A new study conducted by researchers at the Massachusetts Institute of Technology (MIT) has found that the ketogenic diet—a high-fat, low-carbohydrate eating plan—can have opposing effects on tumor development within the gastrointestinal tract. While the diet has been linked to the suppression of colon tumors in previous research, the new findings indicate that it may accelerate tumor growth in the small intestine.
The study, published in Nature, was led by Omer Yilmaz, director of the MIT Stem Cell Initiative and an associate professor of biology at MIT. The research team included lead authors and MIT postdocs Jessica Shay and Fangtao Chi, along with contributors from the labs of Alex K. Shalek and Matthew Vander Heiden.
Distinguishing Dietary Fat from Ketone Bodies
The ketogenic diet forces the body to burn fatty acids for energy rather than glucose, a process that produces ketone bodies such as β-hydroxybutyrate (BHB) and acetoacetate. Because these ketones are generated during ketosis, they have long been the primary focus of research into the diet’s health effects. A 2022 study suggested that BHB was responsible for the diet’s protective effect against colon cancer. However, the MIT researchers discovered that ketone bodies are not the drivers of the effects observed in the small intestine. “Instead, our experiments in genetically engineered mice revealed that these molecules are essentially metabolic bystanders.”
The study found that the biological impact on tumors is instead driven by the metabolism of dietary fat itself. As intestinal cells break down high levels of dietary fat for energy through a process called fatty acid oxidation, they activate a family of proteins known as PPARs. These proteins signal intestinal stem cells to multiply more rapidly.
The Mechanism of Tumor Acceleration
The rapid proliferation of stem cells is a double-edged sword for the body. While increased stem cell activity is beneficial for repairing tissue after injury or illness, the researchers found that excessive proliferation in the small intestine increases the likelihood of cells becoming cancerous.
In the experiment, mice genetically predisposed to intestinal cancer were fed either a ketogenic diet, a standard control diet, or a high-fat, high-calorie diet designed to induce obesity. The results showed that mice on the ketogenic diet developed tumors in the small intestine at rates similar to, or higher than, those fed the obesity-inducing diet, despite the fact that the ketogenic group remained lean.
Tissue-Specific Effects and Clinical Context
The research highlights a significant discrepancy in how different parts of the digestive system respond to the same metabolic inputs. While the ketogenic diet promoted tumor growth in the small intestine, the team confirmed that it continued to suppress tumor development in the colon, consistent with earlier research.
“Ketogenic diets have distinct effects on different tissues even within the gastrointestinal tract,” Yilmaz said. “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.”
Summary of Findings
| Observation | Effect of Ketogenic Diet |
| :— | :— |
| Small Intestine | Accelerated tumor growth |
| Colon | Suppressed tumor growth |
| Primary Driver | Fatty acid oxidation (burning dietary fat) |
| Ketone Bodies | Identified as metabolic bystanders |
The research team is now working to determine why the same diet produces such conflicting consequences in two adjacent sections of the gut. As the ketogenic diet remains popular for weight management and other health goals, the authors emphasize that understanding these tissue-specific effects is critical for future dietary guidance.
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