A molecule produced when on low-carbohydrate ketogenic diets suppresses the growth of colorectal tumors in the lab. The corresponding study was published in Nature.
Colorectal cancer kills around 50,000 people in the US per year, making it the third leading cause of cancer mortality in the country. Lifestyle factors including alcohol use, obesity, red meat consumption, and low-fiber yet high sugar diets are linked to a greater risk of the condition.
In the present study, researchers sought to investigate the effects of different diets on colorectal tumor growth. To do so, they put six groups of mice on diets with varying fat-to-carb ratios and induced colorectal tumors via a standard chemical technique.
They found that the diets with the least amount of carbs at 90% fat-carb ratios- whether using pig lard or soybean oil- were best able to prevent tumor growth. Their protective effect was notable even after colorectal tumors had started growing. On the other hand, animals on other diets, including low fat and high carbs, developed tumors.
The researchers confirmed from further experiments that tumor suppression from low-carb diets was linked to slower production of new epithelial cells lining the colon. This, they found, was in turn linked to increased levels of beta-hydroxybutyrate (BHB), a molecule produced by the liver as part of a ‘starvation response’, and that is typically triggered by keto diets.
In keto diets, BHB often works as an alternative fuel source for key organs. However, in this study, the researchers found that it is also a potent growth-slowing signal.
In further experiments, the researchers were able to replicate the antitumor effects of keto diets on mice by giving them BHB supplements either via water or infusion. In doing so, they found that BHB slows down the growth of gut-lining cells by activating a surface receptor on colorectal tumors called Hcar2. This then activates the growth-slowing gene, Hopx.
The researchers note that not all colorectal tumor cells express Hcar2 and Hopx, meaning that not all colorectal tumors will respond to this treatment. This, they say, means that BHB supplementation could at least offer insight into alternative treatment methods.
The researchers say that while these findings are encouraging, further research is needed before they may inform treatment options.