Keto diet triggers activation of molecule that stops colorectal cancer

Eating a low-carb keto diet could delay the progression of colorectal cancer, suggests a new study from the University of Pennsylvania School of Medicine. The findings show changing your diet may help in treating cancer.

Colorectal cancer ranks as the third leading cause of cancer death, killing over 50,000 Americans each year. In the current study, mice fed with a low-carb, high-fat ketogenic diet slowed down colorectal tumor growth. The reason behind it seemed to come from a small organic molecule in the liver called beta-hydroxybutyrate (BHB). 

“Our findings suggest that this natural molecule, BHB, could someday become a standard part of colorectal cancer care and prevention,” says study co-senior author Maayan Levy, PhD, an assistant professor of Microbiology at Penn Medicine in a press release.

The team categorized mice into six groups based on their diets which had different fat-to-carb ratios. They used a standard chemical technique to trigger colorectal tumor growth.

Mice fed with the most ketogenic diets with a 90% fat-to-carb ratio stopped tumor development in most animals compared to those on other diets. Animals on a low-fat, high-carb diet were more likely to develop tumors. Additionally, mice who already had tumors and then started the ketogenic diet slowed down tumor growth. 

Further experiments pinpointed the reason behind suppression to slower production of new epithelial cells lining the colon. The release of BHB triggered the lack of stem cell differentiation into epithelial cells. The body makes BHB when it reaches starvation mode as it temporarily provides energy for organs. BHB can also be released by a low-carb diet such as the low-carb keto diet eaten by one group of mice. BHB not only acted as an alternative fuel source but also slowed down the growth signal for gut-lining cells. When researchers directly inserted BHB into mice, they found tumors continued to slow down.

BHB delays gut-cell growth by acting a surface receptor known as Hcar2. Receptor activation then triggers the expression of a growth-slowing gene called HopX. Other experiments showed that colorectal tumor cells that don’t express the Hopx gene are less likely to be affected by BHB treatment.

Currently, the team is gearing up to launch a BHB dietary supplement study in people with colorectal cancer.

The study is published in the journal Nature.

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