title: Effect of Vitamin D Supplementation on Blood Pressure: A Systematic Review and Meta-analysis Incorporating Individual Patient Data.
abstract: OBJECTIVE
  Low levels of vitamin D are associated with elevated blood pressure (BP) and future cardiovascular events. Whether vitamin D supplementation reduces BP and which patient characteristics predict a response remain unclear.
  
  
  OBJECTIVE
  To systematically review whether supplementation with vitamin D or its analogues reduce BP.
  
  
  METHODS
  We searched MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and http://www.ClinicalTrials.com augmented by a hand search of references from the included articles and previous reviews. Google was searched for gray literature (ie, material not published in recognized scientific journals). No language restrictions were applied. The search period spanned January 1, 1966, through March 31, 2014.
  
  
  METHODS
  We included randomized placebo-controlled clinical trials that used vitamin D supplementation for a minimum of 4 weeks for any indication and reported BP data. Studies were included if they used active or inactive forms of vitamin D or vitamin D analogues. Cointerventions were permitted if identical in all treatment arms.
  
  
  METHODS
  We extracted data on baseline demographics, 25-hydroxyvitamin D levels, systolic and diastolic BP (SBP and DBP), and change in BP from baseline to the final follow-up. Individual patient data on age, sex, medication use, diabetes mellitus, baseline and follow-up BP, and 25-hydroxyvitamin D levels were requested from the authors of the included studies. For trial-level data, between-group differences in BP change were combined in a random-effects model. For individual patient data, between-group differences in BP at the final follow up, adjusted for baseline BP, were calculated before combining in a random-effects model.
  
  
  METHODS
  Difference in SBP and DBP measured in an office setting.
  
  
  RESULTS
  We included 46 trials (4541 participants) in the trial-level meta-analysis. Individual patient data were obtained for 27 trials (3092 participants). At the trial level, no effect of vitamin D supplementation was seen on SBP (effect size, 0.0 [95% CI, -0.8 to 0.8] mm Hg; P=.97; I2=21%) or DBP (effect size, -0.1 [95% CI, -0.6 to 0.5] mm Hg; P=.84; I2=20%). Similar results were found analyzing individual patient data for SBP (effect size, -0.5 [95% CI, -1.3 to 0.4] mm Hg; P=.27; I2=0%) and DBP (effect size, 0.2 [95% CI, -0.3 to 0.7] mm Hg; P=.38; I2=0%). Subgroup analysis did not reveal any baseline factor predictive of a better response to therapy.
  
  
  CONCLUSIONS
  Vitamin D supplementation is ineffective as an agent for lowering BP and thus should not be used as an antihypertensive agent.
authors.affiliation: Medical Research Institute, University of Dundee, Ninewells Hospital, Dundee, Scotland.
authors.forename: Louise A
authors.initials: LA
authors.lastname: Beveridge
authors.affiliation: Medical Research Institute, University of Dundee, Ninewells Hospital, Dundee, Scotland.
authors.forename: Allan D
authors.initials: AD
authors.lastname: Struthers
authors.affiliation: Medical Research Institute, University of Dundee, Ninewells Hospital, Dundee, Scotland.
authors.forename: Faisel
authors.initials: F
authors.lastname: Khan
authors.affiliation: Tromsø Endocrine Research Group, Institute of Clinical Medicine, UiT (Universitetet i Tromsø), The Arctic University of Norway, Tromsø, Norway.
authors.forename: Rolf
authors.initials: R
authors.lastname: Jorde
authors.affiliation: School of Population Health, University of Auckland, Auckland, New Zealand.
authors.forename: Robert
authors.initials: R
authors.lastname: Scragg
authors.affiliation: School of Medicine and Dentistry, University of Aberdeen, Aberdeen, Scotland.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Macdonald
authors.affiliation: Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Alvarez
authors.affiliation: Division of Geriatric Medicine, University of Colorado School of Medicine, Aurora.
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Boxer
authors.affiliation: Department of Medicine, University of Verona, Verona, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Dalbeni
authors.affiliation: Division of Cardiovascular Medicine, University of Wisconsin School of Medicine and Public Health, Madison.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Gepner
authors.affiliation: Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Isbel
authors.affiliation: Department of Medical Research, Holstebro Hospital, Holstebro, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Larsen
authors.affiliation: Department of Pediatrics and Clinical Epidemiology, Sitaram Bhartia Institute of Science and Research, New Delhi, India.
authors.forename: Jitender
authors.initials: J
authors.lastname: Nagpal
authors.affiliation: Department of Nephrology, Cambridge University Hospitals NHS (National Health Service) Foundation Trust, Cambridge, England.
authors.forename: William G
authors.initials: WG
authors.lastname: Petchey
authors.affiliation: Angiology Unit, Ospedale La Carità, Locarno, Switzerland.
authors.forename: Hans
authors.initials: H
authors.lastname: Stricker
authors.affiliation: Department of Internal Medicine, Asklepios-Paulinenklinik, Wiesbaden, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Strobel
authors.affiliation: Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Vin
authors.initials: V
authors.lastname: Tangpricha
authors.affiliation: Department of Metabolism and Nutrition, Institute of Food Science, Technology, and Nutrition, Spanish National Research Council, Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Toxqui
authors.affiliation: Department of Metabolism and Nutrition, Institute of Food Science, Technology, and Nutrition, Spanish National Research Council, Madrid, Spain.
authors.forename: M Pilar
authors.initials: MP
authors.lastname: Vaquero
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Louise
authors.initials: L
authors.lastname: Wamberg
authors.affiliation: Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum, Bochum, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Zittermann
authors.affiliation: Medical Research Institute, University of Dundee, Ninewells Hospital, Dundee, Scotland.
authors.forename: Miles D
authors.initials: MD
authors.lastname: Witham
mesh_terms: D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D017211:Treatment Failure; D014807:Vitamin D / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D014815:Vitamins / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D014815:Vitamins; D014807:Vitamin D; C104450:25-hydroxyvitamin D