deoxycholic-acid and Hyperlipoproteinemias

Ursodeoxycholic acid reduces biliary saturation with cholesterol and may induce dissolution of cholesterol gallstones in man. In order to characterize the effects of this potentially useful bile acid on plasma lipid metabolism, we determined lipoprotein levels and very low density lipoprotein (VLDL) triglyceride kinetics in six hypertriglyceridaemic and three normolipidaemic subjects before and after 4-6 weeks of ursodeoxycholic acid treatment at a daily dose of 15 mg kg-1 body weight. The plasma levels of low density lipoprotein (LDL), high density lipoprotein (HDL) and total cholesterol were not significantly affected by therapy. Nor were the plasma level and apparent formation of VLDL triglycerides changed. In five subjects, the effects of a low dose (7.5 mg kg-1 body weight day-1 for 4-6 weeks) of ursodeoxycholic acid on biliary lipid composition and kinetics of cholic acid and chenodeoxycholic acid were determined. The relative concentration of cholesterol in bile was reduced to the same level as during treatment with a high dose of ursodeoxycholic acid. The synthesis rates of bile acids were not suppressed with ursodeoxycholic acid. It is concluded that, unlike chenodeoxycholic acid, ursodeoxycholic acid does not suppress endogenous bile acid production. The efficiency at lower doses, and the lack of effects on plasma lipid metabolism, may make ursodeoxycholic acid a more attractive alternative for clinical attempts of gallstone dissolution.

Topics: Adult; Aged; Bile; Bile Acids and Salts; Chenodeoxycholic Acid; Cholesterol; Cholic Acid; Cholic Acids; Deoxycholic Acid; Humans; Hyperlipidemia, Familial Combined; Hyperlipoproteinemia Type IV; Hyperlipoproteinemias; Kinetics; Lipid Metabolism; Lipids; Lipoproteins; Male; Middle Aged; Triglycerides; Ursodeoxycholic Acid

Fasting serum concentrations of the individual bile acids were measured by gas chromatography in 27 patients with primary hyperlipoproteinemia (8 type IIa, 7 type IIb and 12 type IV) and in 14 healthy subjects. Total serum bile acid levels were 1618 +/- 244 ng/ml (SE) in type IIa, 1296 +/- 251 ng/ml in type IIb and 15609 +/- 263 ng/ml in type IV hyperlipoproteinemia. These values did not differ significantly from values in the control group (1505 +/- 200 ng/ml). Serum levels of cholic acid were significantly higher in patients with type IIa (551 +/- 78 ng/ml) than in those with type IIb (190 +/- 57 ng/ml, P < 0.01) and type IV (240 +/- 57 ng/ml, P < 0.02), while intermediate values were recorded in the control group (384 +/- 49 ng/ml). Ursodeoxycholic acid was found in larger amounts in hyperlipidemic patients than in controls. No significant differences with respect to other bile acids were observed between the groups examined. According to the current concepts on the enterohepatic circulation of bile acids, the findings support the hypothesis that the intestinal absorption of cholic acid may differ in various types of hyperlipoproteinemia.

Topics: Adult; Aged; Bile Acids and Salts; Chenodeoxycholic Acid; Cholic Acids; Deoxycholic Acid; Female; Humans; Hyperlipoproteinemias; Lipids; Male; Middle Aged; Ursodeoxycholic Acid