title: Effects of ursodeoxycholic acid on synthesis of cholesterol and bile acids in healthy subjects.
abstract: OBJECTIVE
  Ursodeoxycholic acid (UDCA) decreases biliary secretion of cholesterol and is therefore used for the dissolution of cholesterol gallstones. It remains unclear whether these changes in biliary cholesterol excretion are associated with changes in cholesterol synthesis and bile acid synthesis. We therefore studied the activities of rate-limiting enzymes of cholesterol synthesis and bile acid synthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase and cholesterol 7alpha-hydroxylase, respectively, in normal subjects during UDCA feeding.
  
  
  METHODS
  UDCA was given to 8 healthy volunteers (5 men, 3 women; age 24-44 years) in a single dose of 10-15 mg/kg body weight for 40 days. Before and during (days 3, 5, 10, 20, 30 and 40) UDCA treatment, urinary excretion of mevalonic acid and serum concentrations of 7alpha-hydroxy-4-cholesten-3-one (7alpha-HCO) were determined as markers of cholesterol and bile acid synthesis, respectively. The Wilcoxon signed rank test and Spearman's rank correlation coefficient were used for statistical analysis.
  
  
  RESULTS
  Cholesterol synthesis and serum lipid concentrations remained unchanged during UDCA treatment for 40 days. However, synthesis of bile acids increased during long-term treatment with UDCA as reflected by an increase in 7alpha-HCO serum concentrations from 39.7 +/- 21.3 ng/ml (median 32.8 ng/ml) before treatment to 64.0 +/- 30.4 ng/ml (median 77.5 ng/ml) at days 30-40 of UDCA treatment (p < 0.05).
  
  
  CONCLUSIONS
  UDCA treatment does not affect cholesterol synthesis in the liver, but does increase bile acid synthesis after prolonged treatment. This may represent a compensatory change following decreased absorption of endogenous bile acids as observed with UDCA therapy.
authors.affiliation: Department of Medicine II, Klinikum Grosshadern, Ludwig Maximilians University, Munich, Germany.
authors.forename: Gerd H
authors.initials: GH
authors.lastname: Sauter
authors.forename: Kai
authors.initials: K
authors.lastname: Thiessen
authors.forename: Klaus G
authors.initials: KG
authors.lastname: Parhofer
authors.forename: Christoph
authors.initials: C
authors.lastname: Jüngst
authors.forename: Sven
authors.initials: S
authors.lastname: Fischer
authors.forename: Dieter
authors.initials: D
authors.lastname: Jüngst
mesh_terms: D000328:Adult; D001053:Apolipoproteins / Q000097:blood; D001647:Bile Acids and Salts / Q000096:biosynthesis* / Q000097:blood; D002756:Cholagogues and Choleretics / Q000494:pharmacology; D002784:Cholesterol / Q000096:biosynthesis* / Q000097:blood; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D013997:Time Factors; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
chemical_list: D001053:Apolipoproteins; D001647:Bile Acids and Salts; D002756:Cholagogues and Choleretics; D008055:Lipids; D014580:Ursodeoxycholic Acid; D002784:Cholesterol