title: A systematic review protocol examining the effect of vitamin D supplementation on endothelial function.
abstract: BACKGROUND
  Vitamin D has potential benefits for extraskeletal health. These could include an anti-inflammatory effect as well as a reduction in endothelial dysfunction. We aim to provide quality evidence for the hypothesis that supplementation with vitamin D will improve endothelial function (EF), possibly through the abrogation of systemic inflammation.
  
  
  METHODS
  We will conduct a systematic review of all randomised controlled trials on vitamin D supplementation and EF lasting 12 weeks or more. The search will cover the period 2000-2015 and include studies that describe direct measures of EF, markers of endothelial cell (EC) activation and if concurrently reported, indicators of systemic inflammation. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and study quality will be assessed by the Jadad score in addition to an evaluation of allocation concealment and data analysis. If sufficient data are available, a meta-analysis will be conducted. The effect sizes will be generated using Hedges' g score, for both fixed and random effect models. I(2) statistics and Galbraith plots will be used to assess heterogeneity and identify their potential sources. Potential publication and small sample size bias will be assessed by visual inspections of funnel plots and also Egger's test. Meta-regression analysis (if feasible) will be conducted with restricted maximum likelihood (REML) estimation method, controlling for potential confounders (demographics, study methods, location, etc). A backward elimination process will be applied in the regression modelling procedure. Subgroup analysis, conditional on number of studies retrieved and their sample size, will be stratified on participant disease category, total dose administered, degree of 25(OH)D change and type of supplement used.
  
  
  BACKGROUND
  Formal ethical approval is not required as primary data will not be collected. The results will be disseminated through a peer-reviewed publication, conference presentation and the popular press.
  
  
  BACKGROUND
  International Prospective Register for Systematic Reviews (PROSPERO) number CRD42014013523.
authors.affiliation: Directorate of Nutrition, Dietetics & Food Technology, School of Public Health, Curtin Health Innovation Research Institute of Ageing & Chronic Disease, Curtin University, Perth, Western Australia, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Alyami
authors.affiliation: Directorate of Nutrition, Dietetics & Food Technology, School of Public Health, Curtin Health Innovation Research Institute of Ageing & Chronic Disease, Curtin University, Perth, Western Australia, Australia.
authors.forename: M J
authors.identifier: http://orcid.org/0000-0001-6071-0272
authors.initials: MJ
authors.lastname: Soares
authors.affiliation: Directorate of Nutrition, Dietetics & Food Technology, School of Public Health, Curtin Health Innovation Research Institute of Ageing & Chronic Disease, Curtin University, Perth, Western Australia, Australia.
authors.forename: J L
authors.initials: JL
authors.lastname: Sherriff
authors.affiliation: Directorate of Epidemiology & Biostatistics, School of Public Health, Curtin University, Perth, Western Australia, Australia.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Collaboration for Evidence, Research and Impact in Public Health, School of Public Health, Curtin University, Perth, Western Australia, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Hallett
authors.affiliation: University Health Service, Support Services, Curtin University, Perth, Western Australia, Australia.
authors.forename: F
authors.initials: F
authors.lastname: Coombes
mesh_terms: D019587:Dietary Supplements; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D012107:Research Design; D000078202:Systematic Reviews as Topic; D014807:Vitamin D / Q000494:pharmacology* / Q000627:therapeutic use; D014815:Vitamins / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D014815:Vitamins; D014807:Vitamin D
keywords: NUTRITION & DIETETICS; STATISTICS & RESEARCH METHODS; VASCULAR MEDICINE