Effect of cholestyramine on composition of duodenal bile in obese human subjects

Abstract

The effects of the oral hypocholesterolemic drug, cholestyramine (16 g/day), upon the composition of duodenal bile were studied in four obese, normolipidemic subjects (three female, one male) while they slowly lost weight during prolonged periods of constant liquid formula feeding on the metabolic ward. Four-week periods of drug treatment (during which the anticipated lowering of plasma total cholesterol level occurred) were alternated with similar periods without treatment or with administration of placebo. Fasting duodenal bile samples were obtained at intervals by intubation followed by intravenous cholecystokinin and were analyzed for cholesterol, total phospholipid, and both total and individual bile acids. Cholestyramine treatment resulted in large and significant changes in the relative proportions of the major individual bile acids, which were reversible when the drug was withdrawn. The primary (hepatic-synthesized) cholic acid was increased from 38.0 ± 1.6% (mean ± SE) to 67.3 ± 1.4%; primary chenodeoxycholic acid was decreased from 37.4 ± 1.4% to 26.1 ± 1.1%; and secondary (bacterially modified) deoxycholic acid was decreased from 25.0 ± 2.0% to 6.6 ± 0.8%. The greatly increased rate of hepatic bile acid synthesis under the influence of cholestyramine was probably partly responsible for these changes. In addition, the ratio of glycine-conjugated to taurine-conjugated bile acids in duodenal bile was greatly increased during cholestyramine treatment (from 2.7 ± 0.2% to 7.3 ± 0.6%), so that glycocholic acid became the predominant conjugated bile acid. Evidence that these marked bile composition changes are either beneficial or otherwise in relation to cholelithiasis is not available, but their occurrence should be borne in mind in considering long-term use of cholestyramine or similar bile acid sequestering substances as hypocholesterolemic agents.