Adding a supplement made from pre-ketones, which are part of a high-fat, low-carb ketogenic diet, to a specific cancer treatment in a lab setting was found to be very successful in treating prostate cancer, according to researchers at the University of Notre Dame. Recently, the study by Xin Lu, from the John M. and Mary Jo Boler Collegiate, was published online in the journal “Cancer Research”.An issue that oncologists have been facing is that prostate cancer is not responsive to immune checkpoint blockade (ICB) therapy, a type of immunotherapy. This therapy works by blocking certain proteins that prevent T cells from killing the cancer cells. As an Associate Professor in the Department of Biological Sciences, Lu, along with collaborators, recognized the significance of immunotherapy in treating other cancers but noted its limited effectiveness in prostate cancer, despite it being the most common cancer in American men.rseghian Center for Rare and Neglected Diseases. The main researcher, Sean Murphy, suggested that adding a dietary supplement could potentially overcome this resistance. Murphy, who graduated in 2024 and was a doctoral student in Lu’s lab, had been following a keto diet himself. Understanding that cancer cells thrive on sugar, he believed that cutting off carbohydrates – a crucial aspect of the keto diet – could potentially halt cancer growth in mouse models. He then grouped the models into different categories for testing: immunotherapy alone, ketogenic diet alone, pre-ketone supplement alone, ketogenic diet with immunotherapy, supplement with immunotherapy, and a combination of all three.The tumors showed minimal response to immunotherapy alone, which is typical for prostate cancer patients. However, when combined with a ketogenic diet or pre-ketone supplement, the immunotherapy was more effective in reducing cancer and prolonging the lives of the mouse models.
Of the two combinations, the supplement with the immunotherapy yielded the best results.
Lead researcher Lu commented, “The combination was highly effective, leading to tumor sensitivity to immunotherapy. Twenty-three percent of the mice were cured, and in the remaining cases, the tumors shrank significantly.”
The findings suggest that combining immunotherapy with a ketogenic diet or pre-ketone supplement could be a promising treatment approach.
There is a possibility that a supplement containing ketones, which are produced in the body when people follow a keto diet, could potentially prevent prostate cancer cells from becoming resistant to immunotherapy. This could lead to future clinical research to investigate how ketogenic diets or keto supplements might improve cancer treatment.
Although keto diets involve minimal carbohydrates, the success of this study is not solely due to the lack of carbohydrates, emphasized Murphy and Lu. It is actually about the presence of ketone bodies, which are produced by the liver and used as an energy source when glucose is not available. The ketone body, a substance produced by the liver and used as an energy source when glucose is not available.The supplement works by disrupting the cancer cells’ cycle, allowing T cells to effectively destroy them. This discovery is also exciting on a molecular level, according to Lu. Dietary studies can often be affected by the potential issue of causation, meaning it’s unclear whether the results are due to the diet itself or other changes made because of the diet. However, Lu and his collaborators were able to confirm their results using single-cell RNA sequencing, which examines the gene expression of individual cells within the tumor. They found that the combination of the supplement and immunotherapy reprogrammed the entire immune profile of the tumors and attracted many T cells into the tumors.Lu stated that the therapy successfully killed prostate cancer cells and also decreased the number of a specific type of immune cell known as neutrophils. Neutrophils can have a distorted impact once in the tumor microenvironment, leading to the inhibition of T cell activities and promoting tumor progression. This dysregulation of neutrophils is also linked to various other diseases. Murphy also highlighted the potential for investigating the effects of the keto diet and ketone supplements on conditions such as inflammatory bowel disease and arthritis, as the main ketone body depletes neutrophils.
The researchers are excited about the progress in understanding the mechanism behind why the ketogenic diet works, which is supported by genetic models and observations in the tumors themselves.
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