What is TUDCA (Tauroursodeoxycholic acid)?

What is TUDCA (Tauroursodeoxycholic Acid)?

TUDCA is the taurine conjugate of ursodeoxycholic acid (UDCA), a naturally occurring hydrophilic bile acid that functions primarily as a cytoprotective agent by inhibiting apoptosis, reducing endoplasmic reticulum stress, and stabilizing mitochondrial membranes. 1, 2

Chemical Structure and Origin

• TUDCA is formed when UDCA undergoes taurine conjugation, creating a more hydrophilic bile acid compound 1
• It has been used in traditional Chinese medicine for over 3,000 years 1
• TUDCA is naturally present in small amounts in human bile 2

Primary Mechanisms of Action

Cellular Protection

• TUDCA inhibits apoptosis by interfering with the mitochondrial pathway of cell death, preventing mitochondrial membrane perturbation and reducing oxygen-radical production 1, 3, 4
• It reduces endoplasmic reticulum (ER) stress and stabilizes the unfolded protein response (UPR), earning it the designation as a "chemical chaperone" 1, 2
• TUDCA activates survival pathways including the Akt-1/protein kinase B pathway and induces Bad phosphorylation at Ser-136 5

Anti-Inflammatory and Anti-Oxidative Effects

• It decreases reactive oxygen species production and reduces oxidative stress in various disease models 1, 2
• TUDCA modulates NF-kappaB activity and expression of Bcl-2 family members 5
• It inhibits caspase activation, particularly caspase-3 processing and substrate cleavage 4, 5

Clinical Applications

Established Medical Uses

• TUDCA's parent compound UDCA (13-15 mg/kg/day) is FDA-approved and the established first-line treatment for primary biliary cholangitis (PBC), significantly reducing serum bilirubin, alkaline phosphatase, and cholesterol levels 6, 7
• UDCA is recommended for intrahepatic cholestasis of pregnancy at 10-15 mg/kg/day to reduce spontaneous preterm birth risk and potentially protect against stillbirth 6

Investigational Applications

• Neurodegenerative diseases: Pre-clinical studies demonstrate TUDCA reduces neuronal cell death and improves motor and cognitive function in models of Huntington's disease, Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis 1, 3
• Acute stroke: TUDCA administered within 6 hours after ischemic or hemorrhagic stroke reduced infarct size by approximately 50% and improved neurological function in animal models 4, 5
• Retinal disorders: TUDCA protects against cell death in retinitis pigmentosa models 1
• Metabolic diseases: It reduces ER stress associated with elevated glucose in diabetes models 1, 2

Important Clinical Distinctions

TUDCA vs. UDCA

• While TUDCA shows promise in pre-clinical research for non-hepatic conditions, most clinical guideline recommendations and FDA approval apply specifically to UDCA for cholestatic liver diseases 6, 7
• TUDCA can be delivered to the brain and function as a neuroprotectant, whereas UDCA's clinical applications remain primarily hepatobiliary 3

Conditions Where UDCA Should NOT Be Used

• UDCA is explicitly not recommended for non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) at standard doses (13-15 mg/kg/day), as it showed no significant benefit over placebo 8
• High-dose UDCA (>20 mg/kg/day) is associated with worse outcomes in primary sclerosing cholangitis and should be avoided 6, 7, 9

Dosing Information

FDA-Approved Formulations

• For adults and children ≥12 years: 5 drops under the tongue 1-3 times daily (for TUDCA supplements) 10
• For UDCA in PBC: 13-15 mg/kg/day orally 6, 7
• Post-liver transplant for PBC: 10-15 mg/kg/day lifelong 7

Key Clinical Caveats

• Despite extensive pre-clinical evidence showing TUDCA's cytoprotective effects across multiple organ systems, most therapeutic applications beyond cholestatic liver disease remain investigational and lack robust clinical trial data in humans 1, 2
• TUDCA has been demonstrated safe in clinical use for liver diseases, but large-scale human trials for non-hepatic conditions are still needed 1, 4
• The molecule's ability to cross the blood-brain barrier and reach therapeutic concentrations in neural tissue has been confirmed in animal models 3, 4