Background: A limited amount of data exists regarding the effect of lipoic acid (LA), an oral antioxidant supplement, on cytokine profiles among multiple sclerosis (MS) patients. Objective: We aimed to assess the effect of daily consumption of LA on the cytokine profiles in MS patients. Methods: In this double-blind, placebo-controlled, randomized clinical trial, 52 relapsing-remitting MS patients with an age range of 18-50 years were recruited into 2 groups: LA consumption (1,200 mg/day) or placebo. Patients followed their prescribed supplements for 12 weeks. Fasting blood samples for cytokine profile measurement were collected at baseline and after the intervention. Anthropometric parameters were measured based on the standard guidelines. Results: INF-γ, ICAM-1, TGF-β and IL-4 were significantly reduced in the LA group compared to the placebo group [(INF-γ: 0.82 ± 0.2 vs. 0.2 ± 0.2 pg/ml, p < 0.0001), (ICAM-1: 20.2 ± 9.4 vs. 8 ± 10 ng/ml, p = 0.0001), (TGF-β: 103.1 ± 20.2 vs. 54.9 ± 26 ng/ml, p < 0.0001) and (IL-4: 0.1 ± 0.1 vs. 1.02 ± 1.7 ng/ml, p = 0.0112)]. No significant changes in TNF-α, IL-6, EDSS and MMP-9 were found between the LA and placebo groups (p = 0.6, p = 0.8, p = 0.09 and p = 0.8, respectively). Conclusion: The results suggested that consumption of 1,200 mg LA per day beneficially affects several inflammatory cytokines including INF-γ, ICAM-1 TGF-β and IL-4. Further investigations are needed to verify the beneficial role of LA on other cytokine profiles among MS patients.

Salinthone S, Yadav V, Schillace RV, Bourdette DN, Carr DW: Lipoic acid attenuates inflammation via cAMP and protein kinase A signaling. PLoS One 2010;28:5.
Yadav V, Marracci GH, Munar MY, Cherala G, Stuber LE, Alvarez L, et al: Pharmacokinetic study of lipoic acid in multiple sclerosis: comparing mice and human pharmacokinetic parameters. Mult Scler 2010;16:387-397.
Karg E, Klivényi P, Nemeth I, Bencsik K, Pinter S, Vécsei L: Nonenzymatic antioxidants of blood in multiple sclerosis. J Neurol 1999;246:9-533.
Alonso A, Cook SD, Maghzi AH, Divani AA: A case-control study of risk factors for multiple sclerosis in Iran. Mult Scler 2011;17:550-555.
Jafari N, Hoppenbrouwers IA, Hop WC, Breteler MM, Hintzen RQ: Cigarette smoking and risk of MS in multiplex families. Mult Scler 2009;15:1363-1367.
Roshanisefat H, Bahmanyar S, Hillert J, Olsson T, Montgomery S: Shared genetic factors may not explain the raised risk of comorbid inflammatory diseases in multiple sclerosis. Mult Scler 2012;18:1430-1436.
Ahlgren C, Odén A, Lycke J: High nationwide prevalence of multiple sclerosis in Sweden. Mult Scler 2011;17:901-908.
Etemadifar M, Janghorbani M, Shaygannejad V, Ashtari F: Prevalence of multiple sclerosis in Isfahan, Iran. Neuroepidemiology 2006;27:39-44.
Moghtaderi A, Rakhshanizadeh F, Shahraki-Ibrahimi S: Incidence and prevalence of multiple sclerosis in southeastern Iran. Clin Neurol Neurosurg 2013;115:304-308.
Elhami SR, Mohammad K, Sahraian MA, Eftekhar H: A 20-year incidence trend (1989-2008) and point prevalence (March 20, 2009) of multiple sclerosis in Tehran, Iran: a population-based study. Neuroepidemiology 2011;36:141-147.
Lauer K: The risk of multiple sclerosis in the USA in relation to sociogeographic features: a factor-analytic study. J Clin Epidemiol 1994;47:43-48.
Swank RL, Goodwin J: Review of MS patient survival on a Swank low saturated fat diet1. Nutrition 2003;19:161-162.
Ha H, Lee JH, Kim HN, Kim HM, Kwak HB, Lee S, et al: alpha-Lipoic acid inhibits inflammatory bone resorption by suppressing prostaglandin E2 synthesis. J Immunol 2006;176:111-117.
Zhang Y, Han P, Wu N, He B, Lu Y, Li S, et al: Amelioration of lipid abnormalities by α-lipoic acid through antioxidative and anti-inflammatory effects. Obesity 2011;19:1647-1653.
Zhang WJ, Frei B: α-Lipoic acid inhibits TNF-α-induced NF-κB activation and adhesion molecule expression in human aortic endothelial cells. FASEB J 2001;15:2423.
Sola S, Mir MQS, Cheema FA, Khan-Merchant N, Menon RG, Parthasarathy S, et al: Irbesartan and lipoic acid improve endothelial function and reduce markers of inflammation in the metabolic syndrome. Circulation 2005;111:343-348.
Kiemer AK, Müller C, Vollmar AM: Inhibition of LPS-induced nitric oxide and TNF-α production by α-lipoic acid in rat Kupffer cells and in RAW 264.7 murine macrophages. Immunol Cell Biol 2002;80:550-557.
Yadav V, Marracci G, Lovera J, Woodward W, Bogardus K, Marquardt W, et al: Lipoic acid in multiple sclerosis: a pilot study. Mult Scler 2005;11:159-165.
Chaudhary P, Marracci GH, Bourdette DN: Lipoic acid inhibits expression of ICAM-1 and VCAM-1 by CNS endothelial cells and T cell migration into the spinal cord in experimental autoimmune encephalomyelitis. J Neuroimmunol 2006;175:87-96.
Morini M, Roccatagliata L, Dell'Eva R, Pedemonte E, Furlan R, Minghelli S, et al: α-Lipoic acid is effective in prevention and treatment of experimental autoimmune encephalomyelitis. J Neuroimmunol 2004;148:146-153.
Salinthone S, Schillace RV, Marracci GH, Bourdette DN, Carr DW: Lipoic acid stimulates cAMP production via the EP2 and EP4 prostanoid receptors and inhibits IFN gamma synthesis and cellular cytotoxicity in NK cells. J Neuroimmunol 2008;199:46-55.
Gallo P, Piccinno MG, Tavolato B, Siden A: A longitudinal study on IL-2, sIL-2R, IL-4 and IFN-[gamma] in multiple sclerosis CSF and serum. J Neurol Sci 1991;101:227-232.
Sen CK, Roy S, Khanna S, Packer L: Determination of oxidized and reduced lipoic acid using high-performance liquid chromatography and coulometric detection. Methods Enzymol 1999;299:239-246.
Sook Cho Y, Lee J, Lee TH, Young Lee E, Lee KU, Yeol Park J, et al: α-Lipoic acid inhibits airway inflammation and hyperresponsiveness in a mouse model of asthma. J Allergy Clin Immunol 2004;114:429-435.
Ramos LF, Kane J, McMonagle E, Le P, Wu P, Shintani A, et al: Effects of combination tocopherols and alpha lipoic acid therapy on oxidative stress and inflammatory biomarkers in chronic kidney disease. J Renal Nutr 2011;21:211-218.
Alleva R, Nasole E, Donato FD, Borghi B, Neuzil J, Tomasetti M: alpha-Lipoic acid supplementation inhibits oxidative damage, accelerating chronic wound healing in patients undergoing hyperbaric oxygen therapy. Biochem Biophys Res Commun 2005;333:404-410.
Imitola J, Chitnis T, Khoury SJ: Cytokines in multiple sclerosis: from bench to bedside. Pharmacol Ther 2005;106:163-177.
Salinthone S, Yadav V, Schillace RV, Bourdette DN, Carr DW: Lipoic acid attenuates inflammation via cAMP and protein kinase A signaling. PLoS One 2010;5:e13058.
Petereit H, Nolden S, Schoppe S, Bamborschke S, Pukrop R, Heiss WD: Low interferon gamma producers are better treatment responders: a two-year follow-up of interferon beta-treated multiple sclerosis patients. Mult Scler 2002;8:492-494.
Sharief M, Noori M, Ciardi M, Cirelli A, Thompson E: Increased levels of circulating ICAM-1 in serum and cerebrospinal fluid of patients with active multiple sclerosis. Correlation with TNF-[alpha] and blood-brain barrier damage. J Neuroimmunol 1993;43:15-21.
Kunt T, Forst T, Wilhelm A, Tritschler H, Pfuetzner A, Harzer O, et al: alpha-Lipoic acid reduces expression of vascular cell adhesion molecule-I and endothelial adhesion of human monocytes after stimulation with advanced glycation end products. Clin Sci 1999;96:75-82.
Kim HS, Kim HJ, Park KG, Kim YN, Kwon TK, Park JY, et al: Alpha-lipoic acid inhibits matrix metalloproteinase-9 expression by inhibiting NF-kappaB transcriptional activity. Exp Mol Med 2007;39:106.
Cossins JA, Clements JM, Ford J, Miller KM, Pigott R, Vos W, et al: Enhanced expression of MMP-7 and MMP-9 in demyelinating multiple sclerosis lesions. Acta Neuropathol 1997;94:590-598.
Losy J, Michałowska-Wender G: In vivo effect of interferon-β 1a on interleukin-12 and TGF-β1 cytokines in patients with relapsing-remitting multiple sclerosis. Acta Neurol Scand 2002;106:44-46.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.