From the Guidelines
Ursodeoxycholic acid (UDCA) works primarily by replacing toxic bile acids in the liver and biliary system with a non-toxic bile acid, reducing the concentration of hydrophobic bile acids, decreasing cholesterol saturation in bile, and improving bile flow, as evidenced by studies such as 1 and 1. The mechanism of action of UDCA involves several key processes, including:
- Reducing the concentration of hydrophobic bile acids that can damage cell membranes
- Decreasing cholesterol saturation in bile
- Improving bile flow
- Exerting anti-inflammatory, anti-apoptotic, and immunomodulatory effects
- Protecting hepatocytes by stabilizing cell membranes and preventing cell death
- Stimulating biliary bicarbonate secretion, creating a protective alkaline barrier for cholangiocytes (bile duct cells)
- Enhancing bile acid transport across the liver, improving overall bile flow and reducing the retention of toxic bile acids, as described in 1 and 1.
The standard dosage of UDCA is typically 13-15 mg/kg/day, taken with food to enhance absorption, as recommended in 1. UDCA is generally well-tolerated, with mild gastrointestinal side effects like diarrhea being the most common adverse reaction. However, high doses of UDCA (28-30 mg/kg/day) may be harmful, as suggested by 1. In terms of specific diseases, UDCA is particularly effective for treating cholestatic liver diseases like primary biliary cholangitis, where it can slow disease progression and improve liver biochemistry, as shown in 1 and 1. However, its use in primary sclerosing cholangitis (PSC) is not recommended, as it may not improve outcomes and may even be harmful in high doses, as stated in 1.
Key points to consider when using UDCA include:
- Monitoring liver biochemistry and adjusting the dosage as needed
- Being aware of potential side effects, such as diarrhea
- Avoiding high doses, especially in patients with PSC
- Considering alternative treatments for PSC, as recommended in 1.
From the FDA Drug Label
Ursodiol suppresses hepatic synthesis and secretion of cholesterol, and also inhibits intestinal absorption of cholesterol It appears to have little inhibitory effect on synthesis and secretion into bile of endogenous bile acids, and does not appear to affect secretion of phospholipids into bile. 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. The overall effect of ursodiol is to increase the concentration level at which saturation of cholesterol occurs The various actions of ursodiol combine to change the bile of patients with gallstones from cholesterol-precipitating to cholesterol-solubilizing, thus resulting in bile conducive to cholesterol stone dissolution.
The mechanism of action of Ursodeoxycholic acid (Ursodiol) involves:
- Suppression of hepatic synthesis and secretion of cholesterol
- Inhibition of intestinal absorption of cholesterol
- Solubilization of cholesterol in bile, making it less likely to form gallstones
- Alteration of bile composition, changing it from cholesterol-precipitating to cholesterol-solubilizing, thus resulting in bile conducive to cholesterol stone dissolution 2
From the Research
Udca Mechanism of Action
The mechanism of action of Ursodeoxycholic acid (UDCA) is not fully understood, but several studies have proposed possible mechanisms:
- Improvement of bile acid transport and/or detoxification 3
- Cytoprotection and anti-apoptotic effects 3
- Protection of cholangiocytes against hydrophobic bile acid cytotoxicity 4
- Stimulation of hepatobiliary excretion 4
- Protection of hepatocytes against bile acid-induced apoptosis 4
- Modification of the transcription and translation of proteins essential in the transport of bile acids, correcting the deficit in bile acid secretion in cholestatic liver disease (CLD) 4
- Activation of signaling pathways to translocate bile acid transporters to the sites where they should fulfill their function 4
Clinical Applications
UDCA has been used in the treatment of:
- Cholestatic liver diseases 3, 4
- Gallstone dissolution 3
- Primary biliary cirrhosis 5, 6, 7
- Hepatitis C virus infection to ameliorate elevated alanine aminotransferase levels 3
Effects on Liver Biochemistry and Histology
UDCA has been shown to: