UDCA

Ursodeoxycholic acid, abbreviated UDCA and also called ursodiol, is a bile acid that the body produces in small amounts and that is also manufactured as a medicine for diseases of the liver and bile ducts. It is a secondary bile acid, formed in the gut by bacterial action, and is the epimer of chenodeoxycholic acid, differing only in the orientation of one hydroxyl group; this makes it more water-soluble and less toxic to cells than most bile acids.

The compound owes its name to the Latin ursus, meaning bear, because it was first identified in bear bile, and among mammals bears are unusual in producing it in high proportion. Bear bile has been used in traditional Chinese medicine for well over a thousand years. Chemical synthesis of ursodeoxycholic acid was achieved by Japanese scientists in the 1950s, and the drug was approved in the United States in the late 1980s under the brand name Actigall, later becoming available as a generic.

In medicine, ursodeoxycholic acid is the standard first-line treatment for primary biliary cholangitis, a chronic autoimmune disease of the small bile ducts, where it improves liver blood tests and may slow progression, although trials have not clearly shown a survival benefit ^[2][3]. It is also used to dissolve small, non-calcified cholesterol gallstones by reducing the cholesterol saturation of bile, to relieve itching in intrahepatic cholestasis of pregnancy ^[4], and to prevent gallstones after rapid weight loss such as that following bariatric surgery. It is studied in other cholestatic conditions as well.

At the molecular level the drug works through several complementary actions, replacing more toxic bile acids, protecting liver and bile-duct cells, stimulating bile flow and guarding cells against programmed death ^[1].

Ursodeoxycholic acid is included on the World Health Organization's list of essential medicines and is supplied as capsules, tablets and liquid formulations. It is generally well tolerated; the most common side effect is diarrhoea, thought to arise partly from bacterial conversion back to chenodeoxycholic acid, and other reported effects include abdominal discomfort and, uncommonly, worsening of itching. It is not effective against calcified stones, and prolonged high systemic exposure can be harmful, so treatment is given under medical supervision.

As a prescription drug it should be used under medical guidance. Common side effects include diarrhea and GI upset. It is not appropriate for calcified or pigment gallstones and can interact with other bile acid binding agents. Liver monitoring is standard for its disease uses.

The best-documented interactions with ursodeoxycholic acid are absorptive. Bile acid sequestrants bind it in the gut lumen, and cholestyramine, colestipol and colestimide all reduce how much is absorbed; aluminium hydroxide antacids and smectite do the same. The consequence is simply less drug, so a cholestatic liver disease goes quietly undertreated.

A systematic review of the safety literature also identified metabolic interactions with cytochrome P450 3A substrates, specifically ciclosporin, nitrendipine and dapsone. The ciclosporin signal is not clean; a randomised crossover study in liver transplant recipients found a single 600 mg dose of ursodiol had no effect on ciclosporin absorption, which suggests any real effect belongs to chronic dosing rather than to competition in the gut.

Where ursodeoxycholic acid is being used to dissolve gallstones, estrogens, oral contraceptives and clofibrate work directly against it by raising biliary cholesterol saturation.

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Ursodeoxycholic acid takes its name from the Latin ursus, for bear, because it was first identified in bear bile; Japanese chemists characterized and named the acid in the first half of the twentieth century, and its structure was subsequently confirmed by synthesis. Recognizing that this hydrophilic bile acid was gentler than the body's own cytotoxic bile acids, clinicians in Japan and later worldwide adopted it to dissolve cholesterol gallstones and to treat cholestatic liver disease.

It became the standard first-line therapy for primary biliary cholangitis, where it reliably improves liver biochemistry, and it was approved in the United States as ursodiol in 1987. UDCA now appears on the World Health Organization's List of Essential Medicines, reflecting its established and inexpensive place in hepatology. In a notable modern chapter, a 2022 study in Nature reported that UDCA downregulates the SARS-CoV-2 entry receptor ACE2 by inhibiting the farnesoid X receptor, opening an unexpected line of repurposing research.

UDCA is one of the best-regarded bile acids in medicine, valued for its long clinical track record, low cost, and favorable tolerability. In primary biliary cholangitis it remains the cornerstone of treatment, and its ability to remodel the bile acid pool toward a less toxic composition gives it a clear and well-understood rationale. Beyond the liver, the discovery that it can suppress the ACE2 receptor and reduce SARS-CoV-2 infection across organoids, animals, and human tissues drew considerable scientific excitement and prompted interest in its use as a potential preventive agent.

Its taurine conjugate's chaperone activity has further fueled exploration in neuroprotective and metabolic settings, including trials in amyotrophic lateral sclerosis. While some of these newer applications are still being evaluated, UDCA's combination of proven efficacy and surprising versatility keeps it a compound of enduring interest.