Using a duodenal perfusion technique, the biliary output of bile acids, phospholipid, and cholesterol was measured hourly during three meals and an overnight fast in seven Caucasians with radiolucent gallstones in a functioning gallbladder, and in seven health controls without gallstones, closely matched for age, sex, and weight. Before the perfusion, bile acid kinetics were defined by an isotope dilution procedure, and the biliary lipid composition of fasting gallbladder bile was determined. Total daily biliary lipid output was similar in gallstone and control subjects, and was unrelated to cholesterol saturation of fasting gallbladder bile and to bile acid pool size. There was an inverse relationship between the size and recycling frequency of the bile acid pool, so that secretion rate and hepatic return of bile acids remained constant, despite a wide range of pool sizes. The finding of a normal bile acid synthesis rate in subjects with a small pool size therefore indicated normal feedback regulation of bile acid synthesis. Hourly measurements of biliary lipid output showed a linear relationship between bile acid and cholesterol output, with a similar regression line for gallstone and control subjects, but a non-linear relationship between bile acid and phospholipid output. Consequently, samples from all subjects were consistently supersaturated with cholesterol at low bile acid outputs, especially during overnight fasting, but not at high bile acid outputs. These findings indicate that hepatic secretion of bile supersaturated with cholesterol is physiological in man at low bile acid outputs, that bile acid pool size is probably determined in part by its recycling frequency, and that cholesterol cholelithiasis in some Caucasians may be due to an underlying extrahepatic abnormality.
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