Abstract

BACKGROUND: Several dietary factors have been considered to be involved in the increasing incidence of colorectal cancer in industrialised countries. Experimental and epidemiological evidence has been suggestive but not conclusive for a protective role for high dietary calcium intake. Intervention studies with colorectal cancer as an endpoint are difficult to perform owing to the large number of patients and the long follow-up required; studies using the appearance of colorectal adenomatous polyps as a surrogate endpoint are therefore considered in reviewing the existing evidence.

OBJECTIVES: This systematic review aims to assess the effect of supplementary dietary calcium on the incidence of colorectal cancer and the incidence or recurrence of adenomatous polyps.

SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, the Cochrane Colorectal Cancer Group specialised register, MEDLINE, Cancerlit , and Embase, to July 2007. The reference lists of identified studies were inspected for further studies, and the review literature was scrutinized.

SELECTION CRITERIA: Randomised controlled trials of the effects of dietary calcium on the development of colonic cancer and adenomatous polyps in humans are reviewed. Studies of healthy adults and studies of adults at higher risk of colon cancer due to family history, previous adenomatous polyps, or inflammatory bowel disease were considered; data from subjects with familial polyposis coli are excluded. The primary outcomes were the occurrence of colon cancer, and occurrence or recurrence of any new adenomas of the colon. Secondary outcomes were any adverse event that required discontinuation of calcium supplementation, and drop-outs before the end of the study.

DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data, assessed trial quality and resolved discrepancies by consensus. The outcomes were reported as odds ratios (OR) with 95% confidence intervals (CI). The data were combined with the fixed effects model.

MAIN RESULTS: Two studies with 1346 subjects met the inclusion criteria. Both trials were well designed, double - blind, placebo controlled trials, included participants with previous adenomas. The doses of supplementary elemental calcium used were 1200 mg daily for a mean duration of 4 years, and 2000 mg/day for three years. The rates of loss to follow -up were 14 % and 11%. For the development of recurrent colorectal adenoma, a reduction was found (OR 0.74, CI 0.58,0.95) when the results from both trials were combined.

AUTHORS' CONCLUSIONS: Although the evidence from two RCTs suggests that calcium supplementation might contribute to a moderate degree to the prevention of colorectal adenomatous polyps, this does not constitute sufficient evidence to recommend the general use of calcium supplements to prevent colorectal cancer.

Abstract

INTRODUCTION: Although some have suggested that certain vitamins or calcium supplements may reduce adenoma recurrence, our own prior retrospective study found no such effects. The purpose of this case-control study was to further investigate whether regular vitamin or calcium supplement intake influenced the incidence of recurrent adenomatous polyps in patients with previous neoplasia who were undergoing follow-up colonoscopy.

METHODS: This study enrolled 1,162 patients who underwent colonoscopy by one of three surgeons at Columbia-Presbyterian Medical Center in New York City between March 1993 and February 1997. Of these patients 448 (250 males) had a previous diagnosis of colorectal neoplasia (cancer, adenomas, or dysplasia). Of these, 183 (40.8 percent) had an adenoma at the index colonoscopy. Information was collected on personal and family history of colonic diseases, cigarette smoking, medication, and vitamin and micronutrient supplement usage on a questionnaire that was completed by the patients before the colonoscopy. Odds ratios were obtained by unconditional logistic regression analysis, adjusting for age and gender, and used adenoma recurrence at index colonoscopy as the outcome.

RESULTS: The mean interval between colonoscopic examinations was 37 months for the recurrent adenoma group and 38 months for the nonrecurrent group of patients (P = not significant). In this case-control study we found a protective effect for the use of vitamin supplements in general (any vitamin) on the recurrence of adenomas (odds ratio, 0.41; 95 percent confidence interval, 0.27-0.61). Specifically, this protective effect was observed for the use of multivitamins (odds ratio, 0.47; 95 percent confidence interval, 0.31-0.72), vitamin E (odds ratio, 0.62; 95 percent confidence interval, 0.39-0.98), and for calcium supplementation (odds ratio, 0.51; 95 percent confidence interval, 0.27-0.96). Nonsignificant protective effects were noted for carotene/vitamin A, vitamin D, and vitamin C.

CONCLUSIONS: The use of multivitamins, vitamin E, and calcium supplements were found to be associated with a lower incidence of recurrent adenomas in a population of patients with history of previous colonic neoplasia. Prospective, randomized trials are needed to better assess the impact of these agents and to determine whether the use of these supplements is associated with a protective effect against recurrent adenomas.