A recent clinical trial led by researchers at Vanderbilt University Medical Center indicates that magnesium supplements may enhance gut bacteria that help prevent the development of colorectal cancer. This effect appears to vary based on individuals’ genetic makeup and sex. Although the rise in colonoscopies has contributed to a decline in colorectal cancer rates, it remains the third most prevalent cancer globally and the second leading cause of cancer-related deaths.
The study, published on March 15, 2024, in the American Journal of Clinical Nutrition, highlights the relationship between magnesium intake and gut microbiota. According to Qi Dai, MD, PhD, a professor of medicine at VUMC and the study’s corresponding author, the findings build on previous research showing that magnesium supplementation can elevate blood levels of vitamin D, especially when those levels are low. “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,” Dai explained.
The clinical trial involved 240 participants with a history of colorectal polyps, a known risk factor for colorectal cancer. Participants were randomly assigned to receive either personalized magnesium supplements or a placebo over a 12-week period. The dose of magnesium glycinate was determined based on each participant’s calcium-to-magnesium intake ratio, typically around 2:1 in weight.
Researchers collected various biological samples, including stool, rectal swabs, rectal tissue, and blood, to examine the effects of supplementation on gut bacteria such as Carnobacterium maltaromaticum and Faecalibacterium prausnitzii. Previous studies have linked these bacteria to vitamin D synthesis and reduced cancer development in animal models. The team also explored how variations in the TRPM7 gene, crucial for magnesium regulation, might influence the outcomes.
Distinct genetic variations were scrutinized, specifically a “missense variant” in the TRPM7 gene. This variant alters an amino acid in the protein, potentially affecting magnesium regulation in the body. The trial found that participants without the TRPM7 missense variant exhibited a positive response to magnesium supplementation, which increased the abundance of C. maltaromaticum and, to a lesser degree, F. prausnitzii. Notably, this increase was more pronounced in women, suggesting that estrogen may play a role in this response.
Conversely, individuals with the TRPM7 missense variant sometimes experienced a reduction in these beneficial bacteria. Interestingly, the increased abundance of gut bacteria did not correlate directly with elevated vitamin D levels, indicating that magnesium may influence vitamin D metabolism through different pathways.
Follow-up colonoscopies revealed that participants with the highest levels of F. prausnitzii had a nearly 2.8-fold increased risk of developing new polyps compared to those with lower levels. In contrast, higher levels of C. maltaromaticum were linked to approximately an 85% lower risk of developing serrated polyps, which, while less common, are associated with a heightened risk of colorectal cancer. This finding, though notable, was only marginally significant and should be interpreted cautiously.
The study does have limitations. The increase in F. prausnitzii became statistically insignificant after adjusting for multiple comparisons. Additionally, the specific strains of bacteria responsible for the observed effects were not identified, and changes in microbial composition were measured in relative abundance, which may not reflect absolute numbers. The trial’s participants were predominantly older, White, and from Tennessee, US, potentially limiting the generalizability of the findings. Moreover, the relatively short duration of the study raises questions about the long-term effects of magnesium supplementation.
Despite these limitations, the findings suggest that magnesium supplementation could play a significant role in colorectal cancer prevention, particularly among women and individuals without specific TRPM7 genetic variants. This opens the door for a potential “precision nutrition” approach, where genetic testing could identify individuals who would benefit most from magnesium supplementation. Further research is essential to establish clinical recommendations based on these promising insights.
