title: Magnesium supplementation, metabolic and inflammatory markers, and global genomic and proteomic profiling: a randomized, double-blind, controlled, crossover trial in overweight individuals.
abstract: BACKGROUND
  Dietary magnesium intake has been favorably associated with reduced risk of metabolic outcomes in observational studies; however, few randomized trials have introduced a systems-biology approach to explore molecular mechanisms of pleiotropic metabolic actions of magnesium supplementation.
  
  
  OBJECTIVE
  We examined the effects of oral magnesium supplementation on metabolic biomarkers and global genomic and proteomic profiling in overweight individuals.
  
  
  METHODS
  We undertook this randomized, crossover, pilot trial in 14 healthy, overweight volunteers [body mass index (in kg/m(2)) ≥25] who were randomly assigned to receive magnesium citrate (500 mg elemental Mg/d) or a placebo for 4 wk with a 1-mo washout period. Fasting blood and urine specimens were collected according to standardized protocols. Biochemical assays were conducted on blood specimens. RNA was extracted and subsequently hybridized with the Human Gene ST 1.0 array (Affymetrix, Santa Clara, CA). Urine proteomic profiling was analyzed with the CM10 ProteinChip array (Bio-Rad Laboratories, Hercules, CA).
  
  
  RESULTS
  We observed that magnesium treatment significantly decreased fasting C-peptide concentrations (change: -0.4 ng/mL after magnesium treatment compared with +0.05 ng/mL after placebo treatment; P = 0.004) and appeared to decrease fasting insulin concentrations (change: -2.2 μU/mL after magnesium treatment compared with 0.0 μU/mL after placebo treatment; P = 0.25). No consistent patterns were observed across inflammatory biomarkers. Gene expression profiling revealed up-regulation of 24 genes and down-regulation of 36 genes including genes related to metabolic and inflammatory pathways such as C1q and tumor necrosis factor-related protein 9 (C1QTNF9) and pro-platelet basic protein (PPBP). Urine proteomic profiling showed significant differences in the expression amounts of several peptides and proteins after treatment.
  
  
  CONCLUSIONS
  Magnesium supplementation for 4 wk in overweight individuals led to distinct changes in gene expression and proteomic profiling consistent with favorable effects on several metabolic pathways. This trial was registered at clinicaltrials.gov as NCT00737815.
authors.affiliation: Department of Epidemiology, School of Public Health, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Sara A
authors.initials: SA
authors.lastname: Chacko
authors.forename: James
authors.initials: J
authors.lastname: Sul
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Song
authors.forename: Xinmin
authors.initials: X
authors.lastname: Li
authors.forename: James
authors.initials: J
authors.lastname: LeBlanc
authors.forename: Yuko
authors.initials: Y
authors.lastname: You
authors.forename: Anthony
authors.initials: A
authors.lastname: Butch
authors.forename: Simin
authors.initials: S
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002097:C-Reactive Protein / Q000378:metabolism*; D019343:Citric Acid / Q000008:administration & dosage; D018592:Cross-Over Studies; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000097:blood*; D008274:Magnesium / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D009942:Organometallic Compounds / Q000008:administration & dosage; D010865:Pilot Projects; D020543:Proteome / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014131:Trace Elements / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; D007328:Insulin; D009942:Organometallic Compounds; D020543:Proteome; D014131:Trace Elements; D019343:Citric Acid; D002097:C-Reactive Protein; D008274:Magnesium; C110422:magnesium citrate