Magnesium Can Inhibit Colorectal Cancer by Increasing Vitamin D-Synthesizing Bacteria

A new study from Vanderbilt University Medical Center has found that magnesium supplementation alters the composition of gut microbiota in ways that may influence colorectal cancer risk, particularly in individuals with specific genetic profiles.

The findings, published in The American Journal of Clinical Nutrition, are part of the Personalized Prevention of Colorectal Cancer Trial. Scientists hope that the Trial will help identify people at a high risk of colorectal adenoma and to develop personalized strategies to prevent occurrence of colorectal adenoma, and thus, colorectal cancer through dietary change or nutritional fortification.

Focus on gut-localized vitamin D synthesis

Earlier research by the same team reported that magnesium enhances the production of vitamin D, raising circulating levels in individuals with insufficient vitamin D status.

The new data suggest that magnesium also increases microbial production of vitamin D within the gut. This form of vitamin D does not enter the bloodstream but may act locally within the intestinal environment.

“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.”

Researchers studied 236 individuals with a history of colorectal polyps. Participants were randomly assigned to receive either a magnesium supplement or a placebo. Stool samples, rectal swabs and rectal tissue biopsies were collected and analyzed to characterize microbial changes.

Microbial shifts depend on TRPM7 genotype

Key differences were observed based on the participants’ TRPM7 genotype, a variant of the gene that influences magnesium and calcium regulation. Among those with adequate TRPM7 function, magnesium supplementation led to an increased presence of two bacterial species: Carnobacterium maltaromaticum and Faecalibacterium prausnitzii. These species have previously been associated with vitamin D biosynthesis in the gut and a reduction in colorectal cancer risk.

Conversely, among individuals with impaired TRPM7 function, magnesium reduced the abundance of F. prausnitzii in rectal mucosa. The researchers observed a complex relationship between microbial shifts and polyp development during the trial’s follow-up period.

Sex-specific outcomes

The effect of magnesium supplementation was more pronounced in females. The authors propose that estrogen’s known role in regulating magnesium distribution at the cellular level may contribute to this difference, although further investigation is needed.

A subset of 124 participants underwent colonoscopies with a median follow-up time of 3.5 years. In these participants, it was found that the presence of F. prausnitzii in the rectal mucosa was associated with a nearly threefold increase in the likelihood of developing new colorectal polyps, highlighting the species’ complex role in carcinogenesis depending on host factors such as genotype and sex.

Implications for targeted prevention

Collectively, the findings suggest that magnesium supplementation treatment may decrease colorectal cancer risk in individuals with inadequate TRPM7 function.

The findings also 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: Sun E, Zhu X, Ness R, et al. Magnesium treatment increases gut microbiome synthesizing vitamin D and inhibiting colorectal cancer: Results from a double-blind precision-based randomized placebo-controlled trial. Am J Clin Nutr. 2025. doi: 10.1016/j.ajcnut.2025.09.011

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