Updated September 21, 2020
Since our 2014 review there have been 2 important new clinical trials. A 2015 trial randomized 34 PALS to either TUDCA 1 gram twice daily or placebo for 54 weeks. Those on TUDCA had significantly slower progression on the ALSFRS-R score compared to those on placebo. TUDCA was well tolerated with only mild, mainly GI side effects (Eur J Neuro2016 Jan;23(1):45-52). A trial published in late 2020 randomized 137 PALS to AMX0035 (a combination of TUDCA and sodium phenylbuterate) or placebo for 24 weeks. Those on AMX0035 had statistically significantly slower progression on the ALSFRS-R score compared to those on placebo. AMX0035 was well tolerated, with rare, mild, mainly GI side effects (NEJM 2020;383:919-930). Based upon this new information we change our “Trials” grade to “A” and our “Risks” grade to “B.” We change our conclusion as well. “For PALS who want to self experiment, we now believe TUDCA to be a reasonable option for them to discuss with their doctors.”
Updated June 30, 2026
As of June 2026, we found no new information that would warrant any grade changes.
Updated January 16, 2023
Since our last update, 2 ALS reversals in association with TUDCA (and other products) have been independently verified. We thus change our “Cases” grade from D to B.
Updated April 1, 2024
As of April 1, 2024, we found a new phase 3 trial that reportedly showed no benefits https://www.tudca.eu/top-line-results-announcement/. We therefore change our TOE “Trials” Grade from A to F.”
Key Information
Click on any letter grade below for more info:
Preclinical Trials Grade:
U
Published: Jun 2014
Ursodiol has interesting mechanisms of action, appears reasonably safe and well-tolerated, has anecdotal reports of benefit in 6/21 of patients who report taking it, and a form of it (Yoo’s solution) was associated with slightly slower ALS progression in one out of three outcome measures within a poorly designed study that did not account for large numbers of drop-outs. However, analyses of ursodiol data from the well-conducted randomized, double-blind ceftriaxone trial show that ursodiol 300 mg twice a day is no better than placebo at prolonging survival or slowing ALS progression. Based upon this review, ALSUntangled does not recommend off-label use of ursodiol as a treatment for ALS, at least at doses of 300 mg twice a day. Determining whether higher doses or different formulations are effective will require further well-designed studies.
Grade A: Shown in a peer-reviewed publication to act on a relevant mechanism in humans
Grade B: Shown in a peer-reviewed publication to act on a relevant mechanism in pre-clinical model(s)
Grade C: Theoretically and plausibly acts on an ALS-relevant mechanism in humans
Grade D: Acts on a biological mechanism but it is not clear that this mechanism is relevant in ALS
Grade F: Implausible; would violate known principles or laws of biology
Grade U: No useful information was found for this category
Grade A: Two or more peer-reviewed publications reporting benefits in well-designed studies.
Animal studies are assumed to be ‘well designed’ when they follow published guidelines. When they deviate from these they are considered ‘flawed’.
Grade B: One peer-reviewed publication reporting benefits in a well-designed study.
Animal studies are assumed to be ‘well designed’ when they follow published guidelines. When they deviate from these they are considered ‘flawed’.
Grade C: One or more peer-reviewed publication(s) reporting benefits in flawed studies.
Animal studies are assumed to be ‘well designed’ when they follow published guidelines. When they deviate from these they are considered ‘flawed’.
Grade D: One or more non-peer reviewed studies reporting benefits (published on a website or in an abstract)
Grade F: The only studies available show no benefit
Grade U: No useful information was found for this category
Grade A: One or more peer-reviewed publications reporting benefits with validated diagnosis and benefits
Grade B: More than one unpublished report of benefit with validated diagnosis and benefits
Grade C: One unpublished report of benefit with validated diagnosis and benefits
Grade D: Subjective report(s) of benefit without validated diagnoses and/or benefits
Grade F: The only reports available show no benefit
Grade U: No useful information was found for this category
Two or more peer-reviewed publications describing benefits in well-designed randomized, blinded placebo-controlled phase III trials
Grade C: One or more peer-reviewed publications reporting benefits in a well-designed randomized, blinded, placebo-controlled phase I or II trial
Grade D: One or more peer-reviewed publications reporting benefits in a flawed trial.
Flawed trials means those in which there are identifiable problems with patient selection, randomization, blinding, controls or follow-up. These have ‘high or unclear risk of bias’ according to published criteria. Well-designed trials are those that have ‘low risk of bias’.
Grade F: The only trials available show no benefit
Grade U: No useful information was found for this category
Grade A: No exposed patients appear to have experienced harms
Grade B: More than 0% but less than 10% of exposed patients experienced harms (no hospitalizations or deaths)
Grade B (oral): More than 0% but less than10% of exposed patients experienced harms (no hospitalizations or deaths)
Grade D (intravenous): More than 0% but less than 5% of exposed patients experienced death or hospitalizations
Grade C: At least 10% of exposed patients experienced harms (no hospitalizations or deaths)
Grade D: More than 0% but less than 5% of exposed patients experienced death or hospitalizations
Grade D: More than 0% but less than 5% of exposed patients experienced death or hospitalizations
Grade F: At least 5% of exposed patients experienced death or hospitalization
Grade F: At least 5% of exposed patients experienced death or hospitalization
Grade U: No useful information was found for this category
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