THERAPEUTIC USE OF ALPHA-LIPOIC ACID SUPPLEMENTATION: A REVIEW ON CURRENT USE AND FUTURE PROSPECTIVE
DOI:
https://doi.org/10.22159/ijap.2024v16i6.51319Keywords:
Alpha-lipoic acid, Bioavailability, Formulations, Pharmacological potentialAbstract
Alpha-lipoic acid (ALA, thioctic acid, 5-(1,2-dithiolan-3-yl) pentanoic acid) is an organosulfur compound produced by plants, humans, and animals. ALA plays a crucial role in mitochondrial bioenergetics reactions. It is a natural antioxidant and a dithiol compound. ALA is a coenzyme that plays a crucial role in the function of pyruvate and Alpha-ketoglutarate dehydrogenase complexes found in mitochondria. ALA has cytotoxic and antiproliferative effects on several cancers, including Polycystic Ovarian Syndrome (PCOS). Most of ALA's clinical applications come from its antioxidant properties, but it also shows potential in treating female and male infertility. Although ALA can potentially be a therapeutic agent, its pharmacokinetic profile limits its effectiveness. Research suggests that ALA has a short half-life and low bioavailability (around 30%) because it gets broken down in the liver, has reduced solubility, and is unstable in the stomach. Liquid formulations have higher bioavailability and plasma concentration than solid dose forms. This review covers the current clinical evidence on using ALA to prevent, manage, and cure numerous disorders, including diabetic neuropathy, obesity, central nervous system-related ailments, and pregnancy abnormalities.
Downloads
References
Reed LJ, Debusk BG, Gunsalus IC, Hornberger JR CS. Crystalline α-lipoic acid: a catalytic agent associated with pyruvate dehydrogenase. Science. 1951 Jul 27;114(2952):93-4. doi: 10.1126/science.114.2952.93, PMID 14854913.
Bock E, Schneeweiss J. Ein beitrag zur therapie der neuropathia diabetica. Munchner Med Wochenschr. 1959;43:1911-2.
Brookes MH, Golding BT, Howes DA, Hudson AT. Proof that the absolute configuration of natural α-lipoic acid is R by the synthesis of its enantiomer [(S)-(–)-α-lipoic acid] from (S)-malic acid. J Chem Soc Chem Commun. 1983;19:1051-3. doi: 10.1039/C39830001051.
Ghibu S, Richard C, Vergely C, Zeller M, Cottin Y, Rochette L. Antioxidant properties of an endogenous thiol: alpha-lipoic acid useful in the prevention of cardiovascular diseases. J Cardiovasc Pharmacol. 2009 Nov 1;54(5):391-8. doi: 10.1097/fjc.0b013e3181be7554, PMID 19998523.
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 1;1790(10):1149-60. doi: 10.1016/j.bbagen.2009.07.026, PMID 19664690, PMCID PMC2756298.
Lee SJ, Kang JG, Ryu OH, Kim CS, Ihm SH, Choi MG. Effects of α-lipoic acid on transforming growth factor β1–p38 mitogen-activated protein kinase fibronectin pathway in diabetic nephropathy. Metabolism. 2009 May 1;58(5):616-23. doi: 10.1016/j.metabol.2008.12.006, PMID 19375583.
Wollin SD, Jones PJ. Alpha-lipoic acid and cardiovascular disease. J Nutr. 2003 Nov;133(11):3327-30. doi: 10.1093/jn/133.11.3327, PMID 14608040.
Suh JH, Shenvi SV, Dixon BM, Liu H, Jaiswal AK, Liu RM. Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. Proc Natl Acad Sci USA. 2004 Mar 9;101(10):3381-6. doi: 10.1073/pnas.0400282101, PMID 14985508.
Salehi B, Berkay Yılmaz Y, Antika G, Boyunegmez Tumer T, Fawzi Mahomoodally M, Lobine D. Insights on the use of α-lipoic acid for therapeutic purposes. Biomolecules. 2019 Aug 9;9(8):356. doi: 10.3390/biom9080356, PMID 31405030.
Keith DJ, Butler JA, Bemer B, Dixon B, Johnson S, Garrard M. Age and gender dependent bioavailability of R- and RS-α-lipoic acid: a pilot study. Pharmacol Res. 2012;66(3):199-206. doi: 10.1016/j.phrs.2012.05.002, PMID 22609537.
Ziegler D. Thioctic acid for patients with symptomatic diabetic polyneuropathy: a critical review. Treat Endocrinol. 2004;3(3):173-89. doi: 10.2165/00024677-200403030-00005, PMID 16026113.
Golbidi S, Badran M, Laher I. Diabetes and alpha lipoic acid. Front Pharmacol. 2011 Nov 17;2:69. doi: 10.3389/fphar.2011.00069, PMID 22125537.
OU P, Tritschler HJ, Wolff SP. Thioctic (lipoic) acid: a therapeutic metal-chelating antioxidant. Biochem Pharmacol. 1995 Jun 29;50(1):123-6. doi: 10.1016/0006-2952(95)00116-h, PMID 7605337.
Goraca A, Huk Kolega H, Piechota A, Kleniewska P, Ciejka E, Skibska B. Lipoic acid biological activity and therapeutic potential. Pharmacol Rep. 2011;63(4):849-58. doi: 10.1016/s1734-1140(11)70600-4, PMID 22001972.
Carrier B, Rideout TC. Antiobesity and lipid-lowering properties of alpha lipoic acid. J Hum Nutr Food Sci. 2013;1(1):1008. doi: 10.47739/2333-6706/1002.
Namazi N, Larijani B, Azadbakht L. Alpha-lipoic acid supplement in obesity treatment: a systematic review and meta-analysis of clinical trials. Clin Nutr. 2018 Apr;37(2):419-28. doi: 10.1016/j.clnu.2017.06.002, PMID 28629898.
Key Global Findings; 2021. Available from: https://diabetesatlas.org/#:~:text=Diabetes%20around%20the%20world%20in%202021%3A,%2D%20and%20middle%2Dincome%20countries [Last accessed on 02 May 2024].
Moodley K, Joseph K, Naidoo Y, Islam S, Mackraj I. Antioxidant antidiabetic and hypolipidemic effects of tulbaghia violacea harv (wild garlic) rhizome methanolic extract in a diabetic rat model. BMC Complement Altern Med. 2015 Nov 17;15:408. doi: 10.1186/s12906-015-0932-9, PMID 26577219.
Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res. 2010;107(9):1058-70. doi: 10.1161/circresaha.110.223545, PMID 21030723.
Eason RC, Archer HE, Akhtar S, Bailey CJ. Lipoic acid increases glucose uptake by skeletal muscles of obese diabetic ob/ob mice. Diabetes Obes Metab. 2002 Jan;4(1):29-35. doi: 10.1046/j.1463-1326.2002.00171.x, PMID 11874439.
Agathos E, Tentolouris A, Eleftheriadou I, Katsaouni P, Nemtzas I, Petrou A. Effect of α-lipoic acid on symptoms and quality of life in patients with painful diabetic neuropathy. J Int Med Res. 2018 May;46(5):1779-90. doi: 10.1177/0300060518756540, PMID 29517942.
Goralska M, Dackor R, Holley B, McGahan MC. Alpha lipoic acid changes iron uptake and storage in lens epithelial cells. Exp Eye Res. 2003 Feb;76(2):241-8. doi: 10.1016/s0014-4835(02)00307-x, PMID 12565812.
Islam MT. Antioxidant activities of dithiol alpha-lipoic acid. Bangladesh J Med Sci. 2009;8(3):46-51. doi: 10.3329/bjms.v8i3.3982.
Wang Q, LV C, Sun Y, Han X, Wang S, Mao Z. The role of alpha-lipoic acid in the pathomechanism of acute ischemic stroke. Cell Physiol Biochem. 2018;48(1):42-53. doi: 10.1159/000491661, PMID 29996116.
Karunakaran S, Diwakar L, Saeed U, Agarwal V, Ramakrishnan S, Iyengar S. Activation of apoptosis signal-regulating kinase 1 (ASK1) and translocation of death associated protein daxx in substantia nigra pars compacta in a mouse model of parkinsons disease: protection by alpha-lipoic acid. FASEB J. 2007 Jul;21(9):2226-36. doi: 10.1096/fj.06-7580com, PMID 17369508.
LI DW, Wang YD, Zhou SY, Sun WP. α-Lipoic acid exerts neuroprotective effects on neuronal cells by upregulating the expression of PCNA via the P53 pathway in neurodegenerative conditions. Mol Med Rep. 2016 Nov;14(5):4360-6. doi: 10.3892/mmr.2016.5754, PMID 27665784.
Shinto L, Quinn J, Montine T, Dodge HH, Woodward W, Baldauf Wagner S. A randomized placebo-controlled pilot trial of omega-3 fatty acids and alpha lipoic acid in alzheimers disease. J Alzheimers Dis. 2014;38(1):111-20. doi: 10.3233/JAD-130722, PMID 24077434.
Bastianetto S, Quirion R. Natural antioxidants and neurodegenerative diseases. Front Biosci. 2004 Sep 1;9:3447-52. doi: 10.2741/1493, PMID 15353369.
Micili SC, Goker A, Kuscu K, Ergur BU, Fuso A. α-Lipoic acid vaginal administration contrasts inflammation and preterm delivery in rats. Reprod Sci. 2019 Jan;26(1):128-38. doi: 10.1177/1933719118766266, PMID 29631479.
Granata S, Dalla Gassa A, Tomei P, Lupo A, Zaza G. Mitochondria: a new therapeutic target in chronic kidney disease. Nutr Metab (Lond). 2015 Nov 25;12:49. doi: 10.1186/s12986-015-0044-z, PMID 26612997.
Zhang J, Mc Cullough PA. Lipoic acid in the prevention of acute kidney injury. Nephron. 2016;134(3):133-40. doi: 10.1159/000448666, PMID 27603173.
Lim PS, Wei YH, Yu YL, Kho B. Enhanced oxidative stress in haemodialysis patients receiving intravenous iron therapy. Nephrol Dial Transplant. 1999 Nov;14(11):2680-7. doi: 10.1093/ndt/14.11.2680, PMID 10534512.
Lai S, Petramala L, Muscaritoli M, Cianci R, Mazzaferro S, Mitterhofer AP. α-Lipoic acid in patients with autosomal dominant polycystic kidney disease. Nutrition. 2020 Mar;71:110594. doi: 10.1016/j.nut.2019.110594, PMID 31790890.
Zhao G, HU C, Xue Y. In vitro evaluation of chitosan coated liposome containing both coenzyme Q10 and alpha-lipoic acid: cytotoxicity antioxidant activity and antimicrobial activity. J Cosmet Dermatol. 2018 Apr;17(2):258-62. doi: 10.1111/jocd.12369, PMID 28722258.
Moura FA, DE Andrade KQ, Dos Santos JC, Goulart MO. Lipoic acid: its antioxidant and anti-inflammatory role and clinical applications. Curr Top Med Chem. 2015;15(5):458-83. doi: 10.2174/1568026615666150114161358, PMID 25620240.
Sola S, Mir MQ, Cheema FA, Khan Merchant N, Menon RG, Parthasarathy S. Irbesartan and lipoic acid improve endothelial function and reduce markers of inflammation in the metabolic syndrome: results of the irbesartan and lipoic acid in endothelial dysfunction (island) study. Circulation. 2005 Jan 25;111(3):343-8. doi: 10.1161/01.CIR.0000153272.48711.B9, PMID 15655130.
Genazzani AD, Prati A, Marchini F, Petrillo T, Napolitano A, Simoncini T. Differential insulin response to oral glucose tolerance test (OGTT) in overweight/obese polycystic ovary syndrome patients undergoing to myo-inositol (MYO) alpha lipoic acid (ALA) or combination of both. Gynecol Endocrinol. 2019;35(12):1088-93. doi: 10.1080/09513590.2019.1640200, PMID 31304823.
De Cicco S, Immediata V, Romualdi D, Policola C, Tropea A, DI Florio C. Myoinositol combined with alpha-lipoic acid may improve the clinical and endocrine features of polycystic ovary syndrome through an insulin-independent action. Gynecol Endocrinol. 2017 Sep;33(9):698-701. doi: 10.1080/09513590.2017.1313972, PMID 28434274.
Jungwirth A, Giwercman A, Tournaye H, Diemer T, Kopa Z, Dohle G. European association of Urology Guidelines on Male Infertility: the 2012 update. Eur Urol. 2012;62(2):324-32. doi: 10.1016/j.eururo.2012.04.048, PMID 22591628.
Dong L, Zhang X, Yang F, LI J, YU X, LI Y. Effect of oral alpha-lipoic acid (ALA) on the treatment of male infertility: a protocol for systematic review and meta-analysis. Med (Baltim). 2019 Dec;98(51):e18453. doi: 10.1097/MD.0000000000018453, PMID 31861020.
Balercia G, Regoli F, Armeni T, Koverech A, Mantero F, Boscaro M. Placebo-controlled double-blind randomized trial on the use of L-carnitine L-acetylcarnitine, or combined L-carnitine and L-acetylcarnitine in men with idiopathic asthenozoospermia. Fertil Steril. 2005 Sep;84(3):662-71. doi: 10.1016/j.fertnstert.2005.03.064, PMID 16169400.
Gharagozloo P, Aitken RJ. The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy. Hum Reprod. 2011 Jul;26(7):1628-40. doi: 10.1093/humrep/der132, PMID 21546386.
Buhling KJ, Laakmann E. The effect of micronutrient supplements on male fertility. Curr Opin Obstet Gynecol. 2014 Jun;26(3):199-209. doi: 10.1097/GCO.0000000000000063, PMID 24759120.
Ibrahim SF, Osman K, Das S, Othman AM, Majid NA, Rahman MP. A study of the antioxidant effect of alpha lipoic acids on sperm quality. Clinics (Sao Paulo). 2008 Aug;63(4):545-50. doi: 10.1590/s1807-59322008000400022, PMID 18719769.
Asci H, Erol O, Ellidag HY, Tola EN, Savran M, Ozmen O. Pathology of cigarettes on the reproductive system and ameliorative effects of alpha lipoic acid: a rat model study. Toxicol Ind Health. 2018 Jun;34(6):385-95. doi: 10.1177/0748233718755160, PMID 29591887.
Sayıner S, Şehirli AO, Serakıncı N. Alpha lipoic acid as a potential treatment for COVID-19 a hypothesis. Curr Top Nutraceutical Res. 2020;19(2):172-5. doi: 10.37290/ctnr2641-452X.19:172-175.
Cure E, Cumhur Cure M. Alpha-lipoic acid may protect patients with diabetes against COVID-19 infection. Med Hypotheses. 2020 Oct;143:110185. doi: 10.1016/j.mehy.2020.110185, PMID 33017914.
Xiong Y, LI Q, Ding Z, Zheng J, Zhou D, Wei S. Dietary α-lipoic acid requirement and its effects on antioxidant status carbohydrate metabolism and intestinal microflora in oriental river prawn macrobrachium nipponense (de haan). Aquaculture. 2022 Jan 30;547:737531. doi: 10.1016/j.aquaculture.2021.737531.
Attia M, Essa EA, Zaki RM, Elkordy AA. An overview of the antioxidant effects of ascorbic acid and alpha lipoic acid (in liposomal forms) as adjuvant in cancer treatment. Antioxidants (Basel). 2020 Apr 25;9(5):359. doi: 10.3390/antiox9050359, PMID 32344912.
Yadav S, Dwivedi A, Tripathi A, Tripathi AK. Therapeutic potential of short-chain fatty acid production by gut microbiota in neurodegenerative disorders. Nutr Res. 2022 Oct;106:72-84. doi: 10.1016/j.nutres.2022.07.007, PMID 36152586.
Yang L, Wen Y, LV G, Lin Y, Tang J, LU J. α-Lipoic acid inhibits human lung cancer cell proliferation through Grb2-mediated EGFR downregulation. Biochem Biophys Res Commun. 2017 Dec 9;494(1-2):325-31. doi: 10.1016/j.bbrc.2017.10.030, PMID 28993193.
Moungjaroen J, Nimmannit U, Callery PS, Wang L, Azad N, Lipipun V. Reactive oxygen species mediate caspase activation and apoptosis induced by lipoic acid in human lung epithelial cancer cells through Bcl-2 down-regulation. J Pharmacol Exp Ther. 2006 Dec;319(3):1062-9. doi: 10.1124/jpet.106.110965, PMID 16990509.
Dozio E, Ruscica M, Passafaro L, Dogliotti G, Steffani L, Marthyn P. Erratum to the natural antioxidant alpha-lipoic acid induces p27Kip1-dependent cell cycle arrest and apoptosis in MCF-7 human breast cancer cells [Eur. J. Pharmacol. 641 (2010) 29-34]. European Journal of Pharmacology. 2011;650(1):486. doi: 10.1016/j.ejphar.2010.10.001.
Trivedi PP, Jena GB. Role of α-lipoic acid in dextran sulfate sodium-induced ulcerative colitis in mice: studies on inflammation oxidative stress DNA damage and fibrosis. Food Chem Toxicol. 2013 Sep;59:339-55. doi: 10.1016/j.fct.2013.06.019, PMID 23793040.
Tripathy J, Tripathy A, Thangaraju M, Suar M, Elangovan S. α-lipoic acid inhibits the migration and invasion of breast cancer cells through inhibition of TGFβ signaling. Life Sci. 2018 Aug 15;207:15-22. doi: 10.1016/j.lfs.2018.05.039, PMID 29802942.
Maldonado Rojas W, Olivero Verbel J, Ortega Zuniga C. Searching of protein targets for alpha lipoic acid. J Braz Chem Soc. 2011;22(12):2250-9. doi: 10.1590/S0103-50532011001200003.
Rousseau AS, Sibille B, Murdaca J, Mothe Satney I, Grimaldi PA, Neels JG. α-lipoic acid up-regulates expression of peroxisome proliferator-activated receptor β in skeletal muscle: involvement of the JNK signaling pathway. FASEB J. 2016 Mar;30(3):1287-99. doi: 10.1096/fj.15-280453, PMID 26655383.
Diane A, Mahmoud N, Bensmail I, Khattab N, Abunada HA, Dehbi M. Alpha lipoic acid attenuates ER stress and improves glucose uptake through DNAJB3 cochaperone. Sci Rep. 2020 Nov 24;10(1):20482. doi: 10.1038/s41598-020-77621-x, PMID 33235302.
DI Nicuolo F, D Ippolito S, Castellani R, Rossi ED, Masciullo V, Specchia M. Effect of alpha-lipoic acid and myoinositol on endometrial inflammasome from recurrent pregnancy loss women. Am J Reprod Immunol. 2019 Sep;82(3):e13153. doi: 10.1111/aji.13153, PMID 31148259.
Yan T, Zhang Z, LI D. NGF receptors and PI3K/AKT pathway involved in glucose fluctuation induced damage to neurons and α-lipoic acid treatment. BMC Neurosci. 2020 Sep 17;21(1):38. doi: 10.1186/s12868-020-00588-y, PMID 32943002.
Liu W, Shi LJ, LI SG. The immunomodulatory effect of alpha-lipoic acid in autoimmune diseases. BioMed Res Int. 2019 Mar 20;2019:8086257. doi: 10.1155/2019/8086257, PMID 31016198.
Mignini F, Nasuti C, Gioventu G, Napolioni V, Martino PD. Human bioavailability and pharmacokinetic profile of different formulations delivering alpha lipoic acid. Open Access Sci Rep. 2012;1(8):418. doi: 10.4172/scientificreports.418.
Published
How to Cite
Issue
Section
Copyright (c) 2024 MURTADA TAHA
This work is licensed under a Creative Commons Attribution 4.0 International License.
