Dietitians suggest that a ketogenic diet may lead to significant weight loss, up to 10% of body weight, by tricking the body into burning its own fat with high-fat, low-carb meal plans. Additionally, these diets are believed to have potential in combating various cancers by depriving tumors of the glucose they require for growth. However, emerging research indicates a potentially deadly unintended consequence of ketogenic diets for cancer patients.
In mice with pancreatic and colorectal cancer, ketogenic diets accelerate the onset of a fatal wasting disease known as cachexia. Patients and mice afflicted with cachexia experience symptoms such as loss of appetite, extreme weight loss, fatigue, and immune suppression. This condition, for which there is currently no effective treatment, contributes to approximately 2 million deaths annually.
Assistant Professor Tobias Janowitz and Postdoc Miriam Ferrer from Cold Spring Harbor Laboratory (CSHL) are striving to separate the cancer-fighting benefits of the ketogenic diet from its detrimental side effects. They discovered that combining the ketogenic diet with corticosteroids, a common class of drugs, prevented cachexia in cancer-stricken mice. Notably, the tumors in these mice shrank, and their lifespan increased.
"While healthy mice also experience weight loss on the ketogenic diet, their metabolism adjusts and stabilizes," explains Janowitz. "However, mice with cancer lack the ability to adapt, as they cannot produce sufficient amounts of a hormone called corticosterone, which aids in regulating the effects of the ketogenic diet. Consequently, they continue to experience weight loss."
The ketogenic diet induces the accumulation of toxic lipid byproducts in cancer cells, leading to their demise through a process known as ferroptosis. While this inhibits tumor growth, it also triggers early-onset cachexia. By supplementing with a corticosteroid, researchers were able to shrink tumors without initiating cachexia.
"Cancer affects the entire body, reprogramming normal biological processes to facilitate its growth," Ferrer notes. "Due to this reprogramming, mice are unable to utilize the nutrients from a ketogenic diet and waste away. However, when administered with the steroid, their condition significantly improved, surpassing the outcomes of other treatments attempted."
Janowitz and Ferrer are part of an international effort focused on addressing cancer cachexia through Cancer Grand Challenges. They recently published a comprehensive overview of the condition and are now refining the timing and dosage of corticosteroids to extend the window for effective cancer therapies in conjunction with the ketogenic diet.
"Our aim is to combat cancer even more vigorously, slowing its progression further," Janowitz asserts. "By broadening the scope of this effect and enhancing treatment efficiency, we can ultimately benefit patients and advance cancer therapeutics."
