Low-cal ketogenic diet slows brain cancer in mice

By Will Boggs, MD

NEW YORK (Reuters Health) - A calorically restricted ketogenic diet decreases the growth of malignant brain tumors in laboratory mice, according to an online report in the journal Nutrition & Metabolism.

A ketogenic diet is a high-fat, low-carbohydrate diet that induces excess production of ketone bodies, which are incompletely burned fat molecules. This diet has been used to control epileptic seizures that do not respond to drug treatment.

"In contrast to most conventional brain tumor therapies, which are largely ineffective, are excessively costly, and can diminish the length and quality of life, the calorically restricted ketogenic diet is a natural therapeutic approach to brain cancer management that is based on the principles of evolutionary biology and metabolic control theory," Dr. Thomas N. Seyfried told Reuters Health.

Seyfried and associates at Boston College, Chestnut Hill, Massachusetts evaluated the efficacy of KetoCal, a ketogenic diet formulated to treat unresponsive epilepsy in children, in mice implanted with a malignant mouse brain tumor and a human malignant glioma, a brain tumor that responds poorly to drug therapy.

The mice were fed a regular, high-carbohydrate diet, unlimited amounts of KetoCal, or restricted amounts of KetoCal.

Growth of the two tumors was reduced from 35 percent to 65 percent in mice given restricted KetoCal, compared with mice receiving normal or KetoCal diets that were unrestricted, the researchers report.

Survival was also significantly longer among mice receiving the restricted KetoCal diet, the results indicate.

Blood sugar levels were significantly lower and circulating ketone bodies significantly higher in mice fed the restricted KetoCal diet, the researchers note.

The restricted KetoCal diet starves the brain cancer cells by removing molecules needed for cell growth and survival. While the normal brain cells are sustained by ketones, the tumor cells can't metabolize ketones.

This mouse study was motivated in part by the previous work of Linda Nebeling and co-workers who showed that a calorie-restricted ketogenic diet was effective for the long-term treatment of brain cancer in children, Seyfried explained. "Our work in mice strongly supports the original study."

He concludes that it is important that human trials begin soon to study the effect of the calorically restricted ketogenic diet on brain cancer. "These trials could be conducted at any medical center or clinic currently using the ketogenic diet as a therapy for refractory epileptic seizures."

SOURCE: Nutrition & Metabolism, February 21, 2007.