THE EFFECTS OF URSODEOXYCHOLIC ACID ON SERUM AND BILIARY NONCHOLESTEROL STEROLS IN PATIENTS WITH GALLSTONES

Litholytic bile acid ursodeoxycholic acid (UDCA) reduces biliary chole sterol secretion and alters cholesterol metabolism by mechanisms that are not fully understood. To evaluate cholesterol metabolism during UD CA treatment, we studied serum and biliary lipids and cholesterol prec ursor sterols (lanosterol and other dimethyl and monomethyl sterols, l athosterols, and desmosterol), indicators of cholesterol synthesis, an d plant sterols campesterol and sitosterol, indicators of cholesterol absorption, before and during administration of UDCA, 9 mg/kg/d, for 2 6 weeks in eight patients with radiolucent gallstones. During UDCA adm inistration, serum lipid concentrations were unchanged, but the biliar y concentration and molar percentage of cholesterol were markedly decr eased. The proportions of the cholesterol precursor sterols to cholest erol were significantly interrelated between serum and bile before and especially during UDCA administration. Lanosterol and lathesterol lev els, especially in bile, were significantly decreased by 43% and 34%, suggesting that UDCA may inhibit cholesterol synthesis. Levels of the other methylated precursor sterols were increased in serum and bile. T he esterification percentages of all sterols were unchanged. The plant sterol-to-cholesterol ratios increased significantly in serum and bil e, and there was an inverse correlation between the increment of serum plant sterols and decreased biliary molar percentage of cholesterol. In conclusion, UDCA may inhibit cholesterol synthesis possibly at the squalene synthase or 4 alpha-demethylase steps, resulting in decreased biliary secretion of cholesterol. Reduced biliary sterol secretion pr obably increased serum plant sterol levels, indicating that under thes e conditions they no longer reflect the intestinal efficiency of chole sterol absorption.