TUDCA (tauroursodeoxycholic acid)
Information on nutritional supplements people with ALS have been taking
ALSUntangled evaluation report
Effects on ALS
TUDCA is a taurine-conjugated form of ursodiol and is commonly used for treatment of chronic cholestatic liver diseases and for gallstone. It possesses many additional ancillary features, including the inhibition of mitochondrial-associated apoptosis through different mechanisms. It has been shown that, in a cellular model of superoxide dismutase 1 neurodegeneration, glycine-conjugated UDCA inhibits nitrite production and prevents matrix metallopeptidase 9 activation [1].
At the end of the 54-week treatment period, patients in the TUDCA group had a mean ALSFRS-R score corresponding to that of the placebo group at week 36. This suggests that a 1-year TUDCA treatment may slow ALS deterioration by 18 weeks and leads us to suppose that a longer duration of treatment may produce an even more accentuated between-group divergence [1].
This study was designed to assess the effects of UDCA on oxidative injury and antioxidative systems in cultured rat hepatocytes. The viability of the hepatocytes dose-dependently decreased after hydrogen peroxide or cadmium administration. Pretreatment with UDCA significantly prevented this decrease in viability. The amounts of glutathione (GSH) and protein thiol increased significantly, but the activities of antioxidative enzymes such as superoxide dismutase, glutathione peroxidase and catalase were unchanged in UDCA-treated hepatocytes. The mRNA levels of gamma-glutamylcysteine synthetase and metallothionein (MT) were significantly higher in UDCA-treated hepatocytes than in controls. In conclusion, UDCA increased hepatocyte levels of GSH and thiol-containing proteins such as MT, thereby protecting hepatocytes against oxidative injury. [2]
References
[1] <bibtex> @article{Elia2015, abstract = {BACKGROUND AND PURPOSE: Tauroursodeoxycholic acid (TUDCA) is a hydrophilic bile acid that is produced in the liver and used for treatment of chronic cholestatic liver diseases. Experimental studies suggest that TUDCA may have cytoprotective and anti-apoptotic action, with potential neuroprotective activity. A proof of principle approach was adopted to provide preliminary data regarding the efficacy and tolerability of TUDCA in a series of patients with amyotrophic lateral sclerosis (ALS).
METHODS: As a proof of principle, using a double-blind placebo controlled design, 34 ALS patients under treatment with riluzole who were randomized to placebo or TUDCA (1 g twice daily for 54 weeks) were evaluated after a lead-in period of 3 months. The patients were examined every 6 weeks. The primary outcome was the proportion of responders [those subjects with improvement of at least 15\% in the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) slope during the treatment period compared to the lead-in phase]. Secondary outcomes included between-treatment comparison of ALSFRS-R at study end, comparison of the linear regression slopes for ALSFFRS-R mean scores and the occurrence of adverse events.
RESULTS: Tauroursodeoxycholic acid was well tolerated; there were no between-group differences for adverse events. The proportion of responders was higher under TUDCA (87\%) than under placebo (P = 0.021; 43\%). At study end baseline-adjusted ALSFRS-R was significantly higher (P = 0.007) in TUDCA than in placebo groups. Comparison of the slopes of regression analysis showed slower progression in the TUDCA than in the placebo group (P < 0.01).
CONCLUSIONS: This pilot study provides preliminary clinical data indicating that TUDCA is safe and may be effective in ALS.}, author = {Elia, A E and Lalli, S and Monsurr\`{o}, M R and Sagnelli, A and Taiello, A C and Reggiori, B and {La Bella}, V and Tedeschi, G and Albanese, A}, doi = {10.1111/ene.12664}, issn = {1468-1331}, journal = {European journal of neurology : the official journal of the European Federation of Neurological Societies}, mendeley-groups = {taurine}, month = feb, pmid = {25664595}, title = Template:Tauroursodeoxycholic acid in the treatment of patients with amyotrophic lateral sclerosis., url = {http://www.ncbi.nlm.nih.gov/pubmed/25664595}, year = {2015} } </bibtex>
[2]
<bibtex>
@article{Mitsuyoshi1999,
abstract = {The therapeutic efficacy of ursodeoxycholic acid (UDCA) has been widely demonstrated in various liver diseases, suggesting that UDCA might protect hepatocytes against common mechanisms of liver damage. A candidate for such protection is oxidative injury induced by reactive oxygen species. This study was designed to assess the effects of UDCA on oxidative injury and antioxidative systems in cultured rat hepatocytes. The viability of the hepatocytes dose-dependently decreased after hydrogen peroxide or cadmium administration. Pretreatment with UDCA significantly prevented this decrease in viability. The amounts of glutathione (GSH) and protein thiol increased significantly, but the activities of antioxidative enzymes such as superoxide dismutase, glutathione peroxidase and catalase were unchanged in UDCA-treated hepatocytes. The mRNA levels of gamma-glutamylcysteine synthetase and metallothionein (MT) were significantly higher in UDCA-treated hepatocytes than in controls. In conclusion, UDCA increased hepatocyte levels of GSH and thiol-containing proteins such as MT, thereby protecting hepatocytes against oxidative injury. Our results provide a new perspective on the hepatoprotective effect of UDCA.},
author = {Mitsuyoshi, H and Nakashima, T and Sumida, Y and Yoh, T and Nakajima, Y and Ishikawa, H and Inaba, K and Sakamoto, Y and Okanoue, T and Kashima, K},
doi = {10.1006/bbrc.1999.1403},
issn = {0006-291X},
journal = {Biochemical and biophysical research communications},
keywords = {Animals,Antioxidants,Antioxidants: metabolism,Cholangitis, Sclerosing,Cholangitis, Sclerosing: drug therapy,Glutamate-Cysteine Ligase,Glutamate-Cysteine Ligase: biosynthesis,Glutathione,Glutathione: analysis,Liver,Liver Cirrhosis, Biliary,Liver Cirrhosis, Biliary: drug therapy,Liver: cytology,Liver: drug effects,Liver: metabolism,Male,Metallothionein,Metallothionein: biosynthesis,Oxidative Stress,Oxidative Stress: drug effects,Rats,Rats, Wistar,Reactive Oxygen Species,Reactive Oxygen Species: metabolism,Sulfhydryl Compounds,Sulfhydryl Compounds: analysis,Ursodeoxycholic Acid,Ursodeoxycholic Acid: pharmacology},
mendeley-groups = {taurine},
month = sep,
number = {2},
pages = {537--42},
pmid = {10491327},
title = Template:Ursodeoxycholic acid protects hepatocytes against oxidative injury via induction of antioxidants.,
url = {http://www.ncbi.nlm.nih.gov/pubmed/10491327},
volume = {263},
year = {1999}
}
</bibtex>
