Calcium plus vitamin D supplementation and the risk of colorectal cancer.
- J. Wactawski‐Wende
- J. Kotchen
- G. Anderson
- A. Assaf
- A. Assaf
- R. Brunner
- M. O'sullivan
- K. Margolis
- J. Ockene
- L. Phillips
- L. Pottern
- R. Prentice
- J. Robbins
- T. Rohan
- G. Sarto
- S. Sharma
- M. Stefanick
- L. Horn
- R. Wallace
- E. Whitlock
- T. Bassford
- S. Beresford
- H. Black
- D. Bonds
- R. Brzyski
- B. Caan
- R. Chlebowski
- B. Cochrane
- C. Garland
- M. Gass
- J. Hays
- G. Heiss
- S. Hendrix
- B. Howard
- J. Hsia
- F. Hubbell
- R. Jackson
- K. Johnson
- H. Judd
- C. Kooperberg
- L. Kuller
- A. LaCroix
- D. Lane
- R. Langer
- N. Lasser
- C. Lewis
- M. Limacher
- J. Manson
What this study found
Calcium plus vitamin D did not reduce colorectal cancer incidence in this trial. Invasive colorectal cancer occurred in 168 women in the calcium plus vitamin D group versus 154 in the placebo group (hazard ratio 1.08, 95% CI 0.86 to 1.34; P = 0.51). Death from colorectal cancer was also not reduced (34 vs 41; hazard ratio 0.82, 95% CI 0.52 to 1.29; P = 0.39), and intestinal polyps were unchanged (2983 vs 2997; hazard ratio 0.99, 95% CI 0.94 to 1.04; P = 0.71). Kidney stones were more common with supplementation (449 vs 381; hazard ratio 1.17, 95% CI 1.02 to 1.34; P = 0.02).
- Study & population
- This was a randomized, placebo-controlled trial in healthy postmenopausal women aged 50 to 79 years enrolled at 40 Women's Health Initiative centers in the United States.
- Intervention
- Active treatment was oral calcium carbonate providing 500 mg elemental calcium plus 200 IU vitamin D3 per tablet, taken twice daily for a total daily dose of 1000 mg elemental calcium and 400 IU vitamin D3.
- Key limitation
- The main outcome was null despite a long follow-up of about 7 years, which may still be too short for a cancer endpoint with long latency.
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Open PDFOriginal 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.).