TUDCA
Tauroursodeoxycholic acid, the taurine conjugate of ursodeoxycholic acid
Written by Aaron CuhaReviewed Sep 2026
Also known as: Tauroursodeoxycholic acid, Taurursodiol, TUDC
Twenty obese adults, four weeks: hepatic and muscle insulin sensitivity rose about 30 percent on a clamp, while adipose tissue insulin sensitivity and the endoplasmic reticulum stress markers the drug was meant to fix did not change. In ALS the phase 3 trial of TUDCA combined with sodium phenylbutyrate missed its endpoint and the approved product was voluntarily withdrawn from the market.
Overview
TUDCA is the taurine conjugate of ursodeoxycholic acid, which has its own entry on this site. The two are not interchangeable, and supplement marketing routinely treats them as though they were. TUDCA is the form most of the neuroprotection research uses; UDCA is the form with the liver approvals and the mouse lifespan null.
The human evidence for TUDCA itself divides into one small metabolic study and one long drug development story that ended badly.
The metabolic study is the best-executed human trial this compound has. Twenty obese adults, mean BMI 37, randomised to 1,750 mg a day of TUDCA or placebo for four weeks, assessed with a two-stage hyperinsulinaemic-euglycaemic clamp plus muscle and adipose biopsies. Hepatic and muscle insulin sensitivity rose about 30 percent (p < 0.05); placebo did not change. Muscle insulin signalling improved. And the finding that matters for interpreting the rest: markers of endoplasmic reticulum stress in muscle and adipose tissue did not change after TUDCA, even though relieving endoplasmic reticulum stress was the entire hypothesis the trial was built on. Something happened; the proposed mechanism was not demonstrated.
The drug development story starts with a 34-patient proof of principle trial in ALS, 1 gram twice daily on top of riluzole for 54 weeks, which found 87 percent responders against 43 percent on placebo. Then CENTAUR, a phase 2 trial of TUDCA combined with sodium phenylbutyrate, was positive enough on function and on post hoc survival analyses to win FDA approval. Then the phase 3 PHOENIX trial showed no change in the ALS Functional Rating Scale at 48 weeks, and the sponsor initiated voluntary withdrawal of the marketing authorisations with the FDA and Health Canada.
That sequence, a positive small trial, a positive phase 2, an approval, a failed phase 3 and a withdrawal, is the single most useful thing to know about this compound, and almost none of the supplement listings mention it.
Mechanism of action
A hydrophilic bile acid that acts as a chemical chaperone, stabilising protein folding and reducing endoplasmic reticulum stress, and separately raising the threshold for mitochondrial permeability transition so that less cytochrome c is released and less apoptosis occurs. Conjugation with taurine increases water solubility and changes how the molecule is handled in the enterohepatic circulation relative to unconjugated ursodeoxycholic acid, which is why the two are studied separately. The honest caveat is that the chaperone mechanism was directly tested in the one human trial designed to look for it, and the endoplasmic reticulum stress markers in muscle and adipose tissue did not move while insulin sensitivity did. The authors said as much: additional studies are needed to evaluate the target cells and mechanisms responsible for the effect.
Human evidence
Real but narrow. One well-instrumented four-week metabolic trial in 20 people, one 34-patient ALS proof of principle trial, and a drug development programme in which the combination product was approved on phase 2 data and then withdrawn after phase 3.
- 20 obese adults, 1,750 mg a day for 4 weeks: hepatic and muscle insulin sensitivity up about 30 percent by clamp, adipose tissue unchanged, endoplasmic reticulum stress markers unchanged.
- 34 ALS patients, 1 gram twice daily for 54 weeks on top of riluzole: 87 percent responders against 43 percent on placebo, with slower ALSFRS-R decline.
- CENTAUR phase 2 of the sodium phenylbutyrate and taurursodiol combination supported an FDA approval.
- Phase 3 PHOENIX showed no change in ALSFRS-R at 48 weeks and the sponsor voluntarily withdrew the marketing authorisations.
- A European phase 3 of TUDCA alone is registered as NCT03800524; the registry lists its status as unknown and no results paper was located.
- No human trial has measured lifespan, healthspan, cognition in healthy people, or any ageing endpoint with TUDCA.
What this does not tell you: The insulin sensitivity result is four weeks in twenty people and measures a surrogate, however well measured; a clamp tells you about glucose disposal on the day of the test, not about whether anyone developed diabetes. The ALS pilot used a responder definition based on a slope change against a lead-in period, which is a fragile endpoint in a small trial, and the larger programme built on that signal failed at phase 3. Nothing here supports the liver support, mitochondrial health or longevity uses the compound is actually sold for.
Reading the research record
Read this page next to the ursodeoxycholic acid entry, which covers the parent compound. The distinction between them is not pedantic: UDCA has the liver approvals, a randomised Parkinson's disease trial and a mouse lifespan null; TUDCA has the insulin sensitivity trial and the ALS programme. Evidence for one does not transfer to the other, and products marketed as bile acid support routinely blur the two.
The ALS arc deserves to be stated bluntly because it is a complete worked example of how a mechanism becomes a product and then stops being one. A plausible chaperone mechanism, a small positive trial, a positive phase 2, a regulatory approval, a failed phase 3, a voluntary withdrawal. The compound did not change during that sequence. What changed was the size and rigour of the test applied to it. A supplement buyer reading only the first three steps of that story is reading a version of the evidence that stopped being current in 2024.
A surrogate endpoint is a measurement that stands in for the thing you care about, on the assumption that moving it moves the outcome. That assumption has failed often enough to be treated as a claim rather than a given. Homocysteine is the canonical case: it predicts cardiovascular disease strongly in observational data, it can be lowered reliably by several cheap interventions, and when trials lowered it and then counted heart attacks, the events did not fall. The lesson is not that markers are worthless. It is that a trial reporting a marker has answered a smaller question than the one the buyer is asking, and the page should say which question was answered.
The evidence, charted
Fig. 1 · evidence composition
5of 6 citations (83%) are in people
Counted from the citation list on this page. The Human count is the same number shown in the badge at the top. Both understate any literature larger than the sources we cite.
Fig. 2 · evidence over time
Evidence spans 6 distinct years, 2010 to 2024, counted from the citation list on this page.
Fig. 3 · legal status at a glance
US
Not approved
UK
Not approved
AU
Not approved
CA
Not approved
Not approved in any of the four jurisdictions shown. A jurisdiction's classification is a regulatory fact, not a verdict on the science; see Legal status below for the full text and any notes.
Fig. 4 · dose response
No human dose response curve exists
We draw this figure where the data supports it. For this compound in humans it does not, so the panel stays empty rather than borrowing an animal curve and implying it transfers.
Key studies & citations
- Human2010
Tauroursodeoxycholic Acid may improve liver and muscle but not adipose tissue insulin sensitivity in obese men and women.
20 obese adults, mean age 48 and BMI 37, randomised to 1,750 mg a day of TUDCA or placebo for 4 weeks, with two-stage hyperinsulinaemic-euglycaemic clamps, tracer infusions and muscle and adipose biopsies. Hepatic and muscle insulin sensitivity rose approximately 30 percent (p < 0.05) with no change on placebo, and muscle insulin signalling improved. Markers of endoplasmic reticulum stress in muscle and adipose tissue did not change after either treatment, despite that being the hypothesised mechanism. NIH funded.
Diabetes - Human2016
Tauroursodeoxycholic acid in the treatment of patients with amyotrophic lateral sclerosis.
A proof of principle double blind placebo-controlled trial: 34 ALS patients already on riluzole randomised to TUDCA 1 gram twice daily or placebo for 54 weeks after a three-month lead-in. The proportion of responders, defined as at least a 15 percent improvement in ALSFRS-R slope against the lead-in, was 87 percent on TUDCA against 43 percent on placebo (p = 0.021). Well tolerated with no between-group difference in adverse events. The authors describe it as preliminary data indicating TUDCA is safe and may be effective.
European Journal of Neurology - Human2020
Trial of Sodium Phenylbutyrate-Taurursodiol for Amyotrophic Lateral Sclerosis.
The CENTAUR phase 2 randomised trial of the fixed combination of sodium phenylbutyrate and taurursodiol, the form of TUDCA used in drug development. This is the trial whose functional result, together with post hoc survival analyses, supported the regulatory approval that was later withdrawn.
New England Journal of Medicine - Review2024
Sodium Phenylbutyrate and Tauroursodeoxycholic Acid: A Story of Hope Turned to Disappointment in Amyotrophic Lateral Sclerosis Treatment.
Review tracing the arc: CENTAUR showed an effect on ALSFRS-R and, in post hoc analyses, on risk of death, hospitalisation and tracheostomy or permanent assisted ventilation. The phase 3 PHOENIX trial (NCT05021536) then showed no change in ALSFRS-R total score at 48 weeks, and the sponsor initiated voluntary withdrawal of the marketing authorisations with the US FDA and Health Canada. The authors discuss what conflicting phase 2 and phase 3 data mean for ALS and other neurological disorders.
Clinical Drug Investigation - Human2023
A randomized double-blind clinical trial on safety and efficacy of tauroursodeoxycholic acid (TUDCA) as add-on treatment in patients affected by amyotrophic lateral sclerosis (ALS): the statistical analysis plan of TUDCA-ALS trial.
The published statistical analysis plan for a European phase 3 trial of TUDCA alone, rather than in combination, as an add-on to riluzole, registered as NCT03800524. On the registry the study status is listed as unknown with an estimated completion date of December 2023, and no results publication was located in PubMed for this entry. Disclosed conflicts include an author employed as medical director by the company supplying the investigational product.
Trials - Human2021
Phase III Trial of AMX0035 for Amyotrophic Lateral Sclerosis Treatment
The registry record for PHOENIX, a phase 3 randomised double-blind placebo-controlled multicentre trial of AMX0035, the sodium phenylbutyrate and taurursodiol combination, against placebo over 48 weeks. Actual enrolment 664, started October 2021. This is the trial that showed no change in ALSFRS-R total score and led to the sponsor withdrawing the marketing authorisations.
ClinicalTrials.gov (PHOENIX)
Frequently asked questions
Is TUDCA the same as UDCA?
No. TUDCA is the taurine conjugate. It is the form most neuroprotection research uses and the one sold as a supplement; ursodeoxycholic acid is the unconjugated parent, is an approved prescription medicine for cholestatic liver disease, and produced no lifespan effect in multi-site mouse testing. Evidence for one does not automatically transfer to the other.
Does TUDCA improve insulin sensitivity?
In the one trial that measured it properly, yes, by about 30 percent in liver and muscle in 20 obese adults over four weeks, using a hyperinsulinaemic-euglycaemic clamp. Adipose tissue did not respond, and the endoplasmic reticulum stress markers that were supposed to explain the effect did not change. It is a strong surrogate result in a very small trial and nobody has followed it with a diabetes outcome trial.
What happened with the ALS drug?
A combination of sodium phenylbutyrate and taurursodiol was approved on the strength of the phase 2 CENTAUR trial. The phase 3 PHOENIX trial then showed no change in the ALS Functional Rating Scale at 48 weeks, and the sponsor voluntarily initiated withdrawal of the marketing authorisations with the FDA and Health Canada. A separate European phase 3 of TUDCA on its own is registered but its registry status is unknown and no results paper was located here.
Does TUDCA protect the liver?
The liver approvals belong to ursodeoxycholic acid, in specific cholestatic diseases, not to TUDCA in healthy people. No trial has tested TUDCA as liver support in anyone without liver disease, which is how most of it is sold.
Is there any evidence it slows ageing?
None in humans. The nearest relevant result is on the parent compound: ursodeoxycholic acid produced no significant lifespan effect in either sex in the multi-site mouse testing programme.