A high-fat, low-carbohydrate diet can help some people lose weight, and some research has shown that it may protect against colon cancer. But a new study suggests that such a ketogenic diet may also increase the risk of cancer in the small intestine.

This type of diet forces the body to burn fatty acids instead of carbohydrates for fuel, producing by-products called ketone bodies. One of these, BHB, was thought to be responsible for the protective effect observed against colon cancer.

Omer Yilmaz, director of the MIT Stem Cell Initiative, worked with colleagues including MIT postdocs Jessica Shay and Fangtao Chi to investigate whether the effects were similar in the small intestine. But instead, they found that mice on a ketogenic diet were more likely to develop tumors in that part of the gastrointestinal system than those on a control diet were. 

Additional studies revealed that this tumor growth was driven by the way intestinal cells burn dietary fat for energy—a metabolic pathway called fatty acid oxidation. This pathway activates proteins that signal stem cells to multiply more rapidly. 

“Having more stem cells means that when you injure the small intestine, it can repair itself better, but the downside is that having more active stem cells can lead to tumor formation,” Yilmaz says.

Though the researchers confirmed that a ketogenic diet suppressed the development of colon tumors, their findings suggest that ketone bodies are not involved. “These molecules are essentially metabolic bystanders,” Yilmaz says.

One implication is that commercial ketone supplements probably do little to either help or harm people who take them. But the deeper issue is “why the same diet has opposite consequences in two adjacent parts of the gut,” Chi says. “That is what we are working to understand next.”

Whatever they discover, as Yilmaz says, “the message here is that we need to be very careful in generalizing the effects that these diets can have.”