Chenodeoxycholic acid, or CDCA, is a naturally occurring bile acid produced in the human liver. It plays a fundamental role in the body’s digestive processes and overall metabolism. As a primary bile acid, CDCA is involved in breaking down dietary fats and facilitating the absorption of fat-soluble nutrients. This compound is a key participant in the body’s complex system for managing lipids and maintaining digestive health.
Its Natural Function
Chenodeoxycholic acid is one of the two primary bile acids synthesized in the liver from cholesterol. This synthesis helps the body eliminate excess cholesterol. Once formed, CDCA is conjugated with amino acids like glycine or taurine, increasing its solubility before secretion into bile.
Bile, containing CDCA, is stored in the gallbladder and released into the small intestine after meals. In the intestine, CDCA aids in the emulsification of dietary fats, breaking them into smaller droplets. This increases the surface area for digestive enzymes, facilitating the absorption of fats and fat-soluble vitamins.
After assisting in digestion, CDCA and other bile acids are reabsorbed in the small intestine. They then travel back to the liver through the portal vein, a process known as enterohepatic circulation. This recycling mechanism allows the body to reuse its bile acid pool, minimizing the need for constant new synthesis.
Treating Cerebrotendinous Xanthomatosis
Chenodeoxycholic acid is an established treatment for cerebrotendinous xanthomatosis (CTX), a rare genetic disorder. CTX arises from mutations in the CYP27A1 gene, which leads to a deficiency in the sterol 27-hydroxylase enzyme. This enzyme deficiency impairs normal bile acid synthesis, particularly CDCA, resulting in the accumulation of cholestanol and other abnormal cholesterol metabolites in various tissues.
CDCA therapy works by replacing the deficient bile acid and suppressing the abnormal metabolic pathways that lead to cholestanol buildup. By providing CDCA, the body’s own production of cholestanol is reduced by influencing cholesterol synthesis. This action normalizes bile acid synthesis and lowers harmful cholestanol levels in the blood and tissues.
Treatment with CDCA can impact the progression of CTX, especially when initiated early. It can stabilize or improve many neurological symptoms and may prevent further disease progression. CDCA treatment can normalize biochemical markers and lead to clinical improvements in patients.
Past Use for Gallstones
Historically, chenodeoxycholic acid was one of the first oral medications used to dissolve cholesterol gallstones. It gained approval for this use in the early 1980s. CDCA works by altering the composition of bile by reducing the liver’s production and secretion of cholesterol.
By decreasing the amount of cholesterol secreted into bile, CDCA helps to desaturate the bile, making it less prone to forming cholesterol crystals and stones. This change in bile composition can lead to the gradual dissolution of existing cholesterol gallstones, particularly smaller, non-calcified ones. Treatment typically required prolonged administration, often for two years or more, with dissolution rates ranging from 15% to 30%.
CDCA’s use for gallstone dissolution has largely been superseded by other treatments. Ursodeoxycholic acid (UDCA), another bile acid, emerged as a more effective and better-tolerated alternative, with fewer side effects. Laparoscopic cholecystectomy, a minimally invasive surgical procedure to remove the gallbladder, has also reduced the need for medical therapy for gallstones.
Important Safety Information
While well-tolerated, chenodeoxycholic acid medication can cause side effects. One of the most common is diarrhea, which can range from mild to severe. Other potential gastrointestinal issues include abdominal pain, nausea, and vomiting.
CDCA can also lead to transient elevations in liver enzyme levels, which typically resolve even with continued treatment. Regular monitoring of liver function through blood tests is important for individuals taking CDCA to detect any changes. Increases in cholesterol levels have also been observed.
Chenodeoxycholic acid is contraindicated in individuals with certain liver conditions, such as cirrhosis or significant hepatocyte dysfunction, and in those with bile duct obstructions. It is not recommended for use during pregnancy, as animal studies have shown reproductive toxicity. Women of childbearing potential should use effective contraception. Medical supervision is necessary when using CDCA to ensure appropriate dosing and to manage any potential adverse effects.