Tauroursodeoxycholic Acid: Liver, Insulin and Nerve Disease Trials

Tauroursodeoxycholic acid (TUDCA), also called taurursodiol, is a bile acid made by joining ursodeoxycholic acid to the amino acid taurine. Its history runs from dried bear bile in old Chinese medicine to small liver trials in Italy and China, then to a United States approval for amyotrophic lateral sclerosis that was later withdrawn. This page goes through the human trials one at a time, including the ones that found nothing, and keeps cell and animal work apart from them.

Three results frame the rest of the page. In primary biliary cholangitis, it matched ursodeoxycholic acid on liver blood tests in short trials. In a small study of obese adults, it raised insulin sensitivity in liver and muscle over four weeks. In amyotrophic lateral sclerosis, a small early trial looked promising, but the larger European phase 3 trial of the drug alone did not meet its main goal. The trials that led to the United States approval tested a different thing: tauroursodeoxycholic acid combined with sodium phenylbutyrate.

The site's Bile Flow and TUDCA article covers how bile moves and how this compound is used in detox practice. This page covers the drug itself and its trial record.

Table of Contents

  1. What This Bile Acid Is and Where It Occurs
  2. Bear Bile: The History Behind the Molecule
  3. How It Differs From Ursodeoxycholic Acid
  4. Trials in Primary Biliary Cholangitis
  5. Other Liver Trials, Including Null Results
  6. Insulin Sensitivity, Blood Vessels and Type 1 Diabetes
  7. Amyotrophic Lateral Sclerosis: The Drug Alone
  8. Amyotrophic Lateral Sclerosis: The Combination With Sodium Phenylbutyrate
  9. Multiple Sclerosis, Ulcerative Colitis and Wolfram Syndrome
  10. Retinal Studies: Cells and Animals
  11. Brain and Nerve Disease in Cells and Animals
  12. Reported Side Effects
  13. Reported Interactions
  14. Key Research Papers
  15. Connections
  16. Featured Videos

What This Bile Acid Is and Where It Occurs

Bile acids are made in the liver and released into the intestine, where their main job is to help digest fat (Daruich 2019). More water-repelling bile salts can damage cells, and in laboratory work conjugates of ursodeoxycholic acid protected rat liver cells and human red blood cells against them (Heuman 1991). Tauroursodeoxycholic acid is one of these water-loving bile acids. A 2014 review describes it as the taurine conjugate of ursodeoxycholic acid, meaning the same bile acid with a taurine molecule attached (Vang 2014).

It occurs naturally in the human body. A 2025 review classes it as a secondary bile acid (Vavrušáková 2025), the group formed with the help of gut bacteria, and another paper calls it a microbial bile acid (Moon 2025). The natural source best known in medicine is not human, though: it is the bile of bears.

Modern supply no longer depends on animals of that kind. A 2024 review describes an industrial process that starts from chicken bile powder and uses two enzymes to make the compound (Shijing 2024). A 2025 laboratory paper reports yeast strains engineered to turn chenodeoxycholic acid, a more widely available bile acid, into tauroursodeoxycholic acid (Moon 2025).

Its regulatory position is uneven. Ursodeoxycholic acid is approved by the U.S. Food and Drug Administration for certain cholestatic liver diseases, meaning diseases where bile flow is impaired (Vang 2014). Tauroursodeoxycholic acid on its own has no such approval described in these sources; an Italian research group calls it a commercial drug (Zucchi 2023), and it is sold as a dietary supplement in the United States. Its only United States drug approval came as part of the combination described below, and that approval has been withdrawn.

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Bear Bile: The History Behind the Molecule

Bear bile has been used in traditional Chinese medicine for thousands of years, according to a 2009 review of the subject (Feng 2009). A 2014 review gives the figure as more than 3,000 years for this family of bile acids in Chinese medicine (Vang 2014). Those are statements about use. They do not show that the old preparations worked for the conditions they were given for.

Chemistry explains why bears matter here. A 1993 study measured the bile of six bear species, the giant panda, the red panda and 11 related carnivores (Hagey 1993). Bile acids in all of these species were joined only to taurine. Ursodeoxycholic acid was present in every bear species, averaging 1% to 39% of bile acids depending on the species, and was absent or present only as a trace in the other animals, including the giant panda. American black bears averaged 34%, with a range of 0% to 62%. Polar bears averaged 17% and brown bears 18%. Samples from bears with a surgical bile fistula showed it was formed in the liver itself rather than by gut bacteria. Because bear bile acids carry taurine, the ursodeoxycholic acid in that bile is present in the taurine-joined form this page is about.

The trade has had a heavy cost. Feng and colleagues report that heavy use made bears endangered, and that bear farming began in China in the 1980s, drawing bile from living animals through a fistula. They call the practice extremely inhumane and report that many farmed bears died of illness, including chronic infections and liver cancer. Their review looks at three kinds of replacement: pure compounds from bear bile, bile from other animals, and herbs. Later papers describe the chicken-bile and yeast routes mentioned above as replacements for the same reason (Shijing 2024; Moon 2025).

Crude bear bile is not the same thing as the purified compound. A 2025 case report from Bhutan describes liver injury in a middle-aged woman after she consumed bear bile, and its authors state that consuming it can cause severe liver toxicity (Rabjay 2025). The trials below all used a prepared drug, not raw bile.

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How It Differs From Ursodeoxycholic Acid

The two drugs are close relatives, and the body moves between their forms. A study of patients with primary biliary cirrhosis (the older name for primary biliary cholangitis) found that swallowed tauroursodeoxycholic acid undergoes significant removal and re-attachment of its taurine or glycine as it cycles between liver and gut (Setchell 1996). So a person taking it ends up with a mix of forms in bile, not only the form swallowed.

The differences that have been measured are about absorption and breakdown. In a randomized crossover study, 12 women with the disease took each drug at 750 mg a day for 2 months (Invernizzi 1999). The results:

That conclusion rests on chemistry in bile and stool. The largest head-to-head trial, described next, found similar blood test results for the two drugs. There is also a practical difference in standing: ursodeoxycholic acid is the drug with the regulatory approval, and the comparison trials below all measured short-term blood markers.

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Trials in Primary Biliary Cholangitis

Primary biliary cholangitis is a chronic autoimmune disease of the small bile ducts in the liver. Older papers call it primary biliary cirrhosis. This is the condition in which tauroursodeoxycholic acid has the most direct human testing.

Dose-response study, 1996. In Italy, 24 patients were randomly assigned to 500, 1,000 or 1,500 mg a day for six months (Crosignani 1996). Liver enzyme levels fell significantly after the first month at all three doses, with no significant difference among them, though further reductions over time occurred at the two higher doses. Total cholesterol and high-density lipoprotein cholesterol fell significantly at the two higher doses. Diarrhea was the only side effect. The authors named a dose of about 10 mg per kg of body weight per day for long-term studies. A metabolism study using the same doses reported ursodeoxycholate at 34.4%, 32.8% and 41.6% of bile acids in bile (Setchell 1996).

Crossover study, 1997. Twenty-three patients took both drugs at 500 mg a day, in random order, for two 6-month periods separated by a 3-month break (Larghi 1997). Liver enzymes improved on both, with no significant difference between them. No patient reported side effects. The authors described the drug as safe and at least as effective as ursodeoxycholic acid in the short term.

Multicenter trial in China, 2016. This is the largest comparison. A total of 199 patients were randomized to 250 mg of either drug three times a day for 24 weeks, with a double-dummy placebo design (Ma 2016). The main measure was the share of patients whose alkaline phosphatase, a liver enzyme, fell by more than 25%:

The authors concluded that it was as efficacious as ursodeoxycholic acid and may relieve symptoms better. All of these studies lasted 6 months or less per treatment period and report liver blood tests. Their abstracts report no survival or transplant outcomes.

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Other Liver Trials, Including Null Results

Outside primary biliary cholangitis the record is mixed, and several results were null.

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Insulin Sensitivity, Blood Vessels and Type 1 Diabetes

Interest in diabetes began with endoplasmic reticulum stress. The endoplasmic reticulum is the part of a cell that folds proteins, and when it is overloaded the cell starts a stress response. Tauroursodeoxycholic acid is described as a chemical chaperone, a small molecule that helps proteins hold their shape. In obese and diabetic mice, it and 4-phenylbutyric acid normalized high blood sugar, restored insulin sensitivity and resolved fatty liver (Ozcan 2006).

The insulin-sensitivity trial in people. Twenty obese adults with an average body mass index of 37 were randomized to 1,750 mg a day or placebo for 4 weeks (Kars 2010). Researchers measured insulin action directly, using a two-stage insulin clamp with tracers and muscle and fat biopsies. The results:

The authors wrote that further studies are needed to identify the target cells and mechanisms. It remains a small, short study that measured insulin action, not diabetes outcomes.

Blood vessels after sugar. In a randomized crossover study, 12 young healthy adults took 1,500 mg or placebo capsules before a glucose drink (Walsh 2016). Artery widening, a test of blood vessel function called flow-mediated dilation, fell 32% at 60 minutes and 28% at 120 minutes on placebo, and changed by -4% and +0.3% on the drug. Blood glucose and insulin were not altered by the drug.

Type 1 diabetes. The drug markedly reduced the incidence of diabetes in two mouse models of type 1 diabetes when given before the disease began (Engin 2013). A randomized trial then tested it in people with newly diagnosed type 1 diabetes: 1,750 mg a day or placebo for 12 months, with 20 people enrolled. Results posted on the U.S. trial registry show change in C-peptide, a measure of the body's own insulin production, of -0.07 on both arms at 6 months, -0.10 on placebo and -0.12 on the drug at 12 months, and -0.11 and -0.14 at 18 months (units of nmol/L times 120 minutes; ClinicalTrials.gov NCT02218619). The registry posts no statistical comparison, and those posted numbers show no visible advantage. It lists no serious or other adverse events among the 10 people in each arm. No peer-reviewed report of this trial turned up in the searches for this page.

Age-related changes in mice. In 18-month-old mice, it lowered high insulin levels and improved glucose control (Zangerolamo 2022). In a separate study of aged mice, 20 days of treatment increased muscle mass and muscle insulin sensitivity (Carvalho 2026). These are mouse results. A 2026 meta-analysis of four preclinical studies looked at insulin-secreting beta cells, again in cell lines, rats and mice, and pooled this drug with 4-phenylbutyrate (Ramos-Jiménez 2026).

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Amyotrophic Lateral Sclerosis: The Drug Alone

Amyotrophic lateral sclerosis destroys the nerve cells that control muscles. Trials usually track it with the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised, a 48-point score of daily function that falls as the disease advances.

The small early trial. Thirty-four patients already taking riluzole were randomized to 1 g of tauroursodeoxycholic acid twice daily or placebo for 54 weeks, after a 3-month lead-in period (Elia 2016). A responder was someone whose rate of decline improved by at least 15%. Responders made up 87% on the drug and 43% on placebo (P = .021). Function at the end of the study was higher on the drug (P = .007), and adverse events did not differ. The authors called the data preliminary. A later re-analysis of the same patients found a mean survival difference of 1 month, which did not reach significance (log-rank P = .092), with a borderline Cox regression result (P = .055) (Reggiardo 2023).

A registry study. In the Emilia Romagna region of Italy, 86 patients who took the drug were matched with 172 who did not (Zucchi 2023). Median survival was 49.6 months with the drug and 36.2 months in controls. The lower risk of death was seen at higher doses of 1,000 mg a day or more (hazard ratio 0.56; 95% confidence interval 0.38 to 0.83). This was a retrospective study, treatment was not assigned at random, and the authors called it exploratory.

The European phase 3 trial. This trial was built to settle the question. It was randomized, double-blind and placebo-controlled, gave the drug or placebo in addition to riluzole for 18 months, and counted as a response at least a 20% improvement in the rate of decline (Albanese 2022; Lombardo 2023). The study team announced top-line results on March 27, 2024:

The team said subgroup analyses were continuing and that full results would be presented later. As of November 2026, the searches for this page found a protocol and an analysis plan in PubMed but no peer-reviewed paper of the results, and the U.S. trial registry shows no posted results for this trial (ClinicalTrials.gov NCT03800524). The result on this page therefore comes from the team's own press release, and details such as effect sizes are not available here.

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Amyotrophic Lateral Sclerosis: The Combination With Sodium Phenylbutyrate

The best-known trials of this drug in amyotrophic lateral sclerosis did not test it alone. They tested it combined with sodium phenylbutyrate, a second compound, so their results apply to the pair and cannot be assigned to either ingredient.

The phase 2 trial, CENTAUR. A total of 137 participants were assigned 2:1 to the combination or placebo; the combination gave 3 g of sodium phenylbutyrate and 1 g of tauroursodeoxycholic acid once a day for 3 weeks and then twice a day (Paganoni 2020). Over 24 weeks, the function score fell by 1.24 points a month on the combination and 1.66 on placebo, a difference of 0.42 points (95% confidence interval 0.03 to 0.81; P = .03). Secondary outcomes did not differ significantly. Side effects were mainly gastrointestinal.

A follow-up analysis reported median survival of 25.0 months in those first assigned to the combination and 18.5 months in those first assigned to placebo (hazard ratio 0.56; 95% confidence interval 0.34 to 0.92); participants who completed the first 24 weeks could take the combination afterwards, whichever group they began in (Paganoni 2021). A post hoc comparison with outside control patients reported 23.54 and 13.15 months (Paganoni 2023). These later analyses were authored by the trial's own team and were not its pre-set main test.

Approval. The U.S. Food and Drug Administration approved the combination in adults on September 29, 2022, resting on the single 24-week trial, as covered in detail on the site's approval and withdrawal page.

The phase 3 trial, PHOENIX. This 48-week trial showed no change in the total function score (Ketabforoush 2024). The maker reported to the agency that it did not meet its primary or secondary end points, and the U.S. Food and Drug Administration withdrew approval on August 29, 2025, after the maker asked it to (Federal Register 90 FR 42251). A 2026 meta-analysis of the two randomized trials (801 people) found no statistically significant difference in functional decline (mean difference 1.51; 95% confidence interval -1.01 to 4.02) or survival (hazard ratio 0.90; 95% confidence interval 0.73 to 1.11), with very low certainty of evidence (Jomaa 2026).

Experience in one clinic. At a single United States center, 329 of 441 patients prescribed the combination started it, and 41% of those stopped during the study period (Calcagno 2025). Side effects were the most common reason, in 93 of the 135 who stopped, with gastrointestinal problems leading the list in 69. No hospitalizations, deaths or serious adverse events were considered related to treatment. Two authors of that paper were employed by the maker at the time.

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Multiple Sclerosis, Ulcerative Colitis and Wolfram Syndrome

Three smaller studies in people extend the record beyond the liver and amyotrophic lateral sclerosis.

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Retinal Studies: Cells and Animals

Eye research on this compound is large, and it is preclinical. A 2024 systematic review found 24 eligible studies published through July 2022: six in cells, 17 in live animals and one with both (Li 2024). They covered retinitis pigmentosa, diabetic retinopathy, retinal ganglion cell injury, Leber's hereditary optic neuropathy, new blood vessel growth under the retina and retinal detachment. The authors reported that it delayed the death of retinal nerve cells in these models. The searches for this page found no published trial of it for retinal disease in people.

A 2019 review notes that little is known about how these bile acids act in the retina, which has delayed moving them into the clinic (Daruich 2019).

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Brain and Nerve Disease in Cells and Animals

The hope placed in this drug for brain disease comes mostly from animal work. A 2022 systematic review collected 35 preclinical studies of ursodeoxycholic acid and its two conjugates in models of neurological and psychiatric disease (Huang 2022), and a separate review summarizes the proposed actions: blocking programmed cell death, reducing oxidative stress, protecting mitochondria, calming inflammation in the brain and helping proteins fold (Khalaf 2022).

Not all animal results were positive. In rats with spinal cord injury, it reduced inflammation, but the benefits were transient, and the authors wrote that their data do not support its use for that injury (Wu 2022). In mice with a model of Marinesco-Sjögren syndrome, it did not prevent movement problems or nerve cell loss (Lavigna 2025). Amyotrophic lateral sclerosis itself shows the gap between models and patients: a review listed it among diseases with supportive animal work (Khalaf 2022), and the European phase 3 trial in patients did not meet its main goal.

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Reported Side Effects

In the trials above, the drug alone was generally reported as well tolerated, and the complaints were mostly in the gut.

The combination with sodium phenylbutyrate has a clearer side-effect record, which cannot be assigned to one ingredient. In the U.S. Food and Drug Administration's summary, diarrhea occurred in 25% on the drug and 19% on placebo, abdominal pain in 21% and 13%, nausea in 18% and 13%, and upper respiratory infection in 18% and 10%; the agency also stated that taurursodiol may worsen diarrhea in people with disorders that interfere with bile acid circulation (see the site's approval and withdrawal page).

Most of these trials were small and short, the longest of the drug alone lasting 18 months, so rare or slow-developing harms would be hard to detect. The searches for this page found no trial of the drug in pregnancy. A 2026 case report describes drug-induced liver injury attributed to fenbendazole, an anti-worm drug, in a person who was also taking tauroursodeoxycholic acid in the hope of protecting the liver; the authors describe it as the first published report of that combination (Satinsky 2026). A single case cannot show whether the bile acid helped, harmed or did neither.

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Reported Interactions

The searches for this page found no formal interaction studies of tauroursodeoxycholic acid alone in people. The nearest information comes from its parent compound. The U.S. prescribing label for ursodiol, the drug-label name of ursodeoxycholic acid, states the following:

Those statements are about ursodeoxycholic acid. Applying them to the taurine form is an inference from their shared chemistry, not a tested result. One laboratory study found no interaction between tauroursodeoxycholate and the transporter protein ABCG2 (Vaidya 2006), a pump that moves many drugs across cell membranes, but that finding comes from a laboratory system and does not settle what happens in patients.

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Key Research Papers

  1. Vang S, Longley K, Steer CJ, Low WC. The Unexpected Uses of Urso- and Tauroursodeoxycholic Acid in the Treatment of Non-liver Diseases. Global Advances in Health and Medicine. 2014;3(3):58-69. PubMed PMID: 24891994
  2. Daruich A, Picard E, Boatright JH, Behar-Cohen F. Review: The bile acids urso- and tauroursodeoxycholic acid as neuroprotective therapies in retinal disease. Molecular Vision. 2019;25:610-624. PubMed PMID: 31700226
  3. Heuman DM, Pandak WM, Hylemon PB, Vlahcevic ZR. Conjugates of ursodeoxycholate protect against cytotoxicity of more hydrophobic bile salts: in vitro studies in rat hepatocytes and human erythrocytes. Hepatology. 1991;14(5):920-6. PubMed PMID: 1937396
  4. Vavrušáková B, Bartošová R, Svoboda M, Moráň L. From traditional Chinese medicine to molecular oncology - pleiotropic effects of tauroursodeoxycholic acid. Klinicka Onkologie. 2025;38(4):270-282. PubMed PMID: 40962506
  5. Moon S, Smanski MJ. Biosynthesis of tauro-ursodeoxycholic acid (TUDCA) in Saccharomyces cerevisiae. Microbial Cell Factories. 2025;24(1):212. PubMed PMID: 41039607
  6. Shijing T, Yinping P, Qiong Y, Deshuai L, Liancai Z, Jun T, et al. Synthesis of TUDCA from chicken bile: immobilized dual-enzymatic system for producing artificial bear bile substitute. Microbial Cell Factories. 2024;23(1):326. PubMed PMID: 39623449
  7. Zucchi E, Musazzi UM, Fedele G, Martinelli I, Gianferrari G, Simonini C, et al. Effect of tauroursodeoxycholic acid on survival and safety in amyotrophic lateral sclerosis: a retrospective population-based cohort study. EClinicalMedicine. 2023;65:102256. PubMed PMID: 37842553
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Trial Registry, Regulatory and Study-Team Documents

  1. TUDCA-ALS consortium. Announcement of top-line results from the European phase 3 clinical trial. Press release, March 27, 2024, archived by the Motor Neurone Disease Association. Archived press release (PDF)
  2. ClinicalTrials.gov record for the European phase 3 trial in amyotrophic lateral sclerosis. NCT03800524
  3. ClinicalTrials.gov record and posted results for the trial in new-onset type 1 diabetes. NCT02218619
  4. U.S. Food and Drug Administration. Withdrawal of approval of the new drug application for sodium phenylbutyrate and taurursodiol. Federal Register 90 FR 42251, August 29, 2025. FR Doc. 2025-16646
  5. U.S. National Library of Medicine, DailyMed. Prescribing labels for ursodiol, Drug Interactions section. DailyMed: ursodiol

PubMed Topic Searches

  1. PubMed: tauroursodeoxycholic acid randomized trials
  2. PubMed: tauroursodeoxycholic acid in primary biliary cholangitis
  3. PubMed: tauroursodeoxycholic acid in amyotrophic lateral sclerosis
  4. PubMed: tauroursodeoxycholic acid and retinal degeneration
  5. PubMed: bear bile and ursodeoxycholic acid

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