Circulating ionized magnesium: Comparisons with circulating total magnesium and the response to magnesium supplementation in a randomized controlled trial

Ionized Mg (iMg) is considered the biologically active fraction of circulating total Mg (tMg). It is possible that iMg may be a more physiologically relevant marker than tMg. Using data from a double-blind pilot randomized controlled trial, we tested (1) whether oral Mg supplementation will increase iMg concentrations compared with placebo and (2) the relationship between iMg and tMg at baseline. Additionally, we evaluated the agreement between iMg measured in fresh whole blood versus stored samples. A total of fifty-nine participants were randomized 1:1 to oral Mg supplementation (400 mg/day, Mg Oxide) or placebo for 10 weeks. Fasting blood samples were obtained at baseline and follow-up. The analysis used linear regression and an intent-to-treat approach. Participants were generally healthy, the mean age was 62, and 73% were female. The baseline iMg and tMg were modestly and positively associated (r = 0.50). The ratio of baseline iMg to tMg was 64%. The mean supplement effect on iMg was 0.03 mmol/L (95% CI:0.01, 0.05) for Mg supplementation versus placebo. The supplement effect on iMg was not statistically significantly different according to baseline iMg status (above/below median). Compared to fresh blood, iMg was consistently higher in refrigerated and frozen samples by 0.14 and 0.20 mmol/L, respectively. In this relatively healthy adult population, Mg supplementation over 10 weeks resulted in increased iMg concentrations. Whether iMg is a more appropriate measure of Mg status than tMg, and the public health or clinical utility of measuring iMg remains to be determined.