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Mechanism of the Antiproliferative Effect of Milk Mineral and Other Calcium Supplements on Colonic Epithelium¹

Department of Nutrition, Netherlands Institute for Dairy Research, 6710 BA Ede, The Netherlands

² To whom requests for reprints should be addressed, at Department of Nutrition, Netherlands Institute for Dairy Research (NIZO), P.O. Box 20, 6710 BA Ede, The Netherlands.

Recently we have shown that supplemental dietary calcium precipitates luminal cytolytic surfactants and thus inhibits colonic epithelial proliferation, which may decrease the risk of colon cancer. In Western diets, milk products are quantitatively the most important source of dietary calcium. However, they also contain large amounts of phosphate, which has been hypothesized to inhibit the antiproliferative effect of calcium. Therefore, we studied in rats the possible differential antiproliferative effects of dairy calcium, calcium carbonate, and calcium phosphate, supplemented to a Western high-risk control diet. We observed that fecal bile acid excretion was similar in the various diet groups, whereas fatty acid excretion was stimulated by the calcium supplements in the order calcium carbonate > calcium phosphate > milk mineral. In fecal water, concentrations of bile acids and fatty acids were drastically decreased in the supplemented groups, resulting in decreased cytolytic activity of 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 effects of calcium was a decrease in cell damage and cell proliferation. Only minor differences between the supplements were observed. The concentration of serum gastrin, the possible trophic effect of which could counteract the antiproliferative effect of calcium, was increased by the supplements, but no significant correlation was observed between serum gastrin concentration and epithelial proliferation. We conclude that dietary calcium precipitates luminal surfactants and thus inhibits cytolytic activity, epithelial cell damage, and colonic proliferation. The similar efficacy of calcium carbonate, calcium phosphate, and milk mineral indicates that the antiproliferative effect of milk mineral is mediated by its calcium content and is not inhibited by phosphate.

¹ Supported by Grant 900-562-078 from The Netherlands Organization for Scientific Research (NWO), Medical Sciences.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 7/29/93. Accepted 10/22/93.

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