title: Effect of Vitamin D and Calcium Supplementation on Cancer Incidence in Older Women: A Randomized Clinical Trial.
abstract: Evidence suggests that low vitamin D status may increase the risk of cancer.
  
  
  
  To determine if dietary supplementation with vitamin D3 and calcium reduces the risk of cancer among older women.
  
  
  
  A 4-year, double-blind, placebo-controlled, population-based randomized clinical trial in 31 rural counties (June 24, 2009, to August 26, 2015-the final date of follow-up). A total of 2303 healthy postmenopausal women 55 years or older were randomized, 1156 to the treatment group and 1147 to the placebo group. Duration of treatment was 4 years.
  
  
  
  The treatment group (vitamin D3 + calcium group) received 2000 IU/d of vitamin D3 and 1500 mg/d of calcium; the placebo group received identical placebos.
  
  
  
  The primary outcome was the incidence of all-type cancer (excluding nonmelanoma skin cancers), which was evaluated using Kaplan-Meier survival analysis and proportional hazards modeling.
  
  
  
  Among 2303 randomized women (mean age, 65.2 years [SD, 7.0]; mean baseline serum 25-hydroxyvitamin D level, 32.8 ng/mL [SD, 10.5]), 2064 (90%) completed the study. At year 1, serum 25-hydroxyvitamin D levels were 43.9 ng/mL in the vitamin D3 + calcium group and 31.6 ng/mL in the placebo group. A new diagnosis of cancer was confirmed in 109 participants, 45 (3.89%) in the vitamin D3 + calcium group and 64 (5.58%) in the placebo group (difference, 1.69% [95% CI, -0.06% to 3.46%]; P = .06). Kaplan-Meier incidence over 4 years was 0.042 (95% CI, 0.032 to 0.056) in the vitamin D3 + calcium group and 0.060 (95% CI, 0.048 to 0.076) in the placebo group; P = .06. In unadjusted Cox proportional hazards regression, the hazard ratio was 0.70 (95% CI, 0.47 to 1.02). Adverse events potentially related to the study included renal calculi (16 participants in the vitamin D3 + calcium group and 10 in the placebo group), and elevated serum calcium levels (6 in the vitamin D3 + calcium group and 2 in the placebo group).
  
  
  
  Among healthy postmenopausal older women with a mean baseline serum 25-hydroxyvitamin D level of 32.8 ng/mL, supplementation with vitamin D3 and calcium compared with placebo did not result in a significantly lower risk of all-type cancer at 4 years. Further research is necessary to assess the possible role of vitamin D in cancer prevention.
  
  
  
  clinicaltrials.gov Identifier: NCT01052051.
authors.affiliation: Creighton University Schools of Nursing, Omaha, Nebraska.
authors.forename: Joan
authors.initials: J
authors.lastname: Lappe
authors.affiliation: Creighton University Schools of Nursing, Omaha, Nebraska.
authors.forename: Patrice
authors.initials: P
authors.lastname: Watson
authors.affiliation: Creighton University Schools of Nursing, Omaha, Nebraska.
authors.forename: Dianne
authors.initials: D
authors.lastname: Travers-Gustafson
authors.affiliation: Creighton University Schools of Nursing, Omaha, Nebraska.
authors.forename: Robert
authors.initials: R
authors.lastname: Recker
authors.affiliation: University of California San Diego, Department of Family Medicine and Public Health, La Jolla, California.
authors.forename: Cedric
authors.initials: C
authors.lastname: Garland
authors.affiliation: University of California San Diego, Department of Family Medicine and Public Health, La Jolla, California.
authors.forename: Edward
authors.initials: E
authors.lastname: Gorham
authors.affiliation: Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, University of Texas, Houston.
authors.forename: Keith
authors.initials: K
authors.lastname: Baggerly
authors.affiliation: GrassrootsHealth, La Mesa, California.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: McDonnell
mesh_terms: D000368:Aged; D002118:Calcium / Q000008:administration & dosage* / Q000009:adverse effects; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000139:chemically induced; D015994:Incidence; D057194:Intention to Treat Analysis; D053208:Kaplan-Meier Estimate; D007669:Kidney Calculi / Q000139:chemically induced; D008875:Middle Aged; D009329:Nebraska / Q000453:epidemiology; D009369:Neoplasms / Q000453:epidemiology*; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control; D016016:Proportional Hazards Models; D018401:Sample Size; D013997:Time Factors; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D014815:Vitamins / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D014815:Vitamins; D014807:Vitamin D; D002762:Cholecalciferol; C104450:25-hydroxyvitamin D; D002118:Calcium