This Popular Supplement May Help Inhibit Colorectal Cancer Development

The results of the current study suggest that magnesium also boosts vitamin D production in the gut, where it acts locally rather than entering the bloodstream. Credit: Shutterstock

New clinical evidence indicates that a widely used supplement may alter gut microbes involved in vitamin D biology and colorectal cancer processes.

Researchers at Vanderbilt University Medical Center have shown in a precision-focused clinical trial that taking a magnesium supplement can increase certain gut bacteria in people. These bacteria are known to produce vitamin D and to play a role in limiting the development of colorectal cancer.

The effect was seen mainly in women. The researchers suggest this difference may be linked to estrogen, which can influence how magnesium moves from the bloodstream into cells.

Genetics determine who benefits most

To understand who benefits most, the team examined gut microbiome data and colonoscopy findings from participants grouped according to their TRPM7 genotype. This gene is important for controlling how the body absorbs magnesium and calcium.

In earlier work from the same randomized trial, the investigators found that magnesium boosts vitamin D production and raises vitamin D levels in the blood. The new results indicate that magnesium also promotes vitamin D production directly within the gut. This locally produced vitamin D does not enter the bloodstream and instead acts where it is made.

These results from the Personalized Prevention of Colorectal Cancer Trial were recently published in The American Journal of Clinical Nutrition.

Gut microbes link magnesium to cancer risk

“Our previous study showed magnesium supplementation increased blood levels of vitamin D when vitamin D levels were low,” said Qi Dai, MD, PhD, professor of Medicine. “The current study reveals that magnesium supplementation also increases the gut microbes, which have been shown to synthesize vitamin D in the gut without sunlight and locally inhibit colorectal cancer development.”

Qi Dai, MD, PhD. Credit: Vanderbilt University

The participants were divided into two groups: one that received the magnesium supplement and another that received a placebo. Their gut microbiome was analyzed from stools, rectal swabs, and rectal tissues. Among participants with adequate TRPM7 function, the magnesium supplement increased Carnobacterium maltaromaticum and Faecalibacterium prausnitzii, which were previously found to work synergistically to increase vitamin D and decrease colorectal carcinogenesis.

Among those with inadequate TRPM7 function, the magnesium supplement reduced the abundance of F. prausnitzii in rectal mucosa.

From microbiome shifts to prevention strategies

Among 236 participants who all had a history of colorectal polyps, 124 underwent colonoscopies after completing the trial with a 3.5-year median follow-up time. A higher abundance of F. prausnitzii in rectal mucosa was associated with an almost threefold increase in developing additional polyps.

The findings suggest that magnesium supplementation treatment may decrease colorectal cancer risk in individuals with inadequate TRPM7 function. All together, these findings provide new insights into the interplays between nutrition and gut microbiome contributing to colorectal carcinogenesis and establish the foundation for a precision-based strategy for prevention of colorectal cancer in high-risk populations.

Reference: “Magnesium treatment increases gut microbiome synthesizing vitamin D and inhibiting colorectal cancer: results from a double-blind precision-based randomized placebo-controlled trial” by Elizabeth Sun, Xiangzhu Zhu, Reid M. Ness, M. Andrea Azcarate-Peril, Martha J. Shrubsole, and Qi Dai, November 2025, The American Journal of Clinical Nutrition.

DOI: 10.1016/j.ajcnut.2025.09.011

The researchers received support from the National Cancer Institute (R01 DK110166, R01 CA149633 and R03 CA 189455) and the Vanderbilt-Ingram Cancer Center Endowment Fund. Dai and Martha Shrubsole, PhD, Ingram Professor of Cancer Research and research professor of Medicine, are principal investigators of the grant that funded the microbiome research from the National Institute of Diabetes and Digestive and Kidney Diseases (DK110116).

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