title: Effect of vitamin C on endothelial function in health and disease: a systematic review and meta-analysis of randomised controlled trials.
abstract: BACKGROUND
  Observational studies indicate that higher vitamin C intake is associated with reduced risk for cardiovascular diseases. However, randomised controlled trials (RCT) examining the effect of vitamin C on endothelial function (EF) have reported inconsistent results. The aims of this systematic review and meta-analysis were to determine the effect of vitamin C supplementation on EF and to investigate whether the effect was influenced by health status, study duration, dose and route of vitamin C administration.
  
  
  METHODS
  We searched the Medline, Embase, Cochrane Library, and Scopus databases from inception to May 2013 for studies that met the following criteria: 1) RCT with adult participants, 2) vitamin C administered alone, 3) studies that quantified EF using commonly applied methods including ultrasound, plethysmography and pulse wave analysis.
  
  
  RESULTS
  Pooling the data from 44 clinical trials showed a significant positive effect of vitamin C on EF (SMD: 0.50, 95% CI: 0.34, 0.66, P < 0.001). Stratification of the analysis by health outcome revealed improved EF in atherosclerotic (SMD: 0.84, 95% CI: 0.41, 1.26, P < 0.001), diabetic (SMD: 0.52, 95% CI: 0.21, 0.82, P < 0.001) and heart failure patients (SMD: 0.48, 95% CI: 0.08, 0.88, P < 0.02) after vitamin C supplementation. The effect size appeared to be unaffected by study design, duration, baseline plasma vitamin C concentration or route of administration of vitamin C. The meta-regression showed a significant positive association between vitamin C dose and improvement in EF (β: 0.00011, 95% CI: 0.00001, 0.00021, P = 0.03).
  
  
  CONCLUSIONS
  Vitamin C supplementation improved EF. The effect of vitamin C supplementation appeared to be dependent on health status, with stronger effects in those at higher cardiovascular disease risk. PROSPERO Database registration: CRD42013004567, http://www.crd.york.ac.uk/prospero/
authors.affiliation: Human Nutrition Research Centre, Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle on Tyne NE4 5PL, UK; College of Medicine, University of Al-Mustansiriyah, Baghdad, Iraq. Electronic address: a.w.ashor@newcastle.ac.uk.
authors.forename: Ammar W
authors.initials: AW
authors.lastname: Ashor
authors.affiliation: Human Nutrition Research Centre, Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle on Tyne NE4 5PL, UK.
authors.forename: Jose
authors.initials: J
authors.lastname: Lara
authors.affiliation: Human Nutrition Research Centre, Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle on Tyne NE4 5PL, UK.
authors.forename: John C
authors.initials: JC
authors.lastname: Mathers
authors.affiliation: Human Nutrition Research Centre, Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle on Tyne NE4 5PL, UK.
authors.forename: Mario
authors.initials: M
authors.lastname: Siervo
mesh_terms: D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage; D001205:Ascorbic Acid / Q000008:administration & dosage* / Q000627:therapeutic use*; D050197:Atherosclerosis; D002318:Cardiovascular Diseases / Q000517:prevention & control / Q000628:therapy; D019587:Dietary Supplements; D004727:Endothelium / Q000187:drug effects*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D055815:Young Adult
chemical_list: D000975:Antioxidants; D001205:Ascorbic Acid
keywords: Ascorbic acid; Cardiovascular risk; Flow-mediated dilation; Forearm blood flow; Nutritional supplements