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It is demonstrated that bile acids bind to insoluble calcium phosphate at pH values beyond 5.5. Significant binding occurs with glycine-conjugated dihydroxy bile acids. Results indicate that these bile acids are bound in a micellar mode. Taurine conjugation almost completely inhibits the binding of these bile acids to insoluble calcium phosphate. Since glycine-conjugated dihydroxy bile acids are predominant in the rabbit, but not in the rat, our results suggest an explanation for the intriguing species-dependence of casein-induced hypercholesterolaemia, which is high in the rabbit but absent in the rat.

We fed semipurified diets containing pectin with either a high or low in vitro viscosity at a level of 3 g/100 g air-dried diet to hamsters for 8 wk. A control group was fed cellulose and a positive control group was fed psyllium. The pectins used were a calcium-sensitive pectin (CS-pectin) that has a high viscosity and a noncalcium-sensitive pectin (NCS-pectin) that has a low viscosity. In the presence of calcium, CS-pectin has a more than 80-fold higher viscosity than NCS-pectin which offered the opportunity to investigate the possible role of viscosity in the hypolipidemic properties of pectin. The hamsters fed CS-pectin or psyllium had considerably lower plasma cholesterol concentrations (3.69 +/- 0.44 and 4.21 +/- 0.45 mmol/L, respectively, mean +/- SD, n = 14) than those fed NCS-pectin (5.03 +/- 1.15 mmol/L) or cellulose (5.72 +/- 1. 04 mmol/L). Differences in total plasma cholesterol were reflected in both high density lipoprotein and very low density lipoprotein cholesterol. There was no effect of fiber on low density lipoprotein cholesterol levels. Liver cholesterol concentrations paralleled the plasma cholesterol levels and were 9.91 +/- 2.48 micromol/g of liver for the CS-pectin group, 15.03 +/- 5.75 for the psyllium group, 17. 69 +/- 10.66 for the NCS-pectin group, and 25.57 +/- 9.23 for the cellulose group. Fecal bile acid and neutral steroid excretion tended to be higher in the hamsters fed CS-pectin than in their counterparts fed NCS-pectin. The hamsters fed psyllium had significantly greater fecal excretions of bile acids than the hamsters fed cellulose, CS-pectin or NCS-pectin, whereas the excretion of fecal neutral sterols tended to be lower. Plasma cholesteryl ester transfer protein activity was significantly lower in the hamsters fed CS-pectin than in those fed NCS-pectin. The results of this study suggest that the viscosity of pectins may determine their cholesterolemic effect.

Unconjugated secondary bile acids can promote colon cancer by damaging colonic mucosa and consequently increasing epithelial proliferation. It has been proposed that dietary calcium inactivates intestinal bile acids either by a Ca2(+)-dependent precipitation or by binding to insoluble calcium phosphate (CaPi). We studied the molecular mechanisms of these opposing hypotheses by using hemolysis of erythrocytes as a model parameter for cytotoxicity. Washed human erythrocytes were incubated for 15 min with buffered media (pH 7.4) containing increasing amounts of different bile acids. Deconjugation and 7 alpha-dehydroxylation of mixtures of glycine- or taurine-conjugated cholate and chenodeoxycholate drastically increased their cytotoxicity. Parallel measurements, using a fluorescent micellar probe, indicated that micellar aggregation is a prerequisite for this bile acid-induced lysis. Ca2+ concentrations up to 15 mM did not precipitate bile acids but stimulated cytotoxicity of both deoxycholate (DC) and its glycine conjugate (GDC). Cytotoxicity of the taurine conjugate (TDC) was stimulated to a much lesser extent. Increasing amounts of CaPi precipitated micellar DC and GDC, but not TDC, and consequently inhibited only cytotoxicity of the former two. These findings indicate that 1) hydrophobicity and micellar aggregation are important determinants of bile acid-induced cytotoxicity that explain the high cytotoxic potential of secondary bile acids in colon, and 2) cytotoxicity of bile acids is stimulated by free Ca2+ and inhibited by CaPi. This inhibition is due to binding of carboxylic (including secondary) bile acids to CaPi.

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