Effects of treatment with deoxycholic acid and chenodeoxycholic acid on the hepatic synthesis of cholesterol and bile acids in healthy subjects

The degradation of cholesterol to bile acids is regulated by a negative-fee dback mechanism by the bile acids, especially the hydrophobic bile acids, r eturning to the liver via the portal vein. Chenodeoxycholic acid (CDCA) is a potent suppressor of the cholesterol. 7 alpha -hydroxylase, the rate-dete rmining enzyme in bile acid formation. CDCA may also suppress hepatic 3-hyd roxy-3-methyl glutaryl coenzyme A (HMG CoA) reductase, the rate-limiting en zyme in cholesterol synthesis, Conflicting reports have appeared regarding the suppression on bile acid synthesis by the most hydrophobic bile acid of human bile, deoxycholic acid (DCA), To study the suppressive effects of CD CA and DCA on hepatic cholesterol and bile acid synthesis in humans, 10 hea lthy subjects were treated with CDCA or DCA for 3 weeks in a randomized cro ss-over study with a washout period of 4 weeks in between. Serum levels of 7 alpha -hydroxy-4-cholesten-3-one, reflecting cholesterol 7 alpha -hydroxy lase activity, and I-dehydrocholesterol, reflecting HMG CoA reductase activ ity, and bile acids were repeatedly measured during the study periods. Afte r 3 weeks of treatment with CDCA or DCA, CDCA constituted 70% and DCA 74% o f the total serum bile acids, respectively. CDCA and DCA decreased the seru m levels of 7 alpha -hydroxy-4-cholesten-3-one by 80% and 75%, respectively . Negative correlations between the percentages of CDCA and DCA and the ser um concentration of 7 alpha -hydroxy-4-cholesten-3-one were obtained. CDCA reduced the serum level of 7-dehydrocholesterol by 29%, whereas treatment w ith DCA tended to increase the level of 7-dehydrocholesterol. Treatment of healthy subjects with CDCA and DCA reduces bile acid synthesis. CDCA also i nhibits cholesterol synthesis, whereas DCA does not.