Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Article
  • Published:
Hepatology International Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology 2003;37(5):1202–1219

    Article  Google Scholar 

  2. Salt WB 2nd. Nonalcoholic fatty liver disease (NAFLD): a comprehensive review. J Insur Med 2004;36:27–41

    PubMed  Google Scholar 

  3. McCullough AJ. Pathophysiology of nonalcoholic steatohepatitis. J Clin Gastroenterol 2006;40(1):S17–S29

    CAS  PubMed  Google Scholar 

  4. Angelico F, Burattin M, Alessandri C, et al. Drugs improving insulin resistance for non-alcoholic fatty liver disease and/or non-alcoholic steatohepatitis. Cochrane Database Syst Rev 2007;24(1):CD005166

    Google Scholar 

  5. Matthews DR, Hosker JP, Rudenski AS, et al. Homeostatic model assessment: insulin resistance and beta-cell function from fasting glucose and insulin concentrations in man. Diabetologia 1985;28:412–419

    Article  CAS  Google Scholar 

  6. Angulo P, Hui JM, Marchesini G, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology 2007;45(4):846–854

    Article  CAS  Google Scholar 

  7. Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005;41:1313–1321

    Article  Google Scholar 

  8. Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 1999;94:2467–2474.

    Article  CAS  Google Scholar 

  9. Morisky DE, Ang A, Krousel-Wood M, et al. Predictive validity of a medication adherence measure for hypertension control. J Clin Hypertens (Greenwich) 2008;10(5):348–354

    Article  Google Scholar 

  10. Svedlund J, Sjödin I, Dotevall G. GSRS—a clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease. Dig Dis Sci 1988;33(2):129–134

    Article  CAS  Google Scholar 

  11. Matteoni C, Younossi Z, Gramlich T. Nonalcoholic fatty liver disease: a spectrum of clinical and pathologic severity. Gastroenterology 1999;116:1413–1419

    Article  CAS  Google Scholar 

  12. Harrison SA, Torgerson S, Hayashi P, et al. Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis. Am J Gastroenterol 2003;98:2485–2490

    Article  CAS  Google Scholar 

  13. Ruhl C, Everhart J. Relation of elevated serum alanine aminotransferase activity with iron and antioxidant levels in the United States. Gastroenterology 2003;124:1821–1829

    Article  CAS  Google Scholar 

  14. Dufour JF, Oneta CM, Gonvers JJ. Randomized placebo-controlled trial of ursodeoxycholic acid with vitamin E in nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol 2006;4:1537–1543

    Article  CAS  Google Scholar 

  15. Lindor KD, Kowdley KV, Heathcote EJ. Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology 2004;39:770–778

    Article  CAS  Google Scholar 

  16. Amaral JD, Viana RJ, Ramalho RM, et al. Bile acids: regulation of apoptosis by ursodeoxycholic acid. J Lipid Res 2009;50(9):1721–1734.

    Article  CAS  Google Scholar 

  17. Kugelmas M, Hill DB, Vivian B, et al. Cytokines and NASH: a pilot study of the effects of lifestyle modification and vitamin E. Hepatology 2003;38:413–419

    Article  CAS  Google Scholar 

  18. Neuman M, Angulo P, Malkiewicz I, et al. Tumor necrosis factor-alpha and transforming growth factor-beta reflect severity of liver damage in primary biliary cirrhosis. J Gastroenterol Hepatol 2002;17:196–202

    Article  CAS  Google Scholar 

  19. Ozcan U, Yilmaz E, Ozcan L, et al. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science 2006;313:1114–1137

    Article  Google Scholar 

  20. Kars M, Yang L, Gregor MF, et al. Tauroursodeoxycholic acid may improve liver and muscle but not adipose tissue insulin sensitivity in obese men and women. Diabetes 2010;59:1899–1905

    Article  CAS  Google Scholar 

  21. Khanna S, Roy S, Packer L, et al. Cytokine-induced glucose uptake in skeletal muscle: redox regulation and the role of alpha-lipoic acid. Am J Physiol 1999;276:R1327–R1333

    CAS  PubMed  Google Scholar 

  22. Gianturco V, Bellomo A, D’Ottavio E, et al. Impact of therapy with alpha-lipoic acid (ALA) on the oxidative stress in the controlled NIDDM: a possible preventive way against the organ dysfunction? Arch Gerontol Geriatr 2009;49(1):129–133

    Article  CAS  Google Scholar 

  23. Min AK, Kim MK, Kim HS, et al. Alpha-lipoic acid attenuates methionine choline deficient diet-induced steatohepatitis in C57BL/6 mice. Life Sci 2012;90:200–205

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cardiovascular, Respiratory, Nephrological and Geriatric Sciences, Sapienza University of Rome, Umberto I, Policlinico di Roma, Viale del Policlinico Roma 155, 00161, Rome, Italy

    Vincenzo Gianturco, Giovanni Troisi, Alessia Bellomo, Sciaila Bernardini, Elisa D’Ottavio, Valeria Formosa, Cristina Lo Iacono, Walter Verrusio, Benedetta Marigliano & Vincenzo Marigliano

Authors
  1. Vincenzo Gianturco
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giovanni Troisi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alessia Bellomo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sciaila Bernardini
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Elisa D’Ottavio
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Valeria Formosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Cristina Lo Iacono
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Walter Verrusio
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Benedetta Marigliano
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Vincenzo Marigliano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giovanni Troisi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gianturco, V., Troisi, G., Bellomo, A. et al. Impact of combined therapy with alpha-lipoic and ursodeoxycolic acid on nonalcoholic fatty liver disease: double-blind, randomized clinical trial of efficacy and safety. Hepatol Int 7, 570–576 (2013). https://doi.org/10.1007/s12072-012-9387-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12072-012-9387-y

Keywords

Search

Navigation