Understand Cancer: A Disease Of Mitochondrial Metabolism

Thomas Seyfried, PhD

Well, thank you, Michael. It is a pleasure to be here.

Michael Karlfeldt, ND, PhD

For the audience, Thomas Seyfried is a Professor of Biology at Boston College and received his PhD in Genetics and Biochemistry from the University of Illinois at Urbana in 1976. He did his undergraduate work at the University of New England, where he recently received the Distinguished Alumni Achievement Award. He also holds a Master’s Degree in Genetics from Illinois State University.

Thomas Seyfried also served with distinction in the United States Army First Cavalry Division during the Vietnam War and received numerous medals and commendations. He was a Post-Doctorate Fellow in the Department of Neurology at the Yale University School of Medicine and served on the faculty as an Assistant Professor in Neurology.

Other awards and honors have come from such diverse organizations as the American Oil Chemistry Society, the National Institute of Health, the American Society for Generic Chemistry and Ketogenic Diet, the Special Interest Group of the American Epilepsy Society, and others. You have accomplished a lot.

Dr. Seyfried has over 200 peer-reviewed publications and is the author of the book Cancer as a Metabolic Disease: The Origin, Management, and Prevention of Cancer. His book, also translated into Chinese, describes his research on many podcasts and radio shows, and his work is central to the documentary film The Cancer Revolution. Dr. Seyfried’s full list of peer-reviewed publications can be found on PubMed. You are someone who is frequently, when we talk about cancer and metabolic diseases, your name is a central component of all of those discussions. In your mind, from all the research that you have done. What is cancer, and how do you describe it to people out there?

Thomas Seyfried, PhD

Well, thank you, Michael, for the introduction. It is described in the textbooks as a very simple statement. Cell division: out-of-control cells lose their regulatory behavior and are no longer in a growth-regulatory state. This dysregulated growth persists as long as these cells have access to the fuels that drive their energy metabolism. All other issues associated with dysregulated cell growth are secondary. Without energy, no cell can grow. The difference between a cancer cell and a normal cell is that the cancer cell uses ancient fermentation metabolism to grow, whereas, in normal cells, the quiescent cells will use respiration, and even in the regenerating liver, which is a regulated cell growth that is largely respiratory-regulated. Cancer cells are different from normal cells in the sense that they obtain their energy from fermentation.

The most important thing is that the organelle inside the cell, the mitochondrion, is the organelle that regulates cell growth and the differentiated state of cells. When that organelle becomes corrupted or damaged in some way, the cell controls the regulation of the quiescent state. When that organelle becomes defective, the cell falls back on these ancient fermentation pathways, and the organelle is no longer capable of regulating the growth. These cells proliferate uncontrollably until their fuels are shut down. If you shut down their fuel, they will die. Unfortunately, most of the treatments that we use today to manage cancer are devastating. They will kill anything that grows. Also, if you do not kill all of the cancer cells using these kinds of treatments, the ones that survive come back into vengeance because the body is now more capable of providing fermentable fuels to the surviving tumor cells. You often see that we have over 1600 people a day in the United States dying from cancer. This is a relentless problem that needs to be controlled.

Michael Karlfeldt, ND, PhD

Yes. In regards to the mitochondria, there has been a lot of focus, obviously, on oncogenes and genetic dysfunction that drives cancer. By addressing that, you are then able to solve this issue of cancer. But from what I am hearing, it is more signaling that is taking place from the mitochondria towards the genetic, towards the DNA, that that is where the issue is. It is the health of the mitochondria that then determines the signaling.

Thomas Seyfried, PhD

Yes, well, I think the mitochondria, when they become dysfunctional, throw out reactive oxygen species: ROS. The ROS are carcinogenic and mutagenic. Most of the mutations that we see in cancer cells are downstream effects of damage to oxidative phosphorylation. The mitochondria, the anchor genes, are facilitators of the fermentation metabolism. When the cell falls back on fermentation, which is a very inefficient energy way to generate energy, you have to have large amounts of resources in the environment to observe energy through fermentation. 

The oncogene turns on the transporters, and they are responsible for both bringing in the fuels and throwing out the waste products of fermentation. In other words, the metabolic exhaust is driven, so you have lactic acid and succinic acid as metabolic waste products of the two fermentable fuels, which are sugar glucose and the amino acid glutamine. The anchored genes are facilitators of high-throughput fermentation metabolism. If you put normal mitochondria back into a cancer cell, the oncogene is turned off, and the entire cell becomes growth-regulated and reestablishes its energy normalcy. It is not as complicated as people want to make it out to be. It is a very dumb cell. It does not; it has lost its regular growth. It has all these mutations that prevent it from adapting. They are very vulnerable to death. If you target their energetic fuels. 

The problem is that most therapies today are not targeting their fermentable fuels. They are targeting downstream epiphenomena, the things that happen well after the damage to the mitochondria. Unfortunately, that accounts in large part for the over 1600 people a day dying from cancer. By the time we have treated them with toxic radiation, chemotherapy, and all this crazy stuff, the poor body cannot rally. The body is so damaged from the treatments that it can no longer rally to shut down the fuels that are driving the beast. It is a tragedy when I look at what we are doing to these poor cancer patients and the lack of knowledge or just ignoring the underlying mechanisms that drive this. It is just very sad to see this situation that does not need to happen.

Michael Karlfeldt, ND, PhD

The issue you pointed out is with the chemoradiation, since the mitochondria play such a pivotal role in this whole process, in addition to obviously devastating our immune system, and our immune system to be able to control whatever cancer cells are left and also damaging the mitochondria and the cells. It puts more mitochondria in a place where you have the dysregulation to create more cancer cells.

Thomas Seyfried, PhD

Yes. A lot of these treatments that we give to patients create massive systemic inflammation in the body. Inflammation is one of the provocateurs of damaged respiration. You impair the ability of the normal cell’s respiratory capacity to rally. One of the things about metabolic therapy that we work on is that we transition the whole body over to ketones, which enhances the health and vitality of the normal cells. We lower blood sugar using various calorie restrictions, fasting, or ketogenic diets. When you do that, all the normal cells in the body upregulate transporters to get glucose. What you do then is that the normal body will outcompete the crippled cancer cells. You need to know evolutionary biology. 

You need to know how the body works. You need to know how the body is an entire machine. All these organs work together in unison. We play all these organs off of each other using the concepts of evolutionary biology. Without that knowledge, a lot of this stuff is mysterious to people. But as I said, you need to understand evolutionary biology. Once you understand that, the solution to the cancer problem becomes quite clear.

Michael Karlfeldt, ND, PhD

The fuel source—you are talking about glucose—is one of the main fuel sources. for fermentation, that is greatly needed. If we then shut down the ability or reduce the amount of glucose getting into the cancer cell, then we make the cancer cell very vulnerable to any oxidative stress or any other type of therapy, I would assume.

Thomas Seyfried, PhD

Yes, that is true. If you transition the body over to nutritional ketosis, you can use some of the conventional chemo. The issue is that you can use very low dosages of these, where they will not create minimal toxicity while having much greater therapeutic benefit. But even then, we would prefer other approaches. But I do not want to throw out the entire industry of cancer treatments, and I certainly think that we do not know how to use the tools effectively that we have. The goal is to eradicate the tumor cell while enhancing the health and vitality of the normal cells, not damaging the body in such a way that now you create all kinds of new health issues because you did not know how to use the tools that you were using to manage this. 

The other fermentable fuel, of course, is glutamine. We have interrogated cancer cells and looked for every other fermentable fuel that they could use, and only glucose and glutamine are the ones that are a little disparaging, but nothing can replace glutamine. They do not need much glutamine because they are balanced, the two fermentable fuels work together. They power these cancer cells. You get the glucose on the one hand and the glutamine on the other. If you target both of those fuels together while transitioning the body to nutritional ketosis, you have the upper hand in putting these cancer cells in a very managed state, allowing for greater progression-free survival and quality of life increases for the majority of people who know how to do this and can do it.

Michael Karlfeldt, ND, PhD

The question becomes, glutamine is a very good thing. We have a lot of glutamine in our body. and we use it to a great extent. What are the impacts healthwise by eliminating that source?

Thomas Seyfried, PhD

Well, we do not eliminate it. We were just disrupting it, and that is why my colleagues and I, developed the press pulse therapeutic strategy where you can press glucose down low on the body does not need glucose. The brain is the biggest consumer of glucose, and studies have found that all the neurons have pushed blood sugars down to 0.5 million nine milligrams per liter. Do you think you’d think a person would be dead? Not if their brain has transitioned to ketones. You can push blood sugars down low. We press that. But then you are 100% correct about the importance of glutamine for the immune system, the gut, and the urea cycle. You cannot go in and just push glutamine down without damaging your immune system, your gut, and your urea cycle. That is why we pulse and we hit. Once we have a stranglehold on the glucose, we then use small amounts of glucose glutamine inhibitors and pulse it, putting it on and then taking it off. When you take it off, you allow the immune system to come in and pick up the corpses from the dead tumor cells because you do not want to impair your immune system. This again means understanding evolutionary biology and knowing how you play groups of cells off of each other because you understand what they evolved to do and what fuels they need. Our immune system needs glutamine. If we are too aggressive with glutamine, this is a saying: you must know how to use the tools effectively, and that comes from an understanding of evolutionary biology. I do not know how else to say it, but that is the way it works.

Michael Karlfeldt, ND, PhD

When you are talking about inhibiting glutamine, obviously we want to limit that in our diet.

Thomas Seyfried, PhD

No. We cannot eliminate glutamine from our diet. We all make glutamine. Glutamine is everywhere. This is why you cannot purge your body excessively of glutamine. You might use fennel butyrate, which gets metabolized to fennel acetate, to reduce it in the blood. This was one drug that was used for little kids who had elevated glutamine levels. But you cannot be too aggressive. You have to know how to let your normal cells work while just slowly depriving or interrupting them; otherwise, you create other problems. This is the strategy that we use. We do not want to, and there is no dietary way to eliminate glutamine. 

There is a dietary way to limit glucose. But you are going to need drugs—what we call repurposed drugs—that we can use in a nontoxic way to pulse the glutamine levels. That needs to be further developed. We know how to do it. It is just that we know the drugs that work well. The problem is that they are not available. We have access to them. If I had cancer, I would know exactly where to buy it. I know exactly what you would be applying to me. I buy it from the chemical suppliers. They say, Oh, not for human use. Are you kidding me? Those drugs are more purified than the stuff they are giving to humans. Yes, you can get it. People who have a few bucks can get it. The bottom line is that I know exactly what the drugs are. The pharmaceutical industry is also quite aware of what these glutamine drugs are.

They are trying to patent and make new ones, but they are very similar. They have DON 6-diazo-5-oxo-l-norleucine. You just put a little tail on it, make it new, and something’s going to be different. They are all the same. The problem is that the pharmaceuticals or others will go out and, as you said, they will blast glutamine without knowing evolutionary biology, and they are going to get some therapeutic benefit. But at the same time, they are going to hurt the patients. You have to shut down the glucose at the site. What are you interested in? Are you interested in saving the life of the cancer patient, improving his quality of life, and improving his overall survival? Or are you interested in making $1,000,000,000 on a drug that you do not know how to use? This is the whole problem here. Yes, we know how to use these drugs. We know the system. 

The problem is that it is not part of conventional therapeutic strategies for managing cancer. Our job is to make that more known and available. We are training individuals on how to use these drugs and how to use the whole concept of Press-pulse because that is going to be the future. It is just a matter of time because the current system is broken and does not work for the majority of patients. Once the word gets out that we know how to manage cancer, I am not saying we can cure cancer; I am just saying we can manage it better than what we have currently. If someone can live 30 or 40 years longer, that is great. But if they can live five or seven years longer when they should be dead in a month, then that is also very helpful to you.

Michael Karlfeldt, ND, PhD

Talk to me a little bit about how you mentioned DON and glutamine fermentation too, and inhibiting that through the Press-pulse. One of the big ones that you have that we are dealing with is things like glioblastoma, which does not have a great deal of life; people do not survive very long with it. Tell me how this combined with the ketogenic diet produces ketones in regards to DON and delivery to the brain, and so forth, and how all of that works together.

Thomas Seyfried, PhD

Yes, well, that is good. Glioblastoma. We have not made any advances in 100 years. In 1926, Bailey and Cushing published that GBM glioblastoma patients can live for eight to 14 months. Today they are living eight to 20 to 17 months, or whatever. We have not made any progress on the problem of managing glioblastoma. Glioblastoma is a very deadly, aggressive brain cancer. It used to be called glioblastoma multiforme because it had so many different morphologies. Yes, it is a very bad tumor. If you do not do anything, you are probably going to die in 9 to 10 months. However, given the current standard of care, yes, we need surgery. But the question is, do you have a watchful waiting period before you debunk that tumor? A lot of times, they go in and try to rip it out as quickly as possible. Sometimes that is essential. I am not challenging that. Surgery will become an essential part of the effective management of glioblastoma. The issue is that, when and how you do it, the biggest problem with glioblastoma is the radiation from the brain.

 I have said over and over again that this is malpractice and immoral. We have clearly shown that irradiating someone with a glioblastoma frees up massive amounts of glucose and glutamine in the tumor microenvironment, leading to the rapid recurrence of that tumor and most likely the death of the patient within two years. It is the treatment itself that is preventing these people from being able to survive. I am sorry, I have to say this, but it is malpractice because I have been publishing paper after paper showing how these glioblastoma cells suck down glucose and glutamine and the very act of irradiating the brain and breaking apart the very carefully regulated glutamine glutamate cycle, which is our neurotransmitter system. You break that apart, you create inflammation, and massive amounts of glutamine are in there, driving the cells of this aggressive cancer. You irradiate the brain; you heat the brain. This causes massive systemic inflammation, and then you give high-dose steroids, which raise the blood sugars. The two fuels that you are essential to control are massively released in the microenvironment of this poor soul’s brain, leading to his rapid death. We have shown that the survival of patients with glioblastoma is concurrent with that of every major medical center in the world. You can just see how beautifully everybody’s dead at approximately the same time. They have been doing it for 50 years, and nobody knows why this is happening. I am telling them why it is happening over and over again. I said, Would you want me to do this in crayon? How much more clear do I have to speak slower? Do I have to write the mechanism down in crayon? This is it; it is just so disheartening to see. When I talked to people about this, I said, Oh, and I told the guys that are doing this, and they looked at you like a deer in the headlights, and it was almost like you were coming from a different planet.

They look at you as a different species. I am saying to myself, Well, what is going on in the brains of these guys that are already another member of our species, knowing that this is going to lead to their demise in the rapid recurrence of the tumor? It is so disheartening. You try to be nice about it; you try to explain it. But the bottom line is that you are killing all these people. I am not saying the tumor is the tumor, which, of course, will kill you if you do not do anything. But, man, we do not need to do that. We need to shrink the tumor, debulk it, and then transition the patient over to metabolic therapy. Will it cure them? I do not know. But we have guys living longer than five or seven years, and they do a hell of a lot better with a higher quality of life. I think we can make the mean survival rather than 15 months or five years. Now, what is wrong with that? Why is no one listening? Why? Why do they ignore what I am saying? It makes no sense if you just say it over and over again: podcast after podcast, publication after publication, open-access journal. Every guy in any bar room, restaurant, or medical center can read it, and it is: Let us irradiate this guy. It is. What is going on here? Maybe someone can explain that to me.

I am still lost. I just do not understand how it is talking to a plug socket. It is. What is going on here? Don’t you understand that the standard of care is killing your GBM patients? and it is just terrible. I tried to go through IRBs or Institutional Review Boards, and they said we can only do metabolic therapy after we irradiate the brain. I am saying, What nuts are you people sitting on these boards? They all went to top medical schools, too, which is scary. Do you think these guys would know what they were doing? They are sitting there with the beautiful white coats talking that they know something, and they end up killing their patients. When it is just, give me a break. I look at it, and I am saying this is a tragedy. It is a tragic situation. Only it is medieval. Only when they come to realize that cancer is driven by a fermentation metabolism will they come to realize what the hell they have been doing.

Michael Karlfeldt, ND, PhD

Yes. The thing is that glutamine provides the structure for new cancer cells to develop, and it creates that carbon skeleton.

Thomas Seyfried, PhD

Develop the nitrogen. It is, it is both; you have nitrogen on a glutamine molecule. You have internal nitrogen. You need nitrogen to build new DNA. You need nitrogen to build new amino acids. Then you generate energy through what we call mitochondrial substrate-level phosphorylation. It is another form of energy metabolism. The other thing you have to realize is that many of these GBM cells are microglia. They are derived from the microglia, which is part of our immune system. We know that immune system cells are heavily glutamine-dependent. The very cells that will invade the entire brain are heavily glutamine-dependent. The very act of irradiating the brain frees up massive amounts of glutamine in the microenvironment, and that is why very few people survive. It is always rare to find a guy who survives fire, and you have to love the human body. No matter what you do to it, there is always some guy that can survive, and everybody says, I want to be that one guy. 99% of them are all dead, but they all think they are going to be that one guy. No. They are all going to be dead, and most of them are going to be dead. There is always a chance that somebody hits the billion-dollar lottery. But that does not happen very often; let us put it that way.

Michael Karlfeldt, ND, PhD

In regards to it, I love it, and I see that again and again in my practice once they start that journey. Yes. Where they start to radiate that as they play Whac-A-Mole, you are radiating one spot, then two others appear, and then three others, and then all of a sudden, they just circle the brain, and then they are gone. Yes. It is tragic. In regards to the DON, one of the issues has been the impact on the digestive system and people feeling nauseous, and they have not been able to handle the dosage, how do you manage them?

Thomas Seyfried, PhD

They did not use it right. You have to get the body into therapeutic ketosis before you use it or hyperbaric oxygen or any of these kinds of things you need. The first step is to clean up the body and the metabolism of the individual. You can look at the blood panels, and you can tell whether a person is healthy or not. Just by looking at all the blood biomarkers, you have got to get these people back into a metabolic homeostatic state. Once you do that, then DON was used incorrectly. It was used on too many high dosages. They said DON was toxic. What are the radiation, the temozolomide, and these other crazy things? It is nothing compared to these things. But we showed that we can use very low doses of DON. When the body is in nutritional ketosis, we have published several papers demonstrating that it facilitates the delivery of small molecules through the blood-brain barrier. 

We published papers with electric mass spectrometry, showing how much we get three times more drug on target when the drug is administered under nutritional ketosis. That means the dosages can be significantly reduced, the toxicity is significantly reduced, and the therapeutic efficacy is massively enhanced. Now, you heard what I just said. Did you hear what I just said? Well, how come that falls on deaf ears in the field? I do not know how much more I can make. We published papers showing that when the body is in nutritional ketosis, small molecules can be delivered very effectively through the blood-brain barrier onto the target. We have published that. We have shown that quantitatively. All right, so why does the industry keep saying, Oh, we cannot get through the blood-brain barrier? Do they not know how to read the scientific literature? What again, what do I have to do? I think it is not that they are dumb. I think they are just locked into procedures and a dogmatic ideology that prevents them from looking at anything other than what they have been doing. Okay. I always find it remarkable that they say, Oh, we know it is so hard to get drugs on target in the brain because of the blood-brain barrier. I just told you how to bridge the blood-brain barrier. We have published papers showing that quantitatively, and yet they do not do it. What do you do? How are you supposed to stand on the top of the Empire State Building and wave a flag? It is just that even if I did that, I do not think they would look and say, What is that up there? It is.

Michael Karlfeldt, ND, PhD

Who is that weirdo?

Thomas Seyfried, PhD

I hate to bash these guys. But, after doing this for ten years, telling everybody that I published the paper in Lancet Oncology in 2010, blowing the whistle on this whole thing I do not know what to say. I just do not think these people are stupid. I just think they are incapable of understanding evolutionary biology, and they are locked into doing this because I was trained to do it and everybody does it. Therefore, it must be. Even though I am killing my patients by doing it, it must be done. You have to be a moron to think that.

Michael Karlfeldt, ND, PhD

Yes. Even though I see the same result again and again, I think that the next one is going to be better.

Thomas Seyfried, PhD

Yes, and they do not seem to be bothered. I do not know how they sleep at night. If I were doing that to somebody, I would feel terrible. I am killing my patient. I came into this profession to help people, and I am killing them. This is harsh. What I am telling you is very harsh, okay? Why do you not look at the survival curves throughout the world? On what? I published papers showing survival curves. It is unbelievable. You cannot design experiments that are so reproducible. We have a problem in the cancer field. They cannot reproduce these papers from one lab to the next. But what we can reproduce is how fast people die after the standard of care for glioblastoma that is so reproducible. It is unbelievable. I just do not know what to say about it.

Michael Karlfeldt, ND, PhD

You are right. I know you are right. It is such a wild rouse of a system that knows each individual is locked into it and is self-regulate rated, meaning that one medical oncologist who steps out of line has a group of other medical oncologists that will then make sure that he is put back into line. They all do the same.

Thomas Seyfried, PhD

Yes. It is what the Japanese used to say: if the nail sticks above the board, you have to smash it down. Yes, everybody has to be in lockstep for whatever they are doing. But when it comes to people’s lives, I think you might have to think of something different and do something different. It is such a tragedy. I look at all these poor patients, and after you get diagnosed, the shock of saying that you have a glioblastoma means that you are almost looking at your death certificate there, and you become numb. The family becomes numb, and all the relatives become numb. Then these poor folks never even heard of what a glioblastoma is, and all of a sudden you find out that somebody has it. You look in the literature, and almost everybody that has it is dead. John McCain is dead. Ted Kennedy is dead. President Biden’s son, Beau, is dead. They were supposed to have the best medical care. I looked at it, and they all got the same thing: brain radiation.

It was, and it was just amazing. These poor folks did not know any better than the common guy on the street, so you are so shocked. No. We have to debunk the tumor. Then we are going to give you a big dose of radiation and chemotherapy, and then you are going to be dead, We tried one guy, Pablo Kelley. I published a big paper on this. Yes, a lot of people read it, but very few people cited where he chose no radiation and no chemotherapy. He said I do not want any of this stuff. He has a glioblastoma. They said, Pablo, you are going to be dead in nine months. He said, Okay, I will roll the dice and take my risk. He is still alive. Eight and a half years, going on nine in August. Nine years of survival. No radiation, no chemotherapy, just metabolic therapy. Then they say, Well, Pablo is a fluke. Pablo is just one of those guys. He’s the end of one. Yes, he is. You might get a lot more, Pablo. If you do not irradiate the guy’s brain, you might find it. He might be the rule rather than the exception. Oh, nobody wants to talk about that. You see, nobody wants to talk about that. You try to go through an institutional review board and tell them you want metabolic therapy without the standard of care.

They say we do not do that. You have to go somewhere else. It is a tragedy. I have to say it again: It is one of the great tragedies. Someday in the future, they will recognize this as one of the greatest tragedies in the history of medical science. What we do to these people—not only glioblastoma patients, but most of the cancer patients—is crazy stuff. Everything’s based on the somatic mutation theory. Cancer is a genetic disease. Therefore, all these things and all these approaches are justified by the National Cancer Institute, which says cancer is a gene; it is not a genetic disease; it is a mitochondrial metabolic disease. Once people realize that we are going to stop doing this medieval stuff, they are going to survive a lot better.

Michael Karlfeldt, ND, PhD

Yes. They have followed the same suit since the fifties, and they haven’t changed the result in any way. You would think that they would shift their mindset and focus on other things instead, but it is still very profitable. Yes, well,

Thomas Seyfried, PhD

That happened in 1984 when the federal government and the National Cancer Institute invited pharmaceutical companies into medical schools to facilitate drug development for cancer. That was putting the fox in the henhouse there in 1984. Look it up. The National Cancer Institute brings in pharmaceuticals. Therefore, the mission became profit rather than outcome, health outcome, and this, and we are paying the price for it today. We are paying the price for it today. People want to look back and say, How did all this crazy stuff happen? It is all written there. All I have to do is look at the history of the National Cancer Institute. You will see it there. Bold, big letters, I look at all this stuff, and I say, This is the way it is. Then they say, Well, you got the authorities and the big medical. You get all these grants from the National Cancer Institute, all based on the gene theory of cancer. It is all bad; it is contributing to the problem. It is contributing to the problem and the unnecessary deaths and horrific events that are associated with these poor cancer patients.

Michael Karlfeldt, ND, PhD

So in your mind, just give a few minutes of spiel. For people who are diagnosed with cancer, what should their strategy be? You talked about the ketogenic diet blocking your push and pull on the glutamine with the repurposed drugs, DOM is one of them. I do not know if any other ones are easily accessible.

Thomas Seyfried, PhD

The parasite drugs—Albendazole Fenbendazole, as it turns out, parasites and cancer cells use common energy pathways. Some of the parasite medications work well. We have a paper that we are getting ready to submit now for pediatric brain cancer. Little kids: Brain cancer in children is the number one killer of kids. We have been able to put together different drugs with metabolic therapy in our preclinical We use very young mice. They are at the same general age as a three or four-year-old child. We find that the tumors in these pediatric mouse models behave just like those you see in children that go down the spinal cord. We do not see as much spinal cord invasion for adult glioblastoma, but we see it in children. They have a lot of spinal involvement for their aggressive cancers, and our pediatric models show spinal involvement. What we do is use cocktails of repurposed drugs. We put the animals into nutritional ketosis, and then we deliver the drugs in low doses in a strategic way.

We can get the hell out of these tumors and put them in a growth-inhibitory state. We know that because of the differences in basal metabolic rate between the mouse and the human—50 million years of evolutionary difference between a mouse and a human—the mouse has a diesel metabolic rate seven times faster than that of the human. We do these tests on humans. The human body has so much more opportunity to take advantage of what we are doing. Humans do a hell of a lot better than mice when we put them into clinics and try this, but the problem is they do not want to do it. That is the tragedy. We know what we need to do and how to do it, yet it is not allowed to be done. Now, where is the outcry about that? We know how to use the drugs. We know the strategy. We are writing treatment protocols to help millions of people suffering from cancer, whether you are a child or an adult. Yet it is not being allowed to be done because they say there are no clinical trials. Well, who is going to pay for a clinical trial to show therapeutic efficacy on a treatment that does not generate massive amounts of revenue? You put it all together, and you have this problem. How are you? I am not going to change the minds of the guys at Dana-Farber, and MD Anderson. Those guys are locked into a mindset. We have to create knowledge and scientific literacy on the part of the population. Once the population becomes scientifically literate, they’re the consumers. They’re the ones who will make the change they have to demand. They want metabolic therapy, and we are going to train people to do it. Once we train the physicians to do this, there will be clinics opening that will give cancer patients metabolic therapy and treat their disease the way it should be treated.

Michael Karlfeldt, ND, PhD

You have Fenbendazole, Mebendazole, and Albendazole, are these all the same, or Fenbendazole is your preferred

Thomas Seyfried, PhD

Yes, we are starting to see some differences. Some of my physician colleagues are reporting that Mendbendazole might work better on brain cancer or Fenbendazole might work better on visceral organ cancers. The issue is that they generally work a lot better once the patients are in therapeutic ketosis. That becomes the key because then you can use much lower dosages of these drugs, almost eliminating any toxicity, and then the therapeutic efficacy becomes better. But the cutting edge in our lab now is dosage, timing, and scheduling. What are the best drugs? How do you dose them? How do you schedule them and get them to work off of what we know is happening? We do. We analyze the tissue histologically, just as you would in a conventional clinic. You have to take, we do not do a biopsy, but we look at the progression of the disease, look at the histology, and see how many cells are dead. Are there any cells alive after some of these procedures? We are not completely successful. We bring these tumors into a state of management, but it is hard to eliminate them. But we are pushing the boundaries further and further. When the Wright Brothers first got their plane to fly 50 yards, we got jetliners now and are going to the moon.

But we are going to push the boundaries on how dosage, timing, and scheduling of repurposed drugs under the state of therapeutic ketosis work. Yes, it will be successful. We need guys that are in the lab, in the clinics, mixing and matching these things and doing this. They will come out with something. This is not sexy science, but this is the stuff that gets the job done. You want to live. This is the stuff that we need to have done. But when you write a grant proposal, oh, well, this is not sexy. What is your signaling? We do not care about signaling cascades. We’re only talking about dead cancer cells. But what do you need to study? A signaling cascade in a cell that is already dead. It is not a complicated thing. It is called survival. How long can we keep a person or an animal alive? Far longer than they would have ever been imagined to do. That’s not sexy science, but that is what works.

Michael Karlfeldt, ND, PhD

I love it. Well, I appreciate your work. Because this is what we need. We cannot sit and rely on these big monsters. Yes. They require hundreds of millions of dollars to get new drugs onto the market. None of this repurposes drugs. It cannot have any money on it; are there, in addition to what you just explained, are there other things that you are seeing that have a promise that you feel the public should know?

Thomas Seyfried, PhD

Well, I think we know the strategy for how to do this. Are there better drugs that could be there? I am not against developing new drugs. The problem is, that you have to know how that drug can be used to its maximum level of efficacy. What there seems to be is a tremendous resistance to using the drug with a particular diet, which seems to be something that a lot of the drug developers do not want to do. They want to look at their drug and say, Oh, it has clinical benefits. It keeps a guy alive for an extra month or six weeks. I am more interested in an extra five or six years. The way you do that is that you have to know a strategic, why DON 6-Diaxo-5-Oxo-l-Norleucine is so powerful because it is a pan-glutamate ACE inhibitor, which means it hits multiple glutamate-based targets simultaneously. A lot of drug companies do not do that. They are very specific and targeted. However, the problem is that we have many different families of glutamine aces and many different glutamine transporters. If you are going to hit one, they come through others. It is Whac-A-Mole. If you hit one glutamate ace, they have other glutamate aces. But Don is great because it just shuts down the whole family.

But you cannot make any money on it. Everybody ran out and said, Oh, it is too toxic only because you do not know how to use it yet. Then we found some other drugs that had a very poor track record in the clinic. But when you are now working with the ketogenic diet and calorie restriction, they work well. at much lower dosages. I think we have many drugs already available that are out there that could be repurposed, and reutilized in a new setting. All of a sudden you are going to say, Oh, that drug, that was a crap drug. All of a sudden, it turns out to be a blockbuster only because now you know how to use it in context. I am hopeful about this. I do not think we need to develop any more drugs. We’ve got thousands of drugs that are already out there that can work well if you know how to use them. That is going to be another exciting frontier, dredging up some of these old drugs that you thought did not work while you put them back in context, and all of a sudden you have got some blockbusters. It is going to be exciting to see all this. It is going to happen. It is just a matter of time.

Michael Karlfeldt, ND, PhD

One of the challenges that a lot of people is dealing with repurposed drug is Doxycycline as an example. We also know that it hurts the mitochondria. Here we are trying to protect the mitochondria. What are your thoughts regarding that? 

Thomas Seyfried, PhD

We do not use those. Why would you not want to use the stuff we have that will do the job? Why would we use anything that is going to harm the very organelle that we are trying to enhance? Again, you have to know the biology of the system you are working on. You have all these crazies out now. They are all saying we want to target oxidative phosphorylation in cancer cells, Oxphos inhibitors? Well, the best Oxphos inhibitor that I know of is cyanide. If you want to inhibit oxidative phosphorylation, drink a Kool-Aid with cyanide in it, and the absurdity of these guys; they are out there doing so. Do you think these guys know what they are doing? They are at the top medical schools, and you think they understand stuff. Yet they come out saying, Let us hammer oxidative phosphorylation in cancer. Oh, yes. They think cancer cells use Oxphos, which we and others have clearly shown they do not. They are going to harm the rest of the body. I am telling you, man, it is just scary when you see people that are supposed to know and they do not know Jack, and they are out there doing this to these people and causing more harm than you would have expected. No, you do not want to harm oxidative phosphorylation in any person, period. People should know that.

Michael Karlfeldt, ND, PhD

I love it. Do you mind just saying something? Mentioning the names of some of the drugs that you feel hold the best promise for people out there.

Thomas Seyfried, PhD

Well, I think we have to go back and revisit the parasite drugs. Unfortunately, so many people in the comments on the podcast think cancer is a parasite. Wrong! Cancer is not a parasite. Parasites are completely different organisms. However, parasites and cancers use common energy pathways, so parasite drugs can kill cancer cells. Not because cancer is a parasite, but mainly because they use common pathways. Again, you have to have some knowledge of evolutionary biology if you are going to understand cancer, and you get all these crazies that come in with different crackpot suggestions. But most people are appreciative of what we are saying because we understand the overall picture of what is going on. Yes, there could probably be some additional drugs. We are always finding something new. People always ask me, Can you test this? Can you test that? What about seed oils? What about this or what about that? The idea is that all I know is that let us get rid of the cancer first and keep the patient healthy. Then, if we want to go back and revisit a seed oil or some other thing that somebody said, okay, but we’ve got a crisis on our hands. We’ve got over 1600 people dying from cancer every day. Why do we not take care of that problem first and then go back and worry about signaling cascades and what genes might have been turned on or turned off about this stuff? Let us solve the problem first, and then go back and look at this extraneous stuff. Does that make sense to you?

Michael Karlfeldt, ND, PhD

Absolutely. I love it. Well, and any last words that you want to say before we wrap up, because this is such a, what you have given to this field is tremendous. I have a lot of dear friends, including myself, who are following suit with this to be able to tackle this huge problem that we are dealing with. Any other last words of wisdom that you feel?

Thomas Seyfried, PhD

I can say that we are working on a very comprehensive treatment protocol to manage cancer. It is not only having the knowledge that I and my colleagues have; it is also training people to know that you have to train and retrain large numbers of physicians who are going to apply this to patients. You have to have a place where they can go and logically receive this treatment. We are writing up a very comprehensive protocol now, including how to do it, what to do, and training people. Once that happens, you are going to see a real shift in how we do this. Again, we are at the very early stages of this. I do not want people to say, Oh, let us go. Because it is frustrating, they run down to their oncologist. Tell them what I just told you. The guy has no clue what you are talking about, and that is scary and sad because these guys should understand this. Unfortunately, we have to have retraining, and these guys can be retrained. It is just that we have to, and it takes time. There are revenue issues with challenging an entire paradigm here, and that never happens overnight. It is going to be a gradual change in the way we do this. People just have to hang on and understand it is coming. I had to get it as fast as I could because I felt so bad. I get hundreds of emails from all these poor cancer patients. It is a horrific tragedy. Every day of my life I see this, and I wish I could help them, but we will help them in the future. We could do it faster if people understood. But you go out, you ask the guys at the top medical schools what I just said, and you are going to get the response that you get very different from what I just said.

Michael Karlfeldt, ND, PhD

Yes, well, Dr. Seyfried or Professor Seyfried, this is such an honor and pleasure, and I appreciate everything that you do to tackle this horrendous pandemic that we are dealing with, which is just getting worse. Thank you so much.

Thomas Seyfried, PhD

Well, thank you, Michael. It was a pleasure being here.