Keto Molecule May Help Prevent and Treat Colorectal Cancer

When mice in the lab are on low-carb diets, like the "keto" diet many people follow, the liver makes a ketone that slows the growth of colorectal cancer.

Grantee: Maayan Levy, PhD 
Institution: UPenn Perelman School of Medicine, Philadelphia, PA
Area of Focus: Cancer Detection and Progression
Grant Term: 01/01/2022-12/31/2025

“We studied 6 groups of mice on different diets and found that the liver makes a specific ketone molecule in response to a ketogenic diet. That molecule greatly slows the growth of colorectal cancers.
“What’s more is that we discovered the same protection may be accomplished by taking a supplement of that ketone. Clinical trials are being set up to study the use of that supplement in people with colorectal cancer.”

The Challenge:  Research has shown that certain types of diets are known to increase the risk of developing colorectal cancer.  These include diets high in red meat and processed meats (like deli meat, hot dogs, bacon) as well as diets high in sugar or alcohol.

But little is known about diets that may help prevent, or even treat, colorectal cancer.

Some studies in mice on a fasting diet or with a low number of calories have shown promising effects on slowing progression of colorectal tumors. But these eating styles may be hard to use for people with colorectal cancer, especially for patients who are losing weight and muscle from the disease.

The Research: American Cancer Society (ACS) research scholar, Maayan Levy, PhD, is looking for diets that can slow or stop tumor growth in the intestines. She recently published study results in Nature about how mice on ketogenic diets have a strong resistance to colorectal cancer.

To find out how different diets affect the progression of colorectal cancer in mice, Levy’s lab team collaborated with the lab of Christoph Thaiss, PhD. They fed 6 groups of mice different diets that had constant amounts of protein and varying fat-to-carbohydrate ratios.

Then they used a standard chemical technique that causes colorectal tumors to develop. They observed that the mice who were fed 1 of the 2 most ketogenic diets had a decrease in the number and size of tumors. One of those diets had more fat than carbohydrates by using lard (pig fat) and the other used Crisco, which is mostly soybean oil.

They also found that mice being fed a ketogenic diet with 90% fat from plant or animal sources lived longer with colorectal cancer.

Mice on all the other diets developed colorectal tumors. And when the lab teams put those mice on a ketogenic diet, the growth of their colorectal tumors drastically slowed. Stopping the diet caused tumors to regrow.

The scientists traced the effect to the ketone molecule called beta-hydroxybutyrate (BHB). The liver makes BHB as part of starvation response, which was triggered by the low-carb diets, and BHB strongly suppresses the growth of tumors in the intestine in lab experiments.

They found that biopsies from people with colorectal cancer provided similar evidence.

Why Does It Matter? Together, Levy’s and Thaiss’s mouse study results suggest that a ketogenic diet can strongly slow or stop the development of tumors in the colon or rectum as well as be used to treat existing colorectal cancers. 

Her studies found a new and unexpected role of ketones in the body and added a new type of diet to help prevent colorectal cancer. Some of her findings also raise the possibility that the best outcomes for prevention and treatment may be achieved by adjusting the dietary nutrient composition to a patient’s tumor type according to the production of certain enzymes.

What’s more is that Levy’s work demonstrated that the tumor-slowing effect of a ketogenic diet can be reproduced with a dietary supplement. That’s great news since we all know that staying on a specific diet is hard to keep up and may cause side effects.

BHB is widely available as a dietary supplement marketed for weight loss. Clinical trials are being set up to test ketone supplementation in people with colorectal cancer. Trials will also be run to see the ketone’s potential anticancer effects in other parts of the body.

In the future, the authors say, they can envision a new pillar added to the current cancer care options of surgery, chemotherapy, or immunotherapy they’ve dubbed metabotherapy, which is treatment using metabolic supplements.