Researchers from Vanderbilt University Medical Center have demonstrated in a precision-based clinical trial that a magnesium supplement increases gut bacteria in humans that have been shown to synthesize vitamin D and inhibit colorectal cancer carcinogenesis.
However, the effect was observed primarily in females—an outcome that the researchers surmised may be attributable to the role that estrogen plays in shifting magnesium from circulation into cellular uptake.
Intestinal microbiome data and colonoscopy results were analyzed from participants who were randomized by whether they had the TRPM7 genotype, which plays a crucial role in regulating magnesium and calcium uptake.
Previously, the investigators showed in the same randomized trial that magnesium enhances the synthesis of vitamin D and increases the blood levels of vitamin D. The findings from the current study suggest that magnesium also increases the gut synthesis of vitamin D, which does not go to the blood and takes effect locally.
These results from the Personalized Prevention of Colorectal Cancer Trial were published in The American Journal of Clinical Nutrition.
“Our previous study showed magnesium supplementation increased blood levels of vitamin D when vitamin D levels were low,” said Qi Dai, MD, Ph.D., 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.”
The participants were divided into two arms, 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.
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. Altogether, 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.
More information:
Elizabeth Sun 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, The American Journal of Clinical Nutrition (2025). DOI: 10.1016/j.ajcnut.2025.09.011
The content is provided for information purposes only.