The Dietary Antioxidants Alpha-Tocopherol and Alpha-Lipoic Acid and Their Synergy in Brain Disorders

  • Oscar Gonzalez-Perez


Alpha-lipoic acid (ALA) and vitamin E (VE) are normally present in human diet and their side-effects derived from oral supplementation are very rare. Interestingly, a combination of these antioxidants has shown synergistic effects, as determined in experimental and clinical studies. This chapter summarizes (1) The role of oxygen free radicals in brain injuries; (2) The antioxidant effects of ALA and VE in the brain; (3) The mechanism of action of the synergy between ALA and VE; and (4) The increasing evidence showing that the combination of ALA and VE is more effective than any antioxidant monotherapy for reducing oxidative damage. Specifically, ALA and VE efficiently counteract oxidant radicals in a number of neurological diseases, such as brain ischemia, Parkinson’s disease, multiple sclerosis, Huntington’s disease, amyotrophic lateral sclerosis, diabetic neuropathy, and Alzheimer’s disease. Yet, ALA and VE are also effective in non-neurological diseases, such as rheumatoid arthritis, chemotherapy, high performance exercise, cataracts, heart failure, myocardial infarction, atherosclerosis, chronic fatigue syndrome, and aging process. In summary, although antioxidants by themselves cannot prevent the incidence of neurological diseases, they can delay its occurrence and/or reduce the magnitude of neural damage. Therefore, diets or commercial supplements enriched with these two antioxidants may be ideal for people in risk of suffering from neurological conditions generated by unbalance production of oxygen free radicals.


Amyotrophic Lateral Sclerosis Chronic Fatigue Syndrome Diabetic Neuropathy Oxygen Free Radical Lipoic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.







Adenosine triphosphatase


Alpha-lipoic acid


Deoxyribonucleic acid


Gamma-amino butyric acid


Glutathione peroxidase


Growth-associated protein 43


Nicotinamide adenine dinucleotide oxidized


Nicotinamide adenine dinucleotide phosphate oxidized


Nicotinamide adenine dinucleotide phosphate reduced


Nicotinamide adenine dinucleotide reduced


Reactive oxygen species


Ribonucleic acid


Superoxide dismutase


Vitamin E



This work was supported by the Consejo Nacional de Ciencia y Tecnologia (CONACyT; Ciencia Basica-2008-101476).


  1. Arivazhagan P, Thilakavathy T, Ramanathan K, Kumaran S, Panneerselvam C. J Nutr Biochem. 2002;13:619–24.PubMedCrossRefGoogle Scholar
  2. Bagh MB, Maiti AK, Roy A, Chakrabarti S. Biogerontology 2008;9:421–8.PubMedCrossRefGoogle Scholar
  3. Bailey DM, Davies B. High Alt Med Biol. 2001;2:21–9.PubMedCrossRefGoogle Scholar
  4. Bist R, Bhatt DK. J Neurol Sci. 2009;276:99–102.PubMedCrossRefGoogle Scholar
  5. Blomgren K, Hagberg H. Free Radic Biol Med. 2006;40:388–97.PubMedCrossRefGoogle Scholar
  6. Butterfield DA. Antioxid Redox Signal. 2006;8:1971–3.PubMedCrossRefGoogle Scholar
  7. Cao L, Chen R, Xu J, Lin Y, Wang R, Chi Z. Neuroscience 2009.Google Scholar
  8. Cao X, Phillis JW. Free Radic Res. 1995;23:365–70.PubMedCrossRefGoogle Scholar
  9. Chan A, Shea TB. J Alzheimers Dis. 2009;16:167–71.PubMedGoogle Scholar
  10. Chrissobolis S, Faraci FM. Trends Mol Med. 2008;14:495–502.PubMedCrossRefGoogle Scholar
  11. Conti M, Couturier M, Lemonnier A, Lemonnier F. Int J Vitam Nutr Res. 1993;63:71–6.PubMedGoogle Scholar
  12. Coombes JS, Powers SK, Demirel HA, Jessup J, Vincent HK, Hamilton KL, Naito H, Shanely RA, Sen CK, Packer L, Ji LL. Acta Physiol Scand. 2000a;169:261–9.PubMedCrossRefGoogle Scholar
  13. Coombes JS, Powers SK, Hamilton KL, Demirel HA, Shanely RA, Zergeroglu MA, Sen CK, Packer L, Ji LL. Am J Physiol Regul Integr Comp Physiol. 2000b;279:R2149–55.PubMedGoogle Scholar
  14. Coombes JS, Powers SK, Rowell B, Hamilton KL, Dodd SL, Shanely RA, Sen CK, Packer L. J Appl Physiol. 2001;90:1424–30.PubMedGoogle Scholar
  15. Fruhauf J, Schaider H, Massone C, Kerl H, Mullegger RR. Mayo Clin Proc. 2008;83:502–4.PubMedCrossRefGoogle Scholar
  16. Gaedicke S, Zhang X, Huebbe P, Boesch-Saadatmandi C, Lou Y, Wiswedel I, Gardemann A, Frank J, Rimbach G. Br J Nutr. 2009:1–9.Google Scholar
  17. Garcia-Estrada J, Gonzalez-Perez O, Gonzalez-Castaneda RE, Martinez-Contreras A, Luquin S, de la Mora PG, Navarro-Ruiz A. Neurosci Res. 2003;47:219–24.PubMedCrossRefGoogle Scholar
  18. Gonzalez-Perez O, Gonzalez-Castaneda RE. Nutr Res. 2006;26:1–5.PubMedCrossRefGoogle Scholar
  19. Gonzalez-Perez O, Gonzalez-Castaneda RE, Huerta M, Luquin S, Gomez-Pinedo U, Sanchez-Almaraz E, Navarro-Ruiz A, Garcia-Estrada J. Neurosci Lett. 2002;321:100–4.PubMedCrossRefGoogle Scholar
  20. Gonzalez-Perez O, Moy-Lopez NA, Guzman-Muniz J. Rev Invest Clin. 2008;60:58–67.PubMedGoogle Scholar
  21. Haramaki N, Packer L, Assadnazari H, Zimmer G. Biochem Biophys Res Commun. 1993;196:1101–7.PubMedCrossRefGoogle Scholar
  22. Haramaki N, Assadnazari H, Zimmer G, Schepkin V, Packer L. Biochem Mol Biol Int. 1995;37:591–7.PubMedGoogle Scholar
  23. Heo JH, Han SW, Lee SK. Free Radic Biol Med. 2005;39:51–70.PubMedCrossRefGoogle Scholar
  24. Jesudason EP, Masilamoni JG, Jebaraj CE, Paul SF, and Jayakumar R. Mol Cell Biochem. 2008;313:113–23.PubMedCrossRefGoogle Scholar
  25. Ko KM, Yiu HY. Mol Cell Biochem. 2001;220:141–7.PubMedCrossRefGoogle Scholar
  26. Lexis LA, Fassett RG, Coombes JS. Alpha-tocopherol and alpha-lipoic acid enhance the erythrocyte antioxidant defence in cyclosporine A-treated rats. Basic Clin Pharmacol Toxicol. 2006;98:68–73.Google Scholar
  27. Lockrow J, Prakasam A, Huang P, Bimonte-Nelson H, Sambamurti K, Granholm AC. Exp Neurol. 2009;216:278–89.PubMedCrossRefGoogle Scholar
  28. Maitra I, Serbinova E, Trischler H, Packer L. Free Radic Biol Med. 1995;18:823–9.PubMedCrossRefGoogle Scholar
  29. Manda K, Ueno M, Moritake T, Anzai K. Cell Biol Toxicol. 2007;23:129–37.PubMedCrossRefGoogle Scholar
  30. Mantovani G, Maccio A, Madeddu C, Mura L, Gramignano G, Lusso MR, Murgia V, Camboni P, Ferreli L, Mocci M, Massa E. Free Radic Res. 2003;37:213–23.PubMedCrossRefGoogle Scholar
  31. Marsh SA, Laursen PB, Pat BK, Gobe GC, Coombes JS. J Mol Cell Cardiol. 2005;38:445–51.PubMedCrossRefGoogle Scholar
  32. Marsh SA, Coombes JS. Vitamin E and alpha-lipoic acid supplementation increase bleeding tendency via an intrinsic coagulation pathway. Clin Appl Thromb Hemost. 2006;12:169–73.Google Scholar
  33. Monget AL, Richard MJ, Cournot MP, Arnaud J, Galan P, Preziosi P, Herbeth B, Favier A, Hercberg S. Eur J Clin Nutr. 1996;50:443–9.PubMedGoogle Scholar
  34. Mosca L, Marcellini S, Perluigi M, Mastroiacovo P, Moretti S, Famularo G, Peluso I, Santini G, De Simone C. Biochem Pharmacol. 2002;63:1305–14.PubMedCrossRefGoogle Scholar
  35. Muller U, Krieglstein J. J Cereb Blood Flow Metab. 1995;15:624–30.PubMedCrossRefGoogle Scholar
  36. Murphy ME, Scholich H, Sies H. Eur J Biochem. 1992;210:139–46.PubMedCrossRefGoogle Scholar
  37. Naziroglu M, Cay M, Ustundag B, Aksakal M, Yekeler H. Cell Biochem Funct. 1999;17:253–9.PubMedCrossRefGoogle Scholar
  38. Ozkan Y, Yilmaz O, Ozturk AI, Ersan Y. Cell Biol Int. 2005;29:754–60.PubMedCrossRefGoogle Scholar
  39. Packer L, Witt EH, Tritschler HJ. Free Radic Biol Med. 1995;19:227–50.PubMedCrossRefGoogle Scholar
  40. Packer L, Tritschler HJ, Wessel K. Free Radic Biol Med. 1997;22:359–78.PubMedCrossRefGoogle Scholar
  41. Paravicini TM, Drummond GR, Sobey CG. Drugs 2004;64:2143–57.PubMedCrossRefGoogle Scholar
  42. Parkinson SG. N Engl J Med. 1993;328:176–83.CrossRefGoogle Scholar
  43. Piotrowski P, Wierzbicka K, Smialek M. Folia Neuropathol. 2001;39:147–54.PubMedGoogle Scholar
  44. Poon HF, Calabrese V, Scapagnini G, and Butterfield DA. Clin Geriatr Med. 2004;20:329–59.PubMedCrossRefGoogle Scholar
  45. Roy S, Sen CK, Tritschler HJ, Packer L. Biochem Pharmacol. 1997;53:393–9.PubMedCrossRefGoogle Scholar
  46. Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, Grundman M, Woodbury P, Growdon J, Cotman CW, Pfeiffer E, Schneider LS, Thal LJ. N Engl J Med. 1997;336:1216–22.PubMedCrossRefGoogle Scholar
  47. Schmidt MC, Askew EW, Roberts DE, Prior RL, Ensign WY Jr, Hesslink RE Jr. Wilderness Environ Med. 2002;13:94–105.PubMedCrossRefGoogle Scholar
  48. Scholich H, Murphy ME, Sies H. Biochim Biophys Acta. 1989;1001:256–61.PubMedGoogle Scholar
  49. Schreibelt G, Musters RJ, Reijerkerk A, de Groot LR, van der Pol SM, Hendrikx EM, Dopp ED, Dijkstra CD, Drukarch B, de Vries HE. J Immunol. 2006;177:2630–7.PubMedGoogle Scholar
  50. Scott DL, Kelleher J, Losowsky MS. Biochem Soc Trans. 1976;4:295–6.PubMedGoogle Scholar
  51. Seaton TA, Jenner P, Marsden CD. Biochem Pharmacol. 1996;52:1657–63.PubMedCrossRefGoogle Scholar
  52. Sharman EH, Bondy SC. Neurobiol Aging. 2001;22:629–34.PubMedCrossRefGoogle Scholar
  53. Shirpoor A, Minassian S, Salami S, Khadem-Ansari MH, Yeghiazaryan M. Cell Physiol Biochem. 2008;22:769–76.PubMedCrossRefGoogle Scholar
  54. Stoffel M, Berger S, Staub F, Eriskat J, Jacob K, Baethmann A. J Neurotrauma. 1997;14:339–48.PubMedCrossRefGoogle Scholar
  55. Stoyanovsky DA, Goldman R, Darrow RM, Organisciak DT, Kagan VE. Curr Eye Res. 1995;14:181–9.PubMedCrossRefGoogle Scholar
  56. Suchy J, Chan A, Shea TB. Nutr Res. 2009;29:70–4.PubMedCrossRefGoogle Scholar
  57. Tirosh O, Sen CK, Roy S, Kobayashi MS, Packer L. Free Radic Biol Med. 1999;26:1418–26.PubMedCrossRefGoogle Scholar
  58. van der Worp HB, Bar PR, Kappelle LJ, de Wildt DJ. Stroke 1998;29:1002–5; discussion 1005–6.PubMedCrossRefGoogle Scholar
  59. Villalobos MA, De La Cruz JP, Carrasco T, Smith-Agreda JM, Sanchez de la Cuesta F. Brain Res Bull. 1994;33:313–8.PubMedCrossRefGoogle Scholar
  60. Woltjer RL, McMahan W, Milatovic D, Kjerulf JD, Shie FS, Rung LG, Montine KS, Montine TJ. Effects of chemical chaperones on oxidative stress and detergent-insoluble species formation following conditional expression of amyloid precursor protein carboxy-terminal fragment. Neurobiol Dis. 2007;25:427–37.Google Scholar
  61. Wolz P, Krieglstein J. Neuropharmacology 1996;35:369–75.PubMedCrossRefGoogle Scholar
  62. Yadav V, Marracci G, Lovera J, Woodward W, Bogardus K, Marquardt W, Shinto L, Morris C, Bourdette D. Mult Scler. 2005;11:159–65.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Laboratory of Neuroscience, School of PsychologyUniversity of ColimaColimaMéxico
  2. 2.Neuroscience Department, Centro Universitario de Ciencias de la SaludUniversity of GuadalajaraGuadalajaraMéxico

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