Cancer as a Metabolic Disease – What You Need to Know: Professor Thomas Seyfried

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The Stern Method Podcast Episode 006

Have you heard about the metabolic theory of cancer but still need some clarification on exactly what it is and what it means for your path to wellness and healing cancer? If so you are most certainly in the right place as today on the show we have the scientist, professor and dare I say Godfather of the modern day understanding of cancer as a metabolic disease, Dr. Thomas Seyfried, who has revived this simple truth that was first laid out in the middle of the last century.

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In This Episode:

  • Professor Seyfried explains how there is no consistency in genetic mutations across cancer types or even much across individual cancers but the one hallmark trait that ALL cancer cells share is that they ferment glucose and glutamine to produce energy and why this is so important to our understanding of cancer.
  • How genetic mutations and negative epigenetic changes in gene expression like oncogenes turning on and tumor suppressor genes turning off are not the main drivers of cancer but really the byproducts of damaged cellular respiration along with defective mitochondria, and the many experiments and studies Professor Seyfried has gathered that have been done over the years to prove this.
  • From an implementation perspective Dr. Seyfried got into how lowering blood glucose and raising ketones along with other metabolic therapies will kill many cancer cells outright and leave the rest much more vulnerable to other therapies and how one would get started on this approach through fasting and the ketogenic diet.
  • Professor Seyfried also explained two terms that every cancer patient and preventer alike need to know, autophagy and mitochondrial biogenesis which are the cleaning out of defective mitochondria and the growth of new healthy mitochondrial populations.
  • This is absolutely foundational stuff that you really need to have a firm grasp on if you’re serious about having all of your bases covered in the healing process! Or in prevention for that matter!!

How the Metabolic Theory of Cancer Applies to Childhood Cancer

When attempting to research the particular type of cancer you’re dealing with for your child, especially from an integrative approach, it’s easy to get frustrated as most articles are written for adults, referencing mostly adult cancers. The feeling that “yea this might work for adults, but this is different, my child was born with this or developed it very early on” could be overwhelming at times for us in our research.

The metabolic theory of cancer provides a lens to view cancer through that unites both childhood and adult cancers. The one commonality throughout all cancers of all types in all ages, is that they have an altered respiration pathway – fermenting glucose and glutamine whereas healthy cells respire (breathe and produce energy) through burning glucose or ketones with oxygen (oxidative phosphorylation).

Professor Seyfried notes two of the most common childhood cancers in the interview, neuroblastoma and leukemia, both as utilizing fermentation rather than oxidative phosphorylation.

Try searching the type of cancer your child is healing from in combination with the terms “enhanced glycolysis,” “fermentation,” “Warburg effect,” and “metabolic disease,” and chances are you’ll see studies describing this very feature, whatever the cancer type may be.

Takeaways from the Professor Thomas Seyfried Interview

Our goal for everything we do at The Stern Method is to paint a very clear picture of the areas you need to be focusing on in healing cancer to make sure you’re covering all of your bases and quite possibly the most important area is the same one that many people have the least understanding of and that is cellular metabolism and the mitochondria’s role in cancer.

This is not a new theory it’s been actually been around since nobel prize winning scientist Otto Warburg proposed it back in the 1920’s and even a bit before that as well but only recently has it been revived largely to due to the professors work and he’s the perfect evangelist for it as he has a master’s degree and PhD in genetics so it was certainly something he had to come around to for himself.

The Modern Discovery of Cancer as a Metabolic Disease


Professor Seyfried tells how he stumbled into the metabolic theory of cancer through his work as a geneticist studying cancer. At that particular time he was studying lipids (fats) associated with cancer cells in combination with a particular drug. The drug was not expected to have any effect on the tumor itself, but it did and the tumors shrunk massively. When Seyfried dug into the mechanism of how this happened, it was found that the drug was exerting a caloric restriction effect that was somehow responsible for the phenomenon.

Seyfried’s desire to explain to himself what had happened took his research down a path that lead to Otto Warburg’s work all the way back in the 1920’s, at a time when the debate over the nature of what cancer was at the most fundamental level was still up in the air. Warburg had proposed that instead of genetic mutation, that a cell was turned cancerous by damaged respiration – the process in which the hundreds or thousands of mitochondria in each cell burn oxygen along with glucose to make ATP, the energy that literally powers our bodies. Warburg showed that when a cell was deprived of oxygen, it would revert to an ancient pathway of energy production known as fermentation (which does not require oxygen) of glucose to stay alive, becoming cancerous in the process.

Fermentation of glucose, along with its byproduct of producing huge amounts of lactic acid, is much less efficient than oxidative phosphorylation (normal cellular respiration) however, and requires around 16 times the amount of glucose to produce the same amount of energy which is why cancer cells are always so hungry for it and have an increased number of receptors. Mainstream oncology acknowledges this occurrence in all cancer cells but regards it as a curious side note and not something to be studied as a key symptom of the potential root cause of damaged respiration.

In Warburg’s time the Somatic Mutation Theory (what prevails today, that cancer is at its core a genetic disease) won out for a variety of reasons, whether merited or not, and his metabolic theory died with him in 1970. Until Professor Seyfried came upon it however.

Seyfried took interest and began to look more closely at the mitochondria in cancer cells. Being a geneticist, first he looked at the mitochondrial DNA (mitochondria has its own DNA separate from cellular DNA) and could not find any mutation there. What he did find however across every cancer cell type he looked at was a defect in cardiolipin, a lipid (fat) that makes up the membrane of the mitochondria directly responsible for controlling oxidative phosphorylation.

The Nuclear Transfer Experiments

Digging further into modern research, Professor Seyfried discovered a body of work which certainly appears to be the icing on the cake. There have been a large number of experiments over the years by well-respected researchers conducted over the years transferring the nucleus (which houses the cell’s DNA) of a cancer cell into a healthy cytoplasm (the rest of the cell which houses the mitochondria), and vice versa, taking a healthy nucleus and transferring it into a cancerous cytoplasm.

Without exception, every time a cancerous nucleus is transferred into a healthy cytoplasm, the nucleus itself turns healthy. Every oncogene that was turned on turns back off, and every tumor suppressor gene that was turned off turns back on.

In turn every time a healthy nucleus, with healthy DNA, is transferred into a cancerous cytoplasm (with damaged mitochondria), that healthy nucleus all of a sudden turns cancerous. All of the bad genes turn on, and the good genes turn off.

To the professor, this body of work proves beyond a shadow of a doubt that cancerous genetic expression is a downstream event of, or occurs because of, dysfunctional cellular respiration. In other words, fermentation is not something that happens because a cell’s DNA turns cancerous. A cell’s DNA turns cancerous because the cell needs to ferment. It’s hard to argue with him.

The implications of this are profound.

We’ve Been Looking in the Wrong Place


Professor Seyfried goes on to explain that this means we’ve been looking for the primary driver of cancer in the completely wrong place for the last century. This would certainly explain how it could possibly be that with all to time, money and energy invested into cancer, overall long term survival rates haven’t really improved all that much.

All of the provocative agents, many of the same ones we think of as causing cancer anyways such as toxins, radiation, microbes, inflammation and so on, are really damaging the ability of a cell to respire, and this triggers the epigenetic phenomena of oncogenes turning on to drive the fermentation. The oncogenes are the drivers of fermentation that arise from the need to ferment. If you take away the need to ferment, the oncogenes turn off.

In addition to cancerous genetic expression, genetic mutations are also explained by damaged respiration and fermentation. A huge amount of reactive oxygen species (free radicals) in addition to lactic acid within the cell as a byproduct of the fermentation. The build-up of free radicals and lactic acid within the cell go on to damage the DNA and cause the mutations. Again, the mutations are the downstream event of the respiratory damage.

In his book Tripping over the Truth, Travis Christofferson writes about this as the reason for the failure of the Cancer Genome Atlas Project failed to provide any sort of roadmap to a cure for cancer (look out for Travis’ interview coming soon by the way). This would also explain why despite all the hype and promise of individualized, targeted gene therapy, it has largely failed to deliver. Both are going after byproducts of the cause, not the cause itself.

Could Cancer Really Be as Simple as the Metabolic Theory Proposes?

Dr. Seyfried goes onto say that despite this seemingly incontrovertible proof that cancer is indeed a metabolic disease in origin, it has been ill-received in the conventional, genetic-driven world of oncology because, well… it’s too simple. This whole gigantic multi-billion dollar apparatus of cancer research has been built around understanding cancer as hundreds of different diseases all with their own genetic profiles that need to be understood.

Seyfried has his own simple explanation for this approach: nonsense. Of course each cancer type is going to have its own genetic profile, he explains, it’s occurring in different types of cells (brain, blood, prostate, breast, etc.). While the genetics differ solely because of original cell type, the one commonality across all types of cancer cells is fermentation and lactic acid production, making cancer ONE disease rather than hundreds.

This also explains why you don’t really see cancers arise in certain areas of the body, Thomas explains, as not all cell types are capable of fermentation. Cardiomyocytes, or cells that make up the muscle in the heart, for instance are not capable of fermentation. This is why “heart cancer” is virtually non-existent, and when you do see cancer in the heart it has started as a sarcoma (cancer of soft tissue) or blood cancer somewhere else in the body and only spread to the heart afterwards.

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Taking Away Cancer’s Fuel and Turning the Tables

The point Professor Seyfried really tries to drive home is that if the one commonality throughout all of cancer is the fuel source, then we need to be going after the fuel source. He turns the notion that “cancer cells are so clever” and so good at surviving on its head, stating that the reason cancer cells survive has nothing to do with their “cleverness,” it’s because they ferment.

When you take away the fuel source of glucose, many cancer cells will starve and die outright. Others will become weakened and now extremely vulnerable to oxidative therapies such as chemotherapy on the conventional side or hyperbaric oxygen on the alternative side.

Seyfried notes that some cancer cells will have the ability to ferment glutamine as a backup fuel source, which is why this approach still isn’t an open and shut case and where we still have a little ways to go in accomplishing, but for the time being we do have a very achievable, very high bang for the buck strategy of taking glucose away.

Lowering Blood Glucose Available to Cancer Cells through Nutritional Ketosis

The dramatic lowering of available blood sugar is achieved through what is called nutritional ketosis. Glucose, as it turns out, is not the only fuel source our bodies are designed to run on. Ketones are substances made by our bodies when they break down fat for fuel. The source of the fat can either be directly from the food we eat, or from our bodies’ own fat (which is why this is also turning out to be the most effective weight loss strategy ever seen as well).

Ketosis explains why humans are capable of fasting for such long periods of time, and professor Seyfried explains that fasting is indeed a key tool in entering nutritional ketosis. After three days’ time, the body’s glycogen reserves will be depleted and it will have no choice but to run on fat.

Ideally, we should be able to switch back and forth from one fuel source to the other at will, but given the abundance of non-stop carbohydrates our bodies have become accustomed to the transition may be a bit more of a process. Ultimately though, our bodies do have the innate ability to run on ketones and will adapt. Cancer cells however have lost this ability altogether and are entirely dependent on fermenting glucose and glutamine, and will not adapt.

Speaking of fasting in the context of something we “should” be able to do, Dr. Seyfried also mentioned something that I often like to point out myself. Every major religion in the world places a huge emphasis on fasting… coincidence? Next time you’re wondering what to give up for lent to be kind of like giving up food like Jesus did, how about you just give up food?

Nutritional ketosis allows us to drive our blood sugar way down, to the point we technically should be dead if not for the ability to use ketones as a fuel source. As you begin to implement this strategy, the professor notes that it is something very measurable that you can track. Blood ketones and blood glucose can both be measured (the most popular way is through a finger prick using a device called a Precision Xtra). Ideally we are looking for a ketone to glucose ratio of 1.0 or greater, which can be easily calculated using the glucose ketone index calculator from a company called Heads Up Health, which provides a phone app as well.

The ketogenic diet, which is a low carb / low protein / high fat diet, is the longer term strategy for maintaining nutritional ketosis.

Note that this article is not meant to be an all-inclusive guide to this approach, but rather a starting point to get you pointed in the right direction. Cancer and ketosis researcher Dominic D’agastino has links to more detailed how-to resources at his website Keto Nutrition.

Professor Seyfried notes that oncologists in countries outside of the US with less restrictions around their practice such as Dr. Slocum in Turkey have been integrating his metabolic strategies into their conventional and integrative protocols and have been seeing results far beyond that which could ever be hoped for solely from conventional therapies.

How to Restore Respiration in Healthy Cells and Cancer Cells Alike

Aside from targeting cancer cells for elimination, the other key benefit the Professor Seyfried discussed that is derived from fasting and the metabolic approach as a whole is healthy mitochondria.

“Autophagy” refers to a cell’s “house cleaning” mechanism in which it literally breaks down and recycles defective mitochondria! Autophagy is triggered primarily by nutritional ketosis.

“Mitochondrial biogenesis” refers to the growth of new, healthy mitochondria. There are a few key strategies for mitochondrial biogenesis which we will get into another time and are easily searchable until then, but for now a primary one is… you guessed it, nutritional ketosis.

Professor Seyfried notes that through autophagy and mitochondrial biogenesis, many cancer cells will indeed revert to healthy cells, while others will be too far gone and need to be eliminated.

Cancer as a Metabolic Disease Must Be Viewed in the Big Picture

To wrap up, just as I did on the podcast, although the metabolic theory of cancer provides a very exciting lens to view cancer through, it’s also very important that we zoom back out to see the big picture and always be sure we’re covering our bases. Something did cause the damage to the respiration in the first place, be it toxins, microbial infection, inflammation (or likely a little bit of all of these), there was still a failure of the immune system to allow the cancer cells to proliferate, and so on. If we don’t address these issues and only go after the fuel source then we’ll never fully resolve the problem. As Dr. Paul Anderson put it in our recent interview with him, even if it is truly metabolic in nature, in reality cancer is a polyfactorial disease.

Resources Mentioned