Potential therapeutic effects of alpha lipoic acid in memory disorders

Main Article Content

Leonardo Triggiani


alpha lipoic acid, ALA, memory disorders


With ageing, biological processes promote a gradual loss of the ability to maintain homeostasis,
leading to a progressive deterioration in the body’s biochemical and physiological functions, thereby increasing
susceptibility to disease. ALA, a low-molecular-weight dithiol with a chiral centre, is a dietary supplement
thought to have potential therapeutic effects for the prevention or treatment of neurodegenerative
diseases. In addition, treatment with ALA is able to regulate inflammatory cell infiltration into the central
nervous system and to down-regulate VCAM-1 and human monocyte adhesion to epithelial cells. In neurodegenerative
disease models, treatment with ALA is able to improve the function of the dopamine, serotonin
and norepinephrine neurotransmitters. Scientific evidence shows that ALA possesses the ability to improve
memory capacity in a number of experimental neurodegenerative disease models and in age-related cognitive
decline in rodents. Studies have shown that this substance is able to reduce memory loss

Abstract 1698 | PDF Downloads 1102


1. Snell EE, Strong FM, Peterson WH. Growth factors for bacteria: Fractionation and properties of an accessory factor for lactic acid bacteria. Biochem J. 1937 Oct;31(10):1789-99
2. Reed LJ, DeBusk BG, Gunsalus IC, Hornberger CS Jr. Crystalline alpha-lipoic acid; a catalytic agent associated with pyruvate dehydrogenase. Science. 1951 Jul 27;114(2952):93-4
3. Arivazhagan P, Ramanathan K, Panneerselvam C. Effect of DL-alpha-lipoic acid on glutathione metabolic enzymes in aged rats. Exp Gerontol. 2001 Dec;37(1):81-7.
4. Bilska A, Dubiel M, Sokołowska-Jezewicz M, Lorenc-Koci E, Włodek L. Alpha-lipoic acid differently affects the reserpine-induced oxidative stress in the striatum and prefrontal cortex of rat brain. Neuroscience. 2007 Jun 8;146(4):1758-71
5. De Araújo DP, Lobato Rde F, Cavalcanti JR, Sampaio LR, Araújo PV, Silva MC, Neves KR, Fonteles MM, Sousa FC, Vasconcelos SM. The contributions of antioxidant activity of lipoic acid in reducing neurogenerative progression of Parkinson's disease: a review. Int J Neurosci. 2011 Feb;121(2):51-7
6. Xing ZG, Yu GD, Qin L, Jiang F, Zhao WH. Effects and mechanism of lipoic acid on beta-amyloid-intoxicated C6 glioma cells. Genet Mol Res. 2015 Oct 30;14(4):13880-8
7. Lodge JK, Packer L. Natural sources of lipoic acid in plant and animal tissues. In: Antioxidant food supplements in human health. Eds. Packer L, Hiramatsu M, Yoshikawa T. San Diego, CA: Academic Press. 1999:121-134
8. Hagen TM, Ingersoll RT, Lykkesfeldt J, Liu J, Wehr CM, Vinarsky V, Bartholomew JC, Ames AB. (R)-alpha-lipoic acid-supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rate. FASEB J. 1999 Feb;13(2):411-8
9. Bustamante J, Lodge JK, Marcocci L, Tritschler HJ, Packer L, Rihn BH. Alpha-lipoic acid in liver metabolism and disease. Free Radic Biol Med. 1998 Apr;24(6):1023-39
10. Ambrus A, Tretter L, Adam-Vizi V. Inhibition of the alpha-ketoglutarate dehydrogenase-mediated reactive oxygen species generation by lipoic acid. J Neurochem. 2009 May;109 Suppl 1:222-9
11. Bilska A, Włodek L. Lipoic acid - the drug of the future? Pharmacol Rep. 2005 Sep-Oct;57(5):570-7
12. Jones W, Li X, Qu ZC, Perriott L, Whitesell RR, May JM. Uptake, recycling, and antioxidant actions of alpha-lipoic acid in endothelial cells. Free Radic Biol Med. 2002 Jul 1;33(1):83-93
13. Petersen Shay K, Moreau RF, Smith EJ, Hagen TM. Is alpha-lipoic acid a scavenger of reactive oxygen species in vivo? Evidence for its initiation of stress signaling pathways that promote endogenous antioxidant capacity. IUBMB Life. 2008 Jun;60(6):362-7
14. Zhang WJ, Frei B. Alpha-lipoic acid inhibits TNF-alpha-induced NF-kappaB activation and adhesion molecule expression in human aortic endothelial cells. FASEB J. 2001 Nov;15(13):2423-32
15. Kim HS, Kim HJ, Park KG, Kim YN, Kwon TK, Park JY, Lee KU, Kim JG, Lee IK. Alpha-lipoic acid inhibits matrix metalloproteinase-9 expression by inhibiting NF-kappaB transcriptional activity. Exp Mol Med. 2007 Feb 28;39(1):106-13.
16. Abdelkarem HM, Fadda LH, Hassan AAG. Potential Intervention of α- Lipoic Acid and Carnitine on Insulin Sensitivity and Anti-Inflammatory Cytokines Levels in Fructose-Fed Rats, a Model of Metabolic Syndrome. J Diet Suppl. 2017 Jan 2;14(1):54-64
17. Kunt T, Forst T, Wilhelm A, Tritschler H, Pfuetzner A, Harzer O, Engelbach M, Zschaebitz A, Stofft E, Beyer J. Alpha-lipoic acid reduces expression of vascular cell adhesion molecule-1 and endothelial adhesion of human monocytes after stimulation with advanced glycation end products. Clin Sci (Lond). 1999 Jan;96(1):75-82
18. Guo J, Gao S, Liu Z, Zhao R, Yang X. Alpha-Lipoic Acid Alleviates Acute Inflammation and Promotes Lipid Mobilization During the Inflammatory Response in White Adipose Tissue of Mice. Lipids. 2016 Oct;51(10):1145-1152
19. Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM. Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta. 2009 Oct;1790(10):1149-60
20. Ou P, Tritschler HJ, Wolff SP. Thioctic (lipoic) acid: a therapeutic metal-chelating antioxidant? Biochem Pharmacol. 1995 Jun 29;50(1):123-6
21. Bush AI. Metal complexing agents as therapies for Alzheimer's disease. Neurobiol Aging. 2002 Nov-Dec;23(6):1031-8
22. Suh JH, Moreau R, Heath SH, Hagen TM. Dietary supplementation with (R)-alpha-lipoic acid reverses the age-related accumulation of iron and depletion of antioxidants in the rat cerebral cortex. Redox Rep. 2005;10(1):52-60.
23. Tamaoka A. The pathophysiology of Alzheimer’s disease with special reference to “amyloid cascade hypothesis”. Rinsho Byori 2013;61(11):1060–9
24. Nordberg A. In vivo detection of neurotransmitter changes in Alzheimer’s disease. Ann NY Acad Sci 1993;695(1):27–33
25. Whitehouse PJ, Au KS. Cholinergic receptors in aging and Alzheimer’s disease. Prog Neuropsychopharmacol Biol Psychiatry 1986;10(3):665–76
26. Tomaszewicz M, Roßner S, Schliebs R, Cwikowska J, Szutowicz A. Changes in cortical acetyl-CoA metabolism after selective basal forebrain cholinergic degeneration by 192IgG-saporin. J Neurochem 2003;87(2):318–24
27. Fu W, Jhamandas JH. Role of astrocytic glycolytic metabolism in Alzheimer’s disease pathogenesis. Biogerontology 2014;15(6):579–86
28. Avila-Muñoz E, Arias C. When astrocytes become harmful: functional and inflammatory responses that contribute to Alzheimer’s disease. Ageing Res Rev. 2014;18:29–40
29. Manczak M, Anekonda TS, Henson E, Park BS, Quinn J, Reddy PH. Mitochondria are a direct site of Aβ accumulation in Alzheimer’s disease neurons: implications for free radical generation and oxidative damage in disease progression. Hum Mol Gen 2006;15(9):1437–49
30. Butterfield DA, Boyd-Kimball D, Castegna A. Proteomics in Alzheimer’s disease: insights into potential mechanisms of neurodegeneration. J Neurochem 2003;86(6):1313–27
31. Lovell MA, Markesbery WR. Oxidative damage in mild cognitive impairment and early Alzheimer’s disease. J Neurosci Res 2007;85(14):3036–40
32. Morris M. The role of nutrition in Alzheimer’s disease: epidemiological evidence. Eur J Neurol 2009;16(s1):1–7
33. Galasko DR, Peskind E, Clark CM, Quinn JF, Ringman JM, Jicha GA, et al. Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures. Arch Neurol 2012;69(7):836–41
34. Farr SA, Price TO, Banks WA, Ercal N, Morley JE. Effect of alpha-lipoic acid on memory, oxidation, and lifespan in SAMP8 mice. J Alzheimers Dis 2012;32(2):447–55
35. Moraes TB, Dalazen GR, Jacques CE, de Freitas RS, Rosa AP, Dutra-Filho CS. Glutathione metabolism enzymes in brain and liver of hyperphenylalaninemic rats and the effect of lipoic acid treatment. Metab Brain Dis 2014;29(3):609–15
36. Arivazhagan P, Ramanathan K, Panneerselvam C. Effect of DL-α-lipoic acid on mitochondrial enzymes in aged rats. Chem Biol Interact 2001;138(2):189–98
37. Ajith TA, Nima N, Veena RK, Janardhanan KK, Antonawich F. Effect of palladium α-lipoic acid complex on energy in the brain mitochondria of aged rats. Altern Ther Health Med 2013;20(3):27–35
38. Huang X, Atwood CS, Hartshorn MA, Multhaup G, Goldstein LE, Scarpa RC, et al. The Aβ peptide of Alzheimer’s disease directly produces hydrogen peroxide through metal ion reduction. Biochemistry 1999;38(24):7609–16
39. Suh JH, Zhu B-Z, deSzoeke E, Frei B, Hagen TM. Dihydrolipoic acid lowers the redox activity of transition metal ions but does not remove them from the active site of enzymes. Redox Rep 2004;9(1):57–61
40. Fonte J,Miklossy J, AtwoodC, Martins R. The severity of cortical Alzheimer’s type changes is positively correlated with increased amyloid-β levels: resolubilization of amyloid-β with transition metal ion chelators. J Alzheimers Dis 2001;3(2):209–19
41. Sancheti H, Akopian G, Yin F, Brinton RD,Walsh JP, Cadenas E. Age-dependent modulation of synaptic plasticity and insulin mimetic effect of lipoic acid on a mouse model of Alzheimer’s disease. PloS one 2013;8(7):e69830
42. Haugaard N, Levin RM. Activation of choline acetyl transferase by dihydrolipoic acid. Mol Cell Biochem 2002;229(1–2):103–6
43. de Freitas RM. Lipoic acid increases hippocampal choline acetyltransferase and acetylcholinesterase activities and improvement memory in epileptic rats. Neurochem Res 2010;35(1):162–70
44. Hager K, Marahrens A, KenkliesM, Riederer P, Münch G (2001) Alphalipoic acid as a new treatment option for Alzheimer [corrected] type dementia. Arch Gerontol Geriatr 32:275–282
45. Hager K, Kenklies M, McAfoose J et al (2007) Alpha-lipoic acid as a new treatment option for Alzheimer’s disease–a 48 months follow-up analysis. J Neural Transm Suppl:189–193
46. Galasko DR, Peskind E, Clark CM, Quinn JF, Ringman JM, Jicha GA, Cotman C, Cottrell B, Montine TJ, Thomas RG, Aisen P, Alzheimer's Disease Cooperative Study (2012) Antioxidants for Alzheimer disease. Arch Neurol 69:836–841
47. Shinto L, Quinn J, Montine T, Dodge HH, Woodward W, Baldauf-Wagner S, Waichunas D, Bumgarner L, Bourdette D, Silbert L, Kaye J (2014) A randomized placebo-controlled pilot trial of omega-3 fatty acids and alpha lipoic acid in Alzheimer’s disease. J Alzheimers Dis 38:111–120
48. Bragin V, Chemodanova M, Dzhafarova N et al (2005) Integrated treatment approach improves cognitive function in demented and clinically depressed patients. Am J Alzheimer’s Dis Other Dementias 20(21–26):6p
49. Arivazhagan P, Panneerselvam C. Neurochemical changes related to ageing in the rat brain and the effect of DL-alpha-lipoic acid. Exp. Gerontol. 2002;37,1489–1494
50. Arivazhagan, P, Panneerselvam C. Effect of DL-alpha-lipoic acid on neural antioxidants in aged rats. Pharmacol. Res. 2000;42, 219–222
51. Farr SA, Poon HF, Dogrukol-Ak D, Drake J, Banks WA, Eyerman E. The antioxidants alpha-lipoic acid and Nacetylcysteine reverse memory impairment and brain oxidative stress in aged SAMP8 mice. J. Neurochem 2003;84, 1173–1183
52. Liu J, Head E, Gharib AM, Yuan W, Ingersoll RT, Hagen TM. Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acid. Proc. Natl. Acad. Sci. U.S.A. 2002;99, 2356–2361
53. Dwivedi N, Flora G, Kushwaha P, Flora SJ. Alphalipoic acid protects oxidative stress, changes in cholinergic system and tissue histopathology during co-exposure to arsenic-dichlorvos in rats. Environ. Toxicol. Pharmacol. 2014;37, 7–23
54. Poon HF, Farr SA, Thongboonkerd V, Lynn BC, Banks WA, Morley JE. Proteomic analysis of specific brain proteins in aged SAMP8 mice treated with alpha-lipoic acid: implications for aging and age-related neurodegenerative disorders. Neurochem. Int. 2005;46, 159–168
55. Jesudason EP, Masilamoni JG, Kirubagaran R, Davis GD, Jayakumar R. The protective role of DL-alpha-lipoic acid in biogenic amines catabolism triggered by Abeta amyloid vaccination in mice. Brain Res. Bull. 2005;65,361–367
56. Ahmed HH. Modulatory effects of vitamin E, acetyl-L-carnitine and alpha-lipoic acid on new potential biomarkers for Alzheimer’s disease in rat model. Exp. Toxicol. Pathol. 2012;64, 549–556
57. Mahboob A, Farhat SM, Iqbal G, Babar MM, Zaidi NU, Nabavi SM. Alpha-lipoic acid-mediated activation of muscarinic receptors improves hippocampus- and amygdala-dependent memory. Brain Res. Bull. 2016;122, 19–28
58. Ono K, Hirohata M, Yamada M. Alpha-lipoic acid exhibits antiamyloidogenicity for beta-amyloid fibrils in vitro. Biochem. Biophys. Res. Commun. 2006;341, 1046–1052
59. Lovell MA, Xie C, Xiong S, Markesbery WR. Protection against amyloid beta peptide and iron/hydrogen peroxide toxicity by alpha lipoic acid. J. Alzheimers Dis. 2003;5, 229–239