title: Calcium and vitamin D supplements and health outcomes: a reanalysis of the Women's Health Initiative (WHI) limited-access data set.
abstract: BACKGROUND
  Frequent use of personal, nonprotocol calcium supplements obscured an adverse effect of coadministered calcium and vitamin D (CaD) on cardiovascular risk in the Women's Health Initiative (WHI).
  
  
  OBJECTIVE
  We investigated the effects of the use of personal calcium or vitamin D supplements on other outcomes in the WHI CaD Study (WHI CaD) by using the WHI limited-access clinical trials data set.
  
  
  METHODS
  The WHI CaD was a 7-y, randomized, placebo-controlled trial of CaD (1 g Ca/400 IU vitamin D daily) in 36,282 community-dwelling, postmenopausal women. The incidence of total cancer (excluding nonmelanoma skin cancers), breast and colorectal cancers, hip and total fracture, and mortality was assessed by using Cox proportional hazards models.
  
  
  RESULTS
  In the WHI CaD, interactions between the use of either personal calcium or vitamin D supplements and CaD were found for total, breast, and colorectal cancers but not for fracture or mortality. In 15,646 women (43%) who were not taking personal calcium or vitamin D supplements at randomization, CaD significantly decreased the risk of total, breast, and invasive breast cancers by 14-20% and nonsignificantly reduced the risk of colorectal cancer by 17%. In women taking personal calcium or vitamin D supplements, CaD did not alter cancer risk (HR: 1.06-1.26).
  
  
  CONCLUSIONS
  For women in the WHI CaD who were not taking personal calcium or vitamin D supplements at randomization, CaD decreased the risk of total, breast, and colorectal cancers and did not change the risk of fractures or total mortality. The nonskeletal effects of CaD may be more important than the skeletal effects and should be considered when evaluating these supplements. The WHI CaD trial is registered at clinicaltrials.gov as NCT00000611.
authors: Department of Medicine, University of Auckland, Auckland, New Zealand. m.bolland@auckland.ac.nz
authors: Mark J
authors: MJ
authors: Bolland
authors: Andrew
authors: A
authors: Grey
authors: Greg D
authors: GD
authors: Gamble
authors: Ian R
authors: IR
authors: Reid
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology / Q000517:prevention & control; D002136:Calcium, Dietary / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000517:prevention & control; D015986:Confounding Factors, Epidemiologic; D019587:Dietary Supplements; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology / Q000517:prevention & control*; D006620:Hip Fractures / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009026:Mortality; D009369:Neoplasms / Q000453:epidemiology / Q000517:prevention & control*; D017698:Postmenopause; D016016:Proportional Hazards Models; D012306:Risk; D012648:Self Care; D014481:United States / Q000453:epidemiology; D014807:Vitamin D / Q000627:therapeutic use*
chemical_list: D002136:Calcium, Dietary; D014807:Vitamin D