title: Selenium status and cardiovascular diseases: meta-analysis of prospective observational studies and randomized controlled trials.
abstract: OBJECTIVE
  Selenium was thought to have a role in cardiovascular disease (CVD) owing to its antioxidant properties; however, evidence from observational studies and randomized controlled trials (RCTs) has been inconsistent and controversial. We thus conducted a meta-analysis to assess the discrepancies between observational and randomized trial evidence.
  
  
  METHODS
  We searched MEDLINE and EMBASE for eligible prospective studies regarding the relationship between selenium and CVD up to 15 December 2013 and finally included 16 prospective observational studies and 16 RCTs. Random effects model was used to estimate the pooled relative risk (RR). Generalized least-squares trend test and restricted cubic spline model were performed to assess a linear and a nonlinear dose-response relationship.
  
  
  RESULTS
  Our meta-analysis of prospective studies showed a nonlinear relationship of CVD risk with blood selenium concentrations across a range of 30-165 μg/l and a significant benefit of CVD within a narrow selenium range of 55-145 μg/l. Our meta-analyses of RCTs showed that oral selenium supplements (median dose: 200 μg/day) for 2 weeks to 144 months significantly raised the blood selenium concentrations by 56.4 μg/l (95% confidence interval (CI): 40.9, 72.0 μg/l), whereas oral selenium supplements (median: 100 μg/day) for 6 to 114 months caused no effect on CVD (RR=0.91; 95% CI: 0.74, 1.10).
  
  
  CONCLUSIONS
  Our meta-analysis in prospective studies demonstrated a significant inverse association between selenium status and CVD risk within a narrow selenium range and a null effect of selenium supplementation on CVD was observed in RCTs. These findings indicate the importance of considering selenium status, dose and safety in health assessment and future study design.
authors.affiliation: Department of Epidemiology, Richard M Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: C
authors.initials: C
authors.lastname: Liu
authors.affiliation: Centre for the Youth Sport Research and Development, China Institute of Sport Science, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Epidemiology, Richard M Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Song
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage / Q000032:analysis*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000517:prevention & control; D016022:Case-Control Studies; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D064887:Observational Studies as Topic; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D012643:Selenium / Q000008:administration & dosage / Q000097:blood*
chemical_list: D000975:Antioxidants; D012643:Selenium