Scientists have discovered that a molecule produced through following a low-carb ketogenic diet may help suppress the development of colorectal cancer.
Researchers from the Perelman School of Medicine at the University of Pennsylvania identified a molecule produced in the liver in response to a low-carb ketogenic diet – called beta-hydroxybutyrate (BHB) – that has a robust effect on preventing colorectal cancer tumour growth. The findings may help to develop future preventative treatments for the disease.
The study, published in nature, discovered that mice consuming high-fat, low-carb ketogenic diets had significant resistance to colorectal tumour development and growth. This effect is traced back to BHB, a small organic molecule produced in response to these types of diets or starvation.
Maayan Levy, PhD, an assistant professor of Microbiology at Penn Medicine, commented: “Our findings suggest that this natural molecule, BHB, could someday become a standard part of colorectal cancer care and prevention.”
Can diet influence colorectal cancer risk?
Colorectal cancer is a growing problem globally and is one of the most common forms of cancer, leading to the deaths of over 50,000 people in the US alone each year, making it the nation’s third-highest cause of cancer mortality. Previous research has suggested that alcohol use, obesity, red meat, and low-fibre and high-sugar diets exacerbate colorectal cancer risk.
In their mice study, the team set out to uncover if various types of diet can inhibit the development and growth of colorectal cancer. To achieve this, they put six groups of mice on diets with a range of fat-to-carb ratios and then employed a standard chemical technique that causes colorectal cancer tumours.
The effects of a low-carb ketogenic diet
The results showed that the two most ketogenic diets, which had 90% fat-to-carb ratios, prevented colorectal cancer development in most of the mice on the diet. One of these diets contained lard (pig fat) and the other Crisco (mainly soybean oil).
In contrast, the mice on the other diets, including low-fat, high-carb diets, developed tumours. Moreover, even when the mice started a low-carb ketogenic diet after colorectal cancer tumours had already started growing, the diets elicited a “treatment effect” that considerably mitigated tumour growth and proliferation.
Further analysis identified that this tumour suppression is associated with a slower production of new epithelial cells lining the colon, which they found was attributed to the BHB produced by the low-carb ketogenic diet.
Designing future colorectal cancer treatments
BHB is utilised by the body as an alternative fuel source for vital organs in low-carb conditions. In the study, the researchers demonstrated that BHB is not only a fuel source but a strong growth-slowing signal, at least for gut-lining cells.
By administering BHB to the mice in water or through an infusion that mimicked the liver’s natural secretion of the molecule, they could reproduce the tumour-suppressing effects of a low-carb ketogenic diet. They discovered that BHB achieves this by activating a surface receptor called Hcar2, which stimulates the expression of a growth-slowing gene called Hopx.
Human gut-lining cell experiments have demonstrated that BHB has the same growth-slowing effects on these cells through the human versions of Hcar2 and Hopx. However, colorectal cancer cells that lacked these two genes did not respond to BHB treatment, meaning their presence may predict treatment efficacy.
Christoph Thaiss, PhD, an assistant professor of Microbiology, concluded: “Clinical trials of BHB supplementation are needed before any recommendation can be made about its use in prevention or treatment.”
The team is now aiming to perform a clinical trial of BHB in colorectal cancer patients and is looking to examine the anti-cancer effects of the molecule on other parts of the body.
