Keto diet raised small-intestine tumor risk in mice, MIT team finds

Two neighboring sections of the gut, the small intestine and the colon, respond in opposite ways to the same diet. In a study led by Omer Yilmaz, director of the MIT Stem Cell Initiative, the team found that mice fed a ketogenic diet were more likely to develop tumors in the small intestine than mice on a control diet. In the colon, the same diet had previously been linked to protection.

A ketogenic diet is high in fat and low in carbohydrates. It forces the body to burn fatty acids for fuel instead of sugars, producing by-products called ketone bodies. One of them, beta-hydroxybutyrate, or BHB, was thought to explain why the diet appeared to protect against colon cancer. Some research had already suggested that link, and the diet is widely used for weight loss, which makes the possible downside in the small intestine a question worth asking carefully.

Working with MIT postdocs Jessica Shay and Fangtao Chi, Yilmaz’s team first checked whether the colon results carried over to the small intestine. They did not. Further experiments showed that the tumor growth was driven by fatty acid oxidation, the metabolic pathway through which intestinal cells burn dietary fat. That pathway activates proteins that tell stem cells to multiply more quickly. “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.

The ketone bodies themselves turned out not to be the driver. The researchers confirmed that the diet still suppressed tumors in the colon, but they concluded that ketones are “essentially metabolic bystanders,” in Yilmaz’s words. That points to a practical implication: commercial ketone supplements probably do little to help or harm people who take them. The study does not give figures for tumor rates in mice, and it does not report any test in people.

For now, the immediate beneficiaries are researchers, who gain a clearer map of what drives the effect and what does not. The team says the next task is to understand “why the same diet has opposite consequences in two adjacent parts of the gut,” as Chi puts it. No timeline for that work is given, and nothing in the study changes what anyone should eat today. Yilmaz’s advice is that “we need to be very careful in generalizing the effects that these diets can have.”