title: Selenium supplementation for the primary prevention of cardiovascular disease.
abstract: BACKGROUND
  Selenium is a key component of a number of selenoproteins which protect against oxidative stress and have the potential to prevent chronic diseases including cardiovascular disease (CVD). However, observational studies have shown inconsistent associations between selenium intake and CVD risk; in addition, there is concern around a possible increased risk of type 2 diabetes with high selenium exposure.
  
  
  OBJECTIVE
  To determine the effectiveness of selenium only supplementation for the primary prevention of CVD and examine the potential adverse effect of type 2 diabetes.
  
  
  METHODS
  The following electronic databases were searched: the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 10 of 12, October 2012) on The Cochrane Library; MEDLINE (Ovid) (1946 to week 2 October 2012); EMBASE Classic + EMBASE (Ovid) (1947 to 2012 Week 42); CINAHL (EBSCO) (to 24 October 2012); ISI Web of Science (1970 to 24 October 2012); PsycINFO (Ovid) (1806 to week 3 October 2012); Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database and Health Economics Evaluations Database (Issue 4 of 4, October 2012) on The Cochrane Library. Trial registers and reference lists of reviews and articles were searched and experts in the field were approached. No language restrictions were applied.
  
  
  METHODS
  Randomised controlled trials on the effects of selenium only supplementation on major CVD end-points, mortality, changes in CVD risk factors, and type 2 diabetes were included both in adults of all ages from the general population and in those at high risk of CVD. Trials were only considered where the comparison group was placebo or no intervention. Only studies with at least three months follow-up were included in the meta-analyses, shorter term studies were dealt with descriptively.
  
  
  METHODS
  Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information.
  
  
  RESULTS
  Twelve trials (seven with duration of at least three months) met the inclusion criteria, with 19,715 participants randomised. The two largest trials that were conducted in the USA (SELECT and NPC) reported clinical events. There were no statistically significant effects of selenium supplementation on all cause mortality (RR 0.97, 95% CI 0.88 to 1.08), CVD mortality (RR 0.97, 95% CI 0.79 to 1.2), non-fatal CVD events (RR 0.96, 95% CI 0.89 to 1.04) or all CVD events (fatal and non-fatal) (RR 1.03, 95% CI 0.95 to 1.11). There was a small increased risk of type 2 diabetes with selenium supplementation but this did not reach statistical significance (RR 1.06, 95% CI 0.97 to 1.15). Other adverse effects that increased with selenium supplementation, as reported in the SELECT trial, included alopecia (RR 1.28, 95% CI 1.01 to 1.62) and dermatitis grade 1 to 2 (RR 1.17, 95% CI 1.0 to 1.35). Selenium supplementation reduced total cholesterol but this did not reach statistical significance (WMD - 0.11 mmol/L, 95% CI - 0.3 to 0.07). Mean high density lipoprotein (HDL) levels were unchanged. There was a statistically significant reduction in non-HDL cholesterol (WMD - 0.2 mmol/L, 95% CI - 0.41 to 0.00) in one trial of varying selenium dosage. None of the longer term trials examined effects on blood pressure. Overall, the included studies were regarded as at low risk of bias.
  
  
  CONCLUSIONS
  The limited trial evidence that is available to date does not support the use of selenium supplements in the primary prevention of CVD.
authors: Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry, UK. Karen.Rees@warwick.ac.uk
authors: Karen
authors: K
authors: Rees
authors: Louise
authors: L
authors: Hartley
authors: Camilla
authors: C
authors: Day
authors: Nadine
authors: N
authors: Flowers
authors: Aileen
authors: A
authors: Clarke
authors: Saverio
authors: S
authors: Stranges
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage*; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D019587:Dietary Supplements; D005527:Food, Fortified; D006801:Humans; D011322:Primary Prevention / Q000379:methods; D016032:Randomized Controlled Trials as Topic; D012643:Selenium / Q000008:administration & dosage*
chemical_list: D000975:Antioxidants; D002784:Cholesterol; D012643:Selenium