Keto diet for cancer: How a tweak may help slow tumor growth

Among the wide range of weight-loss diets are several keto-adjacent diets, such as the Atkins diet, paleo diet, and South Beach Diet, each of which has its proponents and detractors.

A true ketogenic diet, however, can be somewhat extreme, as it essentially requires foregoing carbohydrates for fats that account for up to 90% of a person’s daily caloric intake. Some health experts have serious concerns about the value and safety of a keto diet for weight loss purposes.

The new study finds that a keto diet in mice promotes ferroptosis in cancer cells. Ferroptosis is a process that causes an unsustainable buildup of oxidatively damaged lipids within a cell that, in part, interferes with and disrupts the supply of glucose, on which the cell depends for survival and growth.

Healthy mice placed on a keto diet in the study lost weight and then plateaued, as one might expect with a diet. However, mice with cancer could not stop losing weight.

The authors of the study found the ferroptosis effect of a keto diet to be promising if limited. The study’s corresponding author Dr. Tobias Janowitz, from Cold Spring Harbor Laboratory, New York said: “We found that the ferroptosis slowed the tumor growth significantly but did not stop it altogether. We are now looking into ways to augment that effect.”

Dr. Urvi A. Shah, a myeloma specialist at the Memorial Sloan Kettering Cancer Center, New York, who was not involved in the study, noted that a keto diet has been associated with “weight loss, reduction in glucose, insulin, and inflammation, as well as an increase in beta hydroxybutyrate (ketone bodies), which may have anti-cancer anti-inflammatory effects in certain tumors.”

However, Dr. Shah cautioned, “ketogenic diets are hard to sustain long-term given extreme carbohydrate restriction.”

She also noted that “[o]ne must maintain caution when considering a ketogenic diet long-term, given its long-term effects on raising cholesterol levels and the lack of dietary fiber in these diets.”

“[K]etogenic diets are at odds with the cancer prevention recommendations from the American Institute for Cancer Research and World Cancer Research Fund that recommend a diet rich in whole grains, fruits, vegetables, and beans.”
— Dr. Urvi A. Shah

This recommendation against keto diets may be due, in part at least, to the loss of muscle mass that often occurs with such a diet for healthy people and cancer patients alike, Dr. Shah said.

One of the effects of a keto diet in the study in mice was the loss of corticosterone, a hormone equivalent to cortisol in humans that might offset the diet’s wasting impact.

Study co-author Dr. Miriam Ferrer says in a press release that because of how cancer reprograms the body, “mice can’t use the nutrients from a keto diet, and waste away. But with the steroid, they did much better. They lived longer than with any other treatment we tried.”

According to Dr. Janowitz, the “exact molecular pathway by which corticosteroids affect the metabolism during cancer progression” remains unclear.

Caution is also warranted. “Steroids are powerful drugs and have many effects. In particular, long-term steroid administration is associated with adverse consequences in preclinical and clinical studies,” said Dr. Janowitz.

Dr. Shah noted that such effects include “metabolic dysregulation such as weight gain, hyperglycemia, and muscle wasting. This is known as chronic steroid-induced myopathy, and is associated with proximal muscle weakness and eventually atrophy.”

“These side effects of steroid use would be counter-productive to a patient with cachexia and should be avoided,” said Dr. Shah.

Dr. Janowitz added that a study limitation was that they did not optimize the dosing and timing of corticosteroid administration. “We think that dose optimization and optimization of drug administration timing are key aspects when thinking about steroid use.”

Dr. Janowitz also cautioned that a keto diet’s effect on ferroptosis, cachexia, or a corticosteroid deficit in cancer patients has not been confirmed in humans.

According to Cancer Research UK, the word “cachexia” comes from the Greek word “kakos,” which means “bad.” Its full name is “anorexia cachexia syndrome.”

Dr. Shah explained that “the European Palliative Care Research Collaborative defines cancer cachexia as a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass — with or without the loss of fat mass — that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment.”

“Cachexia is usually associated with more advanced or widespread cancer and, given the metabolic dysregulation, is associated with increased risk of death,” said Dr. Shah.