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Dietary Calcium as a Possible Anti-promoter of Colon Carcinogenesis

出版	Lapre, 1992
ISBN	90548500789789054850076
URL	http://books.google.com.hk/books?id=FiFywgEACAAJ&hl=&source=gbs_api

註釋Parameters were closely associated. Thus, dietary supplementation with CaHPO 4 decreased cytotoxicity of fecal water by intestinal precipitation of bile acids. Because bile acids and fatty acids are products of fat digestion, the type of dietary fat may influence the cytotoxic effects of the intestinal contents and the interaction with calcium phosphate. Therefore, three different purified types of dietary fat (milk fat, palm oil and corn oil) were used each at a low (25 μmol CaHPO 4 /g diet) and a high (225 μmol CaHPO 4 /g diet) level (chapter 6). Milk fat contains rather large amounts of short- and medium-chain triglycerides (C 4:0 -C 12:0), palm oil contains triglycerides rich in palmitate (Ca 16:0) and oleate (C 18:1) and corn oil contains linoleate (C 18:2) rich triglycerides. The excretion of fatty acids was dependent on the type of dietary fat and increased in the order corn oil “ milk fat “ palm oil. Supplemental CaHPO 4 drastically stimulated fatty acid excretion with the same fat-type dependency. In contrast, concentrations of soluble fatty acids and bile acids were drastically decreased by supplemental CaHPO 4 . This effect was dependent on the type of dietary fat with palm oil resulting in the highest concentration of fatty acids. Cytotoxicity of fecal water decreased analogous to the decrease in concentrations of soluble surfactants with the same fat-type dependency. Multiple regression analysis showed that the concentrations of soluble bile acids and fatty acids are equally important determinants of cytotoxicity and explain 80% (R = 0.89) of the cytotoxicity of fecal water. Intestinal alkaline phosphatase activity in fecal water as a marker of intestinal epitheliolysis showed that the effects on cytotoxicity of fecal water were reflected in effects on intestinal epitheliolysis (r=0.92, P0.001). Thus, despite increases in total fecal concentrations, dietary calcium phosphate decreased concentrations of soluble surfactants dependent on the type of dietary fat. The decrease in soluble surfactants resulted in a decreased cytotoxicity of fecal water and a decreased intestinal epitheliolysis. To investigate whether the luminal effects of dietary calcium resulted in a change in response of the colonic epithelium, the anti-proliferative effect of calcium was studied in rats fed Western-type high risk diets containing low CaHPO sub4/sub (25 μmol Ca/g), low fibre and high fat (40 en-%) levels (chapter 7). It should be noted that this low calcium diet mimicked a human diet with a calcium consumption of 500 mg/day (mean intake in The Netherlands is about 1000 mg/day). Types of fat used were commercially available fats: butter, mimicking a diet with a high saturated mediumchain triglycerides content, saturated margarine, reflecting a diet with a high long-chain saturated fat content, and polyunsaturated margarine, ressembling a diet with a high polyunsaturated fat content. Diets were also supplemented with CaHP0 sub4/sub to 225 μmol/g diet. Dietary calcium phosphate decreased soluble surfactant concentrations and cytotoxicity of fecal water. These luminal effects of dietary calcium resulted in a lower intestinal epitheliolysis. On the butter and saturated margarine diets, these protective effects of calcium resulted in a decreased colonic proliferation. On the polyunsaturated diet, proliferation was not decreased by supplemental calcium which may suggest an additional mechanism in the induction of hyperproliferation. Multiple regression analysis of soluble surfactants with cytotoxicity, epitheliolysis and colonic proliferation showed highly significant associations. Cytotoxicity and epitheliolysis as well as epitheliolysis and colonic proliferation were highly correlated (resp. r=0.97 and r=0.88) for control and Ca-supplemented groups. This is consistent with the proposed mechanism and may indicate cause-and-effect relationships. Thus the anti-proliferative effect of dietary calcium is mediated by luminal surfactants and dependent on the type of dietary fat. Finally, the luminal effects of supplemental dietary calcium were studied in a pilot intervention trial with young healthy volunteers. In this study supplemental calcium complexated with phosphate to insoluble calcium phosphate, but in contrast to the animal studies the (already low) concentration of soluble bile acids was not further decreased. The free fatty acid concentration in fecal water was lowered by supplemental calcium. Gaschromatographic analysis of fecal water showed that the composition of the bile acids in fecal water was altered from hydrophobic to hydrophilic. The overall effect of dietary calcium supplementation was a decrease in hydrophobicity of fecal water measured as a decrease in free fatty acid concentration, hydrophobic bile acids and neutral sterols. This resulted in a significant decrease in cytotoxicity of fecal water in these healthy volunteers. Thus, luminal effects of dietary calcium supplementation in humans are analogous to the effects in rats. These effects may offer a molecular explanation of the protective effects of dietary calcium supplementation on colonic epithelial proliferation in patients at risk for colon cancer. strong CONCLUDING REMARKS