The ketogenic diet has gone from a 1920s epilepsy treatment to a mainstream weight-loss plan, and researchers have increasingly asked what it does to cancer risk. Earlier work suggested it might protect against colon cancer. A new study from MIT, published in Nature, shows the story is more complicated: in mice, the very same diet fueled tumors in the small intestine while suppressing them in the colon.

A quick refresher on keto

A ketogenic diet is very high in fat, very low in carbohydrates, and moderate to low in protein. With little glucose available, the body switches to burning fatty acids for energy. Breaking down those fats produces ketone bodies such as β-hydroxybutyrate (BHB) and acetoacetate, which also rise during fasting. A 2022 Nature study proposed that BHB was central to keto’s protective effect against colon cancer, so the MIT team set out to see whether the same benefit would appear in the small intestine.

What the researchers did

They used mice genetically predisposed to intestinal cancer and fed them one of three diets: a ketogenic diet, a control diet, or a high-fat, high-calorie “obesogenic” diet. The keto-fed mice developed small-intestinal tumors more often than controls. Even though they did not become obese, their tumor rates were similar to, and in some cases higher than, those of mice on the obesity-inducing diet.

The surprise: it wasn’t the ketones

Ketones are the signature of keto, so they were the obvious suspects. But follow-up experiments cleared them. The increased tumor growth traced back to fatty acid oxidation, the process intestinal cells use to burn dietary fat. Heightened activity in this pathway switches on a family of proteins called PPARs, which push intestinal stem cells to divide faster.

More active stem cells are not inherently bad. They help the gut lining repair itself after injury or illness. The trade-off is that more cell division means more chances for a cell to pick up cancer-causing changes.

What might be beneficial for one tissue may be detrimental for another.

Omer Yilmaz, MIT Stem Cell Initiative

The colon told the opposite story

In the colon, the keto diet suppressed tumors, consistent with the 2022 findings. But the new experiments challenge the explanation: the protective effect also appeared to be independent of ketone bodies. The researchers describe ketones as largely “metabolic bystanders” in both tissues. Why two neighboring parts of the gut respond in opposite ways is the question the team is now chasing.

What it means for ketone supplements

Because both effects seem to be driven by fat metabolism rather than ketones themselves, commercial ketone supplements and drinks would not be expected to reproduce either the risk or the benefit seen here. The authors also note that small-intestinal tumors have been rising in recent decades, and that people with inherited conditions such as familial adenomatous polyposis are especially susceptible, which is why understanding these tissue-specific effects matters.

Keep it in perspective

This is a mouse study, in animals engineered to develop intestinal tumors, so it cannot tell us what a ketogenic diet does to cancer risk in healthy people. What it does show is that a diet’s effects can differ sharply even between adjacent tissues, and that its mechanism may not be the one everyone assumed. The researchers’ own message is caution about generalizing, in either direction.

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