Calcium Intake Plus Vitamin D May Protect Against Colon Adenomas

Laurie Barclay, MD

December 02, 2003

Dec. 2, 2003 — Calcium supplementation reduces the rate of colon adenomas, but only if vitamin D levels are adequate, according to the results of a randomized trial published in the Dec. 3 issue of the Journal of the National Cancer Institute.

"Calcium supplementation and vitamin D status appear to act largely together, not separately, to reduce the risk of colorectal adenoma recurrence," write Maria V. Grau, MD, from the Dartmouth Medical School in Lebanon, New Hampshire, and colleagues. "Although these nutrients are inter-related metabolically in bone and in the normal intestine, their potential interactions in large-bowel carcinogenesis are not well understood."

The Calcium Polyp Prevention Study was a four-year, randomized, double-blind, placebo-controlled trial that showed a protective effect of calcium supplementation for preventing the recurrence of colorectal cancer. Of 2,918 subjects with at least one histologically confirmed colon adenoma removed within three months before recruitment and no additional polyps on colonoscopy, complete follow-up data were available on 803 subjects.

Calcium supplements were associated with reduced risk of adenoma recurrence only among subjects with baseline vitamin D levels above the median level of 29.1 ng/mL (relative risk [RR], 0.71; 95% confidence interval [CI], 0.57 - 0.89; P for interaction = .012). On the other hand, serum vitamin D levels were associated with reduced adenoma recurrence only among subjects taking calcium supplements (RR per 12 ng/mL increase of vitamin D, 0.88; 95% CI, 0.77 - 0.99; P for interaction = .006). These associations were independent of vitamin D receptor polymorphisms.

Study limitations include measurement error, failure to include all subjects from the original clinical trial, and the possibility that risk factors for adenoma recurrence differ from those for de novo occurrence of adenomas or of colorectal cancers.

These findings "provide a strong indication that vitamin D and calcium have a joint antineoplastic effect in the large bowel," the authors write. "Further investigation is needed to understand the mechanistic basis of the vitamin D/calcium interaction and to clarify the amount of intake of each nutrient required for optimum protective effect. Nevertheless, these data clearly suggest the potential for important chemopreventive effects from calcium and vitamin D."

In an accompanying editorial, Elizabeth T. Jacobs and colleagues, from the University of Arizona in Tuscon, note that the role of vitamin D receptor variants should be studied in additional trials with adequate statistical power.

They describe this study as "a catalyst for further exploration of the mechanisms by which calcium and vitamin D may interact to prevent colorectal neoplasia" and "a compelling reminder of the need for large association studies that include consideration of both genetic and environmental components, as well as the need for functional studies of candidate genes."

J Natl Cancer Inst. 2003;95(23):1766-1771

Reviewed by Gary D. Vogin, MD

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