Changes in Bile Acid Composition and Effect on Cytolytic Activity of Fecal Water by Ursodeoxycholic Acid Administration: a Placebo-Controlled Cross-over Intervention Trial in Healthy Volunteers

Abstract

Background: Ursodeoxycholic acid (UDCA) has been shown to affect membrane-damaging effects of bile acids in vitro and fecal bile acid composition in rats. This study evaluates the effect of UDCA on fecal bile acid composition and on cytolytic activity of fecal water in man to clarify the potential chemopreventive role of UDCA for colorectal cancer. Methods: In this placebo-controlled crossover intervention trial, the effect of 900 mg/day UDCA orally in 15 healthy volunteers was studied. At the end of each 4-week period, 72 h feces were collected. Total and individual bile acids in feces were determined by gas chromatography and soluble bile acids were analyzed by high-performance liquid chromatography. Cytolytic activity of fecal water was measured using an erythrocyte lysis assay. Results: In feces, the percentages of primary bile acids--cholic acid (CA) and chenodeoxycholic acid (CDCA)--and of secondary bile acid--deoxycholic acid (DCA)--decreased after supplementation with UDCA, whereas those of UDCA and LCA increased from 2.7 ± 0.4% to 23.7 ± 2.6%, P < 0.0001 and from 26.2 ± 1.2% to 49.4 ± 1.8%, P < 0.0001 respectively. The concentrations of these two bile acids in fecal water also increased after UDCA administration from 7.8 ± 1.9 μmol/l to 47.0 ± 6.7 μmol/l (UDCA), P < 0.0001 and from 2.5 ± 0.6 μmol/l to 18.3 ± 4.1 μmol/l (LCA), P < 0.002, respectively. Cytolytic activity of fecal water was not affected by UDCA. Conclusion: These results do not support a protective effect of UDCA supplementation against colorectal cancer in man.