A study published on Jul. 15 in Nature by researchers at the Massachusetts Institute of Technology reports that a ketogenic diet may increase the risk of small intestine cancer in mice genetically predisposed to intestinal tumors. The research team, led by Ömer H. Yilmaz, found that mice fed a high-fat, low-carbohydrate ketogenic diet developed tumors in the small intestine at rates similar to or higher than those fed an obesogenic high fat/high calorie diet.
The study involved feeding groups of genetically susceptible mice either a ketogenic diet, a control diet, or a high fat/high calorie diet and observing tumor development. According to the researchers, “mice on a ketogenic diet were more likely to develop tumors of the small intestine than those on a control diet.” The findings showed that although these mice did not become obese, they still exhibited increased tumor formation.
Further investigation revealed that ketone bodies produced during fatty acid metabolism did not contribute directly to tumor growth. Instead, tumor acceleration was linked to how intestinal cells burn dietary fat for energy through fatty acid oxidation—a process activating proteins called PPARs 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.
Interestingly, while the ketogenic diet promoted tumors in the small intestine, it suppressed colon tumor development—echoing previous research from 2022 suggesting protective effects against colon cancer but indicating ketone bodies are not responsible for this benefit. “Given how much attention has been paid to ketone bodies like BHB...we fully expected them to be the direct drivers. Instead...these molecules are essentially metabolic bystanders,” Yilmaz said.
The team plans further studies into why this type of diet has opposing effects in adjacent parts of the gut. “The deeper question is why the same diet has opposite consequences in two adjacent parts of the gut. That is what we are working to understand next,” said Fangtao Chi.
Researchers noted their findings have practical implications, as commercial ketone supplements would not be expected to mimic either risks or benefits observed with dietary fat metabolism.
