CrossFit | Cancer as a Mitochondrial Metabolic Disease

Cancer as a Mitochondrial Metabolic Disease

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ByCrossFitJanuary 4, 2019

Cancer is widely considered a genetic disease involving nuclear mutations in oncogenes and tumor suppressor genes. This view persists despite the numerous inconsistencies associated with the somatic mutation theory. In contrast to the somatic mutation theory, emerging evidence suggests that cancer is a mitochondrial metabolic disease, according to the original theory of Otto Warburg. The findings are reviewed from nuclear cytoplasm transfer experiments that relate to the origin of cancer. The evidence from these experiments is difficult to reconcile with the somatic mutation theory but is consistent with the notion that cancer is primarily a mitochondrial metabolic disease.

In the coming weeks, we will consider both the history of the somatic mutation theory and the theory of cancer as a metabolic disease.

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Matthieu Dubreucq
October 20th, 2019 at 1:39 am
Commented on: Cancer as a Mitochondrial Metabolic Disease

I like all the debate that this article brought. I think that regardless of who is right it seams clear that the somatic mutation theory alone is not enough to explain cancers. I like the fresh approach that suggest cancer is a mitochondrial metabolic disease. I hope we will have have some more evidence soon and save lives. While we wait I will stick to reducing carbs and crossfit on a regular basis. That seems to be once again a safe lifeboat to be on.

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drew dreiling
October 17th, 2019 at 8:02 pm
Commented on: Cancer as a Mitochondrial Metabolic Disease

With the glutamine piece- does this mean supplemental glutamine is contra-indicated if battling cancer? Knowing that glutamine is the primary fuel cell for intestinal lining (and is an important part of healing leaky gut in many protocols), I'm a little confused as to its place in a cancer prevention/treatment plan. Any clarity here would be helpful. Thanks

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Jenny Gallus
July 24th, 2019 at 10:31 pm
Commented on: Cancer as a Mitochondrial Metabolic Disease

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Kris Davis
May 24th, 2019 at 5:12 pm
Commented on: Cancer as a Mitochondrial Metabolic Disease

I was diagnosed B-cell lymphomas which are types of lymphoma affecting B cells. Lymphomas are blood cancers" in the lymph nodes. They develop more frequently in older adults and in immunocompromised individuals. I remember being on my knees praying, “God, I will fight as hard as I can if you just let me get through this chemo stuff.” When I went in, Dr. Noy said, “I have something that’s going to help. I’m going to give you Procrit after you get your chemo.” Once I got the Procrit, I never felt again like I had after that first chemo treatment. I got tired and I didn’t feel 100 percent, but I was really okay. My cancer became very real to me once I lost my hair. But by then the mystery, the uncertainty, was sort of gone. Not gone, but it just wasn’t at the forefront. There were things that I started looking forward to doing, like going out and not just staying in the house. By then, the weather had started getting really nice, and I decided I needed to get out. I would go for a long walk or take the subway into the city and look in the store windows. It’s funny, people I didn’t know would chat with me on the bus, on the train. We would talk about anything. That made me feel a lot better. It come a day when i was told by a lady to try and do some research on the internet for help maybe there will be a cure to my Cancer. I google for treatment for cancer and I saw some testimony about the herbal specialist called Dr. SANI and the great work of his Herbal Medicines. With the hope I have in God I believe this to be the end of my problem for I have prayed for a solution from God. I contact Dr. SANI with the giving email and also click on his website to see his work. I finally believed in him and told him about my problem. He prepared some Herbal medicines and which I was advice to take for three weeks, There are lot to say about Dr. Sani, I Thank God that this man was used to end my sorrows. All my pains and sorrows turn to joy and history from the day I came in contact with Dr. SANI, Who really help with his herbal medicines, I WAS TOLD HE IS A HERBAL SPECIALIST AND HE CAN BE OF HELP, I gave him a try and it really work out for me, today here I'm cured of B-cell lymphomas. If you need any help from him, you can contact him via: (perfectherbalcure@gmail.com ) OR Call/WhatsApp: +2348118184266

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Kris Davis
May 24th, 2019 at 5:11 pm
Commented on: Cancer as a Mitochondrial Metabolic Disease

I was diagnosed B-cell lymphomas which are types of lymphoma affecting B cells. Lymphomas are blood cancers" in the lymph nodes. They develop more frequently in older adults and in immunocompromised individuals. I remember being on my knees praying, “God, I will fight as hard as I can if you just let me get through this chemo stuff.” When I went in, Dr. Noy said, “I have something that’s going to help. I’m going to give you Procrit after you get your chemo.” Once I got the Procrit, I never felt again like I had after that first chemo treatment. I got tired and I didn’t feel 100 percent, but I was really okay. My cancer became very real to me once I lost my hair. But by then the mystery, the uncertainty, was sort of gone. Not gone, but it just wasn’t at the forefront. There were things that I started looking forward to doing, like going out and not just staying in the house. By then, the weather had started getting really nice, and I decided I needed to get out. I would go for a long walk or take the subway into the city and look in the store windows. It’s funny, people I didn’t know would chat with me on the bus, on the train. We would talk about anything. That made me feel a lot better. It come a day when i was told by a lady to try and do some research on the internet for help maybe there will be a cure to my Cancer. I google for treatment for cancer and I saw some testimony about the herbal specialist called Dr. SANI and the great work of his Herbal Medicines. With the hope I have in God I believe this to be the end of my problem for I have prayed for a solution from God. I contact Dr. SANI with the giving email and also click on his website to see his work. I finally believed in him and told him about my problem. He prepared some Herbal medicines and which I was advice to take for three weeks, There are lot to say about Dr. Sani, I Thank God that this man was used to end my sorrows. All my pains and sorrows turn to joy and history from the day I came in contact with Dr. SANI, Who really help with his herbal medicines, I WAS TOLD HE IS A HERBAL SPECIALIST AND HE CAN BE OF HELP, I gave him a try and it really work out for me, today here I'm cured of B-cell lymphomas. If you need any help from him, you can contact him via: (perfectherbalcure@gmail.com ) OR Call/WhatsApp: +2348118184266

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Roberto Flores
January 22nd, 2019 at 9:17 pm
Commented on: Cancer as a Mitochondrial Metabolic Disease

Time consuming as it was, I enjoyed reading this now involved thread. Many thanks to Greg Glassman for being the catalyst and to all the others for your thought provoking discussions. As Seyfried’s associate for over 8 years now, it’s nice to see that Warburg’s work continues to captivate journalists, scientists and physicians. In 2009, after comprehensive study of Warburg’s 1956 paper ‘On the origin of cancer cells’ I wanted to study the Warburg Theory of Cancer. Seyfried made that possible; every other scientist was consumed by popular science. Seyfried and I have spent countless hours going back and forth about Warburg’s Theory and the Somatic Mutation Theory.


Some individuals on this thread discuss the Mitochondrial Metabolic Theory (MMT), but I will focus my words on the the Warburg Theory of Cancer (TWC). Having read and thought about each paper carefully, I am extremely familiar with the nuclear transfer experiments that Seyfried discusses in relation to the Somatic Mutation Theory. Eventually and after much deliberation I came to the conclusion that the Warburg Theory of Cancer and the Somatic Mutation Theory can co-exist, quite elegantly by the way. Briefly and simply put, somatic mutations and aneuploidy allow lactate fermentation to increase as carcinogenic agents cause insufficient respiration.


What is clear and established is that a hallmark of cancer is genetic instability and mutation. In other words the genome of the cancer cell is always changing (instability). Currently, most of the cancer field targets cancer cell genetics. It is unwise to target a hallmark of cancer cells that is unstable. What is also clear and established is that another hallmark of cancer cells is deregulated cellular energetics. THE DEREGULATED CELLULAR ENERGETICS HALLMARK IS STABLE. Seyfried wisely chooses to target the stable deregulated energetics hallmark. In fact, the state of a low-protein ketosis can indeed target many other STABLE hallmarks of cancer at the same time, e.g. tumor promoting inflammation.


Another hallmark of cancer cells is sustained proliferative signalling. X-rays and most chemotherapy agents target the sustained proliferative signalling of cancer cells. This is unwise. Many normal healthy cells need to proliferate. Most physicians like Gorski continue in this unwise manner. If they do not, they encounter many problems, e.g. financial issues and/or other physicians calling them quacks.


Scientists never have it right; there is always a more correct answer and more information missing. True science is not about following popular thought, but about mustering the courage and having the insight to ask the right questions at the right time. Seyfried is an excellent true scientist. Warburg and Seyfried are indeed relatively correct. Are they absolutely correct? Impossible.


REFERENCES:


Warburg, O. H. On the Origin of Cancer Cells. Science 123, 309—314 (1956).


Hanahan, D. & Weinberg, R. Hallmarks of cancer: the next generation. Cell 144, 646—74 (2011).

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Mary Russell
January 12th, 2019 at 8:48 pm
Commented on: Cancer as a Mitochondrial Metabolic Disease

Finally, a bit about Dunning Kruger effect: the last paragraph is relevant to the points that Stanley and I are making vis a vis Greg:

https://theness.com/neurologicablog/index.php/misunderstanding-dunning-kruger/

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Mary Russell
January 12th, 2019 at 8:26 pm
Commented on: Cancer as a Mitochondrial Metabolic Disease

Greg: in a verbose and circuitous way, it does. And I think at this point we are just going around in circles- with you living up to reputation as somebody who will sooner or later resort to coarse insults.


Good luck with your efforts changing medical culture- wherever they lead.

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Mary Russell
January 12th, 2019 at 1:42 am
Commented on: Cancer as a Mitochondrial Metabolic Disease

“One of the things that may be required for someone to come to the conclusion that "Seyfried seems to think he invented the hypothesis that cancer is a metabolic disease" would be to never look at anything Seyfried has produced because he's ineligible for honest, fair, or intellectual evaluation because of his associations, where he published, and his "lack of weight given to the mainstream view".


Greg: I’ve read this paragraph five times and still have no idea what you are saying here. Can you clarify?

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Greg Glassman
January 12th, 2019 at 3:48 pm

Mary,


The first quote is your guess as to what Gorski would say about this thread. And my take on that is that your guess makes Gorski seem stupid or political and that you could only come to the conclusion, you, Gorski or anyone else, that Seyfried “thinks he invented the hypothesis that cancer is a metabolic disease” by not reading Seyfried’s research - something you and Stanley said a) was beyond your capacity and b) not worth doing anyway due to his associations. Go back and read the thread and see if it jogs your memory. How ironic is it that the piece you refuse to read is Seyfried giving respect to those who pioneered this very theory long before he came along? All my alarms as to why you are here are going off. That's how ironic it is.


The second quote is the Orwellian rationale, familiar to CrossFitters, for delisting Malcolm Kendrick from Wikipedia. It was a snide internal reference poking fun at you. Your refusal to engage the science while parroting sciencey memes has not gone unnoticed. You and Stanley have brought nothing to the conversation but some clumsy rhetorical jiu-jitsu appropriate for industry hacks.

Let me be clear, I do not need credentials of any sort to parse logic, mathematics, the scientific method, or rhetorical devices designed either to emphasize or deceive - especially, it would seem, from you. I don’t need any formal training to recognize someone unwilling to follow the flow of a conversation or debate.


Mary, in science the results of a valid experiment are considered facts. A theory has the burden of being consistent with those facts. It needs to be able to predict or retrodict those facts to be valid. A theory is improved or refined by being tweaked or tossed out to better predict facts. Two theories competing for the same facts is what science is often about. The obligation for the scientist is to adopt the theory more capable of predicting those facts. Sometimes a theory fits in one domain better than another theory but not in other domains, so scientists will use either depending on the application of the domain. MMT seems to do a better job of accommodating the experimental record than the SMT. This, again, is the discussion that you’ve admitted to not being capable of engaging in intellectually and further explained that you wouldn’t anyway due to Seyfried’s associations, views on nutrition, etc. You’ve wanted this to be a debate about ketogenic diets and cancer therapy and I’m here to tell you that the debate we are going to have at CrossFit.com is SMT vs MMT.


Laura Shelton portrayed this as an argument between a biologist and a surgeon on some nuanced biology where the surgeon seems confused, at best. You’ve given considerable support to that sense of things. I was long familiar with Gorski’s dodge on Seyfried’s thesis and accepted it as a surgeon not understanding science or willing to understand the science at hand. Not a big deal really. It was my suspicion going in and now I’m fairly sure that this is what is going on. And…I’ve come to see you as a troll for whatever interests find it utterly unacceptable to have a rational, honest, scientific discussion on the fascinating subject of oncogenesis.


Does this clarify my position?

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Mary Russell
January 12th, 2019 at 1:39 am
Commented on: Cancer as a Mitochondrial Metabolic Disease

Laura

:”for Dr. Gorski to comment that he would visit the cancer metabolism section at a conference and think, “nothing to see here,”


I’m pretty sure that is not Gorski’s point.


“People too often use their titles to tear down others. Sure Dr. Gorski has an MD, but Dr. Seyfried has a Ph.D ”


Nor is that.


“But automatically writing off an entire field of research simply because Dr. Seyfried was somehow associated with Mercola”


I don’t think anybody has done that here.


“Dr. Seyfried isn’t the danger to society, people like Dr. Gorski are. ”


Merciful heavens!


“Is [the Ketogenic diet] worth trying in conjunction with accepted courses of treatment? Yes. Is it worth trying when all else fails? Absolutely.”


That is, very succinctly put, the mindset that drives all cancer related quackery. And, although you have a good point about the strengths of academic biologists vs. MD oncologists, no clinician with bedside experience could dismiss the harm of alternative cancer treatment as blithely as you just did. It’s not that these unproven treatments have no scientific basis-but that their proponents run far ahead of the evidence- as Taubes puts it, desperate people take desperate measures. The fallout in terms of wasted money and strained relationships ( as well as foregoing actual evidence based treatments that can be effective) are not as benign as you may suppose.

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Laura Shelton
January 14th, 2019 at 6:42 pm

Mary, you're missing the point. The point is that what Dr. Gorski says has larger impacts on society than he or you clearly understand

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Mary Russell
January 12th, 2019 at 1:21 am
Commented on: Cancer as a Mitochondrial Metabolic Disease

“We are going to find someone who believes in the somatic mutation theory of oncogenesis that will explain to us how to square that theory with the nuclear-cytoplasm experiments.“


Greg: I suggest you go to an AACR meeting and find that “someone” to answer your questions! To suppose that non scientists can answer your questions in a meaningful way has been addressed upthread.

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Laura Shelton
January 10th, 2019 at 2:31 pm
Commented on: Cancer as a Mitochondrial Metabolic Disease

I appreciate the level at which most everyone is discussing the issue considering their varying backgrounds. It’s hard to take Dr. Gorski’s article seriously because oncologists are not biologists. They rarely understand actual molecular or biochemical mechanisms and are typically against any kind of “restricted” diet because they erroneously think it means starving the patient, which also means they don’t fully understand whole body physiology. Everyone seems to be harping on the fact that Dr. Seyfried’s work is done in mice. All drugs that are available today were developed in--you guessed it--mouse models. However, those models were what we call xenograft models, where human tumors were grown in a mouse that lacked a functional immune system. How is that representative of the environment in which cancer thrives? The mouse models that Dr. Seyfried uses are syngeneic, meaning the tumor grew in a mouse with a fully functioning immune system. That's a much more realistic set of circumstances, right? So to be clear, ALL research starts in the mouse. Are we lacking clinical data? Yes of course. However, regardless of the “origin” of cancer (a topic which, frankly, is secondary to the main point), the cancer field is in strong agreement that cancer metabolizes sugar differently than most other cells in the body. Cancer also metabolizes amino acids differently than most cells in the body. This hallmark of cancer is the basis for a large and growing number of biotech and pharmaceutical companies looking to do exactly what Dr. Seyfried is doing--stop, slow, or even inhibit cancer. Is Dr. Seyfried passionate about his research? Yes. Can he use too much hyperbole? Yes. And I agree that can hurt his case. But, medical professionals have the responsibility to stay up to date on scientific progress, and for Dr. Gorski to comment that he would visit the cancer metabolism section at a conference and think, “nothing to see here,” is clear evidence that he is missing and misunderstanding a major and important aspect of cancer biology; that is a much bigger disservice to the public than any YouTube video by Dr. Seyfried.


As we all may know, the ketogenic diet is well established for the treatment of epilepsy. Why is it such a stretch to think it could be effective in other diseases that are linked by similar signaling pathways (mTOR)? These discussions tend to bring out too many absolutes that obscure the main points. Can the ketogenic diet “cure” cancer? Probably not. Does that mean that it’s completely useless? Probably not. Scientific research is always in flux. One day we think one thing, the next we think the opposite. But automatically writing off an entire field of research simply because Dr. Seyfried was somehow associated with Mercola and to automatically label him a quack is just plain ignorant. People too often use their titles to tear down others. Sure Dr. Gorski has an MD, but Dr. Seyfried has a Ph.D and has spent his life researching the ketogenic diet. Dr. Gorski seems to have read one article and immediately arrived at an opinion of him. Using his title he can influence a whole host of people, including those who are at the end of their lives and looking for some hope. Dr. Seyfried brings those people hope when nothing else has worked. How many people have decided “oh I shouldn’t do this potentially life extending diet because some physician told me it was bad”? Dr. Seyfried isn’t the danger to society, people like Dr. Gorski are. People that think they’re experts and are not, but can easily portray themselves as such. What makes it pseudoscience? Simply because you don’t buy it? I am a former student of Dr. Seyfried. I have published with him on the metabolic origin of cancer and am currently still in the field. Of course the issue much more complicated than simply “cancer needs sugar." Does the ketogenic diet offer a solution to limit the main fuel of most cancer cells? Yes it does. Plain and simple, the ketogenic diet--like taking oxygen away from a fire--limits the major fuel source of most cancer cells. Is it a dangerous diet? No. Is it a difficult diet? Yes. However, you’d be amazed by the strength of will when faced with a death sentence. Is it worth trying in conjunction with accepted courses of treatment? Yes. Is it worth trying when all else fails? Absolutely. And unless someone has closely studied and possesses an in-depth knowledge of cancer biology (which most MDs unfortunately don't have), they shouldn't dismiss the diet out of hand.

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Mary Russell
January 9th, 2019 at 1:45 am
Commented on: Cancer as a Mitochondrial Metabolic Disease

One last comment: Gorski is not going to engage, but if he did, I’ll bet he would say:

“Seyfried seems to think he invented the hypothesis that cancer is a metabolic disease. He’s a few years behind the times. That was a favorite topic of the studies at the meetings of the American Association for Cancer Research meeting (which I attend almost every year) several years back. Then it faded into the background in favor of immunotherapy and immune checkpoint inhibitors.”


He would also be amused that Taubes doesn’t think he understands about being a maverick!

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Greg Glassman
January 9th, 2019 at 7:43 pm

So you think he'd refuse to offer anything substantive and instead join the ad hominem appeal of your and Stanley's offering? I’d hope he’d be smarter than that. I was hoping someone could explain the unchallenged transfer experiments and what the implications for the origins of cancer might be. You're saying the science cannot and will not be discussed. I'm going to insist that it does. I get that you won't participate.


Gary Taubes yesterday offered three possible resolutions of the question I posed each option being consistent with a sound, logical, and scientific approach to addressing the question. Might not Groski offer something like one of those? You're pretty sure he'd refuse to engage meaningfully or intelligently?


One of the things that may be required for someone to come to the conclusion that "Seyfried seems to think he invented the hypothesis that cancer is a metabolic disease" would be to never look at anything Seyfried has produced because he's ineligible for honest, fair, or intellectual evaluation because of his associations, where he published, and his "lack of weight given to the mainstream view".


I feel compelled to cut-and-paste a paragraph from Gary Taubes' post yesterday:


"So that’s the point. Seyfried may be right about the MMT and that’s vitally important if he is. In his article he quotes Peyton Rous to the effect that; “the somatic mutation theory acts like a tranquilizer on those who believe in it” (Rous, 1959)."


Maybe this isn't dead. What do you call theories that don't comport with observation and yet cannot even be defended because they are settled.


We are going to find someone who believes in the somatic mutation theory of oncogenesis that will explain to us how to square that theory with the nuclear-cytoplasm experiments. I'm so open minded.


For the person who even attempts this in earnest, the SMT is not a dogma but a reasoned scientific conclusion. They won't find need to mention Seyfried's conjectures/hypothesis on diet, low impact journals, Mercola, or current popularity of the view in contradistinction to what Mary and Stanley are offering here even be it sweetly.


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Gary Taubes
January 8th, 2019 at 6:41 pm
Commented on: Cancer as a Mitochondrial Metabolic Disease

When I see Greg saying someone has to explain the nuclear transfer experiments or accept the MMT is valid, three possibilities come to mind:


1. The researchers did the experiments correctly and interpreted the results correctly and these experiments are reproducible in many different mouse models, in which case they represent significant report for the MMT. And, yes, we should all accept it, with the caveat, as we’ll discuss, that some huge proportion of the cancer research community is simply not paying attention (even if, as Gorski says, more are than ever).


2. The researchers did the experiments correctly and interpreted the results correctly, in these cases, but these experiments represent only a small percentage of all the similar experiments ever done. And Tom is selecting the experiments he likes to make his case and ignoring others, perhaps many others. This is common in research and is often necessary. Science is full of misleading research (as we’ll also discuss) and so the researcher has to pick and choose the experiments he or she thinks were most meaningful. If so, he isn’t citing the others either because they weren’t published – as negative results typically aren’t – or because he didn’t find them somehow in his search, or perhaps he found reasons to dismiss them when he did find them, based on his assessment of their quality. Anything is possible.


3. The researchers screwed these experiments up, or misinterpreted the results, and got the wrong answer. On this forum particularly we’re more than willing to accept the fact that much to most medical research is unreliable. Twenty years ago when I wrote about this problem for Technology Review, I quoted the Australian philosopher of science John Ziman suggesting that 90 percent of the research published in physics journals (a much harder science than medicine) was wrong or misinterpreted and that the process of science, was in effect, the process of figuring out which ten percent of the information is actually right or meaningful and transferring that to the text books (which are then 90 percent right and only 10 percent misleading). And this was physics. Lord knows what the percentage of wrong or meaningful results are in medicine and biology but it’s assuredly high. And the fact that a dozen researchers found the same thing could mean it’s right or it could mean that they’re trapped in a cascade, all seeing in their experiments and so believing what they want to believe. Skepticism is always in order.


So that’s the point. Seyfried may be right about the MMT and that’s vitally important if he is. In his article he quotes Peyton Rous to the effect that; “the somatic mutation theory acts like a tranquilizer on those who believe in it” (Rous, 1959). In cases like this (which can also include the amyloid theory of Alzheimer’s and, my favorite, the energy balance theory of obesity) it’s hard to overestimate the effect of the paradigm on not just the thinking of researchers (the tranquilizer effect) but the funding of studies and the publishing of studies that are published and the interpretation of studies that are published. The conventional wisdom infects and influences the science from top to bottom, from past to future. CrossFit Health discussed all of these problems in its summer conference. Everything gets biased to support the accepted paradigm.


It’s also hard for physicians and researchers working inside the medical establishment (Gorski, in this case) to understand the position of the researchers who find themselves challenging that established paradigm, the position of the heretic. Tom is a heretic and Gorski is judging him from the position of someone who seems to think that there are a set of rules that heretics can follow just like any other researchers that will, if they’re patient and if they’re right, lead to the overthrow of the orthodoxy. But there are no rules. No book to read. The heretic is making it up as he or she goes along, trying to overcome a kind of institutionalized cognitive dissonance/groupthink that has such enormous unimaginable inertia that it may be impervious to assault. The heretics in these cases are the equivalent of whistle-blowers in a misconduct or fraud case, but they’re not challenging the work and intellectual integrity of one laboratory or one researcher in one institution, they’re challenging the work and intellectual integrity of virtually all labs and all researchers in their discipline and all institutions. While they may not be claiming that these researchers have acted unethically, they are claiming that they got the wrong answer and believed the wrong thing on the most important question in their field. That may be worse. (When I lectured on obesity and the problems with the energy balance hypothesis at the Pennington Biomedical Research Center half a dozen or more years ago, one of the older researchers in the room raised his hand in the Q&A that followed asked very politely, “Mr. Taubes, is it fair to say that one subtext of your presentation is that we are all idiots?” It was the obvious implication. In response, I prevaricated and said no.)


It’s only when ignored that whistle blowers and heretics have to go outside the lines of institutional processes to be heard. In whistleblower cases, they go to the newspapers or bloggers or whomever they can get to listen. In these paradigm issues, they end up talking to anyone who will listen, even if the people who do listen (Mercola) tend to be a bit too accepting of anything that is outside the mainstream. Calling Seyfried a “bad actor,” as Mary does, is a valid opinion, but it’s almost always the establishment position. If Mary was parenting, I don’t think she’d say he was a bad actor so much as that this particular action was bad, and then try to understand the reason behind this. And the reason is likely to be it’s difficult to stay suitably restrained and scientific when you think you know something that will save lives and the establishment (knock knock knock) is not listening, or not listening enough from your POV.


That said, I think Tom should be more aware of this and he should be more restrained. Gorski’s response and Stanley Nasraway’s comment are proof that Tom hurts his credibility by his pronouncements on the diet and by his lack of understanding of how Mercola is perceived. He has to do better. It’s part of the job of challenging the establishment: Communicating your ideas against enormous institutional inertia while remaining credible in the process. It ain’t easy, and there’s no book, but it goes with the job.


The cancer world is an extreme case. Gorski’s context, as he implies, is that the cancer world is full of people who are desperate and desperate people are targets for quacks and quackery. Despite the fact that I do believe that cancer is a metabolic disease and I do believe that insulin and IGF are drivers, I’m also skeptical that ketogenic diets will make a huge difference in treating the disease. I’m less skeptical of the idea that ketogenic diets or at least LCHF or paleo diets will help prevent cancer, but whether or not I’m skeptical is irrelevant. These latter questions can be studied and answered by trials. But I disagree with Mary that CrossFit is doing a disservice by discussing Seyfried’s article. This science and its implications for medicine and dietary therapy have to be aired. People have to know that ketogenic diets might, maybe, possibly could help. When I wrote about the possibility that sugar causes cancer in the New York Times Magazine (2011), I faced the same problem. I knew that I was pushing the envelope of the science and I knew that I would be accused, perhaps rightfully of scaremongering, but somebody had to say these things. In fact, I assumed the editors wouldn’t want me to, and they were the ones talking me into it. So I said it, but I put it in perspective. It may be right. It has to be said. But it could be wrong. You do with the speculative information what you wish. Those with cancer, though, are desperate. It’s a harder tightrope to walk between conveying the information and not encouraging deleterious behavior.


Re the MMT, even if it’s as surely right as Tom and Greg think, it’s likely to take decades for cancer researchers to shift their perspective. At that point, the general assumption will be that they knew it all along. I agree with Greg that all this is vitally important to clarify, but the way the NIH funds research these days, there’s no mechanism by which the research community can be made to decide en masse that a question or a controversy has to be clarified, that it’s so vitally important all researchers working in related disciplines should do whatever it takes to clarify it, rather than do what they were doing all along.


This is part of the tranquilizing effect that Rous mentioned. Business, as usual, is almost invariably the rule of the day. You study what you can get funded to study and what you can get funded to study is typically what you’ve been doing all along, which is by definition based on conventional thinking. It would be nice if something like the MMT could do the scientific equivalent of going viral, but I’m not sure such a thing is possible in the existing scientific environment. It may happen in slow motion, but we’ll need patience.

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Stanley Nasraway
January 8th, 2019 at 10:06 pm

Gary, Very powerful, comprehensive and civil. Appreciate the balanced point of view. Thank you.

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Mary Russell
January 9th, 2019 at 12:11 am

Thanks for the gracious reply, Gary. A few quibbles: I don’t recall implying that CrossFit has done a disservice to anybody by posting Seyfried’s article. It is Glassman’s blog: obviously, he can post what he wants. And it was I, not Stanley, who criticized Seyfried’s association with Mercola.

Be that as it may, I forwarded this article and the exchange to the editors at Science Based Medicine. It would be interesting to see (if he has any interest in engaging) what Gorski would say about the narrative you are proposing here: tranquilizing inertia (of whom you imply, carefully and in so many words that he is a party) -vs whistle blowers and heretics. I would guess he would propose his own counter narrative, but would leave that to him to say.

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Greg Glassman
January 9th, 2019 at 1:06 am

Mary, Stanley, Gary, Zeynep, Clarke, and Pat, thank you for this discussion. You're all sharp and good. I'm proud and stimulated by sharing this interaction with you.


Mary, yep, it's my blog. That's so true, but it's a tad foreign to my psyche.


Our target is all the smart people anywhere, my L1 staff, 10 year affiliates, and the 30-40 thousand CF physicians inside CF gyms around the world. This is their website, their blog.

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Stanley Nasraway
January 8th, 2019 at 12:45 pm
Commented on: Cancer as a Mitochondrial Metabolic Disease

Greg, you've asked generally for someone to speak directly to the theory of mitochondrial derangements as a cause of neoplastic growth, and to set aside criticisms of Seyfried. Normally, I'd reply to you directly, but you have edited your comments and there is no link to reply to your comments now.

The reason no one has stepped up here is twofold: 1. most of us know our limitations as physicians or physician/scientists, and we understand we are not qualified to speak off the cuff about the nuances of cellular research, dissecting good from bad studies. 2. Seyfried's treatise from Frontiers in Cell and Developmental Biology is a review from a low impact online journal with > 100 references. To dissect his theories and listed references to determine its legitimacy would personally take me weeks of personal time, which I cannot literally afford to do. If you want an educated alternative explanation to Seyfried and Warburg, you need to ask a qualified scientist, preferably an academic oncologist who also runs a research lab, and has 15-20 years of experience with patients and research who really understands the field and origin of cancer. These individuals exist, you need to find them for a legitimate, informed answer.

That said, one has to be skeptical of individuals who publish in low impact online journals. Frontiers is an entity that based on its website has dozens of virtual journals and charges for its publications. In 2015, it was just years old. The trusted best journals such as Science, Cell, Nature, JAMA, Lancet, New England J of Medicine

quite often are many decades or a century old. They have a track record of quality control, and DO NOT charge for publication. The latter is a recent money making invention by for profit entities and take advantage of young academicians' desire to buff their resume and publish, as an example.

I loved that CF published the article by Jeff Glassman which speaks to being exact and factually correct. He stated, "Weak scientists will strengthen their beliefs and stances by promoting their models while demoting the competition."

Thank you for posting this full discussion and comments; it's been civil and thought provoking.


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Greg Glassman
January 8th, 2019 at 4:47 pm

Stanley,


Three of the studies I’ve asked you to look at were published in the very high impact journals you trust so much and recommend that I site. (BTW, we have here number one and two for impact and number one and two for retraction but the problems with medical journals is a subject for another day.)


Howell A.N., et al. (1978). Tumorigenicity and its suppression in cybrids of mouse and Chinese hamster cell lines. Proc. Natl Acad. Sci. U. S. A., 75, 2358—2362 [PMC free article] [PubMed]McKinnell R.G., et al. (1969).


McKinnell R.G., et al. (1969). Transplantation of pluripotential nuclei from triploid frog tumors. Science, 165, 394—396 [PubMed]Mintz B., et al. (1975).


Normal genetically mosaic mice produced from malignant teratocarcinoma cells. Proc. Natl Acad. Sci. U. S. A., 72, 3585—3589 [PMC free article] [PubMed]


These studies are wonderfully elegant (marked by simplicity and efficacy) and I could readily explain them to high-school kids.


I understand the costs of rigor in terms of time, energy, and intellect. One of the hallmarks of groundbreaking science is that most all of it is very approachable.


This science is solid, approachable, replicated, and ignored. We’ve been here before.


I'd better thank you for your time!


This is intriguing to me. I, too, want to thank you for the engagement. This feels done.

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zeynep akgoc
January 8th, 2019 at 8:23 pm

Hi all, I am a former student of Dr. Seyfried,


I just saw the interesting discussion here and am astonished by how well you all read Seyfried’s work and also by the criticism from those not in the field. Criticism is always great for the subject to evolve, as long as it is not done by society's preconceptions. The quality of your work is not defined by journal rankings. Stanley, I am not sure you are aware of the problems in academia, but unfortunately the 1st drive of academics is not always for the benefit of the human anymore. Unfortunately in a world of shrinking funding sources, the academic focus is “publish or perish”. Academics too often have to tailor their grants and research to fit within the boundaries of those deciding who gets funded. “Sexy Science” often dominates grant applications and funding decisions. Often times mistakes are missed or bad experimental designs are published because a big name is attached to the paper. I will not name names but it happens and it is a huge problem. One of our most prestigious journals also has the highest rate of retracted papers due to scientific fraud. To be blunt, researchers publish fake data in order to get published in these top journals which can have far reaching consequences. I have seen and participated in research we did in Dr. Seyfried's laboratory. It was in no way easy. He published in both high and low impact journals, each with their own criticisms, all with tremendous effort. It is not fair to assume that research is not correct because it is published in a 'low impact journal". The same researchers that are deciding funding opportunities are the same people reviewing papers. They apply their own biases to what they read and decide if they like it or not regardless of scientific merit. Dr. Seyfried approached the cancer therapy problem from a very different angle, one that not many people wanted to believe in or support. In time, however, it has become more and more evident that he has discovered something powerful and meaningful. In fact, the driving force for journal selection for his papers was based more on which ones offered public access. Dr. Seyfried felt that if his research was to truly help people, then they should have access to it. Ask yourself, if researchers today are truly invested in bettering peoples’ lives, then why do they care more about publishing in elite “pay for access” journals, than those that are open to the very people they say they are helping? In addition, Dr. Seyfried was the most critical person I met when it came to data. If you showed him a little increase between 2 groups, he would say "It looks the same to me". He always wanted to make sure there is a "real" difference and we didn’t become biased by our own data.



Also unfortunately the reason "no one is stepping in" is basically because not many people have the courage to go against the grain. It is easier to step aside and let other people figure it out. I myself did not have that courage like many of us, therefore I am not in this field anymore. But unlike many of us, I am aware of myself, and I appreciate the people that work to change the status quo. I am guessing we are all in agreement with Dr. Seyfried that: cancer is a devastating disease and the current treatments are no way near perfect. He comes to work every day to resolve a big problem that involves so many people and hopefully will result in some change. He gets no money for what he is doing. He is not out there trying to sell you a gimmick or product, just an alternative to the therapies and drugs that do allow others to profit, including the doctors that prescribe them. Of course there is always the need for more data, and it is not easy to get, and it may take many more years to get. However, Dr, Seyfried is out there advocating for better science, better therapies, and better outcomes.

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Mary Russell
January 7th, 2019 at 11:59 pm
Commented on: Cancer as a Mitochondrial Metabolic Disease

Actually, I would like to apologize to the Flat Earth Society for any comparison to Mercola.

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Mary Russell
January 7th, 2019 at 11:48 pm
Commented on: Cancer as a Mitochondrial Metabolic Disease

Greg: it’s possible Seyfried is correct about cancer pathophysiology and musters all of the evidence in his Cell piece without cherry picking or distortion. But, not being a cell biologist, I am not in a position to weigh the evidence- and neither, I would add, is anyone without a background in the field.


Your responses to various objections about Seyfried also beg the question of why CrossFit posted this article- to have a learned discussion about cell physiology? Or rather because the topic has practical application to a narrative favored by CrossFit? If the second, then pointing out Seyfried’s Fails in the practical application of theory department is not merely an ad hominem. It’s as if an astrophysicist complains that everyone is ignoring his hot new theory- but then allows himself to be interviewed and promoted by the Flat Earth Society. Seyfried’s association with Mercola looks bad for him in the same way. Make a plausible case for a new way to look at cancer physiology and people will listen. But complaining that mainstream medicine has it all wrong while posting YouTube’s of interviews by Mercola will earn him the derision of cancer physicians.

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Stanley Nasraway
January 7th, 2019 at 9:44 pm
Commented on: Cancer as a Mitochondrial Metabolic Disease

Greg, we’re not against a metabolic origin to cancer; just to drawing conclusions beyond what human evidence supports. Otherwise, see Mary who obviously had the best English teacher amongst any of us. ;)

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Greg Glassman
January 7th, 2019 at 10:08 pm

The insistence, it seems is to ad hominem response to some really elegant and important experiments. Can this conversation be turned into a scientific one? Challenging Seyfried on nutrition is a straw-man for addressing the science, impeccably carried out it seems, replicated several times as well, done by others highly regarded (I had a wonderful conversation with Chris Shay recently) that quite conspicuously is being ignored here.

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Greg Glassman
January 7th, 2019 at 10:25 pm

Maybe it's not clear without looking at the paper, but the experiments are not Seyfried's and the conclusions of those are also not Seyfried's. Seyfried simply concludes from those experiments that cancer is a metabolic disease. I've been asking for someone, anyone, to look at those same experiments and come to a conclusion that differs from Tom Seyfried's conclusion.

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Mary Russell
January 7th, 2019 at 6:12 pm
Commented on: Cancer as a Mitochondrial Metabolic Disease

Gorski doesn’t so much object to the mitochondrial theory of cancer, as he says at the outset:

“Dr. Seyfried’s argument that cancer is primarily a metabolic disease (an argument I’ll look at in more depth shortly) is well within the bounds of current oncologic science. Indeed, a few years ago it was all the rage, and I remember attending several sessions and lectures on the Warburg effect and cancer at the AACR meetings three or four years ago, although, oddly enough, I don’t recall as many the last couple of years.”


His distaste (and mine) for Seyfried arises from Seyfried’s statements re: keto diet treatment for cancer. Here Seyfried has been a bad actor, contributing to the swirl of half truths and frank woo that physicians like Gorski and I have to contend with. It’s good, I suppose, that in conversations with you Seyfried has walked back his wilder statements from earlier (quoted by Gorski and referenced by Stanley, upthread). But the damage has been done, and his difficulty understanding how clinical evidence works ( again, referenced by Gorski) means other claims will be met with more skepticism than perhaps they deserve to be.

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Greg Glassman
January 7th, 2019 at 9:43 pm


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Greg Glassman
January 7th, 2019 at 9:58 pm

All,


The nuclear and cytoplasmic experiments are sited in my earlier comment for all to read. They alone strongly support the contention that cancer is primarily a metabolic disease and that the somatic mutation theory is wrong. What Seyfried has done is to call attention to some very important science that has largely been ignored - certainly considering the ramifications if real.


Look at those experiments and answer how can these be solid experiments with valid outcomes and the somatic mutation theory be anything other than wrong?


Gorski doesn’t come close to delivering on his promise to address SMT vs. MMT. He doesn’t even try. He says it’s a little bit of both and the exact proportion depends on the tumor type. Let me show how unsatisfactory a response that is by way of analogy and quote from Warburg.


First the Warburg:


“Just as there are many remote causes of plague, heat, insects, rats, but only one common cause, the plague bacillus, there are a great many remote causes of cancer-tar, rays, arsenic, pressure, urethane- but there is only one common cause into which all other causes of cancer merge, the irreversible injuring of respiration.”


I think this is not only brilliant but likely correct. Here’s how unsatisfactory Gorski’s response is for me.


Imagine arguing that the plague comes from both rats and the plague bacillus. Probably a little bit of both in exact proportion depending on the individual stricken.


It doesn’t work. Gorski didn’t even get close to the discussion. That’s OK, it’s his blog. He’s not obligated to serve any aims beyond his own. I can't say Gorski has the metabolics of cancer wrong because I see know evidence that he's interested in the subject. He certainly doesn't explore it at all in the piece cited.


If cancer is primarily a metabolic disease of the mitochondria where the genetic mess is a downstream effect then, yes, you can take Gorski’s position that it’s a disease of both the nucleus and the mitochondria but it would be to miss the true cause, what Warburg would call the "common cause" and most certainly delay more effective prevention and treatment.


I’m trying to move the discussion here towards the evidence sited. If anyone’s response to the transfer experiments is “Seyfried’s a quack”, you’re ducking. Ducking the question. That’s an ad hominem response to a likely important scientific question.


So, again, What about the nuclear and cytoplasmic transfer experiments and what they reveal about tumerigenicity?

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Stanley Nasraway
January 7th, 2019 at 2:23 pm
Commented on: Cancer as a Mitochondrial Metabolic Disease

This was a good series of comments. I appreciate Mary's deft tact, and citing the Gorski reference, which I think I had also posted many months ago on FB CF Physicians thread. It was a good read. I also appreciate Greg's disclosure as to CF's and his personal relationship with Dr. Seyfried. While Seyfried may not have told you KD "cures cancer", I have listened to him on podcasts and in videos, and he absolutely runs wild and states KD halts or reverses cancer.


Look, I'm all in favor of validating or invalidating a theory with good science. Perhaps cancer has a metabolic component, which can be attacked successfully with a diet strategy. However, promoting pseudoscience or allowing others to do so is dangerous; some patients with real disease or cancer will be convinced to follow these unproven regimens at the expense of other regimens that have an actual chance at remission. That's why giving individuals like Seyfried a forum is dangerous, and misleading, to young physicians, to athletes at the Games via CF Health, and on CF Journal. Since you agree in your comments that Seyfried's position is controversial and his evidence is "thin", at the very least, why not consider a balanced approach, having someone else provide the alternative point of view?


Pat, we've all been touched by cancer, directly or otherwise. The 2nd most common cause of death in Western civilization. I've had my own experience with it. Great inroads have been made with Coronary Artery Disease; lifespans are increasing, mortality is declining. I expect cancer to become the #1 cause of death in the U.S. overtaking CAD.

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Greg Glassman
January 7th, 2019 at 3:43 pm


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Pat Sherwood
January 6th, 2019 at 3:40 am
Commented on: Cancer as a Mitochondrial Metabolic Disease

I have had the pleasure to hear Dr. Seyfried in person on several occasions. He is sharp, extremely well-experienced in his craft, and truly dedicated to improving the current situation and treatment of cancer...which is horrific. Determining if Dr. Seyfried is correct is beyond my capacity, but I hope he is. I have had family members suffer through the current protocols for treating cancer and it seems just as terrible as the disease itself.

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Clarke Read
January 5th, 2019 at 5:56 pm
Commented on: Cancer as a Mitochondrial Metabolic Disease

Taking a step back to Jeff Glassman’s 1/3/19 post…if we looked at Seyfried’s conjecture (MMT, the mitochondrial mutation theory) and compared it to the common alternative (SMT, the somatic mutation theory), which would we find more consistent with existing evidence? Which requires fewer exceptions and modifications?


Seyfried here makes the case nuclear gene mutations are both insufficient and unnecessary to initiate tumorigenesis, which would seem to rule them out as the primary insult. That said, given the frequency with which they are observed, the true primary insult would need to consistently cause these mutations over time, consistently be observed in cancer, and originate in the cytoplasm to be more consistent with the nuclear transfer data Seyfried cites. The MMT seems more consistent with the observations Seyfried presents than the SMT, while remaining sufficient to explain the other defects commonly observed in cancer.


As Seyfried notes, it’s also compelling from an Occam’s Razor perspective. It may be that the genetic heterogeneity observed in cancer reflects the true course of the disease. But if there were an explanation that accounted for this observed heterogeneity but was simpler in itself - and the MMT succeeds on both counts - it would seem worth exploring until it has been clearly supported or discredited. Doesn’t mean it’s right, of course.


I’m curious how the broader cancer community responds to Seyfried’s core conjecture (to use Glassman’s terminology strictly) and his observations. If, as he argues, mitochondrial defects are universal in cancer, and given the prominence of Warburg’s work, this hypothesis cannot be obscure, and can’t have gone unchallenged. Having not yet read his critics, I suspect there are observations this model fails to explain. I see a source has already been suggested here, I look forward to digging into this one and others.

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Mary Russell
January 5th, 2019 at 2:07 pm
Commented on: Cancer as a Mitochondrial Metabolic Disease

Noted skeptic David Gorski MD

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Mary Russell
January 5th, 2019 at 2:06 pm
Commented on: Cancer as a Mitochondrial Metabolic Disease

Seyfried has plenty of critics, and has drawn the attention of noted skeptic and cancer surgeon (no industry shill, he) who wrote the following criticism of Seyfreid:https://sciencebasedmedicine.org/ketogenic-diets-for-cancer-hype-versus-science/

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Clarke Read
January 5th, 2019 at 6:28 pm

Thank you for posting this. It's always helpful to see critics' viewpoints, at the very least to understand where a model is strong and weak.


Gorski focuses on a narrower claim from Seyfried which to me demands a higher burden of proof - his claim that a ketogenic diet is a uniquely effective anticancer regimen. Assuming he quotes Seyfried and the evidence correctly (and I've no reason to believe he doesn't), his pushback seems valid, and while there may be a kernel of truth in this particular Seyfried statement, the whole nut seems shaky at best. The fact that it's only been supported by preliminary data doesn't mean it's wrong, of course, but it does warrant skepticism.


Which is a bit unfortunate, because I'm sure this stronger claim (the KD claim) can be invalid, or only partially valid, without invalidating the core MMT. The first claim in Gorski's final paragraph - that metabolic abnormalities and genetic defects in cancer are a chicken and egg problem - is seriously unsatisfying, but could also be right. I would hope that if we do fall back to the "cancer is really complicated" argument, it's because we are confident it truly is a highly variable disease, not because we've simply failed to understand some simpler underlying character.


Obviously lots more to this discussion.

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Greg Glassman
January 6th, 2019 at 3:19 pm


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Greg Glassman
January 6th, 2019 at 3:35 pm

Thank you, Mary. I too found Gorski looking for a challenge or response to Seyfried’s MMT. That was the best challenge I found.


I also really like Gorski (hopefully not because he slams Mercola who has said some stupid shit about CF, and when confronted via phone made it clear he had no idea what CF was and worse yet hadn’t even looked at the website).


I also know Thomas Seyfried personally and I know of his enthusiasm for ketogenic diets as adjuvant therapies for cancer . I’ve also asked him if ketogenic diets cure cancer and the response was an instant, “no!”. I share Gorski’s enthusiasm for upcoming research examining this hypothesis/theory.


But, Seyfried isn’t the ketogenic-diets-stop-cancer guy, he’s the researcher who posits that the MMT better explains cancer than the SMT, and for me, reading Gorski for any refutation of MMT or support for SMT I find NOTHING!!!


His chicken and egg response is a swing and a miss that would make an engineer or scientist familiar with the natural phenomenon of feedback chuckle.


Metabolic derangement of the mitochondria that initiates genetic damage in the nucleus that further damages metabolism of the mitochondria gives Gorski his chicken and egg and makes Seyfried correct and cancer a metabolic disease.


To refute Seyfried’s theory (Clarke, I think it’s a theory and not a hypothesis while agreeing with Gorski that the evidence is incomplete or currently only thin.) I need explanation of the nuclear transfer experiments referenced in the study shared here today. If Seyfried’s enthusiasm for ketogenic diets is the best response to this study then it looks like Seyfried’s critics are letting his primary assertion go unchallenged.


Gorski is critical of Seyfried, while being somewhat respectful and a tad snarky, but what he didn’t do is bring any serious challenge to MMT or support for the SMT, and the issue is hot, fascinating, and I would think potentially significant for therapeutic advances in oncology and cancer treatment.


I would greatly appreciate any science that challenges Seyfried’s fundamental proposition that cancer has its origins in the mitochondria and that the nuclear damage is a downstream effect.


In disclosure, CrossFit has helped fund some of Seyfried’s research and I consider him to be a personal friend.

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Mary Russell
January 6th, 2019 at 6:21 pm

To be fair, Greg, the Gorski article was from 2014 and the Seyfried piece was published in Cell in 2015, so Gorski’s argument doesn’t sidestep but predates Seyfried’s points.

I find that, whatever the merit of the hypothesis posed by Seyfried, his willingness to run ahead of the evidence IRT the Ketogenic Diet(discusses in detail in the Gorski piece) as well as his history of using poor quality or preliminary research to reach a conclusion before one is warranted, makes me less inclined to be receptive to his arguments.

At any rate, time will tell, and I look forward to more quality research in this area.

Best regards.

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Greg Glassman
January 7th, 2019 at 2:52 pm


Hi Mary,


Continuing the fairness I’ll also point out that Seyfried published his book “Cancer as a Metabolic Disease” in May of 2012, and “Cancer as a Metabolic Disease - Implications for Novel Therapeutics” in Oncogenesis in March of 2014.


Both deal extensively and centrally with the MMT and SMT.


I’m assuming Gorski knew of both works, but it’s possible that he hadn’t. Maybe when he saw Seyfried on Mercola he didn’t look for these other works. That would be odd. I find it more likely that Gorski took personal and professional umbrage, maybe outrage at Seyfried’s impugning Gorski’s profession. I get that. I’d be pissed too.


Check this out from the piece Seyfried published in Oncogenesis:


“Several investigators showed that tumorigenicity is suppressed when cytoplasm from non-tumorigenic cells, containing normal mitochondria, is combined with nuclei from tumor cells (40—44). Moreover, the in vivo tumorigenicity of multiple human and animal tumor types is suppressed when the nucleus from the tumor cell is introduced into the cytoplasm of a non-tumorigenic cell (45—48). Tumors generally did not form despite the continued presence of the tumor-associated mutations. The nuclear gene mutations documented in mouse brain tumors and melanomas were also detected in the normal embryonic tissues of the mice derived from the tumor nuclei (47,48). Some embryos derived from tumor nuclei, which contained major chromosomal imbalances, proceeded through early development forming normal appearing tissues before dying. Despite the presence of tumor-associated aneuploidy and somatic mutations, tumors did not develop from these tumor-derived nuclei (49). Boveri also found that sea urchin embryos with chromosomal imbalances developed normally to gastrulation but then aborted (25,29). Hochedlinger et al. (48) showed that nuclei derived from melanoma cells were unable to direct complete mouse development due presumably to the chromosomal imbalances and irreversible tumor-associated mutations in the melanoma nucleus. Tumors did not arise in the embryos derived from the melanoma nuclei. These findings suggest that the nuclear genomic defects in these tumor cells have more to do with directing development than with causing tumors.”


Here are the references sited:


40. Koura M., et al. (1982). Suppression of tumorigenicity in interspecific reconstituted cells and cybrids. Gann, 73, 574—580 [PubMed]

41. Israel B.A., et al. (1987). Cytoplasmic suppression of malignancy. In Vitro Cell. Dev. Biol., 23, 627—632 [PubMed]

42. Shay J.W., et al. (1988). Cytoplasmic suppression of tumorigenicity in reconstructed mouse cells. Cancer Res., 48, 830—833 [PubMed]

43. Howell A.N., et al. (1978). Tumorigenicity and its suppression in cybrids of mouse and Chinese hamster cell lines. Proc. Natl Acad. Sci. U. S. A., 75, 2358—2362 [PMC free article] [PubMed]

44. Jonasson J., et al. (1977). The analysis of malignancy by cell fusion. VIII. Evidence for the intervention of an extra-chromosomal element. J. Cell Sci., 24, 255—263 [PubMed]

45. McKinnell R.G., et al. (1969). Transplantation of pluripotential nuclei from triploid frog tumors. Science, 165, 394—396 [PubMed]

46. Mintz B., et al. (1975). Normal genetically mosaic mice produced from malignant teratocarcinoma cells. Proc. Natl Acad. Sci. U. S. A., 72, 3585—3589 [PMC free article] [PubMed]

47. Li L., et al. (2003). Mouse embryos cloned from brain tumors. Cancer Res., 63, 2733—2736 [PubMed]

48. Hochedlinger K., et al. (2004). Reprogramming of a melanoma genome by nuclear transplantation. Genes Dev., 18, 1875—1885 [PMC free article] [PubMed]

49. Seyfried T.N. (2012). Mitochondria: the ultimate tumor suppressor. In Cancer As a Metabolic Disease: On the Origin, Management, and Prevention of Cancer. John Wiley & Sons, Hoboken, NJ, pp. 195—205


This was all available on line in Dec. of 2013. If Gorski didn’t see this before writing in One 0f 2014, well, OK. If he didn’t look it up after seeing Seyfried on Mercola, he certainly should have. And most importantly of all, an honest, and yes, Mary, fair, and scientific inquiry would address these experiments in nuclear and cytoplasmic transfers and the challenge they present to the SMT of Oncogenesis.


I’ve got to reject those experiments or reject the SMT, or find someone who can stitch them together somehow, but taking Seyfried to task for his support of ketogenic diets is sidestepping the more important query as to whether our most fundamental appreciation of the biology of cancer is flawed. I think it may be but Gorski didn't address the science. Why?

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Brittney Saline
January 5th, 2019 at 4:31 am
Commented on: Cancer as a Mitochondrial Metabolic Disease

I had the privilege of speaking with Dr. Seyfried a couple years ago.


As he told me, "People say cancer’s a thousand diseases, and this is the result of the gene theory. But they’re all fermenting. They all have the same metabolic malady: They need glucose and glutamine to survive. Whether it’s a colon tumor, whether it’s a brain tumor, whether it’s a breast tumor, they’re all the same … if you look at it from the metabolic perspective, you see a singular disease of respiration.”

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Roberto Flores
January 22nd, 2019 at 9:19 pm

That cancer cells need glucose and glutamine to survive is not entirely true...that is when they are grown in a petri dish. As Warburg himself found in his research in the late 1960s, some cancer cells can survive without glucose (1). Importantly, in this study Warburg found that these cancer cells that can indeed survive without glucose are unable to grow. Survival and growth differ. Since then, other cancer cells have been found that can even grow without glucose, but do require other sugars like fructose (2).


In addition, in the presence of glucose, cancer cells can grow without glutamine as long as another nitrogen source is present (3,4).


These studies are done in a petri dish, but the in the body the environment is most definitely different. In the body, glucose and glutamine are always present in some amounts and targeting these metabolites is highly effective at reducing cancer cell growth (as Seyfried and others have found).


References:


1. Warburg, O. H., Geissler, A. & Lorenz, S. On growth of cancer cells in media in which glucose is replaced by galactose. Hoppe-Seyler’s Zeitschrift Physiol. Chemie 348, 1686 (1967).


2. Wice, B. M., Reitzer, L. J. & Kennell, D. The continuous growth of vertebrate cells in the absence of sugar. J. Biol. Chem. 256, 7812 (1981).


3. Cheng, T. et al. Pyruvate carboxylase is required for glutamine-independent growth of tumor cells. Proc. Natl. Acad. Sci. 1—6 (2011).


4. Meng, M., Chen, S., Lao, T., Liang, D. & Sang, N. Nitrogen anabolism underlies the importance of glutaminolysis in proliferating cells. Cell Cycle 9, 3921 (2010).

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