Calcium plus vitamin D supplementation and the risk of colorectal cancer


Jean Wactawski-Wende, State University of New York
Jane Morley Kotchen, Medical College of Wisconsin
Garnet L. Anderson, Fred Hutchinson Cancer Research Center
Annlouise R. Assaf, Brown University
Robert L. Brunner, University of Nevada School of Medicine
Mary Jo O'Sullivan, University of Miami
Karen L. Margolis, HealthPartners Research Foundation
Judith K. Ockene, University of Massachusetts Medical SchoolFollow
Lawrence Phillips, Emory University
Linda Pottern, National Heart, Lung and Blood Institute
Ross L. Prentice, Fred Hutchinson Cancer Research CenterSearch...
John A. Robbins, University of California at Davis School of Medicine
Thomas E. Rohan, Albert Einstein College of Medicine
Gloria E. Sarto, University of Wisconsin–Madison
Santosh Sharma
Marcia L. Stefanick, Stanford University
Linda Van Horn, Northwestern University
Robert B. Wallace, University of Iowa
Evelyn Whitlock, Kaiser Permanente Center for Health Research
Tamsen Bassford, University of Arizona
Shirley A. A. Beresford, University of Washington - Seattle Campus
Henry R. Black, Rush University Medical Center
Denise E. Bonds, University of Virginia
Robert G. Brzyski, University of Texas
Bette J. Caan, Kaiser Permanente
Rowan T. Chlebowski, University of California
Barbara B. Cochrane, Fred Hutchinson Cancer Research Center
Cedric Garland, University of Cincinnati
Margery Gass, University of Cincinnati College of Medicine
Jennifer Hays, Baylor Medical College
Gerardo Heiss, University of North Carolina
Susan L. Hendrix, Wayne State University School of Medicine
Barbara V. Howard, Medstar Research Institute
Judith Hsia, George Washington University
F. Allan Hubbell, University of California, Irvine
Rebecca D. Jackson, The Ohio State University
Karen C. Johnson, University of Tennessee
Howard Judd
Charles L. Kooperberg, Wake Forest University School of Medicine
Lewis H. Kuller, University of Pittsburgh
Andrea Z. LaCroix, University of Washington
Dorothy S. Lane, State University of New York
Robert D. Langer, Geisinger Health System
Norman L. Lasser, University of California at San Diego
Cora E. Lewis, University of Alabama - Birmingham
Marian C. Limacher, University of Florida
JoAnn E. Manson, Harvard Medical School

UMMS Affiliation

Department of Medicine, Division of Preventive and Behavioral Medicine

Publication Date


Document Type



Adenocarcinoma; Aged; Calcium; Calcium Carbonate; Colonic Polyps; Colorectal Neoplasms; Double-Blind Method; Drug Combinations; Female; Follow-Up Studies; Humans; Incidence; Middle Aged; Postmenopause; Proportional Hazards Models; Vitamin D


Life Sciences | Medicine and Health Sciences | Women's Studies


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.).

DOI of Published Version



N Engl J Med. 2006 Feb 16;354(7):684-96. Link to article on publisher's site

Journal/Book/Conference Title

The New England journal of medicine

Related Resources

Link to article in PubMed

PubMed ID