A Trial of Calcium and Vitamin D for the Prevention of Colorectal Adenomas.

Oct 2015

DOI: 10.1056/NEJMoa1500409

Citations:269

Influential Citations:9

Interventional (Human) Studies

Enhanced Details

Methods

Randomized, multicenter, double-blind, placebo-controlled trial (partial factorial design) conducted at 11 US academic centers; 2259 participants aged 45-75 years with at least one colorectal adenoma removed within 120 days before enrollment and no remaining polyps after complete colonoscopy; generally in good health; no familial colorectal cancer syndromes or serious intestinal disease.

Intervention

Vitamin D3 1000 IU daily; Calcium carbonate 1200 mg daily; regimens included vitamin D3 alone, calcium alone, both, or placebo; taken as two identical tablets daily; duration until planned 3-year or 5-year colonoscopic surveillance (treatment ended Aug 31, 2013; follow-up through Nov 30, 2013).

Results

Daily supplementation with vitamin D3 (1000 IU), calcium (1200 mg), or both after removal of colorectal adenomas did not significantly reduce the risk of recurrent colorectal adenomas over 3 to 5 years. Adjusted risk ratios: Vitamin D vs no vitamin D 0.99 (95% CI 0.89-1.09); Calcium vs no calcium 0.95 (95% CI 0.85-1.06); Calcium plus vitamin D vs calcium alone 1.01 (95% CI 0.88-1.15); Calcium plus vitamin D vs neither agent 0.93 (95% CI 0.80-1.08). Advanced adenomas showed similar results. Adverse events were uncommon. Conclusion: The regimen did not meaningfully reduce recurrence risk over 3-5 years; the vitamin D dose may have been insufficient relative to current recommendations, and higher dose or longer duration might be needed. Results may not apply to individuals without a prior history of adenomas.

Limitations

Vitamin D dose (1000 IU) lower than what some experts now recommend; trial population had prior adenomas, limiting extrapolation to those without such history; higher vitamin D dose or longer duration might be required to detect effects; multiple subgroup analyses raise the possibility of chance findings.

Abstract

BACKGROUND Epidemiologic and preclinical data suggest that higher intake and serum levels of vitamin D and higher intake of calcium reduce the risk of colorectal neoplasia. To further study the chemopreventive potential of these nutrients, we conducted a randomized, double-blind, placebo-controlled trial of supplementation with vitamin D, calcium, or both for the prevention of colorectal adenomas. METHODS We recruited patients with recently diagnosed adenomas and no known colorectal polyps remaining after complete colonoscopy. We randomly assigned 2259 participants to receive daily vitamin D3 (1000 IU), calcium as carbonate (1200 mg), both, or neither in a partial 2×2 factorial design. Women could elect to receive calcium plus random assignment to vitamin D or placebo. Follow-up colonoscopy was anticipated to be performed 3 or 5 years after the baseline examinations, according to the endoscopist's recommendation. The primary end point was adenomas diagnosed in the interval from randomization through the anticipated surveillance colonoscopy. RESULTS Participants who were randomly assigned to receive vitamin D had a mean net increase in serum 25-hydroxyvitamin D levels of 7.83 ng per milliliter, relative to participants given placebo. Overall, 43% of participants had one or more adenomas diagnosed during follow-up. The adjusted risk ratios for recurrent adenomas were 0.99 (95% confidence interval [CI], 0.89 to 1.09) with vitamin D versus no vitamin D, 0.95 (95% CI, 0.85 to 1.06) with calcium versus no calcium, and 0.93 (95% CI, 0.80 to 1.08) with both agents versus neither agent. The findings for advanced adenomas were similar. There were few serious adverse events. CONCLUSIONS Daily supplementation with vitamin D3 (1000 IU), calcium (1200 mg), or both after removal of colorectal adenomas did not significantly reduce the risk of recurrent colorectal adenomas over a period of 3 to 5 years. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00153816.). show less