A novel study has revealed that a ketogenic diet significantly increases the likelihood of tumor development in the small intestine of mice. This same high-fat, low-carbohydrate diet, which some research has linked to a reduced risk of colon cancer, produced the opposite effect in a different section of the gut.
These findings challenge the widely held belief that the keto diet protects the intestines from cancer, demonstrating that its impact can vary depending on the tissue involved. It also serves as a warning for individuals born with a high hereditary risk of intestinal tumors—a group sometimes advised to adopt a low-carbohydrate diet.
This research was conducted in the laboratory of Omer Yilmaz at the Massachusetts Institute of Technology (MIT). He oversaw the current studies on mice. His team fed the rodents a ketogenic diet, where they were found to have a damaged copy of a gene that typically helps curb the development of intestinal cancer. The study’s results have been published in the journal Nature.
In the diet, approximately 80% of energy came from fats, which was eight times the fat content found in the standard feed consumed by the control group animals. Over roughly 150 days, the mice on the keto diet developed more tumors in their small intestines and died earlier.
They never became obese. Nonetheless, the number of tumors they developed was equal to, or even exceeded, that of mice on a high-calorie diet intended to induce weight gain.
When asked what advice people following a keto diet should take from this mouse-based study, Yilmaz replied: “For a healthy person, there’s no reason to change their approach.”
Inside the intestines of mice on a keto diet, the mucosal lining contained an excess of stem cells—the fundamental cells that regenerate the intestinal surface every few days. Additionally, the activity of stem cell division increased. In a healthy gut, this extra activity speeds up recovery after injury.
The problem arises when a mutation predisposing to cancer is present in these same cells. “More stem cells means that if the small intestine is damaged, it can recover better, but the downside is that a greater number of active stem cells can lead to tumor formation,” Yilmaz explained.
Burning that much fat saturates the body with ketone bodies—acids produced by intestinal and liver cells when carbohydrates are scarce. A 2022 study found that the anti-tumor effect of the keto diet in the colon was due to one of these substances, a molecule known as BHB. Therefore, the research team hypothesized that these same molecules might also fuel small intestine tumors.
To test this idea, they gradually disabled ketone production: first in the intestinal lining, then in the liver. They reduced their supply to a minimum. Then, they waited. Tumors continued to appear. Raising ketone levels on a normal diet changed nothing, and disabling the mechanism that burns ketones as fuel resulted in an unchanged number of tumors.
All variations of the experiment pointed to the same pattern: ketones behaved more like passengers than drivers. “Our experiments with genetically modified mice showed that these molecules are essentially metabolic ‘passengers,'” Yilmaz stated.
When the researchers cataloged the genes that were activated in the stem cells, the answer was linked to genes involved in fat metabolism. The cells of mice on the keto diet increased fatty acid oxidation—the breakdown of fats for energy—along with a family of proteins called PPAR, which are activated when a cell processes large amounts of fat.
A single enzyme, CPT1a, guards the “gate” through which long fat molecules enter tiny cellular “furnaces.” When the research team removed it from the intestinal lining, the ketogenic diet lost most of its ability to stimulate tumor development.
This pattern echoes earlier work from the same lab, which found that a high-calorie diet directs intestinal cells toward cancer development through the same fuel-burning pathway. Two different diets converge on a single mechanism. It is this mechanism, not ketones, that poses the danger.
“The real surprise is that the acceleration of tumor growth is entirely due to how stem cells process and burn a large amount of dietary fat,” Yilmaz said.
The most peculiar result came from a few centimeters lower. In the colon, the same diet had the opposite effect, suppressing tumor development instead of fueling it. Again, the effect had nothing to do with ketones. A receptor that a competing theory claimed was responsible for the beneficial impact of the keto diet on the colon was, in fact, completely absent in the tumors and stem cells. The protection was real, but its cause was not what researchers had assumed.
“You can’t expect one intervention to be simultaneously protective and harmful for the same organ,” Yilmaz noted.
Why one diet has such contrasting effects on two adjacent sections of the gut remains unexplained.
“The deeper question is why the same diet has opposite effects on two neighboring parts of the intestine. That’s what we’re trying to figure out next,” said study co-author Fantao Chi.
Those at greatest risk are individuals with familial adenomatous polyposis, a hereditary condition where the intestine becomes covered with polyps. Many have their colon removed at a young age to prevent cancer. This measure buys them time but doesn’t guarantee safety. They then face an increasing risk of developing small intestine cancer: benign growths are found in about nine out of ten patients, and cancer in about one out of ten.
Both the danger and the benefit for the colon are linked to fat metabolism, not ketones. This suggests that ketone drinks and supplements marketed as shortcuts to entering ketosis cannot replicate either effect. To see these effects, one must consume fat and burn it.
This discovery also adds to a series of findings from this research group showing that metabolic states valued for healing can turn against the body. For instance, fasting interrupted by a heavy return to eating directs the same active stem cells toward tumor formation, as a recent study from this team demonstrated.
The main takeaway is that a diet is rarely uniformly beneficial or harmful for the entire body. “The keto diet is explained by ketones. Our data says the real story is about fat and what tissues do with it,” Yilmaz stated.
The findings point to a clearer explanation. A ketogenic diet can accelerate tumor development in the small intestine, and it does so through the fats it contains, rather than the ketones it produces. For those weighing the keto diet against a real risk of cancer, this transforms a simple guideline into a question of which part of the body the diet affects.
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