Generic placeholder image

Current Diabetes Reviews

Editor-in-Chief

ISSN (Print): 1573-3998
ISSN (Online): 1875-6417

General Review Article

The Role of Alpha-lipoic Acid Supplementation in the Prevention of Diabetes Complications: A Comprehensive Review of Clinical Trials

Author(s): Sarah Jeffrey, Punitha Isaac Samraj* and Behin Sundara Raj

Volume 17, Issue 9, 2021

Published on: 18 January, 2021

Article ID: e011821190404 Pages: 12

DOI: 10.2174/1573399817666210118145550

Price: $65

Abstract

Alpha-lipoic acid (ALA) is a substantial antioxidant in the prevention of diabetes and diabetes complications. It can regenerate other antioxidants like vitamin E, vitamin C, Coenzyme Q10 and glutathione and is often known as a universal antioxidant. Antioxidants play a role in diabetes treatment due to hyperglycemia-induced stimulation of the polyol pathway and formation of advanced glycation end products (AGE) and reactive oxygen species (ROS). Clinical trials examining alpha-lipoic acid supplementation on diabetic neuropathy, nephropathy, cardiomyopathy and erectile dysfunction display positive results, particularly in pain amelioration in neuropathy, asymmetric dimethylarginine reductions in nephropathy and improved oscillatory potential and contrast sensitivity in retinopathy. In diabetic cardiomyopathy (DCM), ALA offers protection through inhibition of NF-kB activation, reduction of fas-ligand and decrease in matrix metalloproteinase-2. This comprehensive review summarises and provides an understanding of the importance of alpha- lipoic acid supplementation to prevent diabetes complications.

Keywords: Alpha-lipoic acid, diabetes mellitus, diabetic neuropathy, cardiomyopathy, diabetic nephropathy, reactive oxygen species (ROS).

[1]
Rahimlou M, Asadi M, Banaei Jahromi N, Mansoori A. Alpha-lipoic acid (ALA) supplementation effect on glycemic and inflammatory biomarkers: A Systematic Review and meta- analysis. Clin Nutr ESPEN 2019; 32: 16-28.
[http://dx.doi.org/10.1016/j.clnesp.2019.03.015] [PMID: 31221283]
[2]
Packer L, Kraemer K, Rimbach G. Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition 2001; 17(10): 888-95.
[http://dx.doi.org/10.1016/S0899-9007(01)00658-X] [PMID: 11684397]
[3]
Lin KY, Ito A, Asagami T, et al. Impaired nitric oxide synthase pathway in diabetes mellitus: role of asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase. Circulation 2002; 106(8): 987-92.
[http://dx.doi.org/10.1161/01.CIR.0000027109.14149.67] [PMID: 12186805]
[4]
Boulton AJM, Vinik AI, Arezzo JC, et al. American Diabetes Association. Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care 2005; 28(4): 956-62.
[http://dx.doi.org/10.2337/diacare.28.4.956] [PMID: 15793206]
[5]
Vallianou N, Evangelopoulos A, Koutalas P. Alpha-lipoic Acid and diabetic neuropathy. Rev Diabet Stud 2009; 6(4): 230-6.
[http://dx.doi.org/10.1900/RDS.2009.6.230] [PMID: 20043035]
[6]
Agathos E, Tentolouris A, Eleftheriadou I, et al. Effect of α-lipoic acid on symptoms and quality of life in patients with painful diabetic neuropathy. J Int Med Res 2018; 46(5): 1779-90.
[http://dx.doi.org/10.1177/0300060518756540] [PMID: 29517942]
[7]
Ametov AS, Barinov A, Dyck PJ, et al. SYDNEY Trial Study Group. The sensory symptoms of diabetic polyneuropathy are improved with alpha-lipoic acid: the SYDNEY trial. Diabetes Care 2003; 26(3): 770-6.
[http://dx.doi.org/10.2337/diacare.26.3.770] [PMID: 12610036]
[8]
Hahm JR, Kim BJ, Kim KW. Clinical experience with thioctacid (thioctic acid) in the treatment of distal symmetric polyneuropathy in Korean diabetic patients. J Diabetes Complications 2004; 18(2): 79-85.
[http://dx.doi.org/10.1016/S1056-8727(03)00033-3] [PMID: 15120701]
[9]
Tankova T, Cherninkova S, Koev D. Treatment for diabetic mononeuropathy with alpha-lipoic acid. Int J Clin Pract 2005; 59(6): 645-50.
[http://dx.doi.org/10.1111/j.1742-1241.2005.00452.x] [PMID: 15924591]
[10]
Strokov IA, Manukhina EB, Bakhtina LY, et al. The function of endogenous protective systems in patients with insulin-dependent diabetes mellitus and polyneuropathy: effect of antioxidant therapy. Bull Exp Biol Med 2000; 130(10): 986-90.
[http://dx.doi.org/10.1023/A:1002874125993] [PMID: 11177301]
[11]
Bureković A, Terzić M, Alajbegović S, Vukojević Z, Hadzić N. The role of alpha-lipoic acid in diabetic polyneuropathy treatment. Bosn J Basic Med Sci 2008; 8(4): 341-5.
[http://dx.doi.org/10.17305/bjbms.2008.2894] [PMID: 19125705]
[12]
Garcia-Alcala H, Santos Vichido CI, Islas Macedo S. Treatment with alpha-lipoic acid over 16 weeks in type 2 diabetic patients with symptomatic polyneuropathy who responded to initial 4-week high-dose loading. J Diabetes Res 2015; 2015: 189857.
[http://dx.doi.org/10.1155/2015/189857] [PMID: 26345602]
[13]
Bertolotto F, Massone A. Combination of alpha lipoic acid and superoxide dismutase leads to physiological and symptomatic improvements in diabetic neuropathy. Drugs R D 2012; 12(1): 29-34.
[http://dx.doi.org/10.2165/11599200-000000000-00000] [PMID: 22329607]
[14]
Ibrahimpasic K. Alpha lipoic acid and glycaemic control in diabetic neuropathies at type 2 diabetes treatment. Med Arh 2013; 67(1): 7-9.
[http://dx.doi.org/10.5455/medarh.2013.67.7-9] [PMID: 23678828]
[15]
Jin HY, Joung SJ, Park JH, Baek HS, Park TS. The effect of alpha-lipoic acid on symptoms and skin blood flow in diabetic neuropathy. Diabet Med 2007; 24(9): 1034-8.
[http://dx.doi.org/10.1111/j.1464-5491.2007.02179.x] [PMID: 17490418]
[16]
Anand Vijayakumar PR, Kalshetti SM, Bhatt JK. Supplementation of a-lipoic acid in diabetic peripheral neuropathy: A prospective open label randomized controlled trial. Int J Pharm Pharm Sci 2014; 6(7): 90-3.
[17]
Ziegler D, Ametov A, Barinov A, et al. Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. Diabetes Care 2006; 29(11): 2365-70.
[http://dx.doi.org/10.2337/dc06-1216] [PMID: 17065669]
[18]
Ziegler D, Low PA, Litchy WJ, et al. Efficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. Diabetes Care 2011; 34(9): 2054-60.
[http://dx.doi.org/10.2337/dc11-0503] [PMID: 21775755]
[19]
Ziegler D, Low PA, Freeman R, Tritschler H, Vinik AI. Predictors of improvement and progression of diabetic polyneuropathy following treatment with α-lipoic acid for 4 years in the NATHAN 1 trial. J Diabetes Complications 2016; 30(2): 350-6.
[http://dx.doi.org/10.1016/j.jdiacomp.2015.10.018] [PMID: 26651260]
[20]
Mokini Z, Marcovecchio ML, Chiarelli F. Molecular pathology of oxidative stress in diabetic angiopathy: role of mitochondrial and cellular pathways. Diabetes Res Clin Pract 2010; 87(3): 313-21.
[http://dx.doi.org/10.1016/j.diabres.2009.11.018] [PMID: 20022399]
[21]
Mittermayer F, Pleiner J, Francesconi M, Wolzt M. Treatment with alpha-lipoic acid reduces asymmetric dimethylarginine in patients with type 2 diabetes mellitus. Transl Res 2010; 155(1): 6-9.
[http://dx.doi.org/10.1016/j.trsl.2009.08.004] [PMID: 20004356]
[22]
Chang JW, Lee EK, Kim TH, et al. Effects of alpha-lipoic acid on the plasma levels of asymmetric dimethylarginine in diabetic end-stage renal disease patients on hemodialysis: a pilot study. Am J Nephrol 2007; 27(1): 70-4.
[http://dx.doi.org/10.1159/000099035] [PMID: 17259696]
[23]
Sun H, Yao W, Tang Y, et al. Urinary exosomes as a novel biomarker for evaluation of α-lipoic acid’s protective effect in early diabetic nephropathy. J Clin Lab Anal 2017; 31(6): e22129.
[http://dx.doi.org/10.1002/jcla.22129] [PMID: 28116765]
[24]
Cicek M, Yıldırır A, Okyay K, et al. Use of alpha-lipoic acid in prevention of contrast-induced nephropathy in diabetic patients. Ren Fail 2013; 35(5): 748-53.
[http://dx.doi.org/10.3109/0886022X.2013.790298] [PMID: 23650950]
[25]
Jo SH, Kim SA, Kim HS, Han SJ, Park WJ, Choi YJ. Alpha-lipoic acid for the prevention of contrast-induced nephropathy in patients undergoing coronary angiography: the ALIVE study - a prospective randomized trial. Cardiology 2013; 126(3): 159-66.
[http://dx.doi.org/10.1159/000353812] [PMID: 23988855]
[26]
Rochette L, Ghibu S, Muresan A, Vergely C. Alpha-lipoic acid: molecular mechanisms and therapeutic potential in diabetes. Can J Physiol Pharmacol 2015; 93(12): 1021-7.
[http://dx.doi.org/10.1139/cjpp-2014-0353] [PMID: 26406389]
[27]
Wu M-Y, Yiang G-T, Lai T-T, Li C-J. The oxidative stress and mitochondrial dysfunction during the pathogenesis of diabetic retinopathy. Oxid Med Cell Longev 2018; 2018: 3420187.
[http://dx.doi.org/10.1155/2018/3420187] [PMID: 30254714]
[28]
Kowluru RA, Mishra M. Oxidative stress, mitochondrial damage and diabetic retinopathy. Biochim Biophys Acta 2015; 1852(11): 2474-83.
[http://dx.doi.org/10.1016/j.bbadis.2015.08.001] [PMID: 26248057]
[29]
Gębka A, Serkies-Minuth E, Raczyńska D. Effect of the administration of alpha-lipoic acid on contrast sensitivity in patients with type 1 and type 2 diabetes. Mediators Inflamm 2014; 2014: 131538.
[http://dx.doi.org/10.1155/2014/131538] [PMID: 24665163]
[30]
Nebbioso M, Federici M, Rusciano D, Evangelista M, Pescosolido N. Oxidative stress in preretinopathic diabetes subjects and antioxidants. Diabetes Technol Ther 2012; 14(3): 257-63.
[http://dx.doi.org/10.1089/dia.2011.0172] [PMID: 22044044]
[31]
Haritoglou C, Gerss J, Hammes HP, Kampik A, Ulbig MW. RETIPON Study Group. Alpha-lipoic acid for the prevention of diabetic macular edema. Ophthalmologica 2011; 226(3): 127-37.
[http://dx.doi.org/10.1159/000329470] [PMID: 21811051]
[32]
Ferreiro JL, Gómez-Hospital JA, Angiolillo DJ. Platelet abnormalities in diabetes mellitus. Diab Vasc Dis Res 2010; 7(4): 251-9.
[http://dx.doi.org/10.1177/1479164110383994] [PMID: 20921090]
[33]
Fang ZY, Prins JB, Marwick TH. Diabetic cardiomyopathy: evidence, mechanisms, and therapeutic implications. Endocr Rev 2004; 25(4): 543-67.
[http://dx.doi.org/10.1210/er.2003-0012] [PMID: 15294881]
[34]
Schaffer SW, Jong CJ, Mozaffari M. Role of oxidative stress in diabetes-mediated vascular dysfunction: unifying hypothesis of diabetes revisited. Vascul Pharmacol 2012; 57(5-6): 139-49.
[http://dx.doi.org/10.1016/j.vph.2012.03.005] [PMID: 22480621]
[35]
Hegazy SK, Tolba OA, Mostafa TM, Eid MA, El-Afify DR. Alpha-lipoic acid improves subclinical left ventricular dysfunction in asymptomatic patients with type 1 diabetes. Rev Diabet Stud 2013; 10(1): 58-67.
[http://dx.doi.org/10.1900/RDS.2013.10.58] [PMID: 24172699]
[36]
Phé V, Rouprêt M. Erectile dysfunction and diabetes: a review of the current evidence-based medicine and a synthesis of the main available therapies. Diabetes Metab 2012; 38(1): 1-13.
[http://dx.doi.org/10.1016/j.diabet.2011.09.003] [PMID: 22056307]
[37]
Shi Y, Yang M, Liu L, Pang Y, Long Y, Zheng H. Gtp as a peroxidase-mimic to mediate enzymatic cascade reaction for alkaline phosphatase detection and alkaline phosphatase-linked immunoassay. Sens Actuators B Chem 2018; 275: 43-9.
[http://dx.doi.org/10.1016/j.snb.2018.08.038]
[38]
Mitkov MD, Aleksandrova IY, Orbetzova MM. Effect of transdermal testosterone or alpha-lipoic acid on erectile dysfunction and quality of life in patients with type 2 diabetes mellitus. Folia Med (Plovdiv) 2013; 55(1): 55-63.
[http://dx.doi.org/10.2478/folmed-2013-0006] [PMID: 23905488]
[39]
Zhang L, Zhang HY, Huang FC, Huang Q, Liu C, Li JR. Study on the clinical value of alprostadil combined with α-lipoic acid in treatment of type 2 diabetes mellitus patients with erectile dysfunction. Eur Rev Med Pharmacol Sci 2016; 20(18): 3930-3.
[PMID: 27735021]
[40]
Lee SJ, Jeong SJ, Lee YC, et al. Effects of high-dose alpha-lipoic acid on heart rate variability of type 2 diabetes mellitus patients with cardiac autonomic neuropathy in korea. Diabetes Metab J 2017; 41(4): 275-83.
[http://dx.doi.org/10.4093/dmj.2017.41.4.275] [PMID: 28868825]
[41]
Pop-Busui R, Stevens MJ, Raffel DM, et al. Effects of triple antioxidant therapy on measures of cardiovascular autonomic neuropathy and on myocardial blood flow in type 1 diabetes: a randomised controlled trial. Diabetologia 2013; 56(8): 1835-44.
[http://dx.doi.org/10.1007/s00125-013-2942-9] [PMID: 23740194]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy