RHR: The Ketogenic Diet and Cancer

The conventional view of cancer is that it is caused by DNA mutations in the cell nuclei. However, the metabolic theory of cancer proposes that some cancers are caused by a dysfunction of cellular respiration and that the restriction of glucose in the diet may prevent and even reverse some cancers. Today I’ll review the research supporting this theory and explore how the ketogenic diet may impact cancer tumor growth.

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In this episode we discuss:

• A disorder of energy metabolism
• Metabolic dysfunction may be a root cause
• How the ketogenic diet can help
• Existing research on keto and cancer
• Additional evidence supporting the metabolic theory
• Why keto alone may not be enough

Chris Kresser: Hey, everybody, Chris Kresser here. Welcome to another episode of Revolution Health Radio.

Today, we have a question from Kelsey. Let’s give it a listen.

Kelsey: Hi, Chris, I was just wondering about your thoughts on the ketogenic diet as an approach to cancer prevention and therapy. I just read something about how cancer cells can only thrive on glucose, and in its absence we can prevent cancer potentially. So I was wondering if you could discuss this in a podcast. I think that would be great. Thank you.

Chris: Okay. Thanks, Kelsey, for sending that question in. It’s a really great question, one that’s been on my mind a lot recently, actually, and I’ve been diving into the research on. Most of you probably know that cancer dogma holds that malignancies are caused by DNA mutations inside the nuclei of cells and that these mutations ultimately lead to runaway cellular proliferation, which is the hallmark feature of cancer.

A Disorder of Energy Metabolism

But there are some cancer biologists out there that feel that while mutations are ubiquitous in cancer, they may not be the primary driving force of the disease and, as we’ll discuss later, they may actually be secondary effects of a deeper underlying process. They believe that cancer is as much a disorder of altered energy metabolism or energy production as it is genetic damage. This goes back to the work of German physician Otto Warburg in the 1920s and 1930s, and we know that healthy cells generate energy using an oxygen-based process of respiration. This is what we refer to as cellular respiration, but Warburg was the first to note that cancer cells prefer an anaerobic, or oxygen-free, process of producing cellular energy known as fermentation.

Contemporary researchers like Dr. Thomas Seyfried and Dominic D’Agostino have argued that this dysregulated cellular energy production, or cellular metabolism, is actually what induces malignancy and that by extension, if we limit the fuels available for this process of fermentation, and the fuels are glucose, which is derived from carbohydrate in the diet, and glutamine, which is derived from protein in the diet, then we can actually starve cancer cells and either improve the results of conventional treatment or perhaps even address some cancers independently without conventional treatment.

The ketogenic diet: does it have a place in cancer treatment?

Now, in this view, it’s the mitochondria that are particularly to blame for cancer, and there are studies in the ’70s and ’80s that support this. They showed that if you transfer the cytoplasm, which is where the mitochondria is, from a healthy cell into a cell that has the potential to develop cancer, that potential is suppressed, or that tendency to develop cancer is suppressed in that cell. On the other hand, if you transfer the nucleus of a malignant cell into the cytoplasm, which, again, is where the mitochondria is, of a healthy cell, then the tumor potential of that initially malignant cell is inhibited. Both of these lines of evidence suggest that the issue may be with the mitochondria or the cytoplasm of the cell rather than the cell nucleus, which is what the traditional view of cancer is.

Metabolic Dysfunction May Be a Root Cause

Seyfried agrees that there is clear evidence that cancer is a genetic disease, since we can inherit mutations that are clearly associated with increased cancer risk. That’s not at all controversial. That’s well established, and even Seyfried agrees with that. But he argues that many of these mutations that we can inherit are mutations that actually disturb cellular respiration, maybe that the heritable aspect of cancer is not mutation that drives itself—cellular proliferation—but instead are mutations that actually cause mitochondrial dysfunction and defects in cellular respiration. He also points out that many of the non-inherited causes of cancer that have been identified and are clearly recognized, like radiation, impair mitochondrial function. That may be a common mechanism that is shared between these non-inherited causes of cancer and inherited causes of cancer.

Mitochondrial dysfunction can be caused by any number of different carcinogens—genetic predisposition, but also radiation, chemical exposures, and diet. Again, this is a kind of way of thinking about it that brings together these different causes.

Dominic D’Agostino has argued that the mutations that are often observed in cancer may be secondary to mitochondrial dysfunction because injured mitochondria produce volatile compounds called reactive oxygen species (ROS), and these ROS can damage DNA. In this view, it may be that mitochondrial dysfunction comes first, and then that’s what leads to the mutations that are often observed in cancer.

As you might suspect, this metabolic theory of cancers is controversial in the mainstream cancer paradigm, but there’s already promising initial evidence to support it, and most traditional cancer specialists concede that this metabolic theory has merit, and it may be a piece of the puzzle. I would say that the dominant paradigm idea right now is that metabolic dysfunction is likely one of the pieces of the puzzle, but that cancer is multifactorial and probably does involve genetic mutations that may be independent of metabolic dysfunction and that there are other causes that may not be directly related to metabolic dysfunction.

I’m certainly not an expert in cancer. Please keep that in mind when I say this, but I do tend to agree, just my overall view of most diseases, from what I’ve been able to gather, is that they are multifactorial, and I generally resist theories that seem to suggest that one disease has one cause. That’s unusual in my experience, from everything that I’ve seen. I wouldn’t necessarily say that. Dr. Seyfried and Dominic D’Agostino aren’t making that argument either, but I think what they bring to this is a fresh perspective that in many ways if it’s true, it can be more empowering for people that are dealing with cancer, and the risk of cancer, because it offers a lever for intervention and treatment above and beyond just the idea that “Oh, I have bad genes and there’s not really anything I can do about it.”

Of course, we know that genes alone are not responsible for cancer because we share many of the same genes as our hunter–gatherer ancestors and even just the same genes as our ancestors several generations ago, and yet the rate of cancer keeps going up. It’s expected to overtake cardiovascular disease as the number one cause of death in the U.S. fairly soon, and so that can’t be explained by genes alone.

How the Ketogenic Diet Can Help

Getting back to the ketogenic diet, which was Kelsey’s original question, both ketogenic diet and fasting restrict the availability of glucose to tumor cells. When you eat a ketogenic diet, you’re dramatically limiting the amount of carbohydrate, and thus the amount of glucose, that comes into your body. From this metabolic theory of cancer, that would be why a ketogenic diet, and fasting, of course, which limits not only carbohydrate but everything else, and fasting produces ketones. This is why these two approaches would help with cancer if this theory is correct, because when our energy metabolism shifts to fat or ketones away from glucose, cancer cells cannot utilize ketones, but our healthy cells can. One of the main goals with cancer treatment, as I’m sure you know, is how do we address the cancer cells without also killing the healthy cells. That’s really the Shangri-La when it comes to cancer treatment, and the ketogenic diet is really interesting from that perspective because it offers a possibility of doing that. It’s a change that simply the shift in metabolism from glucose to fat means that the cancer cells won’t thrive, but the healthy cells can thrive.

Existing Research on Keto and Cancer

Let’s talk a little bit about the research that exists so far on ketogenic diet and cancer. It’s pretty thin overall, but what does exist, I would say, is already promising. There’s a decent amount on ketogenic diet in animals—certainly more than humans.

For example, a pretty large number of animal studies have shown that a ketogenic diet can reduce tumor growth and improve survival rates. There was one 22-day study in mice that looked at the differences between the ketogenic diet and other diets. That study found that a ketogenic diet reduced tumor growth by up to 65% and nearly doubled survival time in some cases.

There is another study in mice that tested the ketogenic diet with or without hyperbaric oxygen therapy and compared to the standard diet, the ketogenic diet increased mean survival time by 56 percent and that number increased to 78 percent when it was combined with hyperbaric oxygen.

There’s less research, as I mentioned before, in humans, but the little that does exist, I think, is promising and should lead us to doing more. One study monitored tumor growth in response to a high-carb versus a ketogenic diet in 27 patients with cancer of the digestive tract. Tumor growth increased by 32.2 percent in patients who received the high-carb diet, but actually decreased by 24.3 in the patients on ketogenic diet. However, in this study, the difference was not statistically significant. That’s a whole other discussion about statistical significance that I won’t go into here, but that’s one potential reason to take that study with a grain of salt.

In another study, three out of five patients on a ketogenic diet combined with radiation or chemo experienced complete remission. Interestingly, the other two participants found that the disease progressed after they stopped the ketogenic diet.

Definitely, much more study is needed here, but because of our increased understanding of the metabolic aspects of cancer and some of the research that does exist and some other lines of evidence that support the metabolic theory, which I’m going to mentioned in a second, I’m optimistic about what we can learn here.

Additional Evidence Supporting the Metabolic Theory

What are those lines of evidence? Well, there are drugs which lower insulin and glucose, like metformin. It’s a commonly used drug in diabetes that has shown promising results in cancer treatment. This is not fringe stuff here. Metformin is being studied. There is an article about it for cancer treatment on the NIH Cancer Institute website and on the MD Anderson website, which are two prominent mainstream cancer treatment organizations. There are several studies to support that as well.

Then there are some more experimental drugs that restrict the availability of glucose via inhibition of glycolysis and other processes. One of those drugs is called 2-DG, and that’s shown quite a bit of promise, so there’s not a lot of research on it yet, and then there’s an older drug named DCA, which also limits the availability of glucose. That has shown some promise, although it has known toxicity and side effects. It may not be a good choice for that reason.

Anecdotally, I’ve spoken with some cancer researchers who claim to be virtually curing cancer in animals using a combination of ketogenic diet and PI3K or mTOR, like rapamycin, but these data aren’t published. Again, we need to be cautious about accepting these claims until they’ve gone through the legitimate scientific channels and people have had a chance to review this research.

There are some treatment centers like Care Oncology Clinic in the UK and ChemoThermia Oncology Center in Istanbul that are using ketogenic diet and fasting along with glucose inhibitors and conventional treatment like chemo. They claim to be getting good results, but I don’t know much about these cancer centers above and beyond what I just told you. Note that keto only seems to work with the faster-growing cancers like breast cancer, but not as much with slower-growing cancers like prostate cancer.

In summary, I think the metabolic theory on cancer is really interesting and there’s already some good evidence to support it. Clearly, we need more research. Whether or not this research will get done is the big question because as we know, two-thirds of medical research is sponsored by pharmaceutical companies. It can be difficult for researchers like Dominic D’Agostino to get funding to do this kind of research because nobody can patent the ketogenic diet and fasting. There’s not as much money as there would be in a kind of miracle drug that targets gene therapy and things like that. That’s one of the reasons there isn’t as much research as there might be otherwise.

If I was diagnosed with cancer or one of my relatives or friends were diagnosed, I would certainly put the ketogenic diet and fasting at the top of the list of potential treatments to investigate because I see a high potential for benefit and very little downside. You can’t say that about many cancer therapies. As we talked about earlier, the goal with cancer treatment is to find something that inhibits the growth of cancer cells but doesn’t damage healthy cells. Again, there just aren’t that many therapies out there that do that.

Why Keto Alone May Not Be Enough

I want to be very clear, though, that I don’t believe claims that are made on some websites that the ketogenic diet beats chemotherapy for all cancer treatment. There’s simply no research to support that. I don’t know where those websites are getting that idea, and there’s a lot of snake oil when it comes to cancer treatment out there. It’s a really vulnerable population. Someone who’s diagnosed with cancer, particularly a late-stage cancer that might be terminal, understandably we often feel pretty desperate and might not have the capacity at that moment in time to go through the proper vetting process to make sure that some of the more alternative therapies that are suggested are legitimate, and so you see a lot of wacky stuff recommended for cancer treatment.

Now, I don’t at all think that metabolic theory of cancer is wacky. There’s plenty of both mechanistic, animal, and even some human evidence to support it, but I personally don’t believe the extreme claim that a keto diet will beat chemo for all cancers. I just don’t think there is research to support that.

I also want to be clear that I’m not making any specific recommendation here for treatment of cancer using ketogenic diet or anything else. As I’ve argued earlier in the podcast, I think cancer is a complex multifactorial disease and varies from individual. The ideology and pathology vary from individual to individual, and treatment decisions should be made with the support of an oncologist and other doctors on the care team. Please don’t take anything that I’ve said in this podcast as a recommendation for your particular situation or somebody in your life that’s struggling with cancer.

All that said, it’s really promising, interesting info here, and we know that a ketogenic diet can be therapeutic in many other situations. There’s not really much downside to the ketogenic diet and fasting if they’re done under supervision. Both can have a lot of beneficial effects in terms of upregulating autophagy—cellular repair process, possibly stem cell regeneration in the case of fasting, for both of those. Ketosis has neurological benefits and many other potentially positive effects when it’s done in the right circumstances, so I don’t see any downside at all in continuing to explore these therapies for cancer treatment.

Okay. Thanks again, Kelsey, for sending that question. It’s a really fascinating topic, and everybody else, please do keep sending in your questions to chriskresser.com/podcastquestion, and I’ll see you next time.