The Hidden Cancer Risk of Ketogenic Diets

The same diet may slow cancer in one part of the intestine while accelerating it just a few inches away.

The same diet may protect one part of the gut while increasing cancer risk in another. In a new study published in Nature, MIT researchers found that ketogenic diets, high in fat and extremely low in carbohydrates, produced sharply different effects in the colon and small intestine.

Earlier research suggested that ketosis could help suppress colon tumors. But the new findings show that in the small intestine, heavy reliance on dietary fat may stimulate stem-cell activity and accelerate tumor growth. The study highlights a broader scientific challenge: diets cannot always be classified as simply beneficial or harmful, because their effects may vary dramatically across tissues.

“Ketogenic diets have distinct effects on different tissues even within the gastrointestinal tract. I think the message here is that we need to be very careful in generalizing the effects that these diets can have, because what might be beneficial for one tissue may be detrimental for another tissue,” says Omer Yilmaz, director of the MIT Stem Cell Initiative, an associate professor of biology at MIT, and a member of MIT’s Koch Institute for Integrative Cancer Research.

How Ketosis Changes Metabolism

Ketogenic diets were introduced in the 1920s as a treatment for epilepsy, particularly in children whose seizures did not respond to medication. In recent decades, the diet has become popular for weight loss and has also drawn interest from researchers studying aging, metabolism, and cancer.

The diet contains large amounts of fat, very little carbohydrate, and normal or reduced amounts of protein. Because the body receives little glucose from food, it begins breaking down fatty acids for energy.

That shift produces ketone bodies, primarily β-hydroxybutyrate (BHB) and acetoacetate, as byproducts of fatty acid metabolism. The same compounds appear during fasting or very low-calorie diets, when the body begins drawing on its own fat reserves.

Ketones have attracted intense interest because they are not simply waste products. They can also act as signaling molecules that influence inflammation, gene activity, and cellular metabolism.

A Surprising Small Intestine Risk

A 2022 Nature study found that a ketogenic diet reduced colon tumor formation and suggested that BHB—the most abundant ketone body—was responsible. The MIT team set out to determine whether the diet would produce a similar benefit in the small intestine.

Instead, they found the opposite.

The researchers studied mice genetically predisposed to intestinal cancer. The animals were fed either a ketogenic diet, a control diet, or a high fat/high calorie diet designed to promote obesity.

Mice on the ketogenic diet developed small intestinal tumors more frequently than those on the control diet. They did not become obese, yet their tumor rates were similar to or even higher than those of mice consuming the obesogenic high fat/high calorie diet.

Dietary Fat Fuels Tumor Growth

The increased cancer risk did not appear to come from ketones. Further experiments showed that BHB and other ketone bodies played little role in driving tumor growth.

The key factor was the unusually large supply of dietary fat.

Cells lining the small intestine began burning more of that fat through a process called fatty acid oxidation. This metabolic activity stimulated proteins known as PPARs, which regulate how cells use fat and respond to changes in their energy supply.

When activated, PPARs encouraged intestinal stem cells to divide more rapidly. These stem cells continually replace worn or damaged cells in the intestinal lining, one of the most frequently renewed tissues in the body.

Stem Cell Repair Comes With a Cost

That ability is essential for healing, but it comes with a tradeoff. Every round of cell division creates another opportunity for mutations or abnormal growth to occur.

“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 colon responded very differently. As reported in the earlier Nature study from 2022, the ketogenic diet reduced colon tumor formation. Yet the new experiments suggest that ketone bodies were not directly responsible for that protection either.

“Given how much attention has been paid to ketone bodies like BHB, both as a commercial health trend and in recent high-profile studies suggesting BHB suppresses colon cancer, we fully expected them to be the direct drivers. Instead, our experiments in genetically engineered mice revealed that these molecules are essentially metabolic bystanders. The real surprise is that tumor acceleration is driven entirely by how stem cells process and burn the heavy influx of dietary fat itself,” Yilmaz says.

Why the Colon Responds Differently

“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,” Chi says.

The findings also draw a distinction between following a ketogenic diet and consuming ketone drinks or supplements. Because the tumor effects were driven by the way intestinal cells processed dietary fat, rather than by ketones themselves, commercial ketone products would not be expected to reproduce either the increased small intestinal tumor growth or the protective effect observed in the colon.

The findings may be especially relevant for people with inherited disorders that already raise the risk of intestinal tumors, including familial adenomatous polyposis. That concern has become more pressing as cases of small intestinal cancer have risen in recent decades.

Reference: “Ketogenic diet mediates intestinal tumorigenesis through lipids not ketones” by Jessica E. S. Shay, Fangtao Chi, Constantine N. Tzouanas, Shixun Han, Xiao Zhang, Johanna Ten Hoeve, Kevin J. Williams, Seda Neptun, Tolga Sever, Isabela Fuentes, Sangeeta N. Bhatia, Gizem Calibasi-Kocal, Matthew G. Vander Heiden, Alex K. Shalek and Ömer H. Yilmaz, 15 July 2026, Nature.
DOI: 10.1038/s41586-026-10779-y

The research was funded, in part, by the National Institutes of Health, a Pew-Stewart Trust scholar award, the Kathy and Curt Marble cancer research award, a Koch Institute-Dana Farber/Harvard Cancer Center Bridge project grant, the American Federation for Aging Research, the MIT Stem Cell Initiative, a Damon Runyon Postdoctoral Research Fellowship, and the Koch Institute Support (core) grant from the National Cancer Institute.

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