Your diet and your colon have an intimate relationship. Molecules broken down from food and drink continuously bathe the cells that line the intestines.

It’s these cells, called epithelial cells, that give rise to the most common type of colorectal cancer. This relationship has sparked decades of research into diet and colorectal cancer risk.

In a new study in mice, researchers have found evidence that a compound produced while eating a ketogenic diet — that is, a diet very high in fat and low in carbohydrates — could inhibit the development of colorectal cancer.

The compound, called β-hydroxybutyrate (BHB), jump-started a signaling pathway in epithelial cells in the colon that instructed them to stop dividing.

The study’s leaders and other experts warned, however, that although the study results are intriguing, they do not mean that a ketogenic diet or taking a BHB supplement should be used to prevent or treat colorectal cancer.

In the study, the research team, led by Christoph Thaiss, Ph.D., and Maayan Levy, Ph.D., from the Perelman School of Medicine at the University of Pennsylvania, found that treatment with BHB alone slowed or stopped the growth of colorectal tumors in mice, independent of the diet they were fed.

It also slowed the growth of colorectal cancer cells taken from people and grown in the lab.

“When we treated [colorectal cancer] cells with BHB, they didn’t die, but they seemed to start sleeping, basically,” said Levy.

The study results offer potentially important new insights into one of the most common cancers, said Phillip Daschner, M.Sc., of NCI’s Division of Cancer Biology, who was not involved in the study.

“This is a significant contribution to our understanding of the link between diet and colon cancer risk,” Daschner said. “But additional studies on BHB’s effects in people are needed, such as clinical trials using BHB supplements, before any conclusions can be made about its role in cancer prevention or treatment.”

The research team started by feeding mice one of six different diets containing varying levels of fats and carbohydrates. Two were ketogenic, being composed of 90% fat.

The mice were then exposed to chemicals that caused them to develop colorectal cancer. Mice fed either of the ketogenic diets had fewer tumors and smaller tumors than mice fed diets with a higher percentage of carbohydrates. Mice with colorectal cancer who were fed the ketogenic diets also lived longer.

When mice were fed a ketogenic diet after tumors had already formed, their tumors grew very slowly or stopped growing altogether. When the researchers discontinued the diet, the tumors started growing again.

Further experiments ruled out that the keto diets’ effects on tumor growth were due to differences in calories between the diets, changes in the immune system, or reduced inflammation.

However, the researchers did observe a decrease in cell division (proliferation) in the epithelial cells lining the colon and in colorectal cancer cells in mice fed the ketogenic diet.

A factor potentially complicating the understanding of how BHB works in the human colon is that the current study didn’t touch on the microbiome’s possible role in influencing the body’s response to different nutrients, Daschner said.

The makeup of a given person’s microbiome — the collection of bacteria, fungi, and viruses that live in the human gut and that varies widely from person to person — can affect its interactions with nutrients, medications, and anything else that passes through the gut.

In some people, depending on their microbiome, BHB may not have an effect, he explained.

So, for now, BHB is a “don’t try this at home” scenario, said Daschner. It’s currently sold widely as a dietary supplement, but its risks and benefits need much more study.


“Keto Molecule Offers Clue for Preventing Colorectal Cancer” was originally published by the National Cancer Institute.

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