Ursodeoxycholic acid, or ursodiol, is a secondary bile acid found in the gut. Bile acids are byproducts from the metabolism of gut bacteria/fauna. Ursodeoxycholic acid is found in the human body endogenously and modulates cholesterol levels by breaking apart cholesterol chains and reducing cholesterol absorption in the intestine. It may inhibit apoptosis and may play a chemopreventive role in the body. Ursodiol can be chemically synthesized outside of the laboratory and is used to dissolve gallstones (as a surgery alternative) and is FDA-approved to treat primary biliary cirrhosis.
Kuiper writes that ursodeoxycholic acid is effective in long-term treatment of biliary cirrhosis:
Two hundred and twenty-five patients were included and followed during a median period of 10.3 years. Following 1-year treatment with UDCA 36-100% of the total biochemical improvement was achieved, the maximum response was observed after 3 years. After initial improvements, bilirubin and AST levels increased and albumin levels significantly decreased after 6-10 years. However, these changes were of limited magnitude. The beneficial effects on ALT and ALP were maintained while IgM continued to decrease.CONCLUSION: In non-advanced PBC the biochemical response to UDCA is maintained up to 15 years. The long-term evolution of bilirubin, albumin and ALT differs from that of ALP and AST. The mean IgM level normalised and levels continued to decrease during the period of follow-up.
Jones et al found in a 9-year follow-up study that patients receiving long-term UDCA treatment exhibited a lower mortality rate:
Survival to death or transplant was significantly lower in PBC patients than in the case-control population (88/136 (65%) v 114/136 84% (p<0.001 by log-rank test), with better survival in UDCA responders (defined using the Paris criteria) than in patients not treated with UDCA at study outset. Compared to the whole control group survival was reduced in PBC patients fatigued at study outset but not in those without fatigue (p<0.0001); an effect independent of the beneficial effect of UDCA response and of conventional parameters of liver disease severity. UDCA responders without fatigue at the study outset had a 9year survival which was identical to controls. Patients without fatigue at the study outset who developed fatigue during follow-up had significantly worse survival than patients who remained without fatigue throughout (p<0.05). Fatigued controls had worse survival than non-fatigued controls (p=0.05). CONCLUSIONS: Survival in a comprehensive cohort of PBC patients is substantially reduced compared with case-matched community controls. Development of fatigue and non-treatment with UDCA were specifically (and independently) associated with increased risk of death in PBC.
Leuschner et al find that despite results of previous (uncontrolled) studies, in a controlled study UDCA did not successfully treat non-alcoholich steatohepatitis:
In uncontrolled clinical studies, ursodeoxycholic acid (UDCA) had a beneficial effect on nonalcoholic steatohepatitis (NASH). However, a large controlled trial using UDCA (13-15 mg/kg/day) was unable to confirm these results. Accordingly, a randomized, placebo-controlled study was initiated with a high dose of UDCA (23-28 mg/kg/day). The allocation of patients and the evaluation of liver histology were performed according to a modified Brunt score and the nonalcoholic fatty liver disease activity score (NAS). With the exception of gamma-glutamyl transferase, UDCA did not improve laboratory data. Conclusion: High-dose UDCA failed to improve the overall histology in patients with NASH in comparison with placebo.
In their review Amaral et al reiterate the cytoprotective and anti-apoptosis properties of UDCA:
Bile acids are a group of molecular species of acidic steroids with peculiar physical-chemical and biological characteristics. At high concentrations they become toxic to mammalian cells, and their presence is pertinent in the pathogenesis of several liver diseases and colon cancer. Bile acid cytoxicity has been related to membrane damage, but also to nondetergent effects, such as oxidative stress and apoptosis. Strikingly, hydrophilic ursodeoxycholic acid (UDCA), and its taurine-conjugated form (TUDCA), show profound cytoprotective properties. Indeed, these molecules have been described as potent inhibitors of classic pathways of apoptosis, although their precise mode of action remains to be clarified.
 Kuiper EM, Hansen BE, Lesterhuis W, Robijn RJ, Thijs JC, Engels LG, Koek GH, Aparicio MN, Kerbert-Dreteler MJ, van Buuren HR; for the Dutch PBC study group. The long-term effect of ursodeoxycholic acid on laboratory liver parameters in biochemically non-advanced primary biliary cirrhosis. Gastroenterol Clin Biol. 2010 Aug 30.
 Jones DE, Al-Rifai A, Frith J, Patanwala I, Newton JL. The independent effects of fatigue and UDCA therapy on mortality in primary biliary cirrhosis: Results of a 9year follow-up. J Hepatol. 2010 Aug 1.
 Leuschner UF, Lindenthal B, Herrmann G, Arnold JC, Rössle M, Cordes HJ, Zeuzem S, Hein J, Berg T; NASH Study Group. High-dose ursodeoxycholic acid therapy for nonalcoholic steatohepatitis: a double-blind, randomized, placebo-controlled trial. Hepatology. 2010 Aug;52(2):472-9.
Amaral JD, Viana RJ, Ramalho RM, Steer CJ, Rodrigues CM. Bile acids: regulation of apoptosis by ursodeoxycholic acid. J Lipid Res. 2009 Sep;50(9):1721-34. Epub 2009 May 5.
*The latter article is intended for educational / informational purposes only. THIS PRODUCT IS INTENDED AS A RESEARCH CHEMICAL ONLY. This designation allows the use of research chemicals strictly for in vitro testing and laboratory experimentation only. Bodily introduction of any kind into humans or animals is strictly forbidden by law.