Effects of ursodeoxycholic acid on synthesis of cholesterol and bile acids in healthy subjects

Background/Aims: 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-methyl-glutarylcoenzyme 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.