From the Guidelines
Ursodeoxycholic acid (UDCA), also known as Urso, reduces gallstone formation through two primary mechanisms: decreasing cholesterol secretion into bile and increasing bile acid solubility.
Mechanisms of Action
- First, UDCA decreases cholesterol secretion into bile by inhibiting hepatic cholesterol synthesis and extraction from blood, resulting in less cholesterol-saturated bile that is less prone to stone formation 1.
- Second, UDCA increases bile acid solubility by altering the composition of bile acids, effectively dissolving existing cholesterol gallstones and preventing new ones from forming, as it is more hydrophilic than other bile acids, which helps maintain cholesterol in solution rather than allowing it to precipitate and form stones 1. These mechanisms make UDCA an effective medication for preventing gallstone formation, particularly in patients at high risk such as those undergoing rapid weight loss or those with certain metabolic conditions that predispose them to gallstone development.
Clinical Evidence
Studies have shown that UDCA can significantly reduce postoperative gallstone formation in patients without gallstones at the time of surgery, with a suggested dose of 500-600 mg per day 1. Although the optimal dose remains controversial, the available evidence supports the use of UDCA as a prophylactic measure against gallstone formation in high-risk patients.
From the FDA Drug Label
Ursodiol suppresses hepatic synthesis and secretion of cholesterol, and also inhibits intestinal absorption of cholesterol Thus, even though administration of high doses (e.g., 15-18 mg/kg/day) does not result in a concentration of ursodiol higher than 60% of the total bile acid pool, ursodiol-rich bile effectively solubilizes cholesterol.
Two ways that Urso (UDCA) reduces gallstone formation are:
- Suppressing hepatic synthesis and secretion of cholesterol: UDCA decreases the amount of cholesterol produced in the liver and secreted into bile, reducing the likelihood of cholesterol precipitation and gallstone formation.
- Inhibiting intestinal absorption of cholesterol: UDCA also reduces the absorption of cholesterol from the intestine, which in turn decreases the amount of cholesterol available for secretion into bile and subsequent gallstone formation 2
From the Research
Mechanisms of Urso (UDCA) in Reducing Gallstone Formation
- Ursodeoxycholic acid (UDCA) reduces the viscosity and sedimentable fractions of gallbladder bile, which may contribute to its ability to reduce gallstone formation 3
- UDCA decreases the concentration of total cholesterol and the percentage of vesicular cholesterol in gallbladder bile, making it less likely for cholesterol crystals to form and eventually develop into gallstones 3
Effects of UDCA on Biliary Lipid Metabolism
- UDCA treatment reduces the formation of cholesterol crystals and the total amount of sedimentable fractions in gallbladder bile, which may explain its ability to attenuate the occurrence of biliary pain and complications in gallstone patients 3
- The combination of UDCA and chenodeoxycholic acid (CDCA) has been shown to have complementary effects on biliary lipid metabolism and cholesterol solubilization, although UDCA alone may be sufficient for reducing gallstone formation 4, 5