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Randomized Controlled Trial
. 2018 Dec 1;108(6):1249-1258.
doi: 10.1093/ajcn/nqy274.

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

Qi Dai  1 , Xiangzhu Zhu  1 , JoAnn E Manson  2   3 , Yiqing Song  4 , Xingnan Li  5 , Adrian A Franke  5 , Rebecca B Costello  6 , Andrea Rosanoff  6 , Hui Nian  7 , Lei Fan  8 , Harvey Murff  1 , Reid M Ness  9 , Douglas L Seidner  9 , Chang Yu  7 , Martha J Shrubsole  1
Affiliations
Randomized Controlled Trial

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

Qi Dai et al. Am J Clin Nutr. .

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 metabolism dependent 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, magnesium treatment 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. This trial was registered at clinicaltrials.gov as NCT03265483.

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Figures

FIGURE 1
FIGURE 1
Magnesium and vitamin D metabolism. Dark gray indicates deactivating enzymes, and light gray indicates activating enzymes. CYP, cytochrome P450; 25(OH)D, 25-hydroxyvitamin D; 1,25(OH)2D, 1,25-dihydroxycholecalciferol; 24,25(OH)2D, 24,25-dihydroxyvitamin D; 1,24,25(OH)3D, 1,24,25-trihydroxyvitamin D.
FIGURE 2
FIGURE 2
Flow diagram of trial recruitment and retention. AA, GA, GG, TRPM7 genotypes. TRPM7, transient receptor potential cation channel, subfamily M, member 7.
FIGURE 3
FIGURE 3
Post-treatment plasma vitamin D metabolite concentrations calculated by a linear model. Concentrations were adjusted for age, sex, baseline BMI, eGFR, total 25(OH)D, and blood collection season among 87 participants randomly assigned to the magnesium treatment arm and 93 participants randomly assigned to the placebo arm. The solid curves represent point estimates and the gray regions represent 95% CIs. (A) Adjusted to 25(OH)D3 = 31.37 ng/mL, age = 60 y, sex = female, BMI (kg/m2) = 29.1, baseline GFR = 78 · min−1 · 1.73 m–2, blood sample collection season = summer. (B) Adjusted to 25(OH)D3 = 3.095 ng/mL, age = 60 y, sex = female, BMI = 29.1, baseline GFR = 78 · min–1 · 1.73 m–2, blood sample collection season = summer. (C) Adjusted to 25(OH)D2 = 0.485 ng/mL, age = 60 y, sex = female, BMI = 29.1, baseline GFR = 78 · min–1 · 1.73 m–2, blood sample collection season = summer. eGFR, estimated glomerular filtration rate; GFR, glomerular filtration rate; Mag, magnesium; 25(OH)D, 25-hydroxyvitamin D; 25(OH)D2, 25-hydroxyvitamin D2; 25(OH)D3, 25-hydroxyvitamin D3; 24,25(OH)2D3, 24,25-dihydroxyvitamin D3.
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