title: Vitamin D with calcium reduces mortality: patient level pooled analysis of 70,528 patients from eight major vitamin D trials.
abstract: BACKGROUND
  Vitamin D may affect multiple health outcomes. If so, an effect on mortality is to be expected. Using pooled data from randomized controlled trials, we performed individual patient data (IPD) and trial level meta-analyses to assess mortality among participants randomized to either vitamin D alone or vitamin D with calcium.
  
  
  METHODS
  Through a systematic literature search, we identified 24 randomized controlled trials reporting data on mortality in which vitamin D was given either alone or with calcium. From a total of 13 trials with more than 1000 participants each, eight trials were included in our IPD analysis. Using a stratified Cox regression model, we calculated risk of death during 3 yr of treatment in an intention-to-treat analysis. Also, we performed a trial level meta-analysis including data from all studies.
  
  
  RESULTS
  The IPD analysis yielded data on 70,528 randomized participants (86.8% females) with a median age of 70 (interquartile range, 62-77) yr. Vitamin D with or without calcium reduced mortality by 7% [hazard ratio, 0.93; 95% confidence interval (CI), 0.88-0.99]. However, vitamin D alone did not affect mortality, but risk of death was reduced if vitamin D was given with calcium (hazard ratio, 0.91; 95% CI, 0.84-0.98). The number needed to treat with vitamin D plus calcium for 3 yr to prevent one death was 151. Trial level meta-analysis (24 trials with 88,097 participants) showed similar results, i.e. mortality was reduced with vitamin D plus calcium (odds ratio, 0.94; 95% CI, 0.88-0.99), but not with vitamin D alone (odds ratio, 0.98; 95% CI, 0.91-1.06).
  
  
  CONCLUSIONS
  Vitamin D with calcium reduces mortality in the elderly, whereas available data do not support an effect of vitamin D alone.
authors.affiliation: Dr.Med.Sc., AssociateAarhus University, Department of Endocrinology and Internal Medicine, Aarhus Sygehus, Aarhus University Hospital, Tage-Hansens gade 2, DK 8000 Aarhus C, Denmark. rejnmark@post6.tele.dk.
authors.forename: Lars
authors.initials: L
authors.lastname: Rejnmark
authors.forename: Alison
authors.initials: A
authors.lastname: Avenell
authors.forename: Tahir
authors.initials: T
authors.lastname: Masud
authors.forename: Frazer
authors.initials: F
authors.lastname: Anderson
authors.forename: Haakon E
authors.initials: HE
authors.lastname: Meyer
authors.forename: Kerrie M
authors.initials: KM
authors.lastname: Sanders
authors.forename: Kari
authors.initials: K
authors.lastname: Salovaara
authors.forename: Cyrus
authors.initials: C
authors.lastname: Cooper
authors.forename: Helen E
authors.initials: HE
authors.lastname: Smith
authors.forename: Elizabeth T
authors.initials: ET
authors.lastname: Jacobs
authors.forename: David
authors.initials: D
authors.lastname: Torgerson
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Jackson
authors.forename: JoAnn E
authors.initials: JE
authors.lastname: Manson
authors.forename: Kim
authors.initials: K
authors.lastname: Brixen
authors.forename: Leif
authors.initials: L
authors.lastname: Mosekilde
authors.forename: John A
authors.initials: JA
authors.lastname: Robbins
authors.forename: Roger M
authors.initials: RM
authors.lastname: Francis
authors.forename: Bo
authors.initials: B
authors.lastname: Abrahamsen
mesh_terms: D000368:Aged; D002118:Calcium / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009026:Mortality; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D014807:Vitamin D / Q000008:administration & dosage*
chemical_list: D014807:Vitamin D; D002118:Calcium