Share This Article:

Effect of Vitamin E and Alpha Lipoic Acid in Nonalcoholic Fatty Liver Disease: A Randomized, Placebo-Controlled, Open-Label, Prospective Clinical Trial (VAIN Trial)

Abstract Full-Text HTML Download Download as PDF (Size:444KB) PP. 199-207
DOI: 10.4236/ojgas.2014.45030    5,059 Downloads   7,896 Views   Citations


Objective: Antioxidants, including alpha lipoic acid (ALA) and vitamin E, are efficacious for the treatment of nonalcoholic fatty liver disease (NAFLD). The objective was to evaluate the effects of ALA and vitamin E alone or combined as therapy for patients with NAFLD and nonalcoholic steatohepatitis (NASH). Design: Placebo-controlled, open-label, prospective study in which patients with NAFLD and NASH were randomized to treatment with ALA 300 mg (n = 40), vitamin E 700 IU (n = 40), ALA 300 mg plus vitamin E 700 IU (n = 40), or placebo (n = 35) daily for 6 months. Body mass index, homeostasis model assessment scores, fibrosis and steatosis markers, and diagnostic laboratory tests were assessed at baseline and at the end of the study. Results: Treatment with ALA and vitamin E alone or in combination, improved inflammatory cytokine levels, steatosis scores, homeostasis model assessment scores, and triglyceride levels after 6 months relative to baseline. Conclusion: Alpha lipoic acid and vitamin E, either alone or in combination, were effective treatments for patients with NAFLD and NASH.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Basu, P. , Shah, N. , Aloysius, M. and Brown Jr., R. (2014) Effect of Vitamin E and Alpha Lipoic Acid in Nonalcoholic Fatty Liver Disease: A Randomized, Placebo-Controlled, Open-Label, Prospective Clinical Trial (VAIN Trial). Open Journal of Gastroenterology, 4, 199-207. doi: 10.4236/ojgas.2014.45030.


[1] Erickson, S.K. (2009) Nonalcoholic Fatty Liver Disease. The Journal of Lipid Research, 50, S412-S416.
[2] Lazo, M., Hernaez, R., Bonekamp, S., Kamel, I.R., Brancati, F.L., Guallar, E., et al. (2011) Non-Alcoholic Fatty Liver Disease and Mortality among US Adults: Prospective Cohort Study. BMJ, 343, d6891.
[3] Angulo, P. (2002) Nonalcoholic Fatty Liver Disease. The New England Journal of Medicine, 346, 1221-1231.
[4] Szczepaniak, L.S., Nurenberg, P., Leonard, D., Browning, J.D., Reingold, J.S., Grundy, S., et al. (2005) Magnetic Resonance Spectroscopy to Measure Hepatic Triglyceride Content: Prevalence of Hepatic Steatosis in the General Population. American Journal of Physiology—Endocrinology and Metabolism, 288, E462-E468.
[5] Bugianesi, E., Leone, N., Vanni, E., Marchesini, G., Brunello, F., Carucci, P., et al. (2002) Expanding the Natural History of Nonalcoholic Steatohepatitis: From Cryptogenic Cirrhosis to Hepatocellular Carcinoma. Gastroenterology, 123, 134-140.
[6] Hijona, E., Hijona, L., Arenas, J.I. and Bujanda, L. (2010) Inflammatory Mediators of Hepatic Steatosis. Mediators of Inflammation, 2002, Article ID 837419.
[7] Ibrahim, S.H., Kohli, R. and Gores, G.J. (2011) Mechanisms of Lipotoxicity in NAFLD and Clinical Implications. Journal of Pediatric Gastroenterology and Nutrition, 53, 131-140.
[8] Nehra, V., Angulo, P., Buchman, A.L. and Lindor, K.D. (2001) Nutritional and Metabolic Considerations in the Etiology of Nonalcoholic Steatohepatitis. Digestive Diseases and Sciences, 46, 2347-2352.
[9] Schattenberg, J.M. and Schuppan, D. (2011) Nonalcoholic Steatohepatitis: The Therapeutic Challenge of a Global Epidemic. Current Opinion in Lipidology, 22, 479-488.
[10] Neuschwander-Tetri, B.A. (2010) Hepatic Lipotoxicity and the Pathogenesis of Nonalcoholic Steatohepatitis: The Central Role of Nontriglyceride Fatty Acid Metabolites. Hepatology, 52, 774-788.
[11] Gentile, C.L. and Pagliassotti, M.J. (2008) The Role of Fatty Acids in the Development and Progression of Nonalcoholic Fatty Liver Disease. The Journal of Nutritional Biochemistry, 19, 567-576.
[12] Solis-Herruzo, J.A., Garcia-Ruiz, I., Perez-Carreras, M. and Munoz-Yague, M.T. (2006) Non-Alcoholic Fatty Liver Disease: From Insulin Resistance to Mitochondrial Dysfunction. Revista Española de Enfermedades Digestivas, 98, 844-874.
[13] Videla, L.A. (2009) Oxidative Stress Signaling Underlying Liver Disease and Hepatoprotective Mechanisms. World Journal of Hepatology, 1, 72-78.
[14] Abdelmalek, M.F., Angulo, P., Jorgensen, R.A., Sylvestre, P.B. and Lindor KD. (2001) Betaine, a Promising New Agent for Patients with Nonalcoholic Steatohepatitis: Results of a Pilot Study. The American Journal of Gastroenterology, 96, 2711-2717.
[15] Baumgardner, J.N., Shankar, K., Hennings, L., Albano, E., Badger, T.M. and Ronis, M.J. (2008) N-Acetylcysteine Attenuates Progression of Liver Pathology in a Rat Model of Nonalcoholic Steatohepatitis. Journal of Nutrition, 138, 1872-1879.
[16] Park, K.G., Min, A.K., Koh, E.H., Kim, H.S., Kim, M.O., Park, H.S., et al. (2008) Alpha-Lipoic Acid Decreases Hepatic Lipogenesis through Adenosine Monophosphate-Activated Protein Kinase (AMPK)-Dependent and AMPK-Independent Pathways. Hepatology, 48, 1477-1486.
[17] Sanyal, A.J., Chalasani, N., Kowdley, K.V., McCullough, A., Diehl, A.M., Bass, N.M., et al. (2010) Pioglitazone, Vitamin E, or Placebo for Nonalcoholic Steatohepatitis. The New England Journal of Medicine, 362, 1675-1685.
[18] Lavine, J.E. (2000) Vitamin E Treatment of Nonalcoholic Steatohepatitis in Children: A Pilot Study. The Journal of Pediatrics, 136, 734-738.
[19] Kawanaka, M., Mahmood, S., Niiyama, G., Izumi, A., Kamei, A., Ikeda, H., et al. (2004) Control of Oxidative Stress and Reduction in Biochemical Markers by Vitamin E Treatment in Patients with Nonalcoholic Steatohepatitis: A Pilot Study. Hepatology Research, 29, 39-41.
[20] de Oliveira, A.M., Rondo, P.H., Luzia, L.A., D’Abronzo, F.H. and Illison, V.K. (2011) The Effects of Lipoic Acid and Alpha-Tocopherol Supplementation on the Lipid Profile and Insulin Sensitivity of Patients with Type 2 Diabetes Mellitus: A Randomized, Double-Blind, Placebo-Controlled Trial. Diabetes Research and Clinical Practice, 92, 253-260.
[21] Lavine, J.E., Schwimmer, J.B., Van Natta, M.L., Molleston, J.P., Murray, K.F., Rosenthal, P., et al. (2011) Effect of Vitamin E or Metformin for Treatment of Nonalcoholic Fatty Liver Disease in Children and Adolescents: The TONIC Randomized Controlled Trial. Journal of the American Medical Association, 305, 1659-1668.
[22] Min, A.K., Kim, M.K., Seo, H.Y., Kim, H.S., Jang, B.K., Hwang, J.S., et al. (2010) Alpha-Lipoic Acid Inhibits Hepatic PAI-1 Expression and Fibrosis by Inhibiting the TGF-Beta Signaling Pathway. Biochemical and Biophysical Research Communications, 393, 536-541.
[23] Morsy, M.A., Abdalla, A.M., Mahmoud, A.M., Abdelwahab, S.A. and Mahmoud, M.E. (2011) Protective Effects of Curcumin, Alpha-Lipoic Acid, and N-Acetylcysteine against Carbon Tetrachloride-Induced Liver Fibrosis in Rats. Journal of Physiology and Biochemistry, 68, 29-35.
[24] Packer, L. and Cadenas, E. (2011) Lipoic Acid: Energy Metabolism and Redox Regulation of Transcription and Cell Signaling. Journal of Clinical Biochemistry and Nutrition, 48, 26-32.
[25] Androne, L., Gavan, N.A., Veresiu, I.A. and Orasan, R. (2000) In Vivo Effect of Lipoic Acid on Lipid Peroxidation in Patients with Diabetic Neuropathy. In Vivo, 14, 327-330.
[26] Shay, K.P., Moreau, R.F., Smith, E.J., Smith, A.R. and Hagen, T.M. (2009) Alpha-Lipoic Acid as a Dietary Supplement: Molecular Mechanisms and Therapeutic Potential. Biochimica et Biophysica Acta (BBA)—General Subjects, 1790, 1149-1160.
[27] Parola, M., Leonarduzzi, G., Biasi, F., Albano, E., Biocca, M.E., Poli, G., et al. (1992) Vitamin E Dietary Supplementation Protects against Carbon Tetrachloride-Induced Chronic Liver Damage and Cirrhosis. Hepatology, 16, 1014-1021.
[28] Angulo, P., Hui, J.M., Marchesini, G., Bugianesi, E., George, J., Farrell, G.C., et al. (2007) The NAFLD Fibrosis Score: A Noninvasive System That Identifies Liver Fibrosis in Patients with NAFLD. Hepatology, 45, 846-854.
[29] Neff, G.W., O’Brien, C.B., Reddy, K.R., Bergasa, N.V., Regev, A., Molina, E., et al. (2002) Preliminary Observation with Dronabinol in Patients with Intractable Pruritus Secondary to Cholestatic Liver Disease. The American Journal of Gastroenterology, 97, 2117-2119.

comments powered by Disqus

Copyright © 2019 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.