The Effects of Ursodeoxycholic Acid on Serum and Biliary Noncholesterol Sterols in Patients With Gallstones

Abstract

increase in cholesterol synthesis to maintain the body pool Litholytic bile acid ursodeoxycholic acid (UDCA) reof cholesterol unless the decrease in biliary cholesterol secreduces biliary cholesterol secretion and alters cholesterol tion is sufficient to compensate for reduced cholesterol abmetabolism by mechanisms that are not fully undersorption. However, the effect of UDCA on cholesterol metabostood. To evaluate cholesterol metabolism during UDCA lism, especially on cholesterol synthesis, has not been treatment, we studied serum and biliary lipids and choevaluated thoroughly, and the results available are controlesterol precursor sterols (lanosterol and other dimethyl versial, varying from suppression to no effect. 11,13-15 and monomethyl sterols, lathosterols, and desmosterol), Human serum and bile contains, in addition to cholesterol, indicators of cholesterol synthesis, and plant sterols small amounts of noncholesterol sterols, including cholesterol campesterol and sitosterol, indicators of cholesterol abprecursor 16 and dietary plant sterols. 17 Normally and in many sorption, before and during administration of UDCA, 9clinical conditions, the ratios of serum cholesterol precursor mg/kg/d, for 26 weeks in eight patients with radiolucent sterols to cholesterol have been shown to be correlated with gallstones. During UDCA administration, serum lipid the rate of cholesterol synthesis, 16,[18][19][20][21] whereas the serum concentrations were unchanged, but the biliary concenplant sterol levels indicate cholesterol absorption efficiency. 22 tration and molar percentage of cholesterol were markAccordingly, the serum and biliary noncholesterol sterol levedly decreased. The proportions of the cholesterol els might give some additional information on possible precursor sterols to cholesterol were significantly interchanges in cholesterol absorption and synthesis during related between serum and bile before and especially UDCA treatment. To this end we studied the serum and biliduring UDCA administration. Lanosterol and lathosary cholesterol precursor and plant sterol levels in gallstone terol levels, especially in bile, were significantly depatients before and during UDCA treatment to evaluate the creased by 43% and 34%, suggesting that UDCA may ineffects of this treatment on cholesterol absorption and metabhibit cholesterol synthesis. Levels of the other olism. methylase steps, resulting in decreased biliary secretionAfter the baseline studies they started UDCA, 9 mg/kg/d in two daily of cholesterol. Reduced biliary sterol secretion probably doses. Two patients used UDCA for only 4 weeks, whereas the other increased serum plant sterol levels, indicating that un-six patients used it for 6 months. However, 4 weeks' treatment was der these conditions they no longer reflect the intestinal enough to reach metabolic steady-state because in the six long-term efficiency of cholesterol absorption. (HEPATOLOGY patients the biliary molar percentages of cholesterol were similar 1997;25:514-518.) when analyzed after 4 weeks ...

Serum plant sterols and biliary cholesterol secretion in humans

“…After UDCA treatment, the concentrations of these sterols, as well as their ratios to cholesterol, increased significantly. The results are in agreement with those recently reported in patients with gallstones (16,17) and primary biliary cirrhosis (15). Miettinen et al (15)(16)(17) found a negative relationship between the change of the ratio of campesterol to cholesterol in serum before and during UDCA therapy and the change in cholesterol saturation in gallbladder bile.…”

“…The results are in agreement with those recently reported in patients with gallstones (16,17) and primary biliary cirrhosis (15). Miettinen et al (15)(16)(17) found a negative relationship between the change of the ratio of campesterol to cholesterol in serum before and during UDCA therapy and the change in cholesterol saturation in gallbladder bile. From the results, the authors suggest that under these circumstances levels of plant sterols might be affected by their biliary elimination and therefore reflect changes in biliary cholesterol secretion.…”

“…Therefore, it is likely that UDCA also reduces biliary output of plant sterols and cholestanol. Since UDCA has no effects on lipoprotein metabolism (16,17,28), retained plant sterols in the liver probably lead to higher absolute serum concentrations and their ratios to cholesterol. This led us to consider whether the ratio of cholestanol and plant sterols to cholesterol might be markers of cholesterol secretion into bile.…”

“…Whereas sitosterol is not metabolized to a significant extent in humans (7), a conversion of cholestanol to bile acids has been reported (6). The ratios of cholestanol, campesterol, and sitosterol to cholesterol in serum have been shown to correlate positively with the cholesterol absorption efficiency (2, 8), and have therefore been regarded as markers for changes in the absorption of cholesterol (8-10).Recently it has been reported that treatment with ursodeoxycholic acid (UDCA), a bile acid known to reduce the hepatic secretion of cholesterol (11-14), increases serum concentrations of plant sterols and cholestanol in patients with primary biliary cirrhosis (15) and patients with radiolucent gallstones (16,17). Considering that cholesterol absorption is not affected or even reduced by UDCA (13,14,(18)(19)(20)(21), we thought that these results were not consistent with the observation that the ratio of plant sterols to cholesterol are only markers of cholesterol absorption efficiency.…”

“…Recently it has been reported that treatment with ursodeoxycholic acid (UDCA), a bile acid known to reduce the hepatic secretion of cholesterol (11)(12)(13)(14), increases serum concentrations of plant sterols and cholestanol in patients with primary biliary cirrhosis (15) and patients with radiolucent gallstones (16,17). Considering that cholesterol absorption is not affected or even reduced by UDCA (13,14,(18)(19)(20)(21), we thought that these results were not consistent with the observation that the ratio of plant sterols to cholesterol are only markers of cholesterol absorption efficiency.…”