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Mechanism of the Protective Effect of Supplemental Dietary Calcium on Cytolytic Activity of Fecal Water¹

Department of Nutrition, Netherlands Institute for Dairy Research (NIZO), PO Box 20, 6710 BA Ede, The Netherlands S. M. L. T., R. V d. M.], and Department of Internal Medicine, University Hospital, Groningen, The Netherlands [J. H. K., E. G. E. De V.]

² To whom requests for reprints should be addressed.

Dietary calcium supplementation inhibits hyperproliferation of rectal epithelium, possibly by precipitating luminal surfactants and thus preventing their cell-damaging effects. Therefore, we studied the effects of supplemental dietary calcium (35.5 mmol/day) on composition and cytolytic activity of fecal water and on the release of the epithelial marker alkaline phosphatase in 12 healthy volunteers. Fecal water was isolated by low-speed centrifugation. Cytolytic activity was determined as lysis of human erythrocytes by fecal water. Intestinal alkaline phosphatase activity in fecal water was measured with the use of the uncompetitive inhibitor L-phenylalanine. Supplemental calcium increased soluble calcium and decreased soluble P_i. The logarithm of the concentration product of calcium and phosphate was linearly dependent on pH. These observations indicate formation of insoluble calcium phosphate. Supplemental calcium did not alter the total bile acid concentration in fecal water but significantly decreased the ratio of more hydrophobic to more hydrophilic bile acids from 3.3 to 2.3. Calcium also significantly decreased the concentration of fatty acids (from 2.9 to 2.1 mM). Consistent with these decreases in hydrophobic surfactants, calcium decreased the cytolytic activity of fecal water from 47 ± 9 to 27 ± 8% (n = 12, P < 0.05). Analogous to the decrease in cytolytic activity, the release of the epithelial marker alkaline phosphatase was also lowered by supplemental calcium. We conclude that supplemental dietary calcium decreases luminal cytotoxic surfactant concentrations and thus inhibits luminal cytolytic activity and the release of the epithelial marker alkaline phosphatase as an indicator of intestinal epitheliolysis. This mechanism may explain how dietary calcium could decrease epithelial cell proliferation.

¹ This study was supported by a grant from the European Community (1001/90-32.1) and by the Dutch Cancer Society (GUKC 89-08).

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 7/29/92. Accepted 10/29/92.

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