Effect of cholestyramine treatment on biliary lipid secretion rates in normolipidaemic men

This study was designed to clarify the effect of bile acid sequestrant treatment on the total biliary output rates of cholesterol, phospholipids and bile acids in man, and to correlate these changes with the alterations in plasma lipoprotein levels. For this purpose nine healthy, normolipidaemic men were treated with 16 g of cholestyramine daily over a period of 4 weeks, and the biliary secretion rates were measured by a duodenal perfusion technique. Resin therapy, which profoundly increases de novo synthesis of bile acids, resulted in a lowering of total plasma cholesterol levels, mainly due to a 35% reduction in low density lipoprotein (LDL) cholesterol, and in a 33% increase in plasma triglyceride levels, reflecting enhanced very low density lipoprotein (VLDL) triglyceride concentrations; high density lipoprotein (HDL) levels did not change. However, these lipoprotein changes did not correlate with any alterations in biliary lipid output. Total hepatic secretion rates of the biliary lipids remained generally unchanged during treatment, with a tendency towards lower cholesterol output, resulting in a lower molar percentage of cholesterol in hepatic bile, 3.4 +/- 0.4 vs. 2.9 +/- 0.2 mol %. This is probably due to an increased rate of conversion of cholesterol to bile acids in the hepatocyte. It is concluded that, in man, the liver may adapt well to changes in the enterohepatic circulation of bile acids, thereby maintaining output rates of biliary lipids at a relatively constant level.