The Ketogenic Diet and Cancer: The Myths and Where We Stand in 2018

colinchamp January 23, 2018 27 Comments

I wrote my first blog post on the ketogenic diet and cancer just over five years ago: A Ketogenic Diet for Cancer followed by another article four years ago, The Ketogenic Diet and Cancer: Where We Stand. I have been meaning to update this for the past two years, but then life got in the way. I finally sat down to complete my views (for what they are worth), on the current state of the ketogenic diet and cancer.

The Top Ketogenic Diet and Cancer Myths:

Myth 1: A Ketogenic Diet Fights Cancer by Itself

There is absolutely no data to support that a ketogenic diet, by itself, fights or manages cancer. In fact, when we assessed all animal studies with Rainer Klement at the helm, the diet provided some synergistic effects with treatments, including current treatment like radiation therapy and chemotherapy. When the animals already had cancer, the diet in itself did little to stop growth.¹ In animals that did not have cancer, the diet appeared to be protective. Many people are using the term “manage” to describe the effect. There is not data to support this, and the definition of manage seems to vary based on who is using it.

Many dietary changes appear to help treat, fight, and prevent cancer in mouse models. We previously showed that calorie restriction and alternate daily fasting works synergistically with doses of radiation therapy to enhance cancer cell kill and slow tumor growth, by decreasing several metabolic pathways heavily related to dietary carbohydrates and insulin.

Tumor growth after a single dose of radiation therapy and calorie restriction (left) and alternate daily fasting (right) in mice with breast cancer. Picture from Saleh et. al.

Adrienne Scheck has shown that when applied with curative doses of radiation therapy, the ketogenic diet can make brain tumors vanish in mice.² However, many dietary changes appear to blunt cancer growth in mice,³ and the effects in humans are less clear. Yet, even in the majority of mouse studies, the diet rarely kills cancer as a monotherapy.¹

Myth 2: The Ketogenic Diet Lowers Serum Blood Sugar in Everyone

Many of us were hoping this was the case, but unfortunately, it is not. Our initial study revealed that average blood glucose in patients being treated with chemoradiation for brain tumors experienced an average blood sugar in the upper 80’s,⁴ which is not too shabby, especially since several were on high-dose corticosteroids, which can cause blood sugar to skyrocket. However, in many individuals, blood sugar can be low, normal, or even high. For instance, below are my blood glucose reads during several weeks in ketosis:

The spikes in my blood glucose occurred after my drive to work (yes, I have a road rage problem) and during workouts in the gym (yes, I would prick my finger during workouts in the corner of the gym). In the mornings, my glucose did dip into the 50s, but I have been doing this for almost a decade, and the same effect cannot be expected in patients beginning the diet for the first time.  It seems to be unrelated to how closely the diet is being followed. Ulrike Kämmerer,⁵ a pioneer in the ketogenic diet world, had been very vocal about this years ago. Furthermore, ketone levels are often unrelated to glucose levels. My ketone levels below, seemed unrelated to glucose when I compared values. They were, however, related most closely to how many glasses of red wine I drank at night (more wine = more fun = less ketones):

Many online and armchair “experts” continue to propagate the myth that it is absolutely necessary to increase ketone levels while significantly lowering blood glucose for the diet to be “effective.” There is no data to support this. Furthermore, many individuals can maximize their diet to the fullest, yet still experience normal or high glucose levels. Repeatedly telling these individuals that they need to magically lower their glucose effectively raises their anxiety, which likely raises their cortisol, which, like my drive to work, may end up raising their glucose.

Myth 3: A Ketogenic Diet is Easy for Everyone

This is not true for everyone, and especially cancer patients. Armchair experts continue to propagate this message online, leading to much anxiety in patients that are unable to effectively follow a ketogenic diet. Many metabolic issues exist for patients with cancer, especially those with normal eating barriers from their cancer, side effects from radiation therapy and chemotherapy, digestive issues from their cancer, and those on novel treatments or clinical trials. The diet can be difficult. We do not know which cancers it may help treat, and with which treatments it will enahnce. All we have to go on is preclinical data in mice (and many of these mice are obese and raised in crowded cages⁶), and we must remember this, especially with patients and their families who are at wit’s end because they are unable to effectively follow the diet.

Myth 4: Perpetual Ketosis is Absolutely Necessary

Another anxiety-provoking myth is that 100% ketosis is necessary. Again, we are not even sure if it works and which cancers it may work with, therefore advising all patients that they must be in ketosis 100% of the time is unfounded. Periodic ketosis may work just as well, or no ketosis may be optimal for some cancers. We just do not know, but telling a patient that is struggling to eat any food that he or she has to be in 100% ketosis can cause severe emotional issues. It needs to be considered on a case-by-case basis.

Myth 5: All Preclinical Studies Inform us of the Ketogenic Diet’s Effectiveness

We have now reached a yoyo period where people think a petri dish or animal studies proves or disproves that any food, diet, the ketogenic diet, a low-carb diet, or even a low-fat diet, will “feed” or cure cancer. These studies tell us none of this. Pouring gasoline on a petri dish of cancer cells will kill them, but I am not prescribing this for my patients. Alternatively, if a study reveals that something associated with a low fat diet, like statin usage, may help cancer outcomes, it tells us little about what diet is optimal, and definitely does not signal that ketosis, fats, or even carbohydrates are necessarily bad for cancer patients. Conversely, if studies reveal issues with carbohydrates (and there are many) it does not indicate that a ketogenic diet fixes these issues.

Cancer cells use many sources of nutrients for fuel, and they change phenotypes often, potentially allowing them to use different fuels in the future. Furthermore, they optimize fuels differently – i.e. give them an abundance of sugar and they may be better able to utilize lipids. Does this mean we should be eating a low-fat or ketogenic diet? We absolutely cannot answer this question until we have high-level human trials.

Myth 6: Many Great Ketogenic Diet Studies are being Funded

This is the biggest issue in the field. Many of us spent countless hours (ask my family, friends, and colleagues) meeting fellow researchers and writing clinical trials. We have had potential funding sources out there in the nutrition world (naming none…) that made lots of promises to us and then pulled the funding out from under us. If you are a nutrition company and are already making millions on keto food products, why fund any research? The somber reality is that many of us do not see a light at the end of the tunnel any time soon. Until then, we can only continue to extrapolate from preclinical data, and bring up many of the issues discussed above.

Currently, there are 13 trials on clinicaltrials.gov. Several include a therapeutic view of the diet in addition to conventional treatment for glioblastoma. A devastating disease with a 15-month survival, we certainly need help in the treatment of this Goliath. I would love to see the diet paired up against some more less formidable foes as well, since improving the survival in GBM has eluded us for decades.

Many ketogenic diet researchers, including myself, have nearly given up after being rejected grants and funding from our major cancer organizations for what was considered crazy even five years ago. We then turned toward the industry, but after being made many empty promises, remain unable to run our unfunded studies. I had written my original study over six years ago, and finally after getting promised funding, watched as they pulled out after I had initial review committee approval. Yes, at this point my Italian grandmother would start playing her violin in the air, but it is beyond frustrating to see this potentially effective cancer treatment enhancer go silent. All this being said, if anyone can secure funding and wants the protocol that I spent hundreds of hours writing, I will gladly give it to you for absolutely free if you guarantee me you can run the study at your institution. I will also buy you a case of my favorite red wine. If you complete the trial, I will fly you to Pittsburgh (in coach), take you to dinner (it will include red wine and steak at my favorite restaurant), and then take you to a Steelers game. You have to wear my spare Hines Ward jersey (you can pick if you want the home or away jersey).

Myth 7: Taking Ketone Supplements Obviates the Need for the Ketogenic Diet

This approach would certainly be easier for many patients and would be incredible if we could simply improve treatment by supplementing with a naturally occurring energy source within our bodies. Unfortunately, there is absolutely no data to support this approach. The ketogenic diet provides many global metabolic changes that can affect cancer growth and response to treatment,^7,8 and simply taking ketone bodies does not impact many of these features of metabolism. Adrienne Scheck has shown this impact repeatedly in her important research.^7,8 All these issues aside, I would love nothing more than to see some ketone ester studies for cancer patients.

The issue here, of course, means that there remains little money to be made on the diet, which is the likely explanation for the funding issue mentioned above. Even the attempts for companies to create ketogenic food substitutes have been difficult for patients. The ketogenic desserts, full of ultra-sweet artificial sweeteners, seem to trigger the brain to crave more sweets, making adherence to the diet difficult. These same artificial sweeteners can often promulgate flatulence which, while funny at first, can get quite uncomfortable.

Myth 8: The Weight Loss Data Prove Keto Works for Cancer Treatment

It is great to see that the ketogenic diet is finally being taken seriously for weight loss. JAMA even recently published an article discussing its utility in weight loss and type 2 diabetes, both closely related to several common cancers like breast and prostate cancer.⁹ This effect, in itself, may improve cancer outcomes since weight gain is associated with an increased risk of recurrence and death, thus the mediccal should seriously consider the ketogenic diet, periodic ketosis, or simply low-carb to help patients achieve and maintain a healthy weight and healthy metabolic status.¹⁰ After years of taking continuous shots for their views, the modern day pioneers like Jeff Volek are finally receiving some vindication. Unfortunately, some continue to kick around the calorie counting mummy (even in the same JAMA issue¹¹), but it seems like soon she will be left alone and allowed to rest in peace. However, the significant benefit – backed by much science and randomized studies – of a ketogenic diet for weight loss does not mean it works for cancer.

Myth 9: Keto is Difficult for Everyone and has Many Side Effects

While keto is not for everyone, the side effects have clearly been overblown by the opposition over the past several years. We wrote a response to a recent critique that was unsubstantiated in its discussion of the side effects, which unfortunately are felt to be true by many physicians and dietitians who are unfamiliar with the diet.¹² I have personally seen and lectured on the fact that many patients and their families enjoy applying the ketogenic and other diets to their treatment. It helps to put them back in the driver seat during their treatment, instead of treating them as a passenger as we bombard them with chemotherapy and radiation therapy.

Myths aside, where is the ketogenic diet headed in the cancer world?

This remains unclear. Its acceptance as a weight loss/maintenance tool and its theoretical ability to improve outcomes in several cancers related to obesity and carbohydrate intolerance is very encouraging. Will it synergize with cancer treatment? This remains unknown, and until we actually produce significant studies in humans to test the hypothesis, it remains an intriguing hypothesis, but unfortunately, one without support. I remain hopeful that the ketogenic diet will improve outcomes for cancer patients. I remain most hopeful that as metabolic treatments for cancer continue to expand, the ketogenic diet, and certain diets in general, may help to synergize with these treatments. I also continue to imagine that the side effects of potential metabolic treatments that aim to decrease cancer metabolism through agents like metformin, 2-DG, or other agents that inhibit glucose uptake may be mitigated through dietary changes, including the ketogenic diet. Based on the preclinical data, I continue to see the ketogenic diet, or periodic ketosis, as a potential cancer preventative dietary approach.

This last one will be tough to prove in humans, and may take decades. In the meantime, I will keep my carbs low, chew the fat, fast periodically, intensely exercise and lift heavy weights, and cycle in and out of ketosis.

Ketogenic Diet and Cancer References:

1. Klement, R. J., Champ, C. E., Otto, C. & Kämmerer, U. Anti-Tumor Effects of Ketogenic Diets in Mice: A Meta-Analysis. PLoS One 11, e0155050 (2016).
2. Abdelwahab, M. G. et al. The Ketogenic Diet Is an Effective Adjuvant to Radiation Therapy for the Treatment of Malignant Glioma. PLoS One 7, e36197 (2012).
3. Champ, C. E. et al. Nutrient Restriction and Radiation Therapy for Cancer Treatment: When Less Is More. Oncologist 18, 97–103 (2013).
4. Champ, C. E. et al. Targeting metabolism with a ketogenic diet during the treatment of glioblastoma multiforme. J. Neurooncol. 117, 125–31 (2014).
5. Klement, R. J., Kämmerer, U. & Kammerer, U. Is there a role for carbohydrate restriction in the treatment and prevention of cancer? Nutr Metab 8, 75 (2011).
6. Martin, B., Ji, S., Maudsley, S. & Mattson, M. P. "Control" laboratory rodents are metabolically morbid: why it matters. Proc. Natl. Acad. Sci. U. S. A. 107, 6127–33 (2010).
7. Woolf, E. C. et al. The Ketogenic Diet Alters the Hypoxic Response and Affects Expression of Proteins Associated with Angiogenesis, Invasive Potential and Vascular Permeability in a Mouse Glioma Model. PLoS One 10, e0130357 (2015).
8. Stafford, P. et al. The ketogenic diet reverses gene expression patterns and reduces reactive oxygen species levels when used as an adjuvant therapy for glioma. Nutr. Metab. (Lond). 7, 74 (2010).
9. Abbasi, J. Interest in the Ketogenic Diet Grows for Weight Loss and Type 2 Diabetes. JAMA 319, 215 (2018).
10. Champ, C. E., Volek, J. S., Siglin, J., Jin, L. & Simone, N. L. Weight Gain, Metabolic Syndrome, and Breast Cancer Recurrence: Are Dietary Recommendations Supported by the Data? Int. J. Breast Cancer 2012, 9 (2012).
11. Guth, E. Counting Calories as an Approach to Achieve Weight Control. JAMA 319, 225 (2018).
12. Klement, R. J. et al. Need for new review of article on ketogenic dietary regimes for cancer patients. Med. Oncol. 34, 108 (2017).

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