Ketogenic Diet: Who Benefits and Who Is at Risk?

Sara Gottfried MD Women's Health Article | Ketogenic Diet | Ketogenic Diet: Who Benefits and Who Is at Risk?

The ketogenic diet (“keto”) is often touted as an easy way to lose weight fast, providing impressive weight-loss results for men and women alike. But is it true? How do you separate fact from fiction when it comes to keto when there are so many so-called experts stating keto is safe for everyone? Part of the problem with getting reliable and evidence-based information on the ketogenic diet is that we are witnessing an infodemic, described by the medical journal The Lancet as an “overabundance of information—some accurate and some not—that makes it harder for people to find trustworthy sources and reliable guidance when needed.”1 I want to set the record straight.

What Are the Benefits of a Ketogenic Diet?

Even though keto is on trend right now with substantial research activity, the ketogenic diet was created last century as a therapy for epilepsy. Over the last 50 years, evidence has mounted showing a benefit of ketogenic diets in multiple conditions: neurodegenerative diseases such as Alzheimer’s, as well as metabolic conditions and obesity. Recently, it’s been a potentially powerful tool for Alzheimer’s disease, autism spectrum disorder, multiple sclerosis, as well as weight management.

There is data to show that people on a ketogenic diet experience:

  • Greater improvements in blood sugar control in diabetics compared with a low glycemic index diet2
  • Significant weight loss and improvement in fatty liver disease3,4
  • Better cognition, including enhanced attention and reduced self-reported confusion5
  • Enhanced T cell response against influenza virus6

A recent paper in Nature Medicine suggested that the anti-inflammatory effects of a ketogenic diet might be linked to how ketones can inhibit the NLRP3 inflammasome,7 which is an important driver of inflammatory diseases, particularly COVID-19.

Can Keto Cure Cancer?

Short answer: We don’t know. Keto is hotly debated in the cancer literature with some cancers showing a robust response due to the Warburg effect, which is the reliance of cancer cells on glycolysis rather than oxidation to meet their metabolic needs. Put another way, cancer feeds on sugar, though I would say that concept is oversimplified.

Historically, the Warburg effect has been the most widely accepted hypothesis for energy metabolism in cancer cells and it may potentially be exploited with the use of carbohydrate restriction in some, but not all, types of cancer. While the majority of research on the ketogenic diet in cancer is favorable,8 one animal model suggests keto may worsen a certain form of cancer called Acute Myeloid Leukemia as published in the journal Nature.9

In terms of large clinical trials, the effect of keto on breast cancer is still unknown and the precedent is still the Women’s Health Initiative diet trial, which suggested that a low-fat diet may help reduce breast cancer risk. At this point in time, there are no other diet studies of sufficient quality or size to support other health claims. We do have limited clinical data showing that intermittent fasting with an overnight fasting period of 13 to 14 hours may reduce breast cancer recurrence10 but more research is needed.

Bottom line: When it comes to the ketogenic diet for cancer, it seems that the keto hype promotes false hope and could cause harm. Randomized trials are needed to settle the score and perhaps, well-designed, large-scale, deeply phenotyped n-of-1 trials. When in doubt, ask your doctor for personalized guidance.

What Are the Contraindications to a Ketogenic Diet?

The ketogenic diet is not safe for people who have congenital health conditions that make them unable to metabolize normally fatty acids. These conditions include pyruvate carboxylase deficiency, porphyria, and other fat metabolism disorders. Other common and rare metabolic conditions are listed below. If you have any of these conditions or you are uncertain if keto is right for you, consult your healthcare professional.

Additional health conditions that may be worsened on a ketogenic diet include the following.

  • Pancreatitis
  • Active gallbladder disease
  • Impaired liver function
  • Poor nutritional status
  • Poor cardiovascular status (keto may increase low-density lipoprotein or LDL)
  • History of gastric bypass surgery
  • History of cancer
  • History of chronic kidney disease or failure
  • Pregnancy and breast feeding (I do not recommend keto for women who are pregnant or breastfeeding because of the lack of safety data.)
  • Type 1 diabetes

Other rare metabolic conditions that are contraindicated for the ketogenic diet include:

  • Carnitine deficiency (primary)
  • Carnitine palmitoyltransferase (CPT) I or II deficiency
  • Carnitine translocase deficiency
  • Beta-oxidation defects
  • Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mHMGS) deficiency
  • Medium-chain acyl dehydrogenase deficiency (MCAD)
  • Long-chain acyl dehydrogenase deficiency (LCAD)
  • Short-chain acyl dehydrogenase deficiency (SCAD)
  • Long-chain 3-hydroxyacyl-CoA deficiency
  • Medium-chain 3-hydroxyacyl-CoA deficiency

Additionally, there are specific genetic variants that may make you respond better or worse to saturated fat. That’s why I recommend eating more plant-based whole foods and extra virgin olive oil in a clean, well-formulated ketogenic diet.

In general, the benefits for people who respond to keto include mental acuity, better satiety, improved insulin and glucose sensitivity, and weight loss. However, it’s important to note the contraindications for keto discussed above and if you have a history of any condition or are uncertain, talk to your team of health care professionals before starting on keto. If you have cancer or a history of cancer, it’s especially important to discuss keto with your oncologist.

Women and the Ketogenic Diet

On a final note, anecdotally, about half my female patients do great with keto; half don’t. I have spent the last few years trying to figure out why that is and to understand if the biological wiring as women may make us more resistant to keto. I have identified reasons why so many women fail to lose weight on the classic ketogenic diet and my upcoming book WOMEN, FOOD, AND HORMONES shares my new health plan—a female-friendly keto diet that addresses the unique hormonal needs of women.

Women, Food, and Hormones is out now.

[1] “The Truth Is Out There, Somewhere,” Lancet 396, no. 10247 (2020): 291.

[2] E. Westman, et al. “The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus.” Nutrition & Metabolism 5, no. 36 (2008).

[3] J. Volek, et al. “Metabolic characteristics of keto-adapted ultra-endurance runners.” Metabolism: Clinical and Experimental 65 no. 3 (2016): 100–110.

[4] D.Tendler, et al. “The effect of a low-carbohydrate, ketogenic diet on nonalcoholic fatty liver disease: a pilot study.” Digestive Diseases and Sciences 52, no. 2 (2007): 589–593.

[4] K. D’Anci, et al. “Low-carbohydrate weight-loss diets. Effects on cognition and mood.” Appetite 52, no. 1 (2009): 96–103.

[6] E. Goldberg, et. al. “Ketogenic diet activates protective γδ T cell responses against influenza virus infection.” Science Immunology 4, no. 41(2019).

[7] Y. Youm, et al. “The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease.” Nature Medicine 21, no. 3 (2015): 263–269.

[8] H. Chung, et al. “Rationale, Feasibility and Acceptability of Ketogenic Diet for Cancer Treatment.” Journal of Cancer Prevention 22, no. 3 (2017):127-134.; D. Weber, et al. “Ketogenic Diet in the Treatment of Cancer – Where Do We Stand?” Molecular Metabolism 33 (2020):102-121.

[9] Hopkins BD, et al. “Suppression of Insulin Feedback Enhances the Efficacy of PI3K Inhibitors.” Nature 560, no. 7719 (2018):499-503.

[10] C. Marinac, et al. “Prolonged Nightly Fasting and Breast Cancer Prognosis.” JAMA Oncology 2, no. 8 (2016): 1049-55.