November/December 2019 Issue
Cancer: The Keto Diet’s Impact on Cancer Treatment
By Ginger Hultin, MS, RDN, CSO
Today’s Dietitian
Vol. 21, No. 11, P. 14
The hype about its efficacy to improve health outcomes may not match current evidence.
Since the early 1900s, ketogenic diets have been used in medical care mostly for treating children and adults with refractory epilepsy, but their popularity in the general public has surged in recent years.1-3 This high-fat, moderate-protein, very low-carb diet forces the body into ketosis, a metabolic process that occurs when the body begins to burn fat for energy in lieu of having enough carbohydrate to burn.1,2,4,5 A lack of glycogen stores to pull from for energy causes the body to burn fat stores instead to create the ketone bodies acetoacetate, beta-hydroxybutyric acid, and acetone, which fuel the brain with energy. Interest in this high-fat, low-carb diet is growing in cancer care, and there are now more than a dozen active or completed clinical trials on the ketogenic diet and its association with improved outcomes for a variety of cancers.5,6
One reason the ketogenic diet is being studied for cancer treatment is that its neurological benefits may extend beyond epilepsy. It’s been used to treat aggressive forms of brain cancers (eg, gliomas, including glioblastoma) that often come with poor prognoses and limited treatment options, leading to median survival rates of eight to 15 months.7-9 For example, one animal study found a 50% reduction in glioma tumor progression in rats on a ketogenic diet.2,10 A 2017 Cochrane review of the ketogenic diet for brain tumors reports that, while there are some encouraging small human studies, there’s a lack of prospective validation and potential for selection bias in existing studies.9
Preliminary studies—more so on animals than on humans—exist that show some promise for using a ketogenic diet for prostate, colon, pancreatic, ovarian, endometrial, and lung cancers, though more research is needed before researchers can draw any conclusions.8
Some limited studies support using a ketogenic diet for a variety of cancers during chemotherapy and radiation treatments.4,7,8 The ketogenic diet in cancer treatment is under research and of great interest, but studies often are misinterpreted. Plus, little is known about the diet’s efficacy during cancer treatment, yet it’s being recommended by some without recognizing the differences among cancer types or the challenges the diet may pose when dealing with cancer treatment–related issues, such as potential weight loss, constipation, nutrient deficiencies, kidney damage due to higher protein intake, and dietary restrictions.3,5 Currently, leading cancer organizations don’t recommend the therapeutic use of ketogenic diets because of the lack of research and the fact that the diets go against some key dietary guidelines for cancer prevention.11 With a lack of controlled trials that demonstrate a ketogenic diet can improve health outcomes in cancer populations, it’s considered an adjunctive treatment that needs more research.
Background on Keto and Cancer
Much of the current research on why the ketogenic diet works as an adjunct cancer treatment is based on rodent models.4,7 The diet’s efficacy depends on the type of energy tumor cells require to grow. Normal brain cells can be fueled by both glucose and ketones, but tumors are more dependent on glucose because of their decreased expression of ketolytic enzymes—a biological condition in which cancer cells use glycolysis rather than oxidative phosphorylation to produce energy. The way cancer cells predominantly use glucose anaerobically is called the Warburg effect.1-3,5,7-9
Another reason the ketogenic diet may work as an adjunctive treatment for various cancers is that it affects the way certain proteins associated with angiogenesis are expressed.7 In addition, because cancer cells likely exist under chronic mitochondrial oxidative stress, causing increases in glucose metabolism compared with healthy cells, some researchers hypothesize that the diet may be a beneficial adjunctive therapy to chemotherapy and radiation for different types of cancers.4
The Research
One area that has received more interest among researchers is the use of the ketogenic diet in brain cancer treatment, with some small human studies being performed. A study on two cases of glioblastoma using an energy-restricted ketogenic diet found that one case progressed after four weeks on the diet, while the other didn’t experience progression until 12 weeks on the diet.9,12 These researchers also did a review of 32 glioma patients, finding that some experienced prolonged remissions using adjunctive ketogenic diets (four months to five years).12 A review of 53 glioblastoma participants found that six who followed a ketogenic diet experienced lower blood glucose levels compared with the standard diet group even in patients using high-dose steroids in their treatment protocol.9,13
Studies on nonbrain cancers are even more limited, but there’s some current evidence. Animal studies on the ketogenic diet for non–small cell lung and pancreatic cancers found prolonged survival of animals on a ketogenic diet plus radiation when compared with radiation alone.4 Several studies use improved quality of life as an outcome rather than reduced tumor progression or other cancer-specific markers. A randomized controlled trial on women with ovarian and endometrial cancers found that, after 12 weeks, the ketogenic diet group experienced an improvement in physical function, increased energy, and diminished specific food cravings.1 Researchers in several studies say that the ketogenic diet is safe and without major side effects in their participants.1,12 However, other researchers cite potential risks such as gastrointestinal discomfort, elevated cholesterol levels, and nutrient deficiencies.9
One potential benefit of the ketogenic diet in cancer patients with diabetes is blood sugar control, though currently there isn’t a consensus about its safety and efficacy for this purpose. Angela Martens, RD, a 19-year clinical dietitian at CancerCare Manitoba in Winnipeg, Manitoba, Canada, says, “There is a high incidence of diabetes in the oncology population (either preexisting diabetes or steroid-induced hyperglycemia) as well as evidence demonstrating poorer treatment tolerance and overall worse cancer outcomes in individuals with hyperglycemia and diabetes. Ketogenic diets dramatically improve both glycemia and insulin resistance, with good evidence to support this. This would be a potential benefit to using the diet during cancer treatment.”
Challenges and Contraindications
It’s important to note there’s no single standardized ketogenic diet, which makes studying a high-fat, carb-restricted model challenging in oncology care.3,7 Though the ketogenic diet can potentially show promise in the oncology population, there may be challenges to consider before starting this type of protocol. These include social support, food access and preparation, unintended weight loss, appetite and palatability of a restricted high-fat diet, treatment-related digestive side effects, and the risk of nutrient deficiencies.
One study called for more research on a standardized ketogenic diet in the oncology population, which included twice-daily monitoring of glucose and ketones and dietitian supervision. The researchers also stated that patient compliance with this type of diet will be greater among those who are highly motivated and have excellent social support.7 Note that, in human studies, most participants lose weight, which could be harmful when going through cancer treatment, especially if they have experienced unintended weight loss or cachexia. A ketogenic diet is generally low in fiber, which could compound treatment-related constipation. It also doesn’t include cancer-fighting antioxidant compounds found in a variety of fruits, vegetables, whole grains, and legumes, which are limited in this diet due to carbohydrate restrictions.
Suzanne Dixon, MPH, MS, RDN, an epidemiologist and medical writer with Cambia Health Solutions in Portland, Oregon, has reservations about using the ketogenic diet in cancer care. “At this point, in my mind, the cons of a ketogenic diet during cancer treatment are significant,” Dixon says. “The first thing to consider is there are no controlled trials, short or long term, which demonstrate a ketogenic diet is safe or will improve outcomes in cancer patients. Small pilot studies (without control groups) suggest the diet can be tolerated during treatment, but drop-out rates in these early, single-arm trials are significant. There’s a lot of hype around the (theoretical) benefits of a ketogenic diet, but the hype definitely outpaces the evidence at this point.”
Recommendations for RDs
Because of the ketogenic diet’s growing popularity, patients and medical professionals likely will ask dietitians about its use in oncology patients. Nutrition professionals can speak to the potential benefits and mechanisms, the limits in human research, and the dangers of this diet for those undergoing cancer treatment.
Dietitians can educate clients on evidence-based guidelines for cancer prevention and treatment, including plant-based vegetarian and vegan dietary patterns limited in red and processed meat.14,15 Dixon says that large, long-term studies, including the Women’s Health Initiative (WHI) and Women’s Intervention Nutrition study (WINS), showed significantly improved survival rates during low-fat dietary interventions for breast cancer. A prostate cancer trial also found that a very low-fat plant-based diet—the opposite of the ketogenic diet—had significantly better outcomes than alternative diets.14-18
Nevertheless, many dietitians should take an open-minded approach with their cancer care populations. “Whether a ketogenic diet can actually directly influence cancer growth or synergize with current therapies is still not fully known,” Martens says. “This is an emerging area of research. Unfortunately, many cancer patients don’t have the luxury of time to wait for this research to be conducted. Although the current clinical evidence isn’t robust, it does show that the diet is safe and tolerable if implemented correctly.”
Dixon agrees, adding, “many patients are trying it, and if a patient is absolutely going to do the diet regardless, I strongly encourage consultation with a dietitian who can guide the person on how to actually achieve ketosis. My strongest piece of advice is: Don’t dabble in a ketogenic diet. Either do the diet properly or don’t bother.”
— Ginger Hultin, MS, RDN, CSO, is a nutrition and health writer based in Seattle. She’s a past chair of the Vegetarian Nutrition Dietetic Practice Group, a past president of the Chicago Academy of Nutrition and Dietetics, a spokesperson for the Academy of Nutrition and Dietetics, and owner of concierge nutrition practice Champagne Nutrition LLC.
References
1. Cohen CW, Fontaine KR, Arend RC, Soleymani T, Gower BA. Favorable effects of a ketogenic diet on physical function, perceived energy, and food cravings in women with ovarian or endometrial cancer: a randomized, controlled trial. Nutrients. 2018;10(9):E1187.
2. Branco AF, Ferreira A, Simões RF, et al. Ketogenic diets: from cancer to mitochondrial diseases and beyond. Eur J Clin Invest. 2016;46(3):285-298.
3. Erickson N, Boscheri A, Linke B, Huebner J. Systematic review: isocaloric ketogenic dietary regimes for cancer patients. Med Oncol. 2017;34(5):72.
4. Zahra A, Fath MA, Opat E, et al. Consuming a ketogenic diet while receiving radiation and chemotherapy for locally advanced lung cancer and pancreatic cancer: the University of Iowa experience of two phase 1 clinical trials. Radiat Res. 2017;187(6):743-754.
5. Oliveira CLP, Mattingly S, Schirrmacher R, Sawyer MB, Fine EJ, Prado CM. A nutritional perspective of ketogenic diet in cancer: a narrative review. J Acad Nut Diet. 2018;118(4):668-688.
6. Ketogenic. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/results?cond=Cancer&term=ketogenic&cntry=&state=&city=&dist=. Accessed September 5, 2019.
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11. Nelson M. Ketogenic diet and cancer treatment, what patients should know. American Institute for Cancer Research website. https://blog.aicr.org/2018/09/17/the-ketogenic-diet-and-cancer-treatment-what-patients-should-know/. Published September 17, 2018. Accessed September 5, 2019.
12. Schwartz K, Chang HT, Nikolai M, et al. Treatment of glioma patients with ketogenic diets: report of two cases treated with an IRB-approved energy-restricted ketogenic diet protocol and review of the literature. Cancer Metab. 2015;3:3.
13. Allen BG, Bhatia SK, Anderson CM, et al. Ketogenic diets as an adjuvant cancer therapy: history and potential mechanism. Redox Biol. 2014;2:963-970.
14. Melina V, Craig W, Levin S. Position of the Academy of Nutrition and Dietetics: vegetarian diets. J Acad Nutr Diet. 2016;116(12):1970-1980.
15. Diet, nutrition, physical activity and cancer: a global perspective. World Cancer Research Fund International website. https://www.wcrf.org/dietandcancer/recommendations/during-after-cancer. Accessed September 5, 2019.
16. Prentice RL, Caan B, Chlebowski RT, et al. Low-fat dietary pattern and risk of invasive breast cancer: the Women’s Health Initiative Randomized Controlled Dietary Modification Trial. JAMA. 2006;295(6):629-642.
17. Blackburn GL, Wang KA. Dietary fat reduction and breast cancer outcome: results from the Women’s Intervention Nutrition Study (WINS). Am J Clin Nutr. 2007;86(3):s878-s881.
18. Ornish D, Weidner G, Fair WR, et al. Intensive lifestyle changes may affect the progression of prostate cancer. J Urol. 2005;174(3):1065-1070.