Circulating Ionized Magnesium as a Measure of Supplement Bioavailability: Results from a Pilot Study for Randomized Clinical Trial

Abstract

Oral supplementation may improve the dietary intake of magnesium, which has been identified as a shortfall nutrient. We conducted a pilot study to evaluate appropriate methods for assessing responses to the ingestion of oral magnesium supplements, including ionized magnesium in whole blood (iMg2+) concentration, serum total magnesium concentration, and total urinary magnesium content. In a single-blinded crossover study, 17 healthy adults were randomly assigned to consume 300 mg of magnesium from MgCl2 (ReMag®, a picosized magnesium formulation) or placebo, while having a low-magnesium breakfast. Blood and urine samples were obtained for the measurement of iMg2+, serum total magnesium, and total urine magnesium, during 24 h following the magnesium supplement or placebo dosing. Bioavailability was assessed using area-under-the-curve (AUC) as well as maximum (Cmax) and time-to-maximum (Tmax) concentration. Depending on normality, data were expressed as the mean ± standard deviation or median (range), and differences between responses to MgCl2 or placebo were measured using the paired t-test or Wilcoxon signed-rank test. Following MgCl2 administration versus placebo administration, we observed significantly greater increases in iMg2+ concentrations (AUC = 1.51 ± 0.96 vs. 0.84 ± 0.82 mg/dL·24h; Cmax = 1.38 ± 0.13 vs. 1.32 ± 0.07 mg/dL, respectively; both p < 0.05) but not in serum total magnesium (AUC = 27.00 [0, 172.93] vs. 14.55 [0, 91.18] mg/dL·24h; Cmax = 2.38 [1.97, 4.01] vs. 2.24 [1.98, 4.31] mg/dL) or in urinary magnesium (AUC = 201.74 ± 161.63 vs. 139.30 ± 92.84 mg·24h; Cmax = 26.12 [12.91, 88.63] vs. 24.38 [13.51, 81.51] mg/dL; p > 0.05). Whole blood iMg2+ may be a more sensitive measure of acute oral intake of magnesium compared to serum and urinary magnesium and may be preferred for assessing supplement bioavailability.

Keywords: biomarkers; diet; iMg; magnesium; nutritional status.

Conflict of interest statement

TCW serves on the Scientific Advisory Board for The Vitamin Shoppe and has received research grants from Pfizer Consumer Healthcare. All his conflicts are listed at www.drtaylorwallace.com. CMW is on the scientific advisory boards of the Yogurt in Nutrition Initiative (YINI) and the U.S. Food and Drug Administration and serves on the Board of Trustees of the International Life Sciences Institute (ILSI). JZ, SJB, SC, VA, LAS, and NG-M have no conflicts of interest to disclose.

Figures

Figure 1

Average whole blood concentration of ionized magnesium (iMg2+) and serum total magnesium concentrations, as well as urinary magnesium content (top); total area under the curve (AUC) in mg/dL•24h for iMg2+ and serum total Mg or mg•24h for urine Mg (bottom) over 24 h post-treatment for MgCl2 treatment vs. placebo. * Differences between MgCl2 versus placebo, p < 0.05. To convert between mg/dL and mmol/L, divide by 2.43.