Systematic Review and Meta-Analysis to Estimate a Reference Range for Circulating Ionized Magnesium Concentrations in Adult Populations

Abstract

Background: There is a lack of consensus on a reference range for ionized magnesium (iMg²⁺) in blood as a measure of the status of circulating iMg²⁺ for the screening of populations.

Objectives: We estimated the reference range of iMg²⁺ levels for healthy adult populations and the ranges for populations with cardiovascular disease (CVD), type 2 diabetes, hypertension, and renal disease. We also estimated 95% ranges for circulating magnesium (Mg) in healthy and those with cardiometabolic diseases.

Methods: We searched Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Embase through 24 July, 2020 to identify articles. We included English, peer-reviewed, randomized controlled trials, prospective and retrospective cohort studies, case-control studies, and cross-sectional studies that measured iMg²⁺ in blood or circulating Mg at baseline. The protocol was registered on PROSPERO (CRD42020216100). Estimated ranges were calculated by employing a frequentist random-effects model using extracted (or calculated) means and SDs from each included study. We determined the 95% confidence interval of the pooled mean.

Results: A total of 95 articles were included with 53 studies having data for healthy participants and 42 studies having data for participants with cardiometabolic diseases. The estimated reference range for iMg²⁺ for healthy populations was 0.40-0.68 mmol/L, 0.38-0.64 mmol/L for CVD, 0.34-0.66 mmol/L for type 2 diabetes, 0.39-1.04 mmol/L for hypertension, and 0.40-0.76 mmol/L for renal disease. For circulating Mg, the estimated range was 0.72-1.0 mmol/L for healthy adults, 0.56-1.05 mmol/L for CVD, 0.58-1.14 mmol/L for type 2 diabetes, 0.60-1.08 mmol/L for hypertension, and 0.59-1.26 mmol/L for renal disease.

Conclusions: Estimated reference ranges for cardiometabolic disease states for both iMg²⁺ and circulating Mg were broad and overlapped with the estimated range for healthy populations (0.40-0.68 mmol/L). Further studies should evaluate whether iMg²⁺ can be used as a biomarker of cardiometabolic disease.

Keywords: cardiovascular disease; diabetes; healthy adults; hypertension; ion-selective electrodes; ionized magnesium; magnesium; reference range; renal diseases; serum magnesium.