What are the therapeutic benefits and risks of using Tauroursodeoxycholic acid (Tudca) for medical treatment?

Therapeutic Benefits and Risks of Tauroursodeoxycholic Acid (TUDCA)

TUDCA is a taurine conjugate of ursodeoxycholic acid (UDCA) with potential therapeutic benefits in various conditions, though it lacks FDA approval for most indications beyond its use as a supplement, and clinical evidence supporting its use outside of liver diseases remains limited.

Mechanism of Action

• TUDCA functions primarily as a chemical chaperone that alleviates endoplasmic reticulum (ER) stress, stabilizes the unfolded protein response (UPR), and inhibits apoptosis by interfering with the mitochondrial pathway of cell death 1
• It increases the secretory capacity of hepatocytes through post-transcriptional mechanisms that stimulate vesicular exocytosis and insertion of transporters into the canalicular membrane 2
• TUDCA strengthens the "biliary bicarbonate umbrella" that protects hepatocytes and cholangiocytes from bile acid-mediated damage 2
• It reduces oxidative stress, suppresses apoptosis, and decreases inflammation in various disease models 3

Therapeutic Benefits in Liver Diseases

• UDCA (the parent compound of TUDCA) is FDA-approved and strongly recommended for treatment of primary biliary cholangitis (PBC) at doses of 13-15 mg/kg/day 2

• In intrahepatic cholestasis of pregnancy (ICP), UDCA is recommended for treatment of maternal pruritus and to reduce the risk of spontaneous preterm birth, particularly when serum bile acid concentrations exceed 40 μmol/L 2

• UDCA treatment in ICP has been associated with:

  • Reduction in maternal ALT and bilirubin concentrations 2
  • Protection against adverse fetal outcomes, including reduction in spontaneous preterm birth 2
  • Protection against cholic acid-induced arrhythmia in fetal cardiac myocytes 2

• However, UDCA is specifically not recommended for treatment of primary sclerosing cholangitis (PSC) 2

Potential Therapeutic Applications Beyond Liver Disease

• Neurodegenerative disorders: TUDCA has shown neuroprotective effects in preclinical models of:

  • Amyotrophic lateral sclerosis (ALS) - A pilot study showed TUDCA (1g twice daily) was well-tolerated and potentially effective in slowing ALS progression compared to placebo 4
  • Alzheimer's disease, Parkinson's disease, and Huntington's disease (preclinical evidence only) 1

• Stroke: In animal models, TUDCA demonstrated:

  • Approximately 50% reduction in infarct size when administered after ischemia 5
  • Reduced apoptosis in the area surrounding hemorrhage by about 50% 6
  • Improved neurological function in behavioral tests 6

• Retinal disorders: TUDCA may play a protective role against cell death in certain retinal conditions like retinitis pigmentosa 1

• Metabolic disorders: TUDCA has shown potential in reducing ER stress associated with elevated glucose levels in diabetes by inhibiting caspase activation and reducing reactive oxygen species 1

Safety and Risks

• TUDCA is generally considered safe based on limited clinical studies, with no significant between-group differences in adverse events reported in clinical trials 4
• The FDA-approved label for TUDCA supplements recommends adults and children over 12 years take 5 drops under the tongue 1-3 times daily, or as directed by a healthcare professional 7
• For children under 12 years, physician consultation is required 7
• Long-term safety data for TUDCA specifically (as opposed to UDCA) is limited, particularly for non-liver indications

Clinical Considerations and Limitations

• Despite promising preclinical evidence, TUDCA lacks FDA approval for most therapeutic applications beyond supplemental use
• Most evidence for non-liver applications comes from animal studies or small pilot human trials
• The optimal dosing for various conditions is not well-established outside of liver diseases
• For liver conditions, UDCA (the parent compound) is better studied and has more established clinical guidelines

Practical Recommendations

• For liver conditions like PBC and ICP, UDCA (rather than TUDCA) is the established treatment with strong guideline support 2
• For neurodegenerative conditions, TUDCA shows promise but should be considered experimental pending larger clinical trials 4
• When using TUDCA as a supplement, follow the labeled dosing guidelines of 5 drops under the tongue 1-3 times daily for adults and children over 12 years 7