Ursodeoxycholic acid (UDCA), often known as ursodiol, is a naturally occurring bile acid found in small amounts within human bile. It is also manufactured as a medication. Bile acids play a role in the body’s digestive processes, particularly in the absorption of fats and fat-soluble vitamins. UDCA has been used therapeutically for decades and is recognized for its ability to help manage specific conditions affecting the liver and gallbladder.
Therapeutic Applications of UDCA
UDCA serves as a primary treatment for certain hepatobiliary disorders, particularly those involving bile flow.
Primary Biliary Cholangitis (PBC)
Primary Biliary Cholangitis is a chronic autoimmune liver disease characterized by the progressive destruction of small bile ducts within the liver. This leads to cholestasis, a condition where bile flow is impaired, causing inflammation and scarring. UDCA is the first-line therapy for PBC. Administered orally, typically at a dose of 13-15 mg/kg per day, it helps to slow the disease’s progression by improving liver biochemical markers, such as alkaline phosphatase and bilirubin levels. UDCA can delay the progression of fibrosis and cirrhosis, potentially reducing the need for liver transplantation in patients with early-stage PBC.
Gallstone Dissolution
UDCA also offers a non-surgical option for dissolving certain types of gallstones. It is effective for cholesterol gallstones that are radiolucent (not visible on X-ray) and generally less than 20 mm in diameter. This treatment is considered for patients who may not be suitable for surgical removal of their gallbladder (cholecystectomy). UDCA works by reducing cholesterol saturation in bile, making it less likely for new stones to form and helping to gradually dissolve existing ones. Treatment can take several months, with small stones (less than 5 mm) showing high rates of complete dissolution after extended therapy.
How UDCA Works in the Body
The therapeutic effects of UDCA stem from its multifaceted actions within the body, primarily influencing bile acid composition and liver cell function. Unlike more hydrophobic bile acids, UDCA is hydrophilic, contributing to its protective qualities.
Cytoprotective Effect
UDCA provides protection to liver cells (hepatocytes) and bile duct cells (cholangiocytes) from the damaging effects of toxic bile acids that can accumulate in liver conditions. It achieves this by displacing these harmful bile acids from the bile acid pool, shifting the balance towards less toxic, hydrophilic bile acids. This action helps to stabilize cell membranes and prevent cell death (apoptosis). UDCA also helps to mitigate oxidative stress within liver cells by preventing the production of reactive oxygen species by Kupffer cells, which are resident macrophages in the liver.
Choleretic Effect
The compound stimulates the flow of bile from the liver, a process known as choleresis. This action helps to flush out accumulated toxic substances from the liver and biliary system. UDCA increases the secretion of bile acids into the bile ducts. This enhances bile flow, partly by promoting the activity of transport proteins. The resulting bicarbonate-rich bile flow also creates a protective alkaline barrier for the cholangiocytes.
Cholesterol Reduction
UDCA plays a significant role in managing cholesterol levels within the bile, which is directly relevant to its use in gallstone dissolution. It reduces the amount of cholesterol secreted by the liver into the bile. UDCA also inhibits the absorption of cholesterol from the intestine, decreasing the overall cholesterol content in the bile. These combined actions contribute to desaturating bile with cholesterol, making it less prone to forming solid precipitates.
Potential Side Effects and Safety Profile
While generally well-tolerated, UDCA can cause side effects, ranging from common gastrointestinal disturbances to more infrequent, serious reactions.
Common Side Effects
The most frequently reported side effect of UDCA is diarrhea, which occurs in a small percentage of patients. Other common reactions include abdominal discomfort or pain, nausea, and headache. Some individuals might also experience itching or dry skin, muscle or joint pain, dizziness, or a general feeling of paleness. These common side effects are often mild and may resolve as the body adjusts to the medication.
Less Common/Serious Side Effects
Less frequently, more concerning side effects can occur. These include severe right upper abdominal pain or a severe worsening of liver scarring, especially in patients with primary biliary cholangitis. Rarely, gallstones may harden due to calcium buildup. Signs of a serious allergic reaction, such as swelling of the face, eyes, lips, or tongue, difficulty breathing, or widespread itchy skin rashes, require prompt medical evaluation. UDCA is generally not recommended for individuals with complete biliary obstruction, acute inflammation of the gallbladder or bile ducts, or calcified gallstones.
Emerging and Off-Label Uses
Beyond its approved indications, UDCA is explored for its potential benefits in other conditions, though these uses are considered “off-label” and often require more research.
Primary Sclerosing Cholangitis (PSC)
Primary Sclerosing Cholangitis (PSC) is a chronic liver disease where bile ducts become inflamed and scarred, potentially leading to liver damage. While UDCA has been investigated for PSC, its routine use remains controversial. Some studies indicate that high doses (e.g., 28-30 mg/kg/day) might increase the risk of adverse outcomes, including death or the need for liver transplantation. Standard doses (15-20 mg/kg/day) may improve liver biochemistry but have not consistently shown a significant impact on long-term survival or disease progression.
Intrahepatic Cholestasis of Pregnancy (ICP)
Intrahepatic Cholestasis of Pregnancy (ICP) is a liver condition that can develop during pregnancy, causing intense itching and impaired liver function. UDCA is considered the first-line treatment for ICP, often prescribed to relieve maternal itching and improve liver enzyme levels. It is generally considered safe for both the pregnant individual and the fetus, with some evidence suggesting it may reduce the risk of preterm delivery.
Cystic Fibrosis-related Liver Disease (CFLD)
Cystic Fibrosis-related Liver Disease (CFLD) is a common complication of cystic fibrosis, where thick bile can obstruct bile ducts and lead to liver damage. UDCA is used in some cases to manage CFLD, as it can improve bile secretion, liver histology, and liver stiffness. However, its long-term impact on preventing severe outcomes like portal hypertension is still a subject of ongoing discussion and research.