometimes, like, what are you going to do? You know, you're touching my meal ticket here. You know, I do this for a living, and now you're coming along saying I shouldn't do what I'm doing. I think for certain cases, like radiation of brain cancer, I think that should be eliminated as soon as possible. I think that's an outrage. I have published papers clearly showing how the

radiation of a patient with glioblastoma elicits the rapid recurrence and death of the patients. And I provided the metabolic mechanisms by which that is happening. And we show that why the survival of these patients is so poor is because they're radiating the brain of these patients. Now, that may not be the case for other types of cancers. So in those kinds of situations, we may be able to have a more transitional situation, but certainly not for brain cancer. But when you talk to some oncologists, they're kind of surprised. Most of the oncologists that support our work are those guys that are now retired. It's kind of like, yeah,

I knew what I was doing all my life wasn't, wasn't the best. And now I realize, but I'm no longer practicing medicine. And now I can pretty much come out and say, and say the things that I would have never said if I were practicing. So, so I see that. And I always have to laugh about that. But, you know. So Tom, I have a quick question. In your, you know, being in this field, can you share a few stories before we close of patients, you know, who've been treated or tried themselves or what the stories are? Because I think, you know, we're considering these anecdotes, but anecdotes are

really the beginning of hypotheses and they're the beginning of actually the scientific research method, which is actually observing what you see and being curious about it and creating a hypothesis. So let's talk about some of those cases and what you've seen. Yeah, the most remarkable one was Pablo Kelly from England, who was written up in all the newspapers over there. And he has his own little podcast thing, I think. He came to me in 2014 with, he heard from Andrew Scarborough, his friend who had a high grade glioma, who took one radiation shot. He said, I'm out of here. I'm not doing that again.

So Pablo talked to Andrew. Andrew said, contact Seafree. So he came to me in 2014, Pablo Kelly. He had just been diagnosed with a glioblastoma. And he said to me, do you think the metabolic diet therapy would work? And I said, geez, you know, I think it might, but I don't know. We've done it in mice, but we've never really done it in a human. And he started it. And they said, you're going to be dead in nine months, Pablo. His oncologist got really angry. And if you listen to

his stories, how they brought him in, they had him put him, he threw all that stuff off and just went on the metabolic therapy. And his tumor didn't grow very fast. And finally, no surgery, he had no surgery and nothing, which was really shocking. And then after three years, he kept emailing me and he said, I'm still alive. In fact, I hadn't heard from him for two years. He emails me. He said, I'm Pablo here. I said, Pablo, geez, I thought you would have been dead. I didn't know you were still alive.

So then three years after the diagnosis, he did a surgical. And my colleague's radiation radiologist said, this is growing, so you probably have to have it debulked. So he went in and got debulked surgery for the first time three years after diagnosis. And then we followed him. He has five years of daily and sometimes more than one day glucose ketone index. So in the paper that I published, which is in, again, Frontiers in Nutrition, we put in Pablo's story. So I didn't write Pablo's story up until five years after his initial diagnosis. So I didn't want to write something up prematurely and say, you know, we think, and this poor guy dies, you know, a little longer than what you'd have expected. He's now out almost nine years. He's still alive. And he had a glial

breast moment. Yeah. And then we found out that the IDH1 mutation, which is interesting because it acts like a drug. It's God's gift to the GBM patient. It's a gene that disrupts glycolysis and glutaminolysis. And here's the crazy thing. There are drug companies out there thinking that that mutation is bad. So they make drugs to target what we consider a therapeutic mutation, and their drugs are killing the cancer patients, some of the patients faster. It's like nuts. So unless you understand the biology of the disease you're working with, you can make real major errors.

But anyway, that story of Pablo, and you can get, people can read about him. He's on British television. He was on newspapers. He has his own podcast. And then there's a movie coming, a documentary that will highlight the stories of all of these kinds of patients that should have been dead that are alive. And the documentary is called The Cancer Revolution. It was made by Maggie Jones, another stage four breast cancer person where they metastasized to all her lungs and brain. And she's still alive, who had done metabolic therapy. And her husband is Brad Jones, a documentary movie guy. And then she says, Brad, you got to make a movie on this stuff. So he's making a documentary.

And they're collecting, as you said, these anecdotes. Well, there's not a few. There's now a whole slug of these anecdote guys that are out there. And the question is, why are we not doing clinical trials to prove that this is a very effective way? And the answer is, we don't do clinical trials because we don't have people that are knowledgeable enough to do it. And the hospitals can't generate revenue doing clinical trials when we're not using these kinds of drugs. But I think we can work through all of this.

I think there will be a way to do this because you can't collect so many anecdotal evidences of stage four people that should be dead that are walking on the planet over and over and over again, whether it's brain cancer, lung cancer, colon cancer, kidney cancer, bladder cancer, you know, all of these different cancers in so-called walking dead people. I mean, they all seem to be getting on with their life. They're living, having an high quality of life. You just can't suppress this stuff for any longer. I mean, it's becoming too much. And it's based on hard science. So once you have the mechanisms of the hard science, we're going to start seeing it.

And then some people will say, well, I can't believe it until the clinical trial. They won't believe it even with a clinical trial. So we're always going to have the people that will never believe this through dogmatic ideology. And how do I know that? Because we did clinical trials on ketogenic diet for epilepsy. And some people said, we can never use a ketogenic diet for epilepsy until there's a clinical trial. So we did a clinical, my colleagues did a clinical trial, and they still want to give drugs rather than ketogenic diet. So it's just, you know, it's just part of the system. So it's going to happen. I know it's

definitely going to happen. I can't tell you when, I don't know. But we're still sitting here in 30 years talking about CAR T immunotherapy and PD-L1, this kind of crazy stuff based on a somatic mutation theory. No, no, no. Things will definitely change. The field is changing rapidly. I mean, I think this is one of the most exciting conversations I've ever had about cancer. And all of us are affected either personally or family members or friends. It's really such a widespread condition and we're really not winning the war very much. I think we've made incremental benefits. Some cancers we definitely have had good cures for, but very far and few between. And I think there is some benefit to CAR T therapy and, you know, PD-1 and, you know,, we call it checkpoint inhibitors, there are improvements

in things like cancer vaccines. But I think they're, again, moving around the edges rather than dealing with the fundamental metabolic issue, which is actually driving most cancers. Yeah, well, I think, no, there's no question. If I looked at the data for PD-L1 inhibitors, and you get about 20 to 30% of people that really do really well. Then you have a majority of people that it doesn't do anything. And then you have 20% of the people where you get what we call hyperprogressive disease, where the therapy kills you faster than the tumor does. And that's called hyperprogressive disease. It's well known in the scientific literature.

Okay. So why would anyone want to take a drug that has a remote possibility of killing you? You know, I mean, this is the truth. This is what happens. I have that, again, people should read the literature about hyper-progressive disease. Immunotherapies are based on the somatic mutation theory of cancer. If the theory underlying the treatment is not correct, you're not going to get the results that you would have predicted at the beginning. Okay. So, and I have hundreds of people emailing me who tell me how their immunotherapies have not worked and now they want to do metabolic therapy. So I see a lot of those folks. So basically the message is start with metabolic therapy. Don't wait till the last minute and try it after you've done everything else in your last legs because metabolic therapy is essentially risk-free. It's got no side effects really. Maybe the

glutamate inhibitors do, but I think it's as a whole a very safe, effective, and by the way, almost free therapy because it's just what you're eating. Yeah. Another thing, Mark, listen, it's very important. If you can pare down the size of that tumor to a few cells that are just hanging on, they become extremely vulnerable to a potential immunotherapy because there's where they may all express the same epitope and therefore the immunotherapy could just blast them out of existence. But you wouldn't want to do it when you have the whole hodgepodge of cells at the beginning. Bring them down to a small manageable group of cells by metabolic therapy, and then polish them off with a CAR T immunotherapy or an immunotherapy. So you're

right. Everything is bass-ackwards whether we're doing it now. You got to start with metabolic therapy, shrink the tumor down, make yourself healthy, and then come in with some of these more perfected treatments. Makes sense, right? Yeah, totally makes sense. Well, thank you so much for your work. It's really groundbreaking. I imagine one day you'll be in a number of places and people will figure this crap out.

And I think, you know, you really, you know, we're out in the wilderness for so long, but now mainstream oncologists and mainstream scientists are now applying this in clinical trials. We're seeing more data be promising. I think there's a lot of hope out there. And I think we're possibly at an inflection point for cancer therapy in the world today. And I think it has a lot to do with the kind of thinking that has led your work for so long. And I see we're really in this kind of very hopeful moment in a very hopeless disease. Yeah, I agree. I agree. Thank you. Well, thank you so much for being on the podcast.

If you, everybody listening, love this podcast, know anybody with cancer, had cancer yourself, make sure you share it with them. I think this is a very, very important conversation and is worthy of sharing widely. I think we'd love to hear your comments, how you used your diet or ketogenic diets or others to actually address your cancer. And we'd love to have you subscribe to our podcast

wherever you subscribe. And we'll see you next week on The Doctor's Pharmacy. Hey everybody, it's Dr. Hyman. Thanks for tuning into The Doctor's Pharmacy. I hope you're loving this podcast. It's one of my favorite things to do and introducing you all the experts that I know and I love and that I've learned so much from. And I want to tell you about something else I'm doing, which is called Mark's Picks. It's my weekly newsletter. And in it, I share my favorite stuff from foods to supplements,

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