MIT-Led Study Warns Ketogenic Diet May Boost Small-Intestine Tumor Growth in Mice

A ketogenic diet — high in fat and very low in carbohydrates — has become a popular strategy for weight loss, and some studies have suggested it could lower the risk of colon cancer. New research from an MIT-led team, however, indicates the same eating pattern may carry an unexpected downside: it can increase tumor formation in the small intestine, at least in mice.

The ketogenic approach pushes the body to rely on fat rather than carbohydrates for energy. As fat is broken down, the liver produces molecules known as ketone bodies. One of the most studied ketone bodies is beta-hydroxybutyrate (BHB), which had been proposed as a key factor behind previously reported protection against colon tumors.

To test whether similar mechanisms might apply elsewhere in the gut, Omer Yilmaz — director of the MIT Stem Cell Initiative — and collaborators including MIT postdocs Jessica Shay and Fangtao Chi examined how a ketogenic diet affects cancer risk in different intestinal regions. Their results diverged sharply from expectations. Compared with animals on a standard control diet, mice fed a ketogenic diet were more likely to develop tumors in the small intestine.

Follow-up experiments pointed to a specific biological driver: fatty acid oxidation, the metabolic pathway cells use to extract energy from dietary fats. In the small intestine, this fat-burning program was linked to activation of proteins that prompt intestinal stem cells to proliferate more quickly. The biological tradeoff is clear, the researchers say. A larger, more active stem-cell pool can be beneficial after damage — enabling faster repair of the intestinal lining — but it also increases opportunities for tumor formation.

“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 explains.

Notably, the researchers also verified that the ketogenic diet continued to suppress tumors in the colon, aligning with earlier reports. But their data suggest ketone bodies are not the reason for that benefit. Instead, the team argues, ketone molecules such as BHB appear to be incidental products of the diet rather than direct drivers of the cancer-related effects seen in different parts of the intestine. Yilmaz describes ketone bodies as “metabolic bystanders” in this context.

That distinction has practical implications beyond basic biology. If ketones are not the active ingredient, then commercially marketed ketone supplements are unlikely to meaningfully reduce — or raise — cancer risk on their own, according to the researchers’ interpretation.

The bigger scientific puzzle now is anatomical: why would one diet produce opposite outcomes in two neighboring sections of the gastrointestinal tract? “Why the same diet has opposite consequences in two adjacent parts of the gut” is the question the team is now focused on, Chi says.

For now, the findings underline a broader caution about extrapolating from one tissue — or one set of outcomes — to another. As Yilmaz puts it, the study’s takeaway is that scientists and the public alike should be careful about assuming a diet’s effects are uniform across the body.

Why it matters

Ketogenic diets are widely used for weight management and are often promoted for potential health benefits, making any cancer-related effects especially consequential. This research suggests that even within the gut, responses can differ dramatically, depending on local metabolism and stem-cell behavior. The next key step is determining whether similar risks apply to humans and identifying what distinguishes the small intestine from the colon under the same dietary conditions.