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A ketogenic diet, one of the world’s most popular approaches to weight loss, may increase the risk of small intestine cancer in people who are genetically predisposed to the disease.
In a new study published in Nature, researchers at the Massachusetts Institute of Technology (MIT) found that mice fed a high-fat, low-carbohydrate ketogenic diet developed significantly more tumors in the small intestine than mice on a standard diet.
Since the study was conducted in mice genetically engineered to develop intestinal tumors, the findings don’t show that ketogenic diets cause cancer in healthy people.
However, the researchers said the results could have implications for people with inherited conditions such as familial adenomatous polyposis (FAP), which greatly increases the risk of intestinal cancer.
Ketogenic Diets
Ketogenic diets—high-protein, high-fat diets with lots of meats and very few carbs—force the body to burn fat instead of carbohydrates for fuel, producing compounds known as ketone bodies.
Previous research suggested those ketones could help suppress colon cancer, but the new study found the opposite effect in the small intestine.
“Ketogenic diets have distinct effects on different tissues even within the gastrointestinal tract,” Omer Yilmaz, director of the MIT Stem Cell Initiative and the study’s senior author, said in a press release.
“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.”
The researchers discovered that ketone bodies themselves were not responsible for the increased tumor growth.
Instead, the effect appeared to be driven by fatty acid oxidation—the way intestinal cells process dietary fat for energy.
That process activated proteins known as PPARs, encouraging intestinal stem cells to multiply more rapidly, increasing the likelihood that some cells could become cancerous.
“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.
‘The real surprise’
The findings surprised the researchers because the same ketogenic diet reduced tumor development in the colon, consistent with previous studies.
Further experiments showed that ketone bodies were “essentially metabolic bystanders,” while the high fat content of the diet—and how cells metabolized those fats—was responsible for both the harmful and protective effects seen in different parts of the intestine.
“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,” Yilmaz said.
“The real surprise is that tumor acceleration is driven entirely by how stem cells process and burn the heavy influx of dietary fat itself.”
‘The deeper question’
The researchers cautioned that additional research, particularly in humans, is needed before the findings can be translated into dietary recommendations.
Lead author Fangtao Chi said the team’s next goal is to understand why neighboring sections of the digestive tract respond so differently to the same diet.
“The deeper question is why the same diet has opposite consequences in two adjacent parts of the gut,” Chi said in the release.
“That is what we are working to understand next.”
Newsweek covered a potential immunotherapy breakthrough in colorectal cancer care, as well as a scary way that colon cancer cells can spread.
Newsweek has reached out to the study authors for comment via email.
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