MIT mouse study links ketogenic diet to small-intestine tumors

Some people use ketogenic diets to lose weight, and some research has shown that the diets may protect against colon cancer. The diet forces the body to burn fatty acids instead of carbohydrates for fuel, producing by-products called ketone bodies. One of these, BHB, had been 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. Instead, they found that mice on a ketogenic diet were more likely to develop tumors in that part of the gastrointestinal system than mice on a control diet were.

Additional studies revealed that tumor growth was driven by the way intestinal cells burn dietary fat for energy, a metabolic pathway called fatty acid oxidation. The 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 said.

The researchers confirmed that a ketogenic diet suppressed the development of colon tumors, but their findings suggest that ketone bodies are not involved. "These molecules are essentially metabolic bystanders," Yilmaz said. One implication is that commercial ketone supplements probably do little to either help or harm people who take them.

Chi said the deeper issue is "why the same diet has opposite consequences in two adjacent parts of the gut." "That is what we are working to understand next," Chi said. Yilmaz said the results call for caution in how the effects of such diets are described. "The message here is that we need to be very careful in generalizing the effects that these diets can have," he said.

Editor's Summary

The MIT study found that a ketogenic diet made mice more prone to small-intestine tumors while reducing colon tumors, with fatty acid oxidation and stem-cell activity implicated rather than ketone bodies. The results suggest commercial ketone supplements may have little effect and that diet effects cannot be generalized across the gut. Further work is needed to explain the opposite outcomes in adjacent intestinal regions.