Background: The hydrophilic bile acid, ursodeoxycholic acid (UDCA), may indirectly protect against colon carcinogenesis by decreasing the overall proportion of the more hydrophobic bile acids, such as deoxycholic acid (DCA), in aqueous phase stool. In the AOM rat model, treatment with UDCA resulted in a significant decrease in adenoma formation and colorectal cancer. It was hypothesized that there is a dose-response relationship between treatment with the more hydrophilic bile acid, UDCA, and a reduction in the proportion of the more hydrophobic bile acid, DCA, in the aqueous stool phase, suggesting the potential of UDCA as a chemopreventive agent. Methods: Eighteen participants were randomized to 300, 600, or 900 mg/day UDCA for 21 days in this multiple-dose, double-blinded study. Seventy-two-hour stool samples were collected pretreatment and on days 18-20 of UDCA treatment for bile acid measurements. Pharmacokinetics were performed and blood bile acids were measured at days 1 and 21 of UDCA treatment. Results: There were no serious adverse events associated with UDCA treatment. There was a dose-response increase in the posttreatment to baseline ratio of UDCA to DCA from the 300 mg/day to the 600 mg/day group, but not between the 600 and the 900 mg/day groups, in both aqueous and solid phase stool. This posttreatment increase was statistically significant in aqueous phase stool for the 300 and 600 mg/day treatment groups (P = 0.038 and P = 0.014, respectively), but was only marginally significant in the 900 mg/day treatment group (P = 0.057). Following the first dose administration, a dose-dependent increase in plasma ursodeoxycholic concentrations was observed in fasting subjects; however, when these levels were measured postprandially following 3 weeks of treatment, the areas under the plasma concentration-time profile (AUC) were not statistically different and remained relatively unchanged over time. Conclusions: UDCA treatment did not decrease the quantity of DCA in fecal water or solids; however, it did decrease the proportion of DCA in fecal water and solids in relation to UDCA. Thus, 3 weeks of UDCA treatment resulted in an overall increase in hydrophilicity of bile acids in the aqueous phase stool, with a peak effect observed with a daily dose of 600 mg/day. Much larger studies are needed to determine the effect of ursodeoxycholic administration on deoxycholic concentration, overall hydrophilicity of stool bile acids, and the long-term effects on intermediate biomarkers of cellular damage.
|Original language||English (US)|
|Number of pages||7|
|Journal||Cancer Epidemiology Biomarkers and Prevention|
|State||Published - May 2004|
ASJC Scopus subject areas