Cancer is ferocious. Despite the devotion of umpteen resources to the task of stopping it – it still kills millions of people each year. However, while research is yet to find a cure or means of prevention, green shoots continue to emerge. Research carried out by researchers at the Perelman School of Medicine at the University of Pennsylvania suggests low-carb “ketogenic” diets can halt the growth of bowel cancer, also known as colorectal cancer.
The researchers found a molecule produced in the liver in response to low-carb “ketogenic” diets has a powerful effect in suppressing colorectal tumour growth and may be useful as a preventive and treatment of such cancers.
In the study, published in Nature, researchers initially found that mice on low-carb, high-fat ketogenic diets have a striking resistance to colorectal tumour development and growth.
The scientists then traced this effect to beta-hydroxybutyrate (BHB), a small organic molecule produced in the liver in response to keto diets or starvation.
“Our findings suggest that this natural molecule, BHB, could someday become a standard part of colorectal cancer care and prevention,” said study co-senior author Maayan Levy, PhD, an assistant professor of Microbiology at Penn Medicine, whose laboratory collaborated with the lab of Christoph Thaiss, PhD, also an assistant professor of Microbiology.
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In the study, Professor Levy and Professor Thaiss and their teams set out to determine, with experiments in mice, whether different types of diet could inhibit colorectal cancer development and growth.
They put six groups of mice on diets that had varying fat-to-carb ratios, and then used a standard chemical technique that normally induces colorectal tumours.
They found that the two most ketogenic diets, with 90 percent fat-to-carb ratios – one used lard (pig fat), the other Crisco (mostly soybean oil) – prevented colorectal tumour development in most of the animals on those diets.
By contrast, all the animals on the other diets, including low-fat, high-carb diets, developed tumours.
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Even when the researchers started the mice on these diets after colorectal tumours had started growing, the diets showed a “treatment effect” by markedly slowing further tumour growth and proliferation.
In subsequent experiments, the scientists determined that this tumour suppression is associated with a slower production, by stem cells, of new epithelial cells lining the colon.
Ultimately, they traced this gut-cell growth slowdown to BHB – normally produced by the liver as part of a “starvation response” and triggered in this case by the low-carb keto diets.
BHB is known to work as an alternative fuel source for key organs in low-carb conditions.
However, the researchers showed that it is not only a fuel source but also a potent growth-slowing signal, at least for gut-lining cells.
They were able to reproduce the tumour-suppressing effects of the keto diets simply by giving the mice BHB, either in their water or via an infusion mimicking the liver’s natural secretion of the molecule.
The team showed that BHB exerts its gut-cell growth-slowing effect by activating a surface receptor called Hcar2.
This in turn stimulates the expression of a growth-slowing gene, Hopx.
Experiments with gut-lining cells from humans provided evidence that BHB has the same growth-slowing effect on these cells, via the human versions of Hcar2 and Hopx.
However, “clinical trials of BHB supplementation are needed before any recommendation can be made about its use in prevention or treatment”, Professor Thaiss said.
What is in the keto diet?
The keto diet is very high in fat, enough protein for growth and very low in carbohydrate.
It excludes the following carb-rich culprits:
- Foods high in sugar including sweets, some fizzy drinks, puddings, chocolate, cake
- Cereals and grains.
It includes the following in small amounts:
- Dairy products (which contain a natural sugar called lactose)
- Vegetables – particularly starchy vegetables such as potatoes, butternut squash, cassava, pumpkin, yam, parsnips; and pulses including peas, beans and lentils.