title: The Circulating Concentration and 24-h Urine Excretion of Magnesium Dose- and Time-Dependently Respond to Oral Magnesium Supplementation in a Meta-Analysis of Randomized Controlled Trials.
abstract: BACKGROUND
  Accurate determination of Mg status is important for improving nutritional assessment and clinical risk stratification.
  
  
  OBJECTIVE
  We aimed to quantify the overall responsiveness of Mg biomarkers to oral Mg supplementation among adults without severe diseases and their dose- and time responses using available data from randomized controlled trials (RCTs).
  
  
  METHODS
  We identified 48 Mg supplementation trials (n = 2131) through searches of MEDLINE and the Cochrane Library up to November 2014. Random-effects meta-analysis was used to estimate weighted mean differences of biomarker concentrations between intervention and placebo groups. Restricted cubic splines were used to determine the dose- and time responses of Mg biomarkers to supplementation.
  
  
  RESULTS
  Among the 35 biomarkers assessed, serum, plasma, and urine Mg were most commonly measured. Elemental Mg supplementation doses ranged from 197 to 994 mg/d. Trials ranged from 3 wk to 5 y (median: 12 wk). Mg supplementation significantly elevated circulating Mg by 0.04 mmol/L (95% CI: 0.02, 0.06) and 24-h urine Mg excretion by 1.52 mmol/24 h (95% CI: 1.20, 1.83) as compared to placebo. Circulating Mg concentrations and 24-h urine Mg excretion responded to Mg supplementation in a dose- and time-dependent manner, gradually reaching a steady state at doses of 300 mg/d and 400 mg/d, or after ~20 wk and 40 wk, respectively (all P-nonlinearity ≤ 0.001). The higher the circulating Mg concentration at baseline, the lower the responsiveness of circulating Mg to supplementation, and the higher the urinary excretion (all P-linearity < 0.05). In addition, RBC Mg, fecal Mg, and urine calcium were significantly more elevated by Mg supplementation than by placebo (all P-values < 0.05), but there is insufficient evidence to determine their responses to increasing Mg doses.
  
  
  CONCLUSIONS
  This meta-analysis of RCTs demonstrated significant dose- and time responses of circulating Mg concentration and 24-h urine Mg excretion to oral Mg supplementation.
authors: Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN;
authors: Xi
authors: X
authors: Zhang
authors: Department of Medicine, Division of Cardiovascular Medicine, Stanford University, Stanford, CA;
authors: Liana C
authors: LC
authors: Del Gobbo
authors: Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA;
authors: Adela
authors: A
authors: Hruby
authors: Center for Magnesium Education and Research, Pahoa, HI;
authors: Andrea
authors: A
authors: Rosanoff
authors: Department of Epidemiology and Biostatistics, School of Public Health, Indiana University, Bloomington, IN;
authors: Ka
authors: K
authors: He
authors: Division of Epidemiology, Vanderbilt Ingram Cancer Center, and Department of Veterans Affairs, Tennessee Valley Healthcare System, Geriatric, Research, Education and Clinical Center, Nashville, TN; and.
authors: Qi
authors: Q
authors: Dai
authors: Center for Magnesium Education and Research, Pahoa, HI;
authors: Rebecca B
authors: RB
authors: Costello
authors: Department of Epidemiology, School of Medicine, Fukushima Medical University, Fukushima, Japan.
authors: Wen
authors: W
authors: Zhang
authors: Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN; yiqsong@iu.edu.
authors: Yiqing
authors: Y
authors: Song
mesh_terms: D000284:Administration, Oral; D015415:Biomarkers / Q000097:blood; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008274:Magnesium / Q000008:administration & dosage* / Q000097:blood* / Q000652:urine*; D015596:Nutrition Assessment; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors
chemical_list: D015415:Biomarkers; D008274:Magnesium
keywords: Mg biomarkers; Mg status; circulating and urine Mg; meta-analysis; randomized controlled trial