The Importance of Magnesium in Vitamin D Synthesis and Metabolism

The Inconsistent Effect of Vitamin D

Studies and randomized trials have arrived at inconsistent findings on the effect of vitamin D on bone fractures and chronic diseases like cancer or heart disease. However, large-scale randomized trials continue to test vitamin D supplementation with these diseases as primary outcomes. One notable finding is that there is a lot of variation in the blood levels of the enzyme 25-hydroxyvitamin D [25(OH)D], which is still unexplained.

The Effect of Magnesium on Vitamin D Treatment

Based on the results of the National Health and Nutrition Examination Survey, for those with magnesium-dependent vitamin-D-resistant rickets, a condition where people have reduced levels of 1,25-dihydroxyvitamin D and a poor response to parathyroid hormone, intramuscular infusions of 600,000 or less IU vitamin D alone did not lead to any improvements in biochemical measures of vitamin D deficiency. However, magnesium supplementation did substantially reverse the resistance to vitamin D treatment. Furthermore, magnesium intake significantly interacted with vitamin D and circulating 25(OH)D to possibly lower mortality risk due to CVD and colorectal cancer.

A study was conducted to test the hypothesis that magnesium supplementation affects vitamin D synthesis and metabolism biomarkers differently depending on one’s 25(OH)D concentration at baseline. This study was done as an auxiliary to the Personalized Prevention of Colorectal Cancer Trial (PPCCT) that looked into the relationship between magnesium supplementation and colorectal carcinogenesis.

The Study on Magnesium for Individuals with High Risk of Colorectal Cancer

The study included 180 participants with a high risk of colorectal cancer, randomly assigned into two groups — 87 received magnesium treatment, and 93 had the placebo of microcrystalline cellulose throughout the 12-week intervention period.

Based on their calcium-to-magnesium intake ratio at baseline in the PPCCT, each participant was assigned a customized dose of magnesium supplementation to achieve a calcium-to-magnesium intake ratio of approximately 2.3.

The participants were interviewed about the foods, beverages, and dietary supplements they consumed in the past 24 hours during the intervention period. These interviews were done four times, two during the first six weeks and the other two during the next six weeks.

Clinic visits were scheduled on weeks 1, 6, and 12 to get information on the participants’ medications and nutritional supplements and collect blood samples (after at least eight hours of fasting) and anthropometric measurements.

Changes in plasma 25-hydroxyvitamin D3 [25(OH)D3], 25-hydroxyvitamin D2 [25(OH)D2], 1,25-dihydroxyvitamin D3, 1,25-dihydroxyvitamin D2, and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] were measured by liquid chromatography-mass spectrometry to evaluate the effects of magnesium supplementation on these vitamin D metabolites.

The Results

The interactions between magnesium treatment and plasma concentrations of 25(OH)D3, 25(OH)D2, and 24,25(OH)2D3 were significantly different based on the baseline concentrations of 25(OH)D and remained statistically significant after Bonferroni corrections.

Magnesium supplementation increased the 25(OH)D3 concentration when baseline 25(OH)D concentrations were close to 30 nanograms per milliliter (ng/mL), but decreased it when baseline 25(OH)D was higher (from ∼30 to 50 ng/mL). Magnesium treatment significantly affected 24,25(OH)2D3 concentration when baseline 25(OH)D concentration was 50 ng/mL but not at 30 ng/mL. On the other hand, magnesium treatment increased 25(OH)D2 as baseline 25(OH)D increased.

The Conclusion

Our findings suggest that magnesium status may be essential to optimizing vitamin D status, particularly vitamin D2. Magnesium supplements may enhance vitamin D3 depending on vitamin D concentrations at baseline.

Reference

Magnesium Status and Supplementation Influence Vitamin D Status and Metabolism: Results from a Randomized Trial