TUDCA (tauroursodeoxycholic acid)

What this is

Tauroursodeoxycholic acid is the taurine conjugate of UDCA — more hydrophilic and slightly more cytoprotective than UDCA itself. **Clinical anchors**: Ma 2016 (Medicine) n=199 China PBC trial — TUDCA non-inferior to UDCA at 500-1500 mg/day with possible superior pruritus relief; Kars 2010 (Diabetes) 1750 mg/day x 4 wk improved hepatic and muscle insulin sensitivity in obese subjects (no adipose effect). **Major 2024 negative ALS readout**: AMX0035/Relyvrio (combination of sodium phenylbutyrate + taurursodiol) was FDA-approved September 2022 for ALS based on a controversial Phase 2 signal, but the larger Phase 3 **PHOENIX** trial (n=664; 48 weeks) MISSED its primary ALSFRS-R endpoint (p=0.667) in April 2024. Amylyx discontinued marketing October 2024; FDA formally withdrew approval August 2025. The taurursodiol component was hypothesized to drive efficacy via ER-stress/UPR reduction in motor neurons — its failure substantially weakens the broader "TUDCA for neurodegeneration" narrative biohacker writeups often invoke. **Mechanism nuance**: a 2024 bioRxiv preprint (now PMC11809307) on Saccharomyces cerevisiae challenged the classical chemical-chaperone model — TUDCA may instead form micelles that reduce drug bioavailability and let cells adapt to ER stress. The cytoprotective phenotype is real but the mechanism is less settled than commonly presented. **Biohacker take**: legitimate established use for cholestatic liver disease (esp. PBC); reasonable adjunct for NAFLD/MASLD at higher doses with monitoring; broader "neuroprotection / longevity" framing rests largely on preclinical data plus the now-failed ALS readout. Typical supplement-channel doses (250-1000 mg/day) are below the cholestasis-trial range. Distinct from UDCA (Ursodiol/Actigall) — UDCA is the unconjugated parent; TUDCA is the more polar taurine conjugate, marginally more potent in vitro but with similar clinical effect at equimolar doses.

Mechanism

Hydrophilic conjugated bile acid (taurine + ursodeoxycholic acid) endogenously present at trace levels in humans; acts as a chemical chaperone reducing endoplasmic reticulum stress and unfolded protein response (UPR) — blunts PERK/eIF2α/ATF4/IRE1α/JNK/CHOP signaling; activates hepatic FXR and Nrf2 pathways in cholestasis; inhibits CHOP-DR5-caspase-8 apoptotic cascade; replaces toxic hydrophobic bile acids in the bile pool; 2024 yeast study challenges the classical chaperone framing — suggests TUDCA may instead form micelles that reduce drug bioavailability and let cells adapt to ER stress

Dose & route

250-500 mg/day biohacker hepatoprotection; 500-1500 mg/day clinical PBC range; 1750 mg/day in insulin-sensitivity trial; ~10-13 mg/kg/day typical; take with food

Citations

• https://pmc.ncbi.nlm.nih.gov/articles/PMC5134868/
• https://pmc.ncbi.nlm.nih.gov/articles/PMC2911053/
• https://www.neurologylive.com/view/amylyx-pharmaceuticals-discontinues-amx0035-after-failing-primary-end-point-phase-3-phoenix-trial
• https://www.federalregister.gov/documents/2025/08/29/2025-16646/amylyx-pharmaceuticals-inc-withdrawal-of-approval-of-new-drug-application-for-relyvrio-sodium
• https://www.alzforum.org/therapeutics/relyvrio
• https://pubmed.ncbi.nlm.nih.gov/36795945/
• https://pmc.ncbi.nlm.nih.gov/articles/PMC11809307/

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