Impact of combined therapy with alpha-lipoic and ursodeoxycolic acid on nonalcoholic fatty liver disease: double-blind, randomized clinical trial of efficacy and safety

Background and purpose Nonalcoholic fatty liver disease (NAFLD) is one of the causes of a fatty liver, occurring when fat is deposited (steatosis) in the liver not due to excessive alcohol use. It is related to insulin resistance and the metabolic syndrome. The purpose of the present study was to evaluate the impact of combination therapy with alpha-lipoic acid (ALA) and ursodeoxycholic acid (UDCA) on NAFLD. Methods Alpha-lipoic acid 400 mg/day plus UDCA 300 mg/day (ALAUDCA) was investigated in patients over a period of 12 months using a randomized, placebo (PLA)-controlled study with four parallel groups. Serum concentration of gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin and platelets (PLT) were measured at the beginning and at the end of the treatment. Moreover, the AST/ALT ratio and the NAFLD fibrosis score were examined. Results A total of 120 patients were randomly assigned to the four groups. ALA and UDCA were safe and well tolerated in the oral daily administration only. AST, ALT, GGT (p\0.001) showed a significant difference between ALAUDCA and other three groups. Besides, NAFLD fibrosis score underlined a significant reduction (p\0.04) in the ALAUDCA group, while AST/ALT ratio presented a moderate decline (p[0.05). Conclusion ALAUDCA therapy reduced AST, ALT, GGT values and improved NAFLD fibrosis score and AST/ ALT ratio, especially in patients who were on a hypocaloric diet. These findings will be useful in patient selection in future clinical trials with ALAUDCA in long-term studies.