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MU: Since the publication of your book, have you become aware of more successful cancer cases using your approach?
TS: We are hearing about more cases for sure. I know only of a few, that I've participated in directly, where people are really collecting the key biomarkers to establish the therapeutic efficacy. So the people whom I do know that are responding fairly well are showing me very careful and comprehensive daily blood glucose and ketone values. We have documented blood work from some individuals that go over years. I think up to about 2 years for the most part and sometimes longer.
I have data on a dog, if you can believe; you know dogs respond really well to this therapy, I never saw such responses in some. We have a good case-controlled report we are working on now out of Greece where the person had non-small cell lung cancer metastasized to the brain. He's been on the metabolic therapy now for 4 years and he seems to be doing well. But these are all anecdotal reports. Nevertheless, if you do the case studies correctly, like we did for the Italian woman, that we published in Nutrition & Metabolism, there's a very comprehensive case report that served as a basis for others.
There are some people out there, like any media thing, they'll say, "Oh, the ketogenic diet cures cancer." We know there's no evidence for that. We haven't used it long enough to know if anybody is going to be cured from cancer using a ketogenic diet. All we can say is that the ketogenic diet has the potential to arrest the growth of the tumor. Now whether it's cured in the long run, who knows? It's going to take a long time to figure out whether these people are cured or not.
MU: In your book you mention 2-deoxyglucose as an adjunctive treatment to the CRKD. Many integrative oncology specialists are using DCA (dichloroacetate) in a similar way. Are there any new or exciting metabolic therapies to go along with a CRKD?
TS: Well, I think this is going to be the future. I mean the ketogenic diet by itself is just like step number one. As I said, you bring the patient into a new metabolic homeostasis where ketones become the predominant metabolic fuel and glucose is reduced. At that point now your tumor cells are under metabolic stress to a much greater extent than the normal cells. Now you can have add-ons, you have DCA, you can have 3-bromopyruvate, phenylbutyrate, there are approaches that are attempting to control the glutamine issue with respect to cancer. I think hyperbaric oxygen from the work I've seen with Dominic D'Agostino has tremendous potential, and the mechanism of action become clear once you recognize that cancer is a metabolic disease. The important thing is that in most cases the patient does not need to be harmed by these approaches. So many patients are harmed today from the current standard of care. Some drugs have very little effect when used alone, can have tremendous affect when matched together with CRKD. So there's a lot to be hopeful about I think in the future.
MU: You have written about glutamine being a specific fuel for cancer cells. Several clinical trials have shown that high doses of glutamine significantly reduce chemo- and radiation-related side effects, without interference in outcomes. This has become a controversial issue among naturopathic oncologists. Can you address this concern about glutamine?
TS: The glutamine issue is a really important one. If you go into the basic scientific literature, you see numerous papers in top scientific journals. It's pretty well recognized among the individuals who do basic research that glutamine together with glucose act as a powerful synergistic metabolic stimulus to tumor cells.
So let's talk a little about glutamine. OK, well first of all we know that glutamine is the most abundant amino acid in the body. And it's used extensively by cells of the immune system, like macrophages and lymphocytes, as a prime fuel. In burn patients they give glutamine infusions. You have to jack up the immune system to fight the bacteria. Certainly glutamine is going to be a good metabolite to restore some level of immune function.
On the other hand we have to recognize that many of the metastatic cancer cells are part of the immune system. There's a number of articles from John Pollack at Yale, Melisa Wong at Oregon, and a number of others showing that the cancer metastatic cell is a fusion hybrid between an immune cell like a macrophage and some cancer stem cell. So you have this hybrid cell that has the characteristics of both a stem cell and an immune cell. So what's going to happen to that cell when it gets the glutamine? Of course the cell is going to be rescued. So you're enhancing one aspect of the immune system. Well, on the other hand you could potentially be rescuing cells for eventual reoccurrence sometime down the road. So again you have to make your treatments in line with what we understand about the metabolism of the tumor cell. And the evidence in the literature is huge that glutamine for many different cancers is a primary fuel that is used by tumor cells, especially those tumor cells that have some level of mitochondrial function.
We have a model of metastatic cancer we developed here at Boston College. It's one of the best models for systemic metastasis; it's brutal. It just rips through the mouse's body from the tip of his nose to the tip of his tail. This tumor doesn't respond to anything. We gave them DON (6-diazo-5-oxo-L-norleucine), which is a toxic drug, it's a glutamine analog (cannot be metabolized). We were able to really knock out metastatic cancer throughout the body of the mouse, except the spleen. It turns out the spleen is kind of like a sanctuary for cells like macrophages and these kinds of cells.
We just wanted to use it to get some concept of the role of glutamine. Because we couldn't stop this tumor using calorie restriction alone. The glutamine issue has to be carefully dealt with, I think. We recommended phenylbutyrate (Buphenyl) that's metabolized to phenyl acetate, which binds to glutamine and you excrete it. This will lower some levels of glutamine. And there has to be more cross-talk between the basic scientists and the clinicians about this glutamine issue.
MU: I'm not aware of any treatment which cancer cells cannot ultimately resist. Why can't cancer cells develop the ability to use ketones as a fuel source?
TS: You know, burning ketones requires normal mitochondria. Ketones are even more efficient than fatty acids, which uncouple, and they are more efficient than pyruvate. So ketones are a wonderful, highly sophisticated fuel that reduces oxygen free radicals, but in order to do that your mitochondria must be in good shape. And as I've mentioned and I've shown over and over again, the mitochondria of tumor cells are compromised in one way or another, making them less able to use ketone bodies for energy. That's the reason they ferment. They are fermenting because their mitochondria are insufficient. So, how are they going to adapt, unless they grow new mitochondria? And if they generate new mitochondria, they will be able to burn ketones, but they will no longer be cancer cells. So it's very hard to get around this.
If cancer is viewed as a metabolic disease, then these kinds of ideas and these kinds of understandings become more apparent. Why are all these other cancer cells adapting to the drugs and other therapies? Because you're not targeting their metabolic fuels. If you target their metabolic fuels that they absolutely require, they are not going to do very well. If you're not targeting their glucose or glutamine issues, they look like they're adapting. You're just making them more likely to ferment than respire. Then you get cancer cells that have no mitochondria. All right, well, those cells should be remarkably sensitive to the CRKD. So it's going to take time for this to sink into the minds of people that work in this area.
We have so many ways to manipulate this metabolic therapy. Not only with the diet as the main platform, but then the add-on drugs and hyperbaric oxygen. And I am hopeful we will be able to come up with an approach that is effective for the management of cancer without toxicity for the majority of people who suffer with this disease. It's just a matter of time. I think this is what's going to happen, but how long that time will be I don't know; I'm hopeful that it won't take too long.
Thomas N. Seyfried, PhD, has taught and conducted research in the fields of neurogenetics, neurochemistry, and cancer for more than 25 years at Yale University and Boston College. He has published more than 150 scientific articles and book chapters and is on the editorial boards of Nutrition & Metabolism, Journal of Lipid Research, Neurochemical Research, and ASN Neuro.
Michael Uzick, ND, FABNO, is a graduate of Bastyr University. He is a Fellow American Board of Naturopathic Oncology (FABNO) and a past vice president of the Oncology Association of Naturopathic Physicians (OncANP). He is a cofounder and the medical director of Genesis Natural Medicine Center in Tucson, Arizona.
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