Magnesium status and supplementation influence vitamin D status and metabolism: results from a randomized trial

Dai Q, Zhu X, Manson JE, Song Y, Li X, Franke AA, Costello RB, Rosanoff A, Nian H, Fan L, Murff H, Ness RM, Seidner DL, Yu C, Shrubsole MJ (2018) Am J Clin Nutr. 2018 Dec;108(6): 1249-1258. doi: 10.1093/ajcn/nqy274.

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Abstract:

BACKGROUND:

Previous in vitro and in vivo studies indicate that enzymes that synthesize and metabolize vitamin D are magnesium-dependent.

Recent observational studies found that magnesium intake significantly interacted with vitamin D in relation to vitamin D status and risk of mortality.

According to NHANES, 79% of US adults do not meet their Recommended Dietary Allowance of magnesium.

OBJECTIVES:

The aim of this study was to test the hypothesis that magnesium supplementation differentially affects vitamin D metabolismdependent on baseline 25-hydroxyvitamin D [25(OH)D] concentration.

METHODS:

The study included 180 participants aged 40-85 y and is a National Cancer Institute independently funded ancillary study, nested within the Personalized Prevention of Colorectal Cancer Trial (PPCCT), which enrolled 250 participants.

The PPCCT is a double-blind 2 × 2 factorial randomized controlled trial conducted in the Vanderbilt University Medical Center. Doses for both magnesium and placebo were customized based on baseline dietary intakes.

Subjects were randomly assigned to treatments using a permuted-block randomization algorithm. 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.

RESULTS:

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

Magnesium supplementation increased the 25(OH)D3 concentration when baseline 25(OH)D concentrations were close to 30 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 30 ng/mL. On the other hand, magnesiumtreatment increased 25(OH)D2 as baseline 25(OH)D increased.

CONCLUSION:

Our findings suggest that optimal magnesium status may be important for optimizing 25(OH)D status.

FAB RESEARCH COMMENT:

This rigorously conducted clinical trial found that magnesium intake and status influences the effectiveness (or otherwise) of supplementation with Vitamin D - showing the critical importance of magnesium in regulating Vitamin D levels within the body.

Intakes of magnesium are seriously sub-optimal in modern, western-type diets. As these researchers noted, population studies indicate that almost 4 in every 5 adults in the US currently fail to get enough magnesium from their diets.

Vitamin D deficiencies are similarly widespread - and better known than magnesium deficiencies - so many people are encouraged, or choose to take supplements.

However, findings from this controlled trial showed clearly that:

Vitamin D supplementation is ineffective if magnesium levels are insufficient.

These findings are very important, as

1) They help to explain why many clinical trials of Vitamin D may have failed to show the expected benefits.

When testing the effects of individual nutrients as dietary supplements, the synergy between diifferent nutrients needs to be appreciated; and the nutrient status of individuals for other nutrients known to be important co-factors needs to be taken into account in the study design and analysis - as was done in this trial.

2) They highlight the potential risks of Vitamin D supplementation if magnesium is also lacking

Nutrient interactions also have very important clinical implications - and for individuals who lack sufficient magnesium, supplementation with Vitamin D alone is not just less likely to be effective, but could also increase risks for negative side effects such as vascular calcification, as recently highlighted by the American Osteopathic Association: See: