Calcium Plus Vitamin D Supplementation and the Risk of Colorectal Cancer

N Engl J Med. 2006 Feb 16;354(7):684-96. doi: 10.1056/NEJMoa055222.

Abstract

Background: Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials. However, randomized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking.

Methods: We conducted a randomized, double-blind, placebo-controlled trial involving 36,282 postmenopausal women from 40 Women's Health Initiative centers: 18,176 women received 500 mg of elemental calcium as calcium carbonate with 200 IU of vitamin D3 [corrected] twice daily (1000 mg of elemental calcium and 400 IU of vitamin D3) and 18,106 received a matching placebo for an average of 7.0 years. The incidence of pathologically confirmed colorectal cancer was the designated secondary outcome. Baseline levels of serum 25-hydroxyvitamin D were assessed in a nested case-control study.

Results: The incidence of invasive colorectal cancer did not differ significantly between women assigned to calcium plus vitamin D supplementation and those assigned to placebo (168 and 154 cases; hazard ratio, 1.08; 95 percent confidence interval, 0.86 to 1.34; P=0.51), and the tumor characteristics were similar in the two groups. The frequency of colorectal-cancer screening and abdominal symptoms was similar in the two groups. There were no significant treatment interactions with baseline characteristics.

Conclusions: Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women. The long latency associated with the development of colorectal cancer, along with the seven-year duration of the trial, may have contributed to this null finding. Ongoing follow-up will assess the longer-term effect of this intervention. (ClinicalTrials.gov number, NCT00000611.).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / epidemiology
  • Adenocarcinoma / prevention & control*
  • Aged
  • Calcium / therapeutic use
  • Calcium Carbonate / adverse effects
  • Calcium Carbonate / pharmacology
  • Calcium Carbonate / therapeutic use*
  • Colonic Polyps / epidemiology
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / prevention & control*
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Middle Aged
  • Postmenopause
  • Proportional Hazards Models
  • Vitamin D / adverse effects
  • Vitamin D / blood
  • Vitamin D / pharmacology
  • Vitamin D / therapeutic use*

Substances

  • Drug Combinations
  • Vitamin D
  • Calcium Carbonate
  • Calcium

Associated data

  • ClinicalTrials.gov/NCT00000611