CALCIUM SUPPLEMENTATION AND RECTAL MUCOSAL PROLIFERATION - A RANDOMIZED CONTROLLED TRIAL

Background: Data from studies using rodents suggest that dietary calci um inhibits bile acid-induced mucosal damage and experimental carcinog enesis in the large bowel, However, in humans, the effect of dietary c alcium and calcium supplementation on proliferation and carcinogenesis in the large bowel has been unclear, Purpose: To assess the effect of calcium supplementation on rectal mucosal proliferation in humans, we conducted a multicenter, randomized, placebo-controlled, double-blind ed trial, Methods: Participants were part of a larger multicenter chem oprevention trial; all were at high risk for large-bowel neoplasia, wi th at least one large-bowel adenoma removed endoscopically within the 3 months before study entry but with no known polyps remaining, Subjec ts were randomly assigned to receive daily either 3000 mg of calcium c arbonate (providing 1200 mg elemental calcium) or an identical-appeari ng placebo tablet, During a scheduled endoscopy 6-9 months after rando m assignment (approximately 1 year after the qualifying endoscopy), re ctal mucosal samples were obtained from 333 patients (173 assigned to, calcium and 160 assigned to placebo). Proliferating cell nuclear anti gen (PCNA) labeling indices (LIs) were computed as the measure of prol iferation in specimens from 146 patients receiving calcium and 129 pat ients receiving placebo, Bromodeoxyuridine (BrdU) labeling was used to measure proliferation in a smaller number of specimens (27 calcium-re ceiving and 31 placebo-receiving participants), For each scorable cryp t having at least one labeled cell (or surrounded by crypts with at le ast one labeled cell), a crypt LI was calculated as the number bf labe led cells divided by the total number of crypt cells. Crypt LIs were a veraged to produce a participant's average LI, Results: The overall un adjusted mean PCNA LIs (+/- SE) were similar in the calcium and placeb o groups (3.85% +/- 0.08% versus 3.92% +/- 0.08%, respectively, P = .3 0), The overall unadjusted mean BrdU LIs (+/- SE) were 3.88% +/- 0.30% in the calcium group and 3.54% +/- 0.21% in the placebo group (P = .5 4), PCNA labeling indices in the most luminal 40% of the crypt were sm all but, if anything, were higher in the calcium group, There was no p atient subgroup within which calcium had an antiproliferative effect; the overall findings persisted among patients with high and low calciu m intake, high and low fat intake, and high and low fiber intake, Conc lusions,, Calcium supplementation does not decrease rectal mucosal pro liferation, as measured by PCNA (and BrdU) immunohistochemistry, in pa tients with previous large-bowel adenomas, This study, therefore, does not provide evidence for an anticarcinogenic effect of calcium.