Keto molecule against colon cancer – beta-hydroxybutyrate inhibits tumor growth in mice and human cells

New approach to colon cancer: A molecule produced by the high-fat, low-carb keto diet prevents colon cancer and stops existing tumors from growing, tests in mice and human cell cultures show. Accordingly, oral administration of the ketogenic molecule beta-hydroxybutyrate inhibits the growth of cancer cells and tumors – even with a normal diet. This could open up new possibilities for colorectal cancer therapy and prevention, researchers report in “Nature”.

Fat yes, carbohydrates no: The ketogenic diet is an extreme form of high-fat low-carb nutrition, in which fats make up up to 90 percent of the entire diet. In the long run this is not very healthy, but it can cause health-promoting changes in the metabolism: As with Fasten the body mainly burns fat and this leads to the formation of so-called ketone bodies in the liver – molecules such as acetoacetate and beta-hydroxybutyrate (BHB).

Fatty foods
A ketogenic diet is high in fat but low in carbohydrates. © fcafotodigital/ Getty images

Studies suggest that the keto diet and the ketone bodies it produces strengthen the immune systemn, help with weight loss and den lower blood sugar levels be able. Anti-inflammatory effects are also attributed to the ketogenic molecules.

Keto diet inhibits colon cancer growth

Now, a study has provided evidence that the ketogenic molecule beta-hydroxybutyrate may even be effective against cancer. Oxana Dmitrieva-Posocco from the University of Pennsylvania in Philadelphia and her colleagues first investigated whether a ketogenic diet can influence the formation and growth of colon cancer tumors in mice. The animals received various feed mixtures for this, including a ketogenic feed with a fat content of 70 and 90 percent.

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In fact, there were clear effects: “We observed that the size and number of tumors decreased with increasing fat content in the feed,” reports the team. In the mice, the keto diet inhibited both the formation of new colon cancerous ulcers and the growth of existing tumors. “This suggests that a ketogenic diet is effective both as a preventative and as a treatment for colorectal cancer,” the researchers say.

Ketogenic molecule has anti-cancer effects even without a diet

But what is behind it? Further analysis revealed that one molecule in particular is responsible for the anti-cancer effect of the ketogenic diet: the ketone body beta-hydroxybutyrate. When test mice were given this molecule, colon cancer growth was inhibited even with normal food. “The treatment with BHB alone was sufficient to reduce the tumor burden in the colon,” report Dmitrieva-Posocco and her colleagues.

Subsequent investigations on intestinal organoids and cell cultures, among other things, showed that the ketogenic beta-hydroxybutyrate activates a gene that causes the cells in the intestinal wall to grow more slowly – and which also disrupts the growth of the degenerated cancer cells. Apparently those cells that have a specific receptor, Hcar2, on their surface react to the BHB in particular.

Also works on human cells

The crucial question, however, is whether this cancer inhibition also works in humans. To find out, Dmitrieva-Posocco and her team have already carried out initial experiments with human tumor organoids and colon cancer cell lines. The result: Colon cancer tumors in humans also seem to react to beta-hydroxybutyrate. However, not all colon cancer cell lines are susceptible to the effects of BHB, as the researchers report.

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Nevertheless, the scientists see the ketone body beta-hydroxybutyrate as a promising new approach to the prevention and treatment of colon cancer in humans. “The molecule could one day become a standard component of colorectal cancer therapy and prevention,” says senior author Maayan Levy of the University of Pennsylvania. It would be conceivable, for example, that beta-hydroxybutyrate be administered as a supplement to operations or chemotherapy.

Clinical study in planning

However, the researchers warn colorectal cancer patients not to follow a keto diet permanently or to take beta-hydroxybutyrate on their own. “Even if diet-based interventions appear attractive, chronic consumption of such a specific diet can produce systemic side effects,” they write. The tumor-inhibiting effect of beta-hydroxybutyrate, even with a normal diet, is all the more promising.

However, before the ketogenic molecule can be used for cancer therapy, there is still a lot of research and clinical trials to be done, as the team points out….

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