The effects of ursodeoxycholic acid on serum and biliary noncholesterol sterols in patients with gallstones.
Litholytic bile acid ursodeoxycholic acid (UDCA) reduces biliary cholesterol secretion and alters cholesterol metabolism by mechanisms that are not fully understood. To evaluate cholesterol metabolism during UDCA treatment, we studied serum and biliary lipids and cholesterol precursor sterols (lanosterol and other dimethyl and monomethyl sterols, lathosterols, and desmosterol), indicators of cholesterol synthesis, and plant sterols campesterol and sitosterol, indicators of cholesterol absorption, before and during administration of UDCA, 9 mg/kg/d, for 26 weeks in eight patients with radiolucent gallstones. During UDCA administration, serum lipid concentrations were unchanged, but the biliary concentration and molar percentage of cholesterol were markedly decreased. The proportions of the cholesterol precursor sterols to cholesterol were significantly interrelated between serum and bile before and especially during UDCA administration. Lanosterol and lathosterol levels, 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. The esterification percentages of all sterols were unchanged. The plant sterol-to-cholesterol ratios increased significantly in serum and bile, 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 4alpha-demethylase steps, resulting in decreased biliary secretion of cholesterol. Reduced biliary sterol secretion probably increased serum plant sterol levels, indicating that under these conditions they no longer reflect the intestinal efficiency of cholesterol absorption.
Miettinen
T E
TE
Department of Medicine, University of Helsinki, Finland.
Tarpila
S
S
Gylling
H
H
D001646:Bile / Q000737:chemistry / Q000187:drug effects*; D001647:Bile Acids and Salts / Q000032:analysis* / Q000097:blood; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D002769:Cholelithiasis / Q000097:blood / Q000737:chemistry / Q000188:drug therapy*; D002784:Cholesterol / Q000032:analysis* / Q000097:blood; D005260:Female; D006801:Humans; D007810:Lanosterol / Q000032:analysis* / Q000097:blood; D008055:Lipids / Q000032:analysis* / Q000097:blood; D008297:Male; D008875:Middle Aged; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
D001647:Bile Acids and Salts; D002756:Cholagogues and Choleretics; D008055:Lipids; D007810:Lanosterol; D014580:Ursodeoxycholic Acid; C001521:lathosterol; D002784:Cholesterol