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 Sept. 12 inThe 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, 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.”

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 maltaromaticumand Faecalibacterium prausnitzii, which were previously found to work synergistically to increase vitamin D and decrease colorectal carcinogenesis. Among those with inadequate TRPM7function, the magnesium supplement reduced the abundance of F. prausnitziiin 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 TRPM7function. 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.

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).

Other major Vanderbilt authors on the study include Elizabeth Sun, Xiangzhu Zhu, MD, MPH, Reid Ness, MD, MPH, Harvey Murff, MD, MPH, and Lei Fan, MD, PhD. The first author, Elizabeth Sun, a medical student at Vanderbilt University School of Medicine, was elected for an Early Investigator Travel Award, a young investigator lightning talk, and an in-person poster presentation at the Precision Nutrition Forum and PREDIMED Omics Symposium 2025 held by Harvard University.

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Plant-based diets have become popular for their health and environmental benefits. 

However, these benefits may vary based on the quality of the plant foods and other foods that make up the diet. A recent study at VUMC analyzed the association of plant-based diet patterns with mortality in over 77,000 mostly Black and low-income participants in the Southern Community Cohort Study, which started in 2002.  

Dietary intakes were assessed using a validated, 89-item food frequency questionnaire. The investigators generated three measures to assess the association of diet and risk of premature death: an overall plant-based diet index (PDI) that included both healthy plant foods (such as whole grains, fruits and vegetables) and unhealthy plant foods (such as fruit juices, refined grains and potatoes); a healthy plant-based diet index (hPDI); and an unhealthy plant-based diet index (uPDI).  

The study follow-up was through 2022 with a median duration of almost 17 years. The investigators identified over 26,000 deaths during the duration of the study. The highest PDI and hPDI scores were associated with reduced mortality; while the highest uPDI scores were associated with elevated mortality. 

The findings were reported in the The American Journal of Clinical Nutrition, a journal of the American Society for Nutrition. They show a strong association between high quality plant-based diets and reduced mortality rate among low-income populations, suggesting that efforts to promote diets high in healthy plant foods and low in animal foods could improve health outcomes. 

Wei Zheng, MD, PhD, MPH, the Anne Potter Wilson Professor of Medicine and director of the Vanderbilt Epidemiology Center, is the corresponding author of the study. Fangcheng Yuan, a graduate student in the PhD Program in Epidemiology, is the first author. 

This work was supported by the National Cancer Institute, part of the National Institutes of Health (grant U01CA202979).

Guillermo Sanchez, PhD, is a staff scientist in the lab of Nick Zachos, PhD, associate professor of Surgery and Cell and Developmental Biology at Vanderbilt University.

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