Circulating Ionized Magnesium: Comparisons with Circulating Total Magnesium and the Response to Magnesium Supplementation in a Randomized Controlled Trial

Abstract

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.

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

“…Results showed a significant difference for the absorption of serum total magnesium after four hours of supplement versus placebo ingestion as well as significant differences in total AUC for serum Mg. In a study by Rooney et al [29], of chronic magnesium supplementation for 10 weeks at 400 mg magnesium per day via MgO, the findings were greater increases in both iMg 2+ concentrations in whole blood, and serum total magnesium concentrations after Mg supplementation as compared to placebo.…”

“…In the current study, because we only assessed iMg 2+ after an acute small oral dose of magnesium, we did not evaluate whether iMg 2+ is an appropriate measure of magnesium status. In the crossover, a randomized clinical trial by Rooney in which healthy participants received 10 weeks of chronic supplementation of MgO versus placebo, both fresh blood concentration of iMg 2+ and total circulating magnesium concentrations increased [29]. Although serum magnesium is used more often to assess status, the relationship between serum total magnesium and iMg 2+ in health and chronic disease has not been extensively studied.…”

“…However, the study participants ingested high magnesium diets beforehand, creating magnesium-saturated individuals who are not a representative sample of the population. Our research group is currently evaluating the bioavailability of ReMag ® , a formulation of MgCl 2 against a commonly marketed Mg supplement, MgO, which is often used for bioavailability studies [28][29][30]. We are utilizing a randomized clinical study design and newer technology with analytical advances in the assessment of iMg 2+ to test acute oral doses of these two supplements against a placebo.…”

Influence of Demographic and Lifestyle Variables on Plasma Magnesium Concentrations and Their Associations with Cardiovascular Risk Factors in a Mediterranean Population

“…Thus, some studies have reported inverse associations between dietary magnesium intake and body mass index (BMI) or obesity [39,40], blood pressure [40,41], total cholesterol/LDL-cholesterol concentrations [42], and fasting glucose or type-2 diabetes [41,43,44], but the overall consistency for some of these factors is still low. Regarding the incidence of cardiovascular diseases, some studies have reported that high magnesium intake is associated with a lower risk of stroke, heart failure and total cardiovascular events [45,46], but less agreement has been observed for other cardiovascular events [38,47]. Given the undoubted limitations to assessing the amount of magnesium intake through dietary foods, due to several biases derived from the use of food frequency questionnaires, the use of magnesium intake/status biomarkers is preferred as a more objective measure.…”

“…Given the undoubted limitations to assessing the amount of magnesium intake through dietary foods, due to several biases derived from the use of food frequency questionnaires, the use of magnesium intake/status biomarkers is preferred as a more objective measure. Although there are still no perfect magnesium intake/status biomarkers [15,[47][48][49], plasma/serum magnesium concentrations are the most widely practiced and accepted method of determining magnesium status in epidemiological studies [15,17,19], having more advantages than urinary magnesium concentrations that are more dependent on kidney function [50].…”