The Ketogenic Diet and Cancer

Is there any benefit to a ketogenic diet for a cancer patient? That’s a question that some researchers have begun asking. Theoretically, there may be reasons to consider a ketogenic diet, and we have some evidence in primary brain tumors that being on a ketogenic diet might be helpful. To get to the heart of why this might be so, researchers are asking why the ketogenic diet seems to be especially helpful in treating one type of illness involving the brain, and that is epilepsy or a seizure disorder. (To review what a ketogenic diet is and how it is helpful for weight loss, read parts I and II of this series)

The Beginnings of the Ketogenic Diet and Epilepsy

To talk about why the ketogenic diet may be useful in the treatment of epilepsy, we have to look at this diet’s cousin, fasting. Short term fasting has been used since Hippocrates (around 400 BCE) for the treatment of various ailments including seizure disorders. Like the ketogenic diet, fasting causes a state of ketosis. In 1911, a couple of French physicians (Gulep and Marie) treated patients with epilepsy with fasting and found that they had fewer seizures during treatment. This practice also spread to the US, and in the 1920’s fasting was being tested at Harvard as a treatment for epilepsy. Drs. Cobb and Lennox of Harvard noted that seizures improved after 2-3 days and correctly attributed this finding to metabolic changes that occurred with fasting or with just carbohydrate restriction.

At about the same time, Dr. Wilder at the Mayo Clinic was having success with a high fat diet in the treatment of children with epilepsy. It seems that Wilder was really the first to propose the “ketogenic diet” that produced ketones without fasting and could be maintained as a treatment for a longer period of time than fasting. Throughout the 1920’s and 1930’s the ketogenic diet was widely used to treat epilepsy and was very successful at controlling seizures. In 1938 however, a new drug was discovered for the treatment of seizures (the precursor to phenytoin or Dilantin^®) and medical therapy became the mainstay of treatment.

Interest in the ketogenic diet died down from a research standpoint until 1994 when it was covered in a Dateline NBC news story as a last resort treatment for intractable seizures in a young boy.

Primary brain tumors

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor and one of the most aggressive of all tumors period. Despite surgery, radiation, and chemotherapy, treatment is not all that successful.

The ketogenic diet may be useful here since there is evidence that normal brain cells and brain tumor cells do not have the same ability to utilize ketones as fuel. Normal brain cells can use ketones as fuel, but brain tumor cells may be more dependent on glucose.  Since glucose is in short supply on a ketogenic diet, maybe a state of ketosis can help the other therapies used to treat primary brain tumors. There are other metabolic changes that point to a potential benefit for the ketogenic diet as well.

Brain tumors transplanted in mice had slower growth rates on a ketogenic diet.  In test tubes, GBM cells treated with the main ketone produced on a ketogenic diet (beta-hydroxybutyrate), showed decreased growth. These reports suggest that there might be a role for the ketogenic diet in supporting the treatment of brain tumors. So far we only have case reports of this approach in patients, but clinical trials are being planned (see the Schwartz and Williams articles listed in the references).

Cancer cells' altered metabolism

But will the ketogenic diet be useful for other cancer types? Good question. Possibly. The research isn’t there yet to give this question a firm answer. Since it appears that cancer cells use fuel (mostly glucose) differently than normal cells, it is possible that we could exploit these differences with a ketogenic diet. (There is a very interesting review by Bryan Allen referenced below for those of you who want more of the science.)

The NIH sponsored a small trial in patients with advanced or metastatic cancer following a “modified Atkins diet” (there are some small differences between Atkins and ketogenic). They concluded that the diet was safe but difficult to stick to, and that survival actually improved in some melanoma and lung cancer patients.

At the time of this writing, there are several trials of the ketogenic diet in cancer that are recruiting patients. For more information go to ClinicalTrials.gov.

Who should try the ketogenic diet?

There is no ONE diet for everyone, especially when it comes to weight loss.  But as much of this discussion indicates, diets are about more than just weight loss. They are about your overall health and disease prevention.

So who might benefit from a low-carb or ketogenic diet?

1. If you have insulin resistance or type II diabetes, this may help you control your blood sugars and insulin levels. You must do this with your doctor’s guidance though, as you may require medication adjustments fairly soon after beginning the diet.
2. You just want to try it to see how you feel or to see if you can lose some weight. If you are just trying it on for size, then you may be able to just cut back on carbs without going to the level that you are in a state of ketosis. Cut back on carbs gradually to see what helps you with weight loss or just feeling better.
   • Be sure to get your fats from healthy sources
   • Lots of veggies
   • Whole, unprocessed foods without preservatives, flavorings, colorings, etc
3. Athletes who want to try their sport in a keto-adapted state. There is some research that endurance athletes perform at least as well in a keto-adapted state, and there is not a risk of hitting the wall (running out of glycogen as fuel) during your performance. Your body has a much larger supply of fat to burn than glycogen. If you are interested in this approach, I highly recommend the book, The Art and Science of Low Carbohydrate Performance by Volek and Phinney.

If you are currently going through cancer treatment, please consult with your oncologist before making any changes to your diet.

The ketogenic diet is a healthy way to eat in general and is useful for weight loss. It has many other metabolic benefits as well that may help prevent cardiovascular disease. If you have diabetes or insulin resistance, it is becoming the recommendation of choice, but many physicians and dieticians may not yet have caught up with the research. Since insulin resistance is a significant factor predicting a breast cancer recurrence, the ketogenic diet may be especially important for breast cancer survivors. There is active research into whether or not the ketogenic diet may prove useful as an additional therapy in cancer treatment.

Click here to read part I of this 3 part series.  Click here to read part II. 

References:

Allen BG, Bhatia SK, Anderson CM, et al. Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism. Redox Biol. 2014;2:963-70.

Wheless, J. W. (2008), History of the ketogenic diet. Epilepsia, 49: 3-5. doi:10.1111/j.1528-1167.2008.01821.x

Schwartz KA, Noel M, Nikolai M, Chang HT. Investigating the Ketogenic Diet As Treatment for Primary Aggressive Brain Cancer: Challenges and Lessons Learned. Front Nutr. 2018;5:11. Published 2018 Feb 23. doi:10.3389/fnut.2018.00011

Matt Williams, Helen Cross, Michael D Jenkinson, Kirsty Martin, Susan Wood, Adrienne C Scheck, Nelofer Syed, Kevin O’Neill, Katie Sheen, Catherine Zabilowicz, Kieran Breen, Kathy Oliver, Emma Williams, Mike Johnson, Wendy Fulcher; The ketogenic diet for patients with brain tumours: Two parallel randomised trials, Neuro-Oncology, Volume 20, Issue suppl_1, 31 January 2018, Pages i7–i8, https://doi.org/10.1093/neuonc/nox237.033

Tan-Shalaby JL, Carrick J, Edinger K, et al. Modified Atkins diet in advanced malignancies - final results of a safety and feasibility trial within the Veterans Affairs Pittsburgh Healthcare System. Nutr Metab (Lond). 2016;13:52. Published 2016 Aug 12. doi:10.1186/s12986-016-0113-y