Skip to main content
Search
Search
    Quick Search anywhere
    Quick search in Citations
Advanced Search
Skip main navigationClose Drawer MenuOpen Drawer Menu
Previous article
Next article
Original Communication

Oral administration of alpha-lipoic acid did not affect lipid peroxidation and antioxidant biomarkers in rheumatoid arthritis patients

Published Online:February 21, 2019https://doi.org/10.1024/0300-9831/a000550

Abstract

Abstract. Rheumatoid arthritis (RA) is a chronic inflammatory disease in which oxidative stress could play a substantial pathological role. Alpha-lipoic acid (ALA) has been known as a “universal” and “ideal” antioxidant. The purpose of this study was to investigate the effects of oral administration of Alpha-lipoic acid (ALA) on lipid peroxidation and antioxidant biomarkers in Rheumatoid arthritis (RA) patients. The study was a randomized, double-blinded, placebo-controlled clinical trial. 70 RA patients were randomized 1:1 to two groups using blocked randomization method and received 1200 mg/day ALA or placebo for 8 weeks. Fasting blood samples were obtained before and after the intervention to analyze total antioxidant capacity (TAC), antioxidant enzymes [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and arylesterase (ARE) activities] and malondialdehyde (MDA). We observed significant increase in serum TAC (0.11 mmol/L; p=0.033) and ARE (13.76 U/mL; p=0.046) and significant decline in MDA (−0.36 nmol/L; p=0.002), in ALA group. However, these changes in ALA-treated group were not statistically significant when compared with placebo-treated group (p > 0.05). Also, within- and between-group differences of whole blood SOD and GSH-Px were not statistically significant (p > 0.05). In conclusion, unexpectedly, ALA therapy did not affect the oxidative status of RA patients in the present clinical trial. It seems that more comprehensive clinical trials in RA patients are still warranted to clarify the effectiveness of ALA which has been known as a potent antioxidant.

References

  • 1 Aletaha, D., Neogi, T., Silman, A., Funovits, J., Felson, D., Bingham, C., Birnbaum, N.S., Burmester, G.R., Bykerk, V.P., & Cohen, M.D. (2010) 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum. 62, 2569–2581. First citation in articleCrossref Medline, Google Scholar

  • 2 Phillips, D.C., Dias, H.K., Kitas, G.D., & Griffiths, H.R. (2010) Aberrant reactive oxygen and nitrogen species generation in rheumatoid arthritis (RA): causes and consequences for immune function, cell survival, and therapeutic intervention. Antioxid Redox Signal. 12, 743–785. First citation in articleCrossref Medline, Google Scholar

  • 3 Veselinovic, M., Barudzic, N., Vuletic, M., Zivkovic, V., Tomic-Lucic, A., Djuric, D., & Jakovljevic, V. (2014) Oxidative stress in rheumatoid arthritis patients: relationship to diseases activity. Mol Cell Biochem. 391, 225–232. https://doi.org/10.1007/s11010-014-2006-6 First citation in articleCrossref Medline, Google Scholar

  • 4 Brennan, F., & McInnes, I. (2008) Evidence that cytokines play a role in rheumatoid arthritis. J Clin Invest. 118, 3537. First citation in articleCrossref Medline, Google Scholar

  • 5 Filippin, L.I., Vercelino, R., Marroni, N.P., & Xavier, R.M. (2008) Redox signalling and the inflammatory response in rheumatoid arthritis. Clin Exp Immunol. 152, 415–422. First citation in articleCrossref Medline, Google Scholar

  • 6 Wood, A.J., & O’Dell, J.R. (2004) Therapeutic strategies for rheumatoid arthritis. N Engl J Med. 350, 2591–2602. First citation in articleCrossref Medline, Google Scholar

  • 7 Mueller, M., Hobiger, S., & Jungbauer, A. (2010) Anti-inflammatory activity of extracts from fruits, herbs and spices. Food Chem. 122, 987–996. First citation in articleCrossref, Google Scholar

  • 8 Reed, L.J. (1974) Multienzyme complexes. Acc Chem Res. 7, 40–46. First citation in articleCrossref, Google Scholar

  • 9 Shay, K.P., Moreau, R.F., Smith, E.J., Smith, A.R., & Hagen, T.M. (2009) Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta. 1790, 1149–1160. First citation in articleCrossref Medline, Google Scholar

  • 10 Petersen-Shay, K., Moreau, R.F., Smith, E.J., & Hagen, T.M. (2008) Is α-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. 60, 362–367. First citation in articleCrossref Medline, Google Scholar

  • 11 Lee, H., & Hughes, D. (2002) Alpha-lipoic acid modulates NF-κB activity in human monocytic cells by direct interaction with DNA. Exp Gerontol. 37, 401–410. First citation in articleCrossref Medline, Google Scholar

  • 12 Lee, E., Lee, C., Lee, K., Park, J., Cho, K., Cho, Y., Lee, H., Moon, S., Moon, H., & Yoo, B. (2007) Alpha-lipoic acid suppresses the development of collagen-induced arthritis and protects against bone destruction in mice. Rheumatol Int. 27, 225–233. First citation in articleCrossref Medline, Google Scholar

  • 13 Hah, Y., Sung, M., Lim, H., Jun, J., Jeong, Y., Kim, H., Kim, J., Hur, H., Davaatseren, M., & Kwon, D. (2010) Dietary alpha lipoic acid supplementation prevents synovial inflammation and bone destruction in collagen-induced arthritic mice. Rheumatol Int. 31, 1583–1590. First citation in articleCrossref Medline, Google Scholar

  • 14 Bae, S.C., Jung, W.J., Lee, E.J., Yu, R., & Sung, M.K. (2009) Effects of antioxidant supplements intervention on the level of plasma inflammatory molecules and disease severity of rheumatoid arthritis patients. J Am Coll Nutr. 28, 56–62. First citation in articleCrossref Medline, Google Scholar

  • 15 Mirtaheri, E., Pourghassem-Gargari, B., Kolahi, S., Dehghan, P., Asghari-Jafarabadi, M., Hajalilou, M., Shakiba-Novin, Z., & Mesgari-Abbasi, M. (2015) Effects of alpha-Lipoic acid supplementation on inflammatory biomarkers and matrix metalloproteinase-3 in rheumatoid arthritis patients. J Am Coll Nutr. 34, 310–317. First citation in articleCrossref Medline, Google Scholar

  • 16 Aldridge, W.N. (1953) Serum esterases. 1. Two types of esterase (A and B) hydrolysing p-nitrophenyl acetate, propionate and butyrate, and a method for their determination. Biochem J. 53, 110–117. First citation in articleCrossref Medline, Google Scholar

  • 17 Del-Rio, D., Pellegrini, N., Colombi, B., Bianchi, M., Serafini, M., Torta, F., Tegoni, M., Musci, M., & Brighenti, F. (2003) Rapid fluorimetric method to detect total plasma malondialdehyde with mild derivatization conditions. Clin Chem. 49, 690–692. First citation in articleCrossref Medline, Google Scholar

  • 18 Van-Vugt, R.M., Rijken, P., Rietveld, A., Van-Vugt, A., & Dijkmans, B.C. (2008) Antioxidant intervention in rheumatoid arthritis: results of an open pilot study. Clin Rheumatol. 27, 771–775. First citation in articleCrossref Medline, Google Scholar

  • 19 Kolahi, S., Hejazi, J., Mohtadinia, J., Jalili, M., & Farzin, H. (2011) The evaluation of concurrent supplementation with vitamin E and omega-3 fatty acids on plasma lipid per oxidation and antioxidant levels in patients with rheumatoid arthritis. Internet J Rheumatol. 7. First citation in articleGoogle Scholar

  • 20 Deng, H., Zuo, X., Zhang, J., Liu, X., Liu, L., Xu, Q., Wu, Z., & Ji, A. (2015) α-lipoic acid protects against cerebral ischemia/reperfusion-induced injury in rats. Mol Med Rep. 11, 3659–3665. First citation in articleCrossref Medline, Google Scholar

  • 21 Palaniyappan, A., & Alphonse, R. (2011) Immunomodulatory effect of DL-α-lipoic acid in aged rats. Exp Gerontol. 46, 709–715. First citation in articleCrossref Medline, Google Scholar

  • 22 Khalili, M., Eghtesadi, S., Mirshafiey, A., Eskandari, G., Sanoobar, M., Sahraian, M., Motevalian, A., Norouzi, A., Moftakhar, S., & Azimi, A. (2014) Effect of lipoic acid consumption on oxidative stress among multiple sclerosis patients: A randomized controlled clinical trial. Nutr Neurosci. 17, 16–20. First citation in articleCrossref Medline, Google Scholar

  • 23 Masharani, U., Gjerde, C., Evans, J.L., Youngren, J.F., & Goldfine, I.D. (2010) Effects of controlled-release alpha lipoic acid in lean, nondiabetic patients with polycystic ovary syndrome. Diabetes Sci Technol. 4, 359–364. First citation in articleCrossref Medline, Google Scholar

  • 24 Kasama, T., Kobayashi, K., Sekine, F., Negishi, M., Ide, H., Takahashi, T., & Niwa, Y. (1988) Follow-up study of lipid peroxides, superoxide dismutase and glutathione peroxidase in the synovial membrane, serum and liver of young and old mice with collagen-induced arthritis. Life Sci. 43, 1887–1896. First citation in articleCrossref Medline, Google Scholar

  • 25 Sharman, J.E., Gunaruwan, P., Knez, W.L., Schmitt, M., Marsh, S.A., Wilson, G.R., Cockcroft, J., & Coombes, J. (2004) Alpha-lipoic acid does not acutely affect resistance and conduit artery function or oxidative stress in healthy men. Br J Clin Pharmacol. 58, 243–248. First citation in articleCrossref Medline, Google Scholar

  • 26 Vidović, B., Milovanović, S., Dorđević, B., Kotur-Stevuljević, J., Stefanović, A., Ivanišević, J., Miljković, M., Spasić, S., Stojanović, D., & Pantović, M. (2014) Effect of alpha-lipoic acid supplementation on oxidative stress markers and antioxidative defense in patients with schizophrenia. Psychiatr Danub. 26, 205–213. First citation in articleMedline, Google Scholar

  • 27 Zhao, L., & Hu, F.X. (2014) α-Lipoic acid treatment of aged type 2 diabetes mellitus complicated with acute cerebral infarction. Eur Rev Med Pharmacol Sci. 18, 3715–3719. First citation in articleMedline, Google Scholar

  • 28 Jia, R., Bao, Y.H., Zhang, Y., Ji, C., Zhao, L.H., Zhang, J.Y., Gao, C.Q., & Ma, Q.G. (2014) Effects of dietary α-lipoic acid, acetyl-l-carnitine, and sex on antioxidative ability, energy, and lipid metabolism in broilers. Poult Sci. 93, 2809–2817. First citation in articleCrossref Medline, Google Scholar

  • 29 Arivazhagan, P., Ramanathan, K., & Panneerselvam, C. (2001) Effect of dl-α-lipoic acid on glutathione metabolic enzymes in aged rats. Exp Gerontol. 37, 81–87. First citation in articleCrossref Medline, Google Scholar

  • 30 Obrosova, I.G., Fathallah, L., & Greene, D.A. (2000) Early changes in lipid peroxidation and antioxidative defense in diabetic rat retina: effect of DL-α-lipoic acid. Eur J Pharmacol. 398, 139–146. First citation in articleCrossref Medline, Google Scholar

  • 31 Isik, A., Koca, S.S., Ustundag, B., Celik, H., & Yildirim, A. (2007) Paraoxonase and arylesterase levels in rheumatoid arthritis. Clin Rheumatol. 26, 342–348. First citation in articleCrossref Medline, Google Scholar

  • 32 Aryaeian, N., Djalali, M., Shahram, F., Jazayeri, S., Chamari, M., & Nazari, S.A. (2011) Beta-carotene, vitamin E, MDA, glutathione reductase and arylesterase activity levels in patients with active rheumatoid arthritis. Iran J Public Health. 40, 102–109. First citation in articleMedline, Google Scholar

  • 33 Ghorbanihaghjo, A., Kolahi, S., Seifirad, S., Argani, H., Hajialilo, M., & Khabazi, A. (2012) Effect of fish oil supplements on serum paraoxonase activity in female patients with rheumatoid arthritis: a double-blind randomized controlled trial. Arch Iran Med. 15, 549–552. First citation in articleMedline, Google Scholar

  • 34 Baskol, G., Demir, H., Baskol, M., Kilic, E., Ates, F., Kocer, D., & Muhtaroglu, S. (2005) Assessment of paraoxonase 1 activity and malondialdehyde levels in patients with rheumatoid arthritis. Clin Biochem. 38, 951–955. First citation in articleCrossref Medline, Google Scholar

  • 35 Hegazy, S.K., Tolba, O.A., Mostafa, T.M., Eid, M.A., & El-Afify, D.R. (2013) Alpha-lipoic acid improves subclinical left ventricular dysfunction in asymptomatic patients with type 1 diabetes. Rev Diabet Stud. 10, 58–67. First citation in articleCrossref Medline, Google Scholar

  • 36 Noori, N., Tabibi, H., Hosseinpanah, F., Hedayati, M., & Nafar, M. (2013) Effects of combined lipoic acid and pyridoxine on albuminuria, advanced glycation end-products, and blood pressure in diabetic nephropathy. Int J Vitam Nutr Res. 83, 77–85. First citation in articleLink, Google Scholar

  • 37 Khabbazi, T., Mahdavi, R., Safa, J., & Pour-Abdollahi, P. (2012) Effects of alpha-lipoic acid supplementation on inflammation, oxidative stress, and serum lipid profile levels in patients with end-stage renal disease on hemodialysis. J Ren Nutr. 22, 244–250. First citation in articleCrossref Medline, Google Scholar

  • 38 Goraca, A., Piechota, A., & Huk-kolega, H. (2009) Effect of alpha - lipoic acid on LPS-induced oxidative stress in the heart. J Physiol Pharmacol. 60, 61–68. First citation in articleMedline, Google Scholar