Introduction
Dr. Eric Westman: It is my pleasure to have Dr. Thomas Seyfried here today. Thank you for taking the time to talk today.
Dr. Thomas Seyfried: It is a pleasure to have this opportunity to speak with you.
Dr. Eric Westman: Who are you, where are you from, and how did you get into this area that we know you for?
Tertiary background and training
Dr. Thomas Seyfried: Right now I am a professor of biology at Boston College. I teach graduate students, and I have an active research lab with professional scientists and technicians. I teach General Biology to the non-majors, and also cancer metabolism to the advanced undergraduates in the biology program. I have a broad background, but over the many years that I’ve been here at Boston College, 39 years now, I’ve taught neurobiology, neurochemistry, and a variety of other subjects.
I worked for many years in the field of epilepsy, which started when I was a postdoc and then a faculty member in the Department of Neurology at Yale University in New Haven, Connecticut. I did a lot of work on epilepsy, and mapped genes in mice, which would hope to lead to better management of epilepsy. I did most of that at Yale because everybody was interested in it.
Keto Diet and Epilepsy
When we came up to Boston College one of my students said, ‘You should do the ketogenic diet for epilepsy; it really works.’ I said, ‘No, when I was at Yale, I tried to write an internal grant on the ketogenic diet for epilepsy and the animal models that I had.’ They said, ‘Oh no, nobody cares about ketogenic diets for epilepsy.’ Are you kidding me? I said that it is one of the top, non-toxic, non-pharmacological managements of cancer that really works.
To this day, we are really not sure about the multiple mechanisms by which ketogenic diets work for managing epilepsy or seizures. It was started in 1921 by Wilder at the Mayo Clinic. What we found here at Boston College was that it had a lot to do with the levels of blood sugar. We could keep mice and people managed in their seizures for quite a while, but even a slight elevation in blood sugar from whatever, within a short period, would trigger an epileptic seizure.
It was not clear whether it was the elevation of ketones or the management of low sugar that was responsible for maintaining a non-epileptic or, let’s put it that way, a non-epileptic event in the brain. To this day, we are not sure how all this is stopping. There are a lot of hypotheses, but it is still not clear.
Dr. Eric Westman: This makes sense to me a little more now that you had that background with the ketogenic diet and epilepsy, then applying that more to cancer. Have you kept up with the research on seizures? There seems to be a subset who have GLUT4 deficiency.
Generally, everyone gets a little bit better, or two-thirds get better, if you have seizures and you go on a keto diet. Still, it is not well known in the epilepsy world because they are mostly drug-focused.
Dr. Thomas Sefried: Yes, that has been in medical care today in general.
Dr. Eric Westman: That is really it. The puzzle is coming together a little bit. How did you pivot then to other types?
Dr. Thomas Seyfried: We realized the way the ketogenic diet seemed to be linked to blocking seizures was by having low blood sugar and elevated ketones. When we put mice that had epilepsy on calorie-restricted diets, where blood sugar would go down and ketones would go up naturally without a ketogenic diet, we got the same management of seizures. It was clearly a ratio of glucose to ketones that was blocking epileptic seizures. The molecular mechanism by which that happens in neural circuitry is still debatable, whether it is an increase in inhibitory neurotransmitters, a reduction in excitatory neurotransmitters, or the signaling pathways that are involved is still up for debate.
Brain tumors
Dr. Thomas Seyfried: At the same time, we were doing a lot of biochemistry on brain cancer. We were looking at glycolipid metabolism in brain tumors. I had a number of mice that were built with brain tumors, and we were always asking whether the glycolipid patterns in mouse brain tumors were similar to those in human brain tumors. I did some comparisons, and there were some similarities, but there were also a lot of differences.
The main problem was it was hopelessly complicated. Whether you have a human brain tumor or a mouse brain tumor, it turns out that a lot of the blood vessels have different glycolipid patterns. The angiogenesis, the blood vessels, and the infiltrating immune cells all had their own unique ganglioside glycolipid patterns mixed together. It was very difficult to figure out who was responsible for what. It turned out that I was looking at glycolipid finger lipids, and a company gave me a drug. We were working on Tay Sachs disease, which is a glycolipid storage disease, and we were looking at blockers of ganglioside biosynthesis. Like everything that comes into my lab, I always throw it on an epileptic mouse or brain tumor mouse.
I put this on the epilepsy mice, this ganglioside inhibitor, and the seizures were reduced. I said, “This is really exciting!” The drug company decided to give me a lot more money. Not only that, I put it on brain cancer mice with brain tumors, and they got very excited because it was shrinking the brain tumors. I said, “What is going on with this drug? This is really an unbelievable drug! It blocks epileptic seizures in mice that have genetic epilepsy, and it shrinks glioblastoma models in the mouse.”
The company gave me a substantial amount of money to figure out what the mechanism was by which this drug was working. It was interesting. When we fed the drug either to the mice with epilepsy or to the mice with brain cancer, their body weights went down as if they were calorie-restricted. The epilepsy or the brain cancer, the tumors, stopped growing or grew very, very slowly. The seizures gradually dissipated, but the animals lost body weight.
I was saying, “What’s going on with that?” It was acting like a calorie restriction because when you calorie restrict mice with brain tumors, also the tumor went down and shrunk. So, I decided to put in a bodyweight control on this drug. I would just feed the animals less food to match exactly the body weight of the drug, and sure enough, it was equally powerful in stopping seizures or shrinking the brain tumor.
I said, “What is this drug doing?” It turns out the drug blocked sucrose in the gut. The animals ate the food, but they couldn’t digest it to get the carbohydrates out of the food. The drug was causing an indirect calorie restriction, and that is the reason why it works so well. When I told the company that this drug was working indirectly through calorie restriction, immediately, all my support and funding disappeared.
Dr. Eric Westman: Sometimes you don’t want to be quite so honest.
Dr. Thomas Seyfried: They dropped it like a hot potato. The drug actually worked on gangliosides; it was shrinking that, and that is what made them think that it was working. But it was not the gangliosides, we ruled that out. It was the calorie restriction that lowered the blood sugar.
I started to think about how this works, and then I found out about Warburg’s work from years and years ago, the great German scientist.
The Otto Warburg effect
Dr. Eric Westman: How did you rediscover the Otto Warburg effect?
Dr. Thomas Seyfried: Linda Nebling at Case Western Reserve University got her PhD there in nursing, and she was giving little children ketogenic diets that were hopeless cases. They were both poisoned, irradiated, and surgically mutilated. These little children with high-grade gliomas were given up on. As a nursing student, she said, ‘We have got nothing to lose, why don’t we give them ketogenic diets?’ That immediately brought us in because we knew about ketogenic diets and epilepsy, and we knew that the ketogenic diet worked because it was lowering glucose and elevating ketones.
She said that she got dramatic results on these little children who had gliomas with a ketogenic diet. She said it might have something to do with what Otto Warburg said. So, I said, ‘I’ve heard of Otto Warburg, everybody’s heard of this guy, what did he do?’ I went back and started to unpack all the work that he had done, and I said, ‘This guy had it right.’ From that point on, from about the year 2000 up until the present, we started to look deeper into this cancer thing, looking at the metabolism.
Dr. Eric Westman: The analogy is very interesting because I rediscovered the treatment of diabetes and obesity from 100 years ago, and it was a low-carb diet. What did Otto Warburg do, and what did he learn? I know it is more complicated than that, but did you go back and read the articles?
Dr. Thomas Seyfried: From his work in the 1930s, it goes back to the late middle 1920s up to the 1960s. He said that cancer was a metabolic disorder, and all cancers had chronic damage to oxidative phosphorylation, the ability to produce ATP through oxygen. As a result of dysregulated growth, they had to compensate by switching to energy that involved no oxygen, like fermentation. Energy without oxygen is fermentation.
He said that to get cancer, you have to have chronic damage to the ability of the organelle, the mitochondria, to produce energy through oxygen, but it has to be compensated by that cell’s same ability to upregulate a fermentation metabolism. Therefore, there are two steps to getting cancer: Number one, chronic damage to oxidative phosphorylation, and step two, a compensatory substrate-level phosphorylation, or what we call fermentation.
He clearly showed that all major cancers had a reduction in oxygen consumption and an excessive production of lactic acid, which is the end product of the glycolysis pathway, the Embden-Meyerhof-Parnas pathway. He said this was the characteristic of all cancers. I read the papers very, very carefully in light of what I was seeing for the first time in my research, and I am saying, “This guy was right.” But he was not completely right, and I did not realize at the beginning where he made some mistakes and why his critics misinterpreted a lot of what he said, and continue to this day, as you and I are speaking, to misunderstand what Warburg did and the mistakes that Warburg made.
In those days, oxygen consumption was considered a direct linkage to ATP production through oxidative phosphorylation. Warburg made this connection based on Hans Krebs’ work of the Krebs cycle, that each mole of oxygen breathed produces seven moles of ATP, which is the energy from oxidative phosphorylation. He showed that all these cancer cells were breathing less, they were consuming less oxygen, and they were all producing excessive amounts of lactic acid. Everybody knows that if you hold your breath or have a heart attack, or whatever, lactic acid builds up in your bloodstream. Even sometimes with epileptic seizures, when the patient stops breathing during the seizure, lactic acid explodes in the bloodstream because the tissues are now deprived of oxygen. To prevent themselves from dying, you immediately upregulate a powerful fermentation metabolism, which is energy without oxygen, but the waste product, the end product, is lactic acid.
So, you see lactic acid build-up, and what Warburg said is that all cancers have a deficiency of oxygen consumption and a buildup of lactic acid, and that is because they have chronic damage to oxidative phosphorylation, which is compensated for by lactic acid. He showed that even in 100% oxygen, all tumor cells continued to throw out lactic acid, and that could only happen if there was chronic damage in their mitochondria and the ability to oxidative phosphorylation. While that was logical and all cancers seemed to have this, they referred to it now as the Warburg effect, and everybody seems to be comfortable with that, although most people misinterpret what it means. I looked at that and all different kinds of things, and what I found was that his attackers, the people who did not agree with him, said, “There are some cancer cells that have completely normal oxygen consumption, and therefore Warburg must be wrong.” The reason why they continue to produce so much lactic acid is because they have a defect in lactic acid in glycolysis, not a defect in oxidative phosphorylation. This argument is still ongoing today. Many people refuse to believe that Warburg was correct.
What my colleagues and I did was we carefully examined oxygen consumption. Is it an accurate marker for ATP synthesis through oxidative phosphorylation? Is there a direct relationship? The answer is, only in normal cells and tissues is there a direct relationship, and not in cancer. This is where Warburg and all of his critics made this big mistake. They assumed that the oxygen consumption in a cancer cell was producing ATP as efficiently as oxygen consumption in a normal cell. We and others have shown that oxygen is consumed in cancer cells but not used entirely for ATP production.
Oxygen consumption and cancer cells
Dr. Eric Westman: What else does it do? What is it that they use?
Dr. Thomas Seyfried: They produce reactive oxygen species (ROS), so a lot of the cancer cells take in oxygen and use it for the production of reactive oxygen species and a variety of other activities independent of ATP production through oxidative phosphorylation. You can’t use oxygen consumption in a cancer cell as a reliable substitute for oxidative phosphorylation as a reliable surrogate. This is the new stuff that we are presenting now as we speak in some of our new writings, which then throws the whole cancer field into a tiff because now everybody was using oxygen consumption and saying oxidative phosphorylation is normal in cancer cells.
Warburg was right that mitochondria are defective. His quantification using oxygen consumption was not correct, and to this day, it is not correct with most of the people who say Warburg was wrong. We cleared that up, and then we also found out that the mitochondria in cancer cells produce ATP through a fermentation metabolism, specifically amino acid fermentation. The mitochondria in cancer cells can ferment … nobody knew this, we have new evidence now that glutamine, which everybody knew was used by tumor cells in huge amounts, is fermented. We now have direct evidence that glutamine is a fermentable amino acid.
When you look at a tumor cell, you see it is consuming oxygen and making ATP, making it look like it is normal. But the oxygen consumption is used for reactive oxygen species, and the ATP is coming from a glutamine fermentation metabolism. This throws the whole field into a frenzy. They are going to come to know this, and they are going to come to know real soon because Otto Warburg was not incorrect; he just did not have all the parts of the puzzle like we now have. Therefore, cancer can grow without oxygen because it ferments, and it ferments glucose and glutamine, the amino acid. Now that we have put this together, we know how to manage cancer; we know how to prevent it.
Dr. Eric Westman: You learned that a keto diet was something that children with epilepsy could have, and it probably made you more comfortable with the whole concept of not feeding animals and humans carbs. Then, the idea of blocking the sugar absorption with a drug started having these effects even on a brain tumor, the glioblastoma brain tumor model. How did that alter or shift the science that you wanted to create and generate?
Cancer cells cannot survive without fermentation
Dr. Thomas Seyfried: That is an excellent point, which is still not understood by the majority of oncologists and is refused to be accepted by the cancer industry itself. These tumor cells can’t survive without fermentation, and the two fuels that ferment are glucose (the sugar) and the amino acid glutamine. When they say, “Cancer cells can switch to other amino acids,” no, they can’t. We tested them, and none of them were as effective as glutamine. “Oh, they can go to fatty acids,” no, they can’t.
I threw it out, I said, “Challenge me. Show me any tumor cell that can live in the absence of glucose and glutamine on fatty acids and can survive, not just for an hour, but for several days.” Normal cells can do this. Normal cells don’t need glucose and glutamine; they can survive on other fuels, such as ketone bodies and certain things like this. Nobody can show that. We know cancer cells are absolutely dependent on two fermentable fuels for survival, very clear. Although it is not accepted, because they think that some gene mutation is involved, we showed that all those gene mutations are downstream epiphenomena, they are not the cause; they are the effects of the abnormal energy metabolism.
Let me get right to the core. Once you understand, just like with epilepsy, you can manage seizures if you lower glucose and elevate ketones. When you lower your blood sugar, whether it is through water-only fasting, ketogenic diets, or low-carb diets, however, you want to speak about it, and we built the Glucose Ketone Index (GKI) calculator, which calculates the ratio of glucose to ketones in the blood, and when you have low GKI values, the tumors start to get hammered big time. They can’t adapt, they are locked into a fermentation metabolism dependent on two fuels. Then people say to me, “You will never get glucose to be as low as you need to kill the tumor.” Yes, you can, absolutely. If you remember the study by Dr. Drenick, where he took obese people, he published the paper, I think it was several very obese men, and he fasted them for 21 days, just water only for 21 days, and then injected them with insulin. The blood sugar was brought down to 0.5 millimoles or 9 milligrams per deciliter. As a physician, you know most normal people would be dead. Yet, these guys were perfectly cognitive.
We don’t recommend doing that at home, but the study showed that there were no adverse effects. They attributed this to the ketone bodies replacing glucose for the brain, keto adaptation. Keto adaptation allowed these guys to be resistant to very, very low glucose levels.
Dr. Eric Westman: If you are running your body on ketones, the glucose level doesn’t have to be so high. The puzzle today is still how to prevent glutamine from being present.
The press-pulse therapeutic strategy
Dr. Thomas Seyfried: That is why we developed, with my physician colleagues, the press-pulse therapeutic strategy, which has its linkage to paleobiology. What I do in my research is look deeply into evolutionary biology and concepts of science. Paleobiologists were trying to figure out what caused great extinctions of organisms on the planet over the history of Earth. These massive extinctions seemed to happen when two unlikely events occurred together: chronic stress on large numbers of organisms on the planet, killing off the weak ones while many of the strong ones survived; then, some sort of impact, like a comet or an explosion of volcanoes all over the Earth, was the pulse. The chronic environmental stress, together with some pulse, caused the complete extermination of almost all organisms.
I developed that concept for managing cancer. I said, “If we can lower the blood sugar and put tremendous stress on the cancer cells, but a few of them survive on the low glutamine, then we come in with a drug that just pulses the glutamine – short pulses, which wipes out large numbers of cancer cells.” We also know, based on our research and the research of others, that our immune system needs glutamine to function, our gut needs glutamine to function, and our urea cycle needs glutamine to function appropriately. So, if we stress too much on the glutamine, we cause harm to the body. But if we come in short with pulsing while keeping the chokehold on the glucose, with the diet pressing the glucose down massively, we can then target the glutamine with short pulses, keeping the gut and immune system healthy.
When we pull off the glutamine targeting, our immune system comes in and picks up the dead cancer cells and then gets rid of them. We come back and pulse it again. It is a press-pulse concept that gradually degrades the tumor while allowing the body’s normal functions to work, without paralyzing them, to eliminate the tumor. It is a beautiful approach. You have to understand human systems physiology, biochemistry, evolutionary biology, and genetics. You put all that together, and you can come up with a nice, non-toxic therapy for managing cancer. It doesn’t require all these toxic drugs hunting for genes, which are all downstream epiphenomena. Once you understand the biology of the problem, you can then design non-toxic therapeutic strategies.
Those folks who do it and understand how it works, you can’t believe the therapeutic efficacy these people achieve. Cancers go into remission. I am not saying we cure cancer, but we certainly can manage it for long periods without toxicity, and maybe there are some resolutions.
What glutamine is
Dr. Eric Westman: Let me just see if I understand this. You use some kind of diet to get the glucose low, and then, what’s the pulse again? Do you take away glutamine?
Dr. Thomas Seyfried: Glutamine is a non-essential amino acid. It is made from glucose, so if I am lowering glucose, I am also not producing as much glutamine by lowering the glucose. But we also know it is extremely important for physiology, so I come in with glutamine-targeting drugs.
Dr. Eric Westman: Okay.
Dr. Thomas Seyfried: These drugs, like 6-diazo-5-oxo-L-norleucine (DON), which was not available to people, are very powerful. They should be. When they have all these other crazy drugs out there that cause your hair to fall out, your gums to bleed, diarrhea, and nausea. They say these are the drugs you should take, but the very drug that works the best is not available for you to take. Can you believe this?
Dr. Eric Westman: Has that changed? Are they still not available?
Dr. Thomas Seyfried: No, they are not available, which is crazy. Why the Food and Drug Administration allows all these toxic poisons to be used to treat cancer patients, I don’t know. But I don’t think the FDA is getting paid off by the pharmaceutical industry, are they? Maybe they are, I don’t know.
Dr. Eric Westman: No, but it takes a lot of money to generate the studies that would be needed, I think.
Dr. Thomas Seyfried: We have already done the studies. Don’t forget, DON was used in little kids with leukemias, and DON was used in the past. It had some therapeutic benefits, but not for everybody. They did not target the glucose when they were using the DON. It is not going to work the way it should work.
Dr. Eric Westman: What would you need? A lot of people will watch this who have other day jobs for which that might be helpful. Is there an available drug, you can purchase it from a drug company, but it is not approved for human use?
Dr. Thomas Seyfried: Yes, not approved for human use.
Dr. Eric Westman: You get in hot water because you are not an MD.
Dr. Thomas Seyfried: Oh, yes. If I had cancer, I would buy it from a chemical company and use it because I’ve seen how it works.
Dr. Eric Westman: Some years ago, I worked with the inventor of the nicotine patch, and I was asked to get drugs, which would then be prepared by our university pharmacy for human use. They make sure there is no mold and so forth, so under some sort of investigational drug research, this could be done and changed into human use.
I would like it if young oncologists watching this, who want to try a treatment that you’ve done. How many years or how many models of cancer have you used this press-pulse therapy on?
Press-pulse therapy on humans
Dr. Thomas Seyfried: We did it in mice first, but now, when humans try, they do much better than the mice. Our basal metabolic rate is seven times slower than that of the mouse, so our bodies can deal with this much better. Then you have a physician looking at the patient and monitoring how they feel today. The mouse can’t tell us that.
The success of ketogenic metabolic therapy for humans is so much more powerful than it is in the mouse. We look at the mouse, and, if he’s breathing heavily, not moving, his hair looks disheveled, we know he’s not feeling well. We try to move him away from those states, but we can’t ask him; we can only know by the way he eats and the way he moves around that he’s okay.
Dr. Eric Westman: Are you working with any research setting or with doctors who are using this with people?
Dr. Thomas Seyfried: No one is using DON. There might be a few people. Wealthy people can get whatever they want. If you have a lot of money, you just go out, buy it, pay a physician to give it to you, and here’s the dosage because it has already been published in the scientific literature. It has been used on people, and the evidence is there. How much should I use? When should I use it? It has all been there.
Dr. Eric Westman: I would still like some young oncologists or, or even older ones, sometimes there are people at the end of their careers who have not fixed anything, and they say, “We will let one of our postdocs look at a keto diet.” Now, there is a whole neurodegenerative field based on what seems to be what Jong Rho and Adrienne Scheck were exploring. It seemed like they were at the end of their careers and said, “Let those postdocs do what they want,” and now they are stuck on this.
Cancer is not a genetic disease
Dr. Thomas Seyfried: It works. The thing is, you’ve got to know the tools that you have and how to use them. I find that in medical training, no one speaks about metabolic therapy as the future for managing cancer. They are all indoctrinated to think cancer is a genetic disease, and they are going to find these drugs that target your ALK mutation, your EGFR receptor, or these crazy things that are all downstream epiphenomena.
I published a major paper showing that cancer is a mitochondrial metabolic disorder, not a genetic disorder.
Dr. Eric Westman: Tell me about this study; it was brilliant.
The study
Dr. Thomas Seyfried: It was several studies that I put together, and I said you have to be cognitively challenged to think that cancer is a genetic disease. Either that or you have to be a hopeless ideologue. Anybody with a few functional brain cells who reads the papers would have to realize cancer is not a genetic disease.
What I did was I went through a lot of different things, and where did this idea come from in the first place, that cancer was a genetic disease? It came from Theodor Boveri in 1914, who studied sea urchins, and he had a hunch that cancer might involve some chromosomal abnormalities. He said, “I am probably completely wrong, I am an interloper, and I don’t know anything about cancer.” Yet, the field regards him as the founding father of gene theory.
What I found is that if you look at some of the papers, like Sir Michael Stratton, who is very well-known in the field of cancer genetics, found several breast cancers that had no mutations. How can you say in the somatic mutation theory that cancer is a genetic disease if I find cancer cells that have no mutations? How do you explain that? How can you say that?
What I find is happening, also, is Parsons with glioblastoma found a patient that had none of the mutations, no mutations in what they predicted. So, what do they do? They ignore it. They don’t say anything about it. They absolutely ignore it. I said, “What do you mean? You have direct evidence that these cancers are not due to mutations, and yet you are saying cancer is a genetic disease. How could you say something like that?”
The National Cancer Institute (NCI) says on its homepage that cancer is a genetic disease consisting of 100 different diseases, all with different genetic mutations. Nothing could be further from the truth. Don’t these people at the NCI read the scientific literature?
Dr. Eric Westman: How did you convince yourself that it is not?
Dr. Thomas Seyfried: I am going through the list, and we find that not all mutations are bad, only the driver mutations are the ones that cause dysregulated cell growth. Now, we are finding new papers coming out that show driver mutations in our normal tissues that never become cancer. That throws cold water on all those suggestions that maybe cancer is not a genetic disease.
When you go back and look at the nuclear-mitochondria transfer experiments, that is the nail in the coffin. Where scientists, Israel and Schaeffer from Vermont took the nucleus of a tumor cell and put it in the cytoplasm of a normal cell, and they got complete regulated growth despite the continued mutations in the nucleus. And when they did the reverse experiment, where they took the nucleus of a normal cell and put it in the cytoplasm of a tumor cell, they got dysregulated cell growth and cancer. This was done in frogs, in mice, and it was done in vivo, in vitro, repeated over and over again by some of the best developmental biologists in the field.
None of them were testing Warburg’s theory; they were asking how far a cancer nucleus could drive normal development. In each case, it drove it to a certain extent, and then the whole system aborted because the mutations in the nucleus were aborting development. At no time did those mutations lead to dysregulated cell growth, which is the definition of what cancer is.
When you look at the transfer experiments and all these others, you have to be cognitively challenged to think that cancer is a genetic disease.
How a cancer cell works
Dr. Eric Westman: Non-scientists list says the genetic material is in the nucleus. If you argue that cancer is entirely genetic, and you are changing the nucleus, which has the genetic material, to other cells, this does throw a wet blanket on that. And then, if you change the mitochondria from cell to cell.
Dr. Thomas Seyfried: It is very interesting, all these oncogenes and tumor suppressor genes, these things that people think are important when you put new mitochondria into the cytoplasm, they all turn off because you don’t need to ferment anymore. The reason those oncogenes are there is to facilitate fermentation metabolism.
When a cancer cell becomes dysregulated, it has to have all of this glucose and glutamine pouring into the cell. The cell needs to replace oxidative phosphorylation (OxPhos), so you have to open the floodgates to get in a poorly used fuel because you are wasting so much of it as a waste product. They are driven by oncogenes, but if you put a new mitochondrion in there, it is like putting a new engine in the car, everything’s working again. The oncogenes are all turned off. It is very clear what’s going on here.
Genetic mutation is an epiphenomenon
Dr. Eric Westman: Something you said earlier if you could just explain, the genetic mutation is an epiphenomenon. Explain that to the general public.
Dr. Thomas Seyfried: When you look at cancer, yes, they are full of mutations. All cancer cells are loaded with them, and now, over millions, this is the big genome project, they’ve identified millions of mutations. Where do all these millions of mutations come from in these cancer cells?
Dr. Eric Westman: They come from radiation?
Dr. Thomas Seyfried: Yes, radiation can do that. Chemical carcinogens can do that, but how do chemical carcinogens cause mutations in the nucleus? They base their studies on salmonella, which is a bacteria. You put a chemical carcinogen on the bacteria, and you get mutations, but in humans, the chemical carcinogen goes into the mitochondria. The oxygen we breathe forms oxygen radicals called ROS (reactive oxygen species). These include the superoxide anion and the hydroxyl oxygen molecule, which damage DNA, proteins, and lipids.
The mutations that we see in the nucleus are downstream effects of the mutagenic process in the mitochondria. Bad mitochondria that don’t function properly produce ROS that are carcinogenic and mutagenic as a secondary effect of the damaged oxidative phosphorylation. Our nucleus collects all these mutations, and almost the entire cancer field is focused on all these mutations that are all downstream epiphenomena.
That is why you have Keytruda, Opdivo, and all these immunotherapies you hear about because they are trying to allow the immune system to function despite all these different kinds of mutations. So, most of the therapies now, here’s the situation, the immunotherapies like CTLA-4, PD-1 inhibitors, and all these things you hear advertised on TV at night, how they are going to do so wonderfully, they are all based on the somatic mutation theory of cancer. If the gene theory of cancer is not correct, you are not going to make any major progress.
We have almost 1,700 people a day in this country dying from cancer, which comes to about 70 people an hour. It gets worse and worse every year, and every year we hear about a new drug, or a new therapy, all based on the somatic mutation theory. If the somatic mutation theory is not the correct theory, you are not going to get an optimal outcome any more than the geocentric theory could explain the movements of the planets. Copernicus came along with Kepler and Galileo and said, “No, the Earth moves and circles the sun,” and once that happened, everybody said, “Oh yes.” But for 1,800 years, people thought the Earth was immovable and the sun revolved around the Earth.
Right now, the whole cancer industry thinks that nuclear gene mutations are the drivers of dysregulated cell growth. No, they are the effects, not the drivers.
The future and mitochondrial transplantation
Dr. Eric Westman: So how? If we could only transplant the mitochondria in every cell in the cancer tumor, or do you fix the mitochondria? Cut the sugar down? Is there any way to fix that mitochondria?
Dr. Thomas Seyfried: That is the future. I have been approached by entrepreneurs, these guys say the future of cancer is mitochondrial transplantation. That is not going to be in my lifetime, so I am not going to be around long enough to see mitochondrial transplantation. Yes, in culture, it was shown that if you can put new mitochondria in the cells, you can bring them back to growth regulation.
I am alive long enough to kill the tumor cells without toxicity so that we can also let people live longer. Right now, we know they can’t live without fermentation, and they can’t burn ketones or fatty acids. I published a big paper showing that all cancer cells accumulate fatty acids in the cytoplasm. It is because they can’t use them, and if they try to burn them, they get reactive oxygen species and kill themselves, it is like a protection. Yet most of the people in the cancer field think that those fatty acids are there to drive the dysregulated cell growth. These people have no clue, they don’t read the scientific literature, nor do they understand evolutionary biology. The fatty acids can’t be used as tumor cell energy, nor can ketone bodies. They are driven by fermentation. Fatty acids and ketones are non-fermentable fuels. Cancer cells thrive on fermentable fuels. What are they? The sugar glucose and the amino acid glutamine. Yes, we looked at other amino acids. We interrogated them all. Yes, asparagine can do a little bit, and glutamate can do a little bit, but not like glutamine. Glutamine is the big dog in the amino acids that can be fermented. So you have glucose fermentation, and you have glutamine fermentation. They can’t use fatty acids and ketone bodies.
The solution to the cancer problem is quite simple: lower the blood sugar, elevate the ketones, and then come in with the pulsing of the glutamine pathway. You should be able to manage these cancers quite effectively without toxicity. This is why we are seeing these parasite medications, they attack the same metabolic pathway that the tumor cell is dependent on, and they are very non-toxic. They work together with the whole transition of the body away from sugars, away from carbohydrates, and elevated ketones.
This is a planned attack on cancer that will be strategic, based on evolutionary biology, and it is non-toxic. The question you’d ask is, “How come all the big cancer centers don’t know about this?” The answer is, I don’t think they want to know about it. They are also indoctrinated to think it is a genetic disease. So how are you going to move the needle?
Dr. Eric Westman: Although some doctors will be frustrated with the lack of success, in my experience, I did not want to go into oncology because I wanted, most of the time, to win. So there is a selection bias of the personality of someone who goes into oncology. Then the other phenomenon that I noticed is that if you are a researcher and you just get funded to study exercise because that is what you are interested in, you will never study diet.
When Coca-Cola was funding an exercise researcher, he did not care that it came from Coca-Cola. What Coca-Cola was doing was keeping other people away from the researcher, to make him focus on something other than Coca-Cola. So the chemotherapy industry is going to keep these vouchers busy with radiation and chemo, the traditional tools.
It seems in some areas of oncology, there have been some victories, but there is a lot of change going on. I had a patient come to my office with aggressive cancer. I am not known for treating cancer; it is more obesity and diabetes, but he learned about keto and cancer and had read your book. He went to other universities, and I thought, “I’ll just go to PubMed.” I typed in “invasive thyroid carcinoma” and then “keto,” and there was a paper that popped up from Matthew Yeh at Harvard, who is a surgeon and has an animal model. He came to this because his wife went to a keto meeting and then told her husband. Her husband started studying this, and it turned out that it had some benefits, reducing tumor growth in the animal model.
I am hopeful that there will be people who will study this. One of the criticisms I got 25 years ago for studying a diet that was unusual and ostracized was that Dr. Atkins funded that first study. I say through the years, the hallmark of science is replication. In your world, is there another center or investigator that has replicated what you’ve done? That is important.
Replications and mitochondrial metabolic disorder
Dr. Thomas Seyfried: I think the replications come here and there. Maggie and Brad Jones are doing a big documentary on the cancer revolution, showing that it is actually a mitochondrial metabolic disorder. They are categorizing and putting these folks into a group, all telling their stories of how they used metabolic therapy to manage their so-called terminal stage four cancers. We are collecting a group of these folks, and everyone that I get, because I get several people emailing me, I send them my information, a kit of information, and they use it. Then you don’t hear from them, and all of a sudden, a year or two, three years later, they come back and say, “I am still alive.”
The doctors are always miffed; they have no clue what happened. A lot of them don’t even ask, “What did you do?” They just say, “Whatever you did, just keep doing it.” They don’t even want to know what the person did.
Dr. Eric Westman: Is anyone helping you assemble these stories?
Dr. Thomas Seyfried: Yes, I now have a registry of folks, and I share them with Maggie and Brad Jones. Maggie and Brad then put these people into their documentary. It used to start with a few people, and they would say, “They are flukes.” They, by the grace of God, something happened, and their tumor disappeared. All of a sudden, you get more of them, and then more of them, and more and more of them. It’s starting to be a stampede of flukes.
Why are these stage four terminal cancer patients still alive years after they were told to put their lives together and get ready for the end? I find that when we get these people, and they start the metabolic therapy right after their diagnosis, and they are major participants in the management of their disorder, their condition, they are the ones that do the best. The ones that feel, “I don’t want to do that. No, low carb? Forget it.” Those guys can go out and look for tombstones because they are not going to be the survivors. The survivors are the ones that take an active role in the management of their disease.
Metabolic therapy is not a cure
I should also point out that metabolic therapy does not guarantee a cure for cancer. Metabolic therapy is a way to manage your disorder and keep you alive for a longer period with a higher quality of life. If you live to be 95 years old when you were diagnosed at 35 with terminal cancer and you die from heart disease at 95 and your cancer never came back, only then could someone say that that guy was cured. Pablo Kelly in the UK was diagnosed with a glioblastoma 10 years ago, and he’s still alive today. It is very funny; he was diagnosed with an inoperable glioblastoma, and if he did not do standard care, he was not expected to live more than 9 or 10 months.
He chose no radiation, no chemo, no steroids, nothing. The tumor continued to grow slowly. He had his first debulking surgery three years after his first diagnosis. Then, he went on metabolic therapy again. Another three years went by, he had another debulking surgery, and the tumor continued to grow. He’s just finished his third debulking surgery, no radiation, no chemo. We were laughing the other day with Pablo. He says, “I am still alive for over 10 years now with a glioblastoma, and they said it was inoperable.” Now, it’s been operated on three times, but he’s still alive. He got married, and he has two kids.
The issue here is, is he cured? No, he’s not cured. Is he alive? Yes, he’s alive, and he has a fairly good quality of life other than a few seizures that he manages with a ketogenic diet.
Glioblastomas and keto responsiveness
Dr. Eric Westman: Is that a coincidence that you had a glioma model and it seems like glioblastomas are somewhat keto-responsive? You had an epilepsy and a glioma model?
Dr. Thomas Seyfried: I did not have epilepsy in it. I had mice that had two tumors that arose spontaneously in the brain of a mouse, and they were glioblastomas. Then, I produced several by putting chemical carcinogens into the brain. So, I produced a range of glioblastoma models that replicate the different kinds of neoplastic cells you would see in a human with GBM.
They are highly invasive mesenchymal cells, and then there are these rapidly proliferating stem cells. You hear a lot about stem cell gliomas, you hear a lot about stem cells. Whatever the cell is, whether it is stem cell biology or whether it is mesenchymal biology, they are all dependent on fermentation for survival.
Dr. Eric Westman: Dr. Nez at Harvard explained to me, just by email, that some tumors are very glucose-dependent. He’s a surgeon who takes out these fast-growing tumors but knows they are going to come back. Can you test how responsive a tumor might be by taking a biopsy and putting it on a petri dish?
Glioblastoma – glucose and glutamine dependent
Dr. Thomas Seyfried: What we found is that he is right. The human glioblastoma, they used to call it “multiforme”; they don’t use that term anymore, they just call it a glioblastoma, but the reason why they had multiforme was because it consisted of so many different types of cells in there. You wouldn’t know which part. Some people have a lot of what we call mesenchymal cells, which are a highly invasive part of the GBM, and others have a lot of stem cells, which are the most rapidly growing part, but they don’t invade; they just grow rapidly. A lot of angiogenesis, a lot of blood vessels, inflammation, all this kind of stuff. Some of them are indeed more glucose than glutamine-dependent, and the mesenchymal cells are more glutamine than glucose-dependent. The way you kill them is you have to target both fuels simultaneously. Then you kill both kinds of tumor cells. It doesn’t make any difference what they are; they are going to die because they need the fermentation fuels to survive.
That is why you target both together while transitioning the body over to ketones because neither the stem cell nor the mesenchymal cell can burn fatty acids or ketone bodies. We tested all those studies and we know now that how to kill these cancer cells is not that complicated. They are driven by a fermentation metabolism, and they can’t switch to fatty acids or ketones. Regardless of whether it is a mesenchymal cell, a stem cell, or whether it is bladder cancer, colon cancer, or breast cancer, they are all the same. They are all fermentable. It is a fermentation machine, just like Warburg said. Once you understand that, then you know how to go and strategically manage cancer without toxicity.
The problem is that I can speak until I am purple in the face, and when I talk to some of these oncologists, it is like I am talking to a plug socket. They just can’t seem to understand what I am saying, and they don’t read the scientific literature. They are indoctrinated to think cancer is a genetic disease, and the promise of the immune therapies, the genome projects, and all this stuff was to do precision medicine, target the gene, kill the tumor cell. That has not materialized because cancer is not a genetic disease.
We still poison and irradiate people, only that was supposed to disappear when we realized the new precision medicine was coming. it is not coming because it is based on the wrong theory. Once you understand the theory, then you will be able to manage cancer effectively without toxicity. The problem is, I can’t get that word out. I publish in good journals, I give podcasts, I tell people, I’ve got all this anecdotal evidence that it works, it does really well, and then people go to their oncologist, and they say, “We have to use radiation, toxic poisons, and all this other stuff.” We are going to use some CTLA-4 immunotherapy and Opdivo, which is a checkpoint inhibitor that should have been removed from the market. They are still using drugs that don’t work, cost a lot of money, and hurt people.
What is wrong with that? Doesn’t anybody have a soul? Don’t they understand what’s going on here?
Dr. Eric Westman: I’ll never forget a wonderful teacher in my experience who was into mismatched bone marrow transplants, which at that time, not many of them were done at all. You would watch people be very sick, and there was this saying or quotation, “Desperate times, desperate measures.”
With the ongoing research, I am optimistic about Jeff Volek at Ohio State being funded to do research. He had a paper recently on the feasibility of a low-carb keto diet for, I think, breast cancer, stage four or metastatic breast cancer. Do you think that just the keto diet itself, without the pulse therapy, is going to have the same possibility of effect? Or is this going to be like the Women’s Health Initiative study? Half a billion dollars, and they studied the wrong diet. We don’t want to study the wrong diet.
Metabolic therapy without drugs but needing pulsing of the glutamine problem
Dr. Thomas Seyfried: I think some people do, in fact, respond remarkably well just to metabolic therapy without drugs. What we think, though, is to get more people to respond, you are going to need some pulsing of the glutamine problem. There are several reasons for that. Number one, you can manage the cancer faster. you are going to kill tumor cells faster with pulse therapy. What we do in the world, and in fact, we have a big paper under review right now on this whole thing, is when the person is diagnosed, regardless of what cancer they might be diagnosed with, we do very comprehensive blood work.
We check many blood parameters and all the panels, the lipid panels, the nutrient panels, the micronutrient panels, all these different panels, and see how far they are from normal. Generally, we put them on a low-carbohydrate diet. For some, it is much easier to jump into water-only fasting if you’ve been on a very low-carb diet for a week or so.
When you jump into water-only fasting, it is much less traumatic to the system. Then we start to see all the blood work getting into the right ranges, the right parameters, and then we monitor the blood glucose ketone index, using the Keto Mojo meter or whatever meter you have, sometimes FreeStyle Libre and all these different ways to measure blood sugar levels, when you get into a low GKI of 2.0 or below, that is when we start coming in with the pulsing. That is when we hit them with the glutamine-targeting drugs. These drugs work so much more powerfully when the patient is in low GKI therapeutic ketosis, which is the biomarker, the physiological state of nutritional ketosis.
We are also realizing that even some of these poisonous, toxic chemicals they are using on cancer patients can work so much better when the patient is in nutritional ketosis. We are seeing that the dosages can be cut in half, one-third of what they used to give the patients, and still, now the drug is doing what it is supposed to do with minimal toxicity to the patient. Even radiation therapy and all the different methods, when we do surgery, for example, with glioblastoma, you can shrink these tumors down, and then when the surgeon comes in, they can debulk a much greater part of the tumor. This will allow the patients to live so much longer, rather than trying to go after the tumor when it is at its most aggressive state. Shrink it down, make it indolent, then debulk it.
We have all the tools needed for managing cancer effectively without toxicity available today, as we speak. The problem is most folks just don’t know how to use all the tools they have. They are not aware that this is a metabolic disorder and not a genetic disorder. Once they realize that, we will be able to manage cancer so much more effectively without the trauma, the toxicity, and all the terrible things that we now associate with this disorder. It is just a matter of time once people understand this.
Dr. Eric Westman: That brings me to a practical matter in my office with my patients. I won’t tell people that this guarantees anything. I don’t think this guarantees that a keto diet will change your outcome, but the studies are ongoing. The idea that cancer is a metabolic disease, not just a genetic disease, is still evolving. I understand the toxicities aside, but I will still tell people to follow what their cancer doctor recommends. What you were just mentioning is using the diet as an adjuvant, as an added benefit, or something to add to current treatments.
I say this because I have to play a little of the politics, myself. If I tell someone that they shouldn’t follow what their oncologist is recommending, I am hearing what you say, though, that you may be able to get away with similar medicine or treatment with fewer side effects at lower doses. What I’ll say is, while there are no guarantees, this is something that I’ll teach you how to do and follow you over time. I am hopeful because, of all the diseases, when Jeff Volek told me that he was going to study cancer, I was, “Jeff, of all the things, if you did one big study on diabetes, we could turn the whole medical community around.” But he will have a lot of funding. Hopefully not too long; hopefully, he can crack this code at Ohio State.
Thank you so much for your time. On a personal note, thanks for meeting with my dad some years ago. He finally passed in his early 90s. Thank you for all the help you’ve given us. Your book, Cancer as a Metabolic Disease, is a must-read. How do people find you today? Where would you like people to be directed?
How to contact Dr. Thomas Seyfried
Dr. Thomas Seyfried: All my research support now comes from private foundations and philanthropy. People make donations to my research directly through the university, Boston College. They just put “Seyfried’s Cancer Research Program” but also Travis Christopherson’s Foundation for cancer metabolic approaches. He supports a lot of my research, a large amount of it. It is a 501(c)(3) kind of foundation, so this keeps us going to keep testing with the press-pulse therapy. Dosage timing and scheduling are crucial. Once you know how to use the tools you have concerning doses, timing, and scheduling, we are going to be able to manage this cancer quite effectively.
The tools and participation of the patient
People who want to do this, yes it requires some participation on the part of the patient. They must play a key role in the ultimate management of their disorder. They are no longer a bystander; they are an active participant. The more they understand the scientific concepts and what we are doing and why we are doing it, the more successful they will be.
They will be the ones that survive well from this treatment and this new strategy because, one of the things we notice, when you do metabolic therapy the right way, is that we have many people who have diabetes, obesity, high blood pressure, hypertension, they have a whole range of different problems besides having cancer. When they start managing their cancer, we see that the diabetes goes away, the high blood pressure goes away, and the hypertension goes away. A lot of the chronic problems that they were suffering from disappeared. They lose weight, they look healthier, they feel fit. You are seeing a whole range of chronic problems go away with cancer treatment.
Dr. Eric Westman: Maybe they are interrelated.
Dr. Thomas Seyfried: People need to know that, though. Once they realize that all these chronic diseases are interrelated, they might embrace the whole thing and ask, “What are we doing? How did we get here?”
Dr. Eric Westman: You talk to a cardiologist and they only talk about the heart. You talk to a pulmonologist and it is just the lungs. You talk to a nephrologist and it is just the kidneys. We have subdivided the body up so much.
Thank you so much for your time. Thank you for what you’ve done as a teacher and mentor to so many of us in the low-carb world.
Dr. Thomas Seyfried: Thank you for the interview.
You can watch the video here.