Does diet or fasting impact cancer outcomes?

Questions from the Clinic:

What is a ketogenic diet? Does adoption of a ketogenic diet make cancer treatments more effective and easier to tolerate? Does fasting before treatments impact outcomes?

Figure 1: In a ketogenic diet, a person consumes fats for a majority of his calories and avoids carbohydrates, which forms the base of the standard food pyramid popularized by the United States Department of Agriculture in the 1990s.

I. Introduction

Accumulating scientific evidence is fortifying the long-suspected links between diet and the development of certain cancers.(1) As recognition of this relationship grows, so too will interest in nutritional regimens that can impact the progression of the disease. Already, nearly half of patients with cancer (48%) adopt some kind of diet with hopes of maximizing survival and preventing recurrence.(2) Among the most compelling, controversial options that patients with cancer consider is the ketogenic diet (Figure 1). First formulated as a treatment for childhood epilepsy in the 1920s, the ketogenic diet may have additional utility in making malignancies more susceptible to chemotherapy and radiation.(3,4) Clarifying the value and mechanisms underlying this natural, adjunctive intervention is imperative, as cancer remains a leading cause of mortality despite advances in pharmacotherapy.

II. The Science Underlying the Ketogenic Diet

In a ketogenic diet, individuals predominantly consume high-fat foods while limiting the consumption of carbohydrates. Traditionally, strict ketogenic dieters consume 4 grams of fat for every gram of carbohydrate and protein combined, such that fat provides upwards of 90% of caloric intake.(5) By restricting the consumption of carbohydrates, ketogenic dieters may selectively stress cancer cells that preferentially metabolize glucose to satisfy their energetic needs.(6) Notably, this cancer cell dependence on glycolysis occurs even in the presence of oxygen; this process is known as the Warburg effect.(7) Ordinary cells, in contrast, adapt to low glucose levels by entering ketosis and using fats to make ketones and then produce ATP efficiently with fewer metabolic byproducts (Figure 2). Because cancer cells cannot use ketones as substrates to generate adenosine triphosphate, they starve while the metabolically flexible and healthy cells survive. Low glucose levels additionally reduce concentrations of circulating insulin and insulin-like growth factor. These hormones bind receptors expressed by many cell types and a