MECHANISM OF THE ANTIPROLIFERATIVE EFFECT OF MILK MINERAL AND OTHER CALCIUM SUPPLEMENTS ON COLONIC EPITHELIUM

Recently we have shown that supplemental dietary calcium precipitates luminal cytolytic surfactants and thus inhibits colonic epithelial pro liferation, which may decrease the risk of colon cancer. In Western di ets, milk products are quantitatively the most important source of die tary calcium. However, they also contain large amounts of phosphate, w hich has been hypothesized to inhibit the antiproliferative effect of calcium. Therefore, we studied in rats the possible differential antip roliferative effects of dairy calcium, calcium carbonate, and calcium phosphate, supplemented to a Western high-risk control diet. We observ ed that fecal bile acid excretion was similar in the various diet grou ps, whereas fatty acid excretion was stimulated by the calcium supplem ents in the order calcium carbonate > calcium phosphate > milk mineral . In fecal water concentrations of bile acids and fatty acids were dra stically decreased in the supplemented groups, resulting in decreased cytolytic activity or fecal water. In vitro incubation of fecal water from the control group with insoluble calcium phosphate also decreased the high concentrations of surfactants and their cytolytic activity. The response of the colonic epithelium to these primary luminal effect s of calcium was a decrease in cell damage and cell proliferation. Onl y minor differences between the supplements were observed. The concent ration of serum gastrin, the possible trophic effect of which could co unteract the antiproliferative effect of calcium, was increased by the supplements, but no significant correlation was observed between seru m gastrin concentration and epithelial proliferation. We conclude that dietary calcium precipitates luminal surfactants and thus inhibits cy tolytic activity epithelial cell damage, and colonic proliferation. Th e similar efficacy of calcium carbonate, calcium phosphate, and milk m ineral indicates that the antiproliferative effect of milk mineral is mediated by its calcium content and is not inhibited by phosphate.