The Metabolic Theory of Cancer and the Key to Cancer Prevention and Recovery
February 07, 2016
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By Dr. Mercola
Each day, some 1,600 people die of cancer in the United States. That number goes up 10-fold, up to 21,000 if you include the global population.
While conventional medicine has little to offer outside the standard "cut, poison, burn" approach, new evidence suggests simple dietary modifications could effectively both treat and prevent the majority of these cancers.
Travis Christofferson is the author of a phenomenal book called "Tripping Over the Truth: The Return of the Metabolic Theory of Cancer Illuminates a New and Hopeful Path to a Cure."
I read 150 books last year and this was one of the best. In my view, it's required reading for anyone who has cancer or knows someone who has cancer. This book has inspired me to passionately review the medical literature on mitochondrial metabolism for a book that will be published next year.
The Return of the Metabolic Theory of Cancer
In this interview, Travis — who has a Pre-Medical undergraduate degree and a Master's degree in Materials Engineering and Science — reviews some of the details covered in his book.
"I was doing a class on cancer theory and I stumbled on this book by Thomas N. Seyfried, Ph.D. called 'Cancer as a Metabolic Disease,'" Travis says. "It was just an incredibly well-written book ....Upon his return, Travis dove into the data from the Cancer Genome Atlas project, which started in 2006. It was the largest government project ever conceived to sequence the genomes of cancer cells. It involved 10,000 times the amount of genetic sequencing done by the Human Genome Project.
It laid out this elegant argument for this non-genetic origin of cancer; the metabolic origin of cancer.
I was so stunned and taken aback by this, and that more people didn't know about it, that I compiled a huge list of questions and actually flew out to see Tom in Boston ... He answered all my questions, which really served to pique my interest more."
The goal was to ferret out mutations found within cancer cells. Once Travis began looking at all this data, he realized there was a lot of confusion even among the top ranking scientists as to what the data was really showing. It didn't conform to their original expectations.
Travis thought the whole story really needed to be told, and hence his book, "Tripping Over the Truth" was born.
The Warburg Effect
Travis' book highlights the pioneering work of Dr. Otto Warburg, MD, PhD, and those who followed in his footsteps.
Most students of natural health are familiar with Dr. Warburg's name, as he won the Nobel Prize for medicine in 1931 for his discovery that cancer cells have a fundamentally different energy metabolism compared to healthy cells.
But they don't know he was a personal friend of German physicists Albert Einstein and Max Planck, and was awarded a second Nobel Prize in 1944 but Hitler prevented him from going to Stockholm to pick it up. He is considered by most experts to be the greatest biochemist of the 20th century.
Dr. Warburg discovered that in the presence of oxygen, cancer cells overproduce lactic acid. This is known as The Warburg Effect. A cell can produce energy in two ways: aerobically, in the mitochondria, or anaerobically, in the cytoplasm, which generates lactic acid — a toxic byproduct.
The former is far more efficient, capable of generating 32 times more adenosine triphosphate (ATP) than anaerobic energy generation. Dr. Warburg concluded that the prime cause of cancer was reversion of energy generation from aerobic energy generation to anaerobic fermentation.
That, he said, was the prime cause of cancer until his death in 1970. One of his life goals was to discover the cure for cancer. Sadly, many, including myself, believe he did, but his theories were never accepted by conventional science despite his academic pedigree.
The Somatic Theory of Cancer
Yet despite winning a Nobel Prize, his ideas on cancer didn't gain recognition by conventional medicine, which rejected and ridiculed them. His case was further sabotaged by the revolution in genetics that occurred once Watson and Crick discovered DNA. From that point on, all the attention went to genetics.
"1976 was when Harold Varmus and Michael Bishop won the Nobel Prize for finding viral oncogenes within the DNA of cancer cells ... There was a viral theory that was competing with it — that viruses could cause cancer — but nobody knew how.The evidence clearly showed that something other than mere gene mutation was at play, and this fact was not lost on the top scientists in the field. As noted by Travis, they've had to retool their gene theory to make it fit. One theory is called "dark matter."
These guys found that the viral gene that was being inserted in the gene was just a copy of the gene we already had, but it was distorted.
So now this somatic theory was off to the races — the theory that cancer is just a distorted version of normal cellular division checkpoints; mutations in other words ...
But then you get to 2006 and the Cancer Genome Atlas project, which was ... to ferret out all the mutations thought to be causative for cancer. This was to be the final concluding effort to [end] cancer.
We would know every single detail, every aspect of how it operated. But once the sequencing started up and this data came out ... it was much more random than people would have suspected.
If you have 10 people in the room with, say, pancreatic cancer and you sequence each of their tumors, what you'll find is there are a couple of commonly mutated genes, but from one patient to the next, there not much of a pattern. It's very random.
You'll even find some cases with one single driving mutation. You cannot explain that through a genetic origin of cancer, through the somatic mutation theory. You'll even find tumors with zero mutations."
There's something else driving cancer that we don't know about. Shockingly, many of these scientists have never heard of either Seyfried's work, or Dr. Warburg's, both of whom have compiled compelling evidence showing an altogether different origin of cancer, namely mitochondrial damage followed by an epigenetic response.
To Make a Dent in Cancer Statistics, We Must Focus on Cancer Metabolism
If you are dying from cancer there is something seriously wrong, because the treatment is so radically simple, and Travis' book clearly and carefully explains this process. Even James Watson, who got the Nobel Prize in '54 for discovering the structure of DNA has turned his focus to the metabolic roots of cancer.
Watson was focused on targeted therapy and the somatic mutation theory of cancer, trying to target the protein derivatives of the mutations within the DNA. But the drugs developed based on this theory have all been very disappointing, despite the idea that this was the path to a cure.
It's since become clear that this is not the case. There's simply too much random diversity within the genes. There's also the phenomenon of intra-heterogeneity, which is the difference in mutations from cell to cell within the same tumor.
James Watson noticed this and is claimed to have said: "[I]f we're ever going to cure cancer, we're clearly going to have to go back to the days of Otto Warburg and focus on the metabolism to make any real progress." So even this genetic expert has made an abrupt shift in how he thinks we should approach cancer therapeutically.
"When you look at cancer metabolically, the whole paradigm of therapy has changed. You go from this targeted paradigm to all of a sudden you're targeting the metabolism," Travis says. "You're trying to restore mitochondria function. You're trying to increase mitochondrial numbers.
You can probably rescue some cells within a tumor and divert them back into living within the collective of the multicellular organism. They will revert to being normal. Some you can send over this tipping point. You can kill them through these various therapies metabolically. It's an interesting time. The paradigm of cancer is being turned therapeutically and our understanding of it."
Why Do Cancer Cells Revert to Anaerobic Energy Generation?
So why exactly do cancer cells revert from aerobic energy generation to anaerobic energy generation? Pete Pedersen, Ph.D. at Johns Hopkins took Dr. Warburg's theory to the next level, morphologically determining that there's a radically reduced number of mitochondria in cancer cells.
Typically there are several hundred to several thousand in each cell, comprising about one-third to 50 percent of the volume of the inside of each cell. These generate the ATP, the energy, of your cells. If you have a radical reduction of mitochondria, and the ones that are left are mostly dysfunctional, if they're working at all, then you've got a problem.
These cancer cells have no choice but to revert to this primitive and inefficient metabolism. Healthy mitochondria send these epigenetic signals between themselves and the nucleus. This epigenetic signaling from the mitochondria is actually what's responsible for initiating a significant percentage of the genetic damage that has been identified from the DNA sequencing project. As noted by Travis:
"There's mitochondrial damage, that's irrefutable. We look at cancer cells and the numbers are vastly reduced. When you isolate the mitochondria, you look at them and morphologically, they're messed up. There are protein problems, lipid problems, and all kinds of structural abnormalities.
There's always been this debate: Why is the cancer cell doing the Warburg Effect? Why is it reverting to anaerobic energy generation? Nobody really tied that to the terrible structure of the mitochondria. They didn't have the tools to see the mitochondria, and now we do.
Tom Seyfried has done a great job of piecing together these events. This relationship between mitochondria and the nucleus is so important in biology ... They constantly cross-talk, and mitochondrial health is correlated to the health of the entire organism. The dominant theory of aging explains that you age because your mitochondria age. They take the brunt of metabolism.
When you generate energy, you create free radicals. They're constantly under stress. They get banged up and beat up, and you look at the antioxidants within mitochondria, there's decline about 50 percent within age, with advanced age. "
Mitochondrial Function Determines Cancer Growth and Repression
To clarify even further, cancer cells burn glucose, an inherently "dirty" fuel as it generates far more reactive oxygen species (ROS) than fat and ketones. But in order to burn ketones, the cell must be healthy and normal. Cancer cells cannot burn fat, and this is the heart of successful cancer treatment, and why ketogenic diets appear to be so effective. They essentially starve the cancer, while nourishing healthy cells.
"The clincher with this theory is that once there's enough mitochondrial damage — it's called a retrograde response or epigenetic signal to the nucleus — once this happens, you start to see the genomic instability. You start to see the accumulation of mutations. So the whole crux of this theory is, which comes first?Seyfried has done a remarkable job of compiling supporting evidence for the metabolic theory of cancer. For example, he dug up so-called nuclear transfer studies, most of which date back to the 1980s. They were very simple, elegant experiments in which they took the nucleus of a cancer cell and put it into a normal cell with its nucleus removed. The cells are then grown in a petri dish, after which they're injected into mice, to see what happens.
The argument in the metabolic theory is that this mitochondrial damage happens first, and then you see the mutations. The mutations appeared [to be] the cause, but in fact they're a downstream signal from the true cause. So you can see why researchers were led on this wild goose chase, trying to find what these mutations were and why they were important," Travis says.
What they discovered was that when you take the nucleus of a cancer cell, put it in a normal cell, and put it in mice, nothing happens. No cancers develop, and the cells revert back to normal. This despite the fact that you have just inserted cells that have all the driving mutations purported to cause cancer! So why don't you get cancer?
At the time, all they could say was that something in the cytoplasm suppresses cancer. The experiment was then flipped, and when the nucleus of a normal cell was put into a cancer cell, which was then injected into mice, about 98 percent of the animals developed cancer. This is irrefutable evidence that something in the cytoplasm is not only repressing cancer, but is driving cancer too.
"When I interviewed the top guys in the field (I won't say who they are) and asked them about these nuclear transfer experiments, they didn't know about them, for one thing. When I explained it to them, they said, 'Well, if those are true, they're going to turn cancer biology on its head.' But they just hadn't been exposed to these data yet.
It's incredible. [Seyfried] did an incredible job of compiling evidence that builds up. It's almost like you're building a case for a murder mystery. There's just so much evidence here and there, and you connect all these dots, the nuclear transfer experiments provide so much compelling data. When you put it all together, it's impossible to deny that this, if not the origin of cancer, it has to be explored further," Travis says.
Novel Treatment Offers Tremendous Hope for Cancer Patients
Working with Pedersen at Johns Hopkins is a brilliant Korean biochemist, Young Ko, Ph.D. whom I predict will receive a Nobel Prize for her work. I believe she has the answer to a large number of intractable metastatic cancers.
What the two of them noticed was that when cancer cells overproduce lactic acid, they have to produce more pores, called monocarboxylic acid transfer phosphates, to let lactic acid out, or else the cancer cell will die from the inside out. Lactic acid is a very toxic substance. Travis recounts the chain of events that led to one of her most remarkable discoveries:
"Young's sitting here, thinking, 'Well, you know, this is a functional difference between a normal cell and a cancer cell. How can we exploit that?' Pete was trying to do it through a sort of a backdoor method, from gene expression angle, and that wasn't working.
She remembered this compound she had worked with while getting her Ph.D. from Washington, called 3-bromopyruvate (3bp). It's a very interesting little molecule that looks like lactic acid, but it's very reactive.
She started wondering, 'What if we gave this drug and it could slip in that pore, that opening, that's allowing lactic acid to get out?' She tested it against the common chemotherapy drugs, cisplatin and so forth. She did the first test, and 3bp just blew them away. She's like, 'this can't be right.'
She did the test a hundred times over because she just can't believe her eyes. She continued to develop this drug. It went through animal models, and just blew everybody away. It melts tumors away. The preclinical data is incredible.
But then, Young got mired in this in-fighting at Johns Hopkins. It began with the Vice Dean of Research. They were arguing about grant applications, and this sort of devolved into this multi-year lawsuit that hung 3-bromopyruvate up. There were patent-fights over it.
That's how it got derailed, otherwise it would have marched through clinical trials by now. It's still pending. Young is working very hard. She does have offers on the table for clinical trials. It's just a matter of getting it done."
Efforts Underway to Bring 3BP Into Cancer Treatment Centers
As it happens, I'm currently in discussion with Ko to see if we can make this therapy available to the public. My best strategy to make it widely available is to have Cancer Treatment Centers of America (CTCA), who initially refused her request to take it on. I'm going to see if I can convince them that this is something they need to integrate into their program, or at least offer it as an option. Granted, 3-bromopyruvate (3BP) is not a magic pill. But it needs to be made available.
Naturally, the foundational aspect that must be addressed is the metabolic mitochondrial defect, which involves radically reducing the non-fiber carbohydrates in your diet, and increasing high quality fats to maybe 85 percent of your dietary calories, along with a moderate amount of high quality protein, as excessive protein can also trigger cancer growth.
That's really the solution. If you don't do that, 3BP probably will not work. However, I believe that if you're on a ketogenic diet and you add 3BP, you can likely reverse just about any cancer. That's my current impression. It may be flawed, and I will revise it as necessary, but everything I've seen points in that direction. Travis agrees, saying:
"Absolutely. It looks like the dietary therapies, like nutritional ketosis is a foundation of this therapeutic approach, because it does incredible things to the body where it differentiates between cancer cells and normal cells.
When you switch from glucose metabolism to ketone metabolism, you put energetic pressure on the cancer cells because they have to burn ketones in mitochondria, which is something they don't have much of. They're put under this energetic pressure, and they're put under oxidative stress. Whereas the same time, normal cells are given better fuel, oxidative pressure is reversed, they generate more antioxidants, and so forth.
We've noticed that once you put people under this dietary state, everything becomes more effective, even traditional chemotherapy and radiation. At the same time, you're mitigating side effects because healthy tissues are able to withstand the toxic payload from traditional chemotherapy. But the exciting thing is you add on these other metabolic therapies, their synergistic mechanisms overlap."
Mitochondrial Function Is Critical for Health
We're now starting to realize that mitochondrial dysfunction is at the core of virtually all diseases, and support for nutritional ketosis is growing by leaps and bounds. For over 80 years, it's been the standard of care for intractable seizures in children. But now we're also finding it can benefit a wide array of other diseases, including neurodegenerative diseases such as Alzheimer's and Parkinson's, obesity, diabetes, heart failure, heart disease, and arthritis, just to name a few.
One of the basic reasons why it works so well is because it drives your inflammation down to almost nothing. I'm doing this myself. I just had my high-sensitivity C-reactive protein (HS-CRP) test done, and it was at 0.7, which is a healthy level. And when inflammation disappears, your body can heal.
It will also take the proverbial foot off the gas pedal of aging. Sadly, my guess is that over 99 percent of the population is not receiving the benefits of this approach simply because they either haven't heard of it or don't understand it.
My next book will explain how to tie this all together. There are so many lives at stake, and people are going to die prematurely if they don't have access to this information. I've never been so driven before about cancer prevention — it's like a whole new phase of life for me, because now I'm really beginning to understand what the answers are.
Jury's Still Out on Ketogenic Diet for Body Builders and Strength Athletes
While the ketogenic diet appears to be very beneficial for most disease states, one thing it might not be excellent for is building really big muscles. For that you typically need more protein, which will cause gluconeogenesis, so you may not get the benefits of ketosis.
Some will argue this point though. Dominic D'Agostino, Ph.D. who teaches Molecular Pharmacology and Physiology at the University of South Florida College of Medicine lives on a ketogenic diet and is phenomenally muscular and strong.
I interviewed him about the benefits of nutritional ketosis back in 2013. One of the ameliorating factors is that the ketogenic diet does have a branched-chain amino acid-sparing effect, because ketones have a very similar structure to the branched-chain amino acids valine, leucine, and isoleucine. These three are also the most important amino acids for building muscle. According to Travis:
"[D'Agostino] has done a study — I don't think it's published yet; it's getting kicked around by a couple of journals — where they took resistant-trained athletes and put them on a normal Western diet, and a ketogenic diet, and then monitored them over a period of time. They found no decrease in muscle mass and no decrease in performance.Interestingly, Tim Ferriss, author of "The 4-Hour Workweek," is also a staunch advocate of the ketogenic diet after it reversed his Lyme disease.1 It had debilitated him to the point that he was essentially on sick leave for nine months. Virtually any chronic infection is likely to improve on this kind of diet. It will also radically improve your resistance to colds and flus.
The interesting thing is, when you look at all those pathways, you're right. It looks like that's one thing it would inhibit. But it's got this protein-sparing effect, because you burn fat. So it spares the protein tissue. I think the jury's still out. It may be that if you want to get to an anabolic state and build muscle mass, you might still get by with a ketogenic diet."
I think the next phase of the research is the signaling properties of the [ketone] molecules. Because we know as a fuel, they're thermodynamically incredible. They're so superior to glucose. They just burn cleaner, they're more efficient, and there's more energy there.
When you look at the ATP content of a cell burning a ketone body, the ratio of ATP to ADP is shifted in favor of ATP tremendously. The ratio of reduced glutathione to oxidized glutathione is shifted in favor of the reduced form, which is the antioxidant form.
So as a fuel, it's incredible what it does within the cell. Now as a signaling molecule, what it does to the architecture of the DNA and the expression of genes, that's equally compelling. We're going to sort that out slowly. But that's where the new phase of the research is, because it tampers down all these anti-inflammatory effects.
It looks like it has a very similar effect to just a sustained caloric restriction. The jury is out on humans, but all evidence points to maybe not a huge increase in life span, but definitely a huge increase in health span. Like if you were predisposed to getting type 2 diabetes in mid-life, if you were in that state, you may never get it. If you want to live well for a long time, that's what you're after. That's what it looks like the benefit will be."
Unpublished Research Confirms Sugar May Be Directly Responsible for Cancer Growth
In researching his book, Travis had long discussions with Ko about sugar, and its ability to promote cancer. Her research — much of it still unpublished — shows that simply giving too much sugar to a cell will provoke it to start exhibiting all the phenotypes of cancer.
So glucose by itself, at least within the model she was using, can start to shift cells toward cancer. It does this by upregulating the expression of a critically important enzyme called hexokinase II, which by itself, is responsible for the Warburg Effect.
It's also largely responsible for the immortalization of the cancer cell, meaning it doesn't allow the cancer cell to die as programmed. Hexokinase II inhibits apoptosis, or programmed cell death, thereby allowing the defunct cell to proliferate, when under normal circumstances it should have died and been eliminated from the system.
To tie back to what we discussed earlier, hexokinase II is the enzyme 3-bromopyruvate inhibits. By inhibiting hexokinase II, the lactic acid builds up and poisons the cancer cell to death from the inside.
More Information
I have never given away a book as much as I have given away Travis' book, "Tripping Over the Truth: The Return of the Metabolic Theory of Cancer Illuminates a New and Hopeful Path to a Cure," and if you or someone you know has cancer, I cannot stress its importance enough. Get yourself a copy, and read it.
If you end up being as convinced of the merits of this theory as I am, there are several really good resources out there that you can peruse to put these dietary recommendations into practice:
DietaryTherapies.com2 A resource provided by Miriam Kalamian, nutritionist who has worked with Seyfried since the very beginning, and has counseled many cancer patients about the ketogenic diet he recommends "Keto Clarity" and Livin' La Vida Low-Carb3 "Keto Clarity" by Jimmy Moore is another excellent book worth reading. While it doesn't go into the theories behind it, it does provide a comprehensive overview of how to implement the ketogenic diet.
You can also find information on his Livin' La Vida Low-Carb WebsiteThe Charlie Foundation for Ketogenic Therapies4 A resource for people seeking help for a diverse array of conditions, including epilepsy, migraines, depression, neurological disorders, and cancer Single Cause, Single Cure Foundation Travis started the foundation, "Single Cause, Single Cure" together with Young Ko. Together, they're working to find the best route to bring 3-bromopyruvate to the public MetabolicOptimization.com5 He's also started a blog with Dominic D'Agostino. called "Metabolic Optimization," which in time will provide interviews with some of the scientists involved in ketogenic research
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