Ursodiol is the drug name for ursodeoxycholic acid (UDCA), a bile acid that is normally present in small amounts in human bile. In the US it is a prescription medicine, sold first as Actigall capsules (approved in 1987) and later as URSO 250 and URSO Forte tablets (approved in 1997), and now mostly as generics.
The FDA-approved uses are narrow: dissolving certain gallstones, preventing gallstones during rapid weight loss, and treating primary biliary cholangitis (PBC), an autoimmune disease of the small bile ducts. In bodybuilding circles it is often described as “liver protection” during oral steroid use. No controlled trial has tested that use; the human evidence for steroid-related liver injury consists of case reports and case series.
This page summarizes what the FDA labels, the clinical trials and published reviews report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Hydrophilic bile acid (3α,7β-dihydroxy-5β-cholan-24-oic acid) |
| Brands and approval | Actigall capsules (NDA 019594, approved Dec 31, 1987); URSO 250 / URSO Forte tablets (NDA 020675, approved Dec 10, 1997; now listed as discontinued); generics |
| Route | Oral capsules and tablets |
| Strengths on US labels | 300 mg capsules; 250 mg and 500 mg tablets; 200 mg and 400 mg capsules are also listed on DailyMed |
| Labeled adult doses | Gallstone dissolution: 8–10 mg/kg/day; gallstone prevention: 300 mg twice daily; PBC: 13–15 mg/kg/day |
| Half-life | No plasma half-life on the US labels; bile levels reach steady state in about 3 weeks and fall to 5–10% of that level about 1 week after stopping |
| Main mechanism | Replaces more toxic, water-repelling bile acids in the bile pool and lowers the cholesterol saturation of bile |
| US status | Prescription only (Rx); no controlled-substance schedule on the label |
| WADA status | Not named on the 2026 Prohibited List |
The library also has a separate entry for UDCA, the same molecule listed as a supplement, and for TUDCA, its taurine-conjugated form. This page covers ursodiol as an approved prescription drug.
What it is
Ursodiol is a dihydroxy bile acid with the formula C₂₄H₄₀O₄ and a molecular weight of about 392.6 g/mol. It is a bitter white powder that is practically insoluble in water. The labels note that it occurs in small amounts in normal human bile and in larger amounts in the bile of certain bear species (URSO label).
Ursodiol is closely related to chenodiol (chenodeoxycholic acid), an older gallstone drug, and part of an ursodiol dose is converted to chenodiol in the body. The label describes ursodiol as hydrophilic (water-attracting), in contrast to the hydrophobic bile acids that are toxic to the liver when they build up.
The URSO label lists these mechanisms:
- Bile acid replacement. With regular dosing, ursodiol becomes a major bile acid and displaces the more toxic, hydrophobic bile acids that build up in cholestatic liver disease (disease where bile flow is impaired).
- Bile duct protection. It protects the cells lining the bile ducts (cholangiocytes) from the toxic effects of bile acids.
- Anti-apoptotic and immune effects. It inhibits programmed death of liver cells and has immunomodulatory effects.
- Increased bile flow. It stimulates bile secretion by liver cells and bile duct cells.
For gallstones, the capsule label adds that ursodiol lowers liver cholesterol output and intestinal cholesterol absorption. It also keeps cholesterol dispersed in bile as liquid crystals, so bile changes from cholesterol-precipitating to cholesterol-dissolving (ursodiol capsule label).
| Compound | Relationship | Library page |
|---|---|---|
| Ursodiol (UDCA) | Unconjugated bile acid; the FDA-approved drug | This page |
| UDCA | Same molecule, listed as a supplement | UDCA |
| TUDCA | UDCA conjugated with taurine; the liver also forms it from ursodiol | TUDCA |
Pharmacokinetics
Ursodiol acts mainly in the liver, bile and gut, not in the bloodstream. It cycles between the gut and the liver many times (enterohepatic circulation), so only small amounts reach the general circulation (Crosignani et al., Clin Pharmacokinet 1996).
| Parameter | What the labels report |
|---|---|
| Absorption | About 90% absorbed in the small bowel (capsule label); the URSO label calls absorption incomplete |
| Liver uptake | About 50% extracted on first pass in people without liver disease; less as liver disease worsens (URSO label) |
| Metabolism | Conjugated in the liver with glycine or taurine, secreted into bile, then reabsorbed; gut bacteria convert some to lithocholic acid and 7-keto-lithocholic acid |
| Share of bile acid pool | Normally about 5%; 30–50% of biliary and plasma bile acids at 13–15 mg/kg/day (URSO label); not above 60% even at 15–18 mg/kg/day (capsule label) |
| Protein binding | At least 70% (unconjugated form, healthy subjects) |
| Time to steady state in bile | About 3 weeks |
| Washout | Bile levels fall to about 5–10% of steady state about 1 week after stopping |
| Excretion | Mainly in feces; urinary excretion under 1% except in severe cholestasis |
Neither US label gives a conventional plasma half-life. In cholestatic liver disease, liver uptake and biliary secretion of ursodiol are reduced. This leads to lower bile enrichment and higher blood levels than in healthy people (Crosignani et al., Clin Pharmacokinet 1996).
One metabolite matters for safety. Lithocholic acid, formed by gut bacteria, causes cholestatic liver injury in animals that cannot sulfate it. Humans can sulfate it, and ursodiol produces less lithocholic acid than an equal dose of chenodiol. The labels note that some people may have reduced sulfation capacity, although this has not been clearly shown.
Approved medical use
| Indication | Product | Labeled adult dose |
|---|---|---|
| Dissolving radiolucent, noncalcified gallbladder stones under 20 mm, in patients at high surgical risk or who refuse surgery | Capsules (Actigall and generics) | 8–10 mg/kg/day in 2–3 divided doses |
| Preventing gallstones in obese patients losing weight rapidly | Capsules | 600 mg/day (300 mg twice daily) |
| Primary biliary cholangitis | Tablets (URSO 250, URSO Forte and generics) | 13–15 mg/kg/day in 2–4 divided doses with food |
The capsule label states that safety beyond 24 months of use for gallstones is not established. It also warns that dissolution takes months, does not happen in every patient, and that stones come back within 5 years in up to 50% of patients whose stones dissolved (ursodiol capsule label).
Drugs@FDA lists Actigall 300 mg as a current prescription product. The URSO 250 and URSO Forte brands are listed as discontinued, with generic tablets still on DailyMed (Drugs@FDA NDA 019594; Drugs@FDA NDA 020675).
What the research shows
Gallstone dissolution
The capsule label pooled 8 studies with 868 patients treated for 6 to 78 months at about 5–20 mg/kg/day. About 8–10 mg/kg/day was the best dose. At about 10 mg/kg/day for up to 2 years, complete dissolution occurred in about 30% of unselected patients with uncalcified stones under 20 mm. It occurred in 81% of patients with stones up to 5 mm. Calcified stones and stones over 20 mm rarely dissolved.
Gallstone prevention during rapid weight loss
Two double-blind, placebo-controlled trials enrolled 1,316 obese patients. Gallstone rates from the label’s intent-to-treat analysis (ursodiol capsule label):
| Trial | Placebo | 300 mg/day | 600 mg/day | 1,200 mg/day |
|---|---|---|---|---|
| Very-low-calorie diet, 16 weeks (n = 1,004, BMI ≥ 38) | 23% | 6% | 3% | 2% |
| Gastric bypass, 6 months (n = 312, BMI ≥ 40) | 23% | 9% | 1% | 5% |
Weight loss was similar across arms in both trials. The published reports analyzed patients with follow-up ultrasound and give somewhat higher placebo rates: 28% vs 3% on 600 mg/day in the diet trial (Shiffman et al., Ann Intern Med 1995), and 32% vs 2% on 600 mg/day in the 233 bypass patients with at least one scan (Sugerman et al., Am J Surg 1995).
Primary biliary cholangitis
The URSO label rests on two 2-year randomized, placebo-controlled trials. Results below are as reported on the URSO label:
| Trial | Design | Main result |
|---|---|---|
| US multicenter (Lindor et al., Gastroenterology 1994) | n = 180; 13–15 mg/kg/day in 3–4 doses | Treatment failure 23% vs 47% on placebo (p under 0.01); deaths or transplants 7 vs 12 in the published report (p = 0.18, not significant) |
| Canadian multicenter (Heathcote et al., Hepatology 1994) | n = 222; 14 mg/kg/day once daily | Median bilirubin −17% vs +20%; transaminases −41% vs +6%; alkaline phosphatase −48% vs −6%; no difference in symptoms, death or transplant in the published report |
Whether this biochemical improvement translates into longer survival has been debated:
- A Cochrane review of 16 randomized trials (1,447 patients) found no significant effect on all-cause mortality (RR 0.97, 95% CI 0.67–1.42) or on death or transplant. UDCA did lower bilirubin and alkaline phosphatase (mean difference −257 U/L) and slowed histologic progression. All but one trial had a high risk of bias (Rudic et al., Cochrane 2012).
- An international cohort of 3,902 patients found 10-year transplant-free survival of 79.7% with UDCA vs 60.7% without (hazard ratio 0.46, 95% CI 0.40–0.52) (Harms et al., J Hepatol 2019). This was an observational study, so it cannot fully rule out differences between treated and untreated patients.
Drug-induced and steroid-related liver injury
Ursodiol is not approved for drug-induced liver injury (DILI). A 2021 systematic review found 33 publications: 25 case reports and 8 case series, with no adequate randomized trial. In 18 of the 25 case reports the authors described improvement with UDCA; 7 showed no clinical or biochemical improvement. The authors concluded that the study designs do not allow a firm conclusion on efficacy (Robles-Díaz et al., Front Pharmacol 2021).
For anabolic-androgenic steroids specifically, a 2020 review assessed 52 published cases of steroid-induced liver injury, most often linked to methyldrostanolone (methasterone) (Abeles et al., BMJ Open Gastroenterol 2020). The typical pattern was jaundice and itching with “bland” cholestasis (blocked bile flow without much inflammation). Key findings:
- 12 patients received UDCA alone and 12 received UDCA with corticosteroids. In 3 of those, steroids were added because UDCA had “failed”.
- The authors note that most cases resolve on their own once the steroid is stopped, and that all treatment data come from uncontrolled case reports.
- In one of their own cases, bilirubin kept rising despite UDCA and fell only after prednisolone was started.
- 43% of patients developed kidney injury. No patient died or needed a liver transplant.
No published trial has tested ursodiol taken alongside oral 17α-alkylated steroids (such as oxymetholone, methyltestosterone or stanozolol) to prevent liver injury.
About “liver protection” on cycle. UDCA is often presented as making oral steroids safe for the liver. The evidence does not show this. There are no prevention trials in steroid users, treatment evidence is limited to case reports with mixed results, and lower liver enzymes on UDCA do not by themselves show that the underlying injury has stopped.
Conditions where trials were negative
Several large trials found that ursodiol improved blood tests without improving clinical outcomes:
| Condition | Trial | Dose | Result |
|---|---|---|---|
| Nonalcoholic steatohepatitis (fatty liver with inflammation) | Lindor et al., Hepatology 2004; n = 166, 2 years | 13–15 mg/kg/day | No difference vs placebo in steatosis, inflammation or fibrosis on biopsy |
| Primary sclerosing cholangitis | Lindor et al., Hepatology 2009; n = 150, stopped at 6 years for futility | 28–30 mg/kg/day | Primary endpoints in 39% vs 26%; risk 2.3 times higher on UDCA; serious adverse events 63% vs 37% |
| Intrahepatic cholestasis of pregnancy | PITCHES, Chappell et al., Lancet 2019; n = 605 | 1,000 mg/day (adjustable) | Adverse perinatal outcome 23% vs 27% (adjusted RR 0.85, 95% CI 0.62–1.15), not significant |
The sclerosing cholangitis trial is the main evidence that very high doses, about twice the PBC dose, can cause harm in some liver diseases.
Ursodiol vs TUDCA
One double-blind trial randomized 199 Chinese patients with PBC to TUDCA or UDCA, 250 mg three times daily, for 24 weeks. Alkaline phosphatase fell by more than 25% in 76% vs 81% of patients (p = 0.453). Itching increased in the UDCA group but not the TUDCA group (Ma et al., Medicine 2016). See TUDCA for more.
Side effects and risks
Common side effects
In the gallstone trials, most side effects occurred at similar rates on ursodiol and placebo (ursodiol capsule label):
| Adverse event | Dissolution: ursodiol 8–10 mg/kg/day (n = 155) | Dissolution: placebo (n = 159) | Prevention: ursodiol 600 mg/day (n = 322) | Prevention: placebo (n = 325) |
|---|---|---|---|---|
| Diarrhea | 27.1% | 21.4% | 25.2% | 20.9% |
| Dyspepsia | 16.8% | 11.3% | not listed | not listed |
| Nausea | 14.2% | 17.0% | 17.4% | 13.2% |
| Abdominal pain | 43.2% | 44.0% | 6.2% | 12.0% |
| Dizziness | not listed | not listed | 16.5% | 12.9% |
| Back pain | 7.1% | 11.3% | 11.8% | 6.5% |
The URSO label lists the most common reactions in PBC use (≥1%) as abdominal discomfort, abdominal pain, hair loss (alopecia), diarrhea, nausea, itching and rash (URSO label).
Liver tests and jaundice
Postmarketing reports include rises in ALT, AST, alkaline phosphatase, GGT and bilirubin, and jaundice or worsening of existing jaundice. The URSO label advises liver tests every month for the first 3 months, then every 6 months. It says stopping should be considered if values rise to a clinically significant level in patients whose tests were previously stable.
Enteroliths
Rare postmarketing reports describe enteroliths (bezoars, hard masses in the intestine) that caused obstruction and needed surgery. These occurred in patients with intestinal narrowing or slow transit, such as after bowel surgery or with Crohn’s disease. Both labels advise holding ursodiol if obstructive symptoms appear.
Interactions
Both labels list the same interactions:
- Bile acid sequestrants (cholestyramine, colestipol) can reduce ursodiol absorption.
- Aluminum-based antacids bind bile acids in vitro and may act the same way.
- Estrogens, oral contraceptives and clofibrate (and perhaps other lipid-lowering drugs) increase liver cholesterol secretion and may counteract ursodiol’s effect on gallstones.
Who should not use it
- People with complete biliary obstruction, or with known hypersensitivity to ursodiol or bile acids.
- For gallstone treatment: people with calcified, radiopaque or bile pigment stones, which ursodiol cannot dissolve. Also people with acute cholecystitis, cholangitis, biliary obstruction, gallstone pancreatitis or a biliary–intestinal fistula, who need surgery or other care instead.
Pregnancy
The current URSO label states that published data from trials, observational studies and case series have not identified a drug-associated risk of major birth defects, miscarriage or other adverse outcomes. Most exposures were in the second and third trimesters. The generic capsule label, written in an older format, says the drug is not recommended in pregnancy.
Legal status and use outside medicine
Ursodiol is a prescription-only drug in the US. It does not appear on the WADA 2026 Prohibited List. Its use by people taking anabolic steroids is off-label, and as described above, no trial supports it as a preventive measure.
Key takeaways
- An approved bile acid drug with narrow uses. The FDA-approved uses are gallstone dissolution, gallstone prevention during rapid weight loss, and primary biliary cholangitis.
- Best evidence is in gallstone prevention. At 600 mg/day, gallstone rates during rapid weight loss fell from 23% on placebo to 1–3%.
- Better blood tests do not always mean better outcomes. In PBC, randomized trials showed biochemical gains but no clear survival effect, while a large cohort suggests longer transplant-free survival. Trials in fatty liver and pregnancy cholestasis were negative.
- High doses can be harmful. At 28–30 mg/kg/day in sclerosing cholangitis, serious adverse events and clinical endpoints were more common than on placebo.
- No proof of “liver protection” for steroid users. Evidence in steroid-related liver injury comes from case reports with mixed results, and most cases resolve after the steroid is stopped.
- Generally well tolerated. Diarrhea and other GI effects are the most common side effects; the labels recommend periodic liver tests.
Sources
- Allergan. URSO 250 and URSO Forte (ursodiol) tablets prescribing information, revised January 2023. DailyMed.
- Actavis Pharma. Ursodiol capsules USP, 300 mg, prescribing information. DailyMed.
- Food and Drug Administration. Drugs@FDA: Actigall (ursodiol), NDA 019594. FDA.
- Food and Drug Administration. Drugs@FDA: URSO 250 and URSO Forte (ursodiol), NDA 020675. FDA.
- Crosignani A, Setchell KD, Invernizzi P, et al. Clinical pharmacokinetics of therapeutic bile acids. Clin Pharmacokinet. 1996;30(5):333–358. PubMed.
- Shiffman ML, Kaplan GD, Brinkman-Kaplan V, et al. Prophylaxis against gallstone formation with ursodeoxycholic acid in patients participating in a very-low-calorie diet program. Ann Intern Med. 1995;122(12):899–905. PubMed.
- Sugerman HJ, Brewer WH, Shiffman ML, et al. A multicenter, placebo-controlled, randomized, double-blind, prospective trial of prophylactic ursodiol for the prevention of gallstone formation following gastric-bypass-induced rapid weight loss. Am J Surg. 1995;169(1):91–96. PubMed.
- Lindor KD, Dickson ER, Baldus WP, et al. Ursodeoxycholic acid in the treatment of primary biliary cirrhosis. Gastroenterology. 1994;106(5):1284–1290. PubMed.
- Heathcote EJ, Cauch-Dudek K, Walker V, et al. The Canadian Multicenter Double-blind Randomized Controlled Trial of ursodeoxycholic acid in primary biliary cirrhosis. Hepatology. 1994;19(5):1149–1156. PubMed.
- Rudic JS, Poropat G, Krstic MN, et al. Ursodeoxycholic acid for primary biliary cirrhosis. Cochrane Database Syst Rev. 2012;(12):CD000551. PubMed.
- Harms MH, van Buuren HR, Corpechot C, et al. Ursodeoxycholic acid therapy and liver transplant-free survival in patients with primary biliary cholangitis. J Hepatol. 2019;71(2):357–365. PubMed.
- Robles-Díaz M, Nezic L, Vujic-Aleksic V, et al. Role of ursodeoxycholic acid in treating and preventing idiosyncratic drug-induced liver injury. A systematic review. Front Pharmacol. 2021;12:744488. PubMed.
- Abeles RD, Foxton M, Khan S, et al. Androgenic anabolic steroid-induced liver injury: two case reports assessed for causality by the updated Roussel Uclaf Causality Assessment Method (RUCAM) score and a comprehensive review of the literature. BMJ Open Gastroenterol. 2020;7(1):e000549. PubMed.
- Lindor KD, Kowdley KV, Heathcote EJ, et al. Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology. 2004;39(3):770–778. PubMed.
- Lindor KD, Kowdley KV, Luketic VA, et al. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology. 2009;50(3):808–814. PubMed.
- Chappell LC, Bell JL, Smith A, et al. Ursodeoxycholic acid versus placebo in women with intrahepatic cholestasis of pregnancy (PITCHES): a randomised controlled trial. Lancet. 2019;394(10201):849–860. PubMed.
- Ma H, Zeng M, Han Y, et al. A multicenter, randomized, double-blind trial comparing the efficacy and safety of TUDCA and UDCA in Chinese patients with primary biliary cholangitis. Medicine (Baltimore). 2016;95(47):e5391. PubMed.
- World Anti-Doping Agency. The 2026 Prohibited List. WADA 2026 Prohibited List.