Alpha-lipoic acid effect on leptin and adiponectin concentrations: a systematic review and meta-analysis of randomized controlled trials

  • Fahimeh Haghighatdoost
  • Ali Gholami
  • Mitra HaririEmail author



New evidence suggests that dysregulation of adipocytokines caused by excess adiposity plays an important role in the pathogenesis of various obesity comorbidities. Our aim in this meta-analysis was to determine the effect of alpha-lipoic acid (ALA) supplementation on serum levels of leptin and adiponectin.


We searched Scopus, PubMed, Google Scholar, and ISI Web of Science from inception up to July 2019. Mean difference for leptin and adiponectin were calculated by subtracting the change from baseline in each study group. Summary estimates for the overall effect of ALA on serum leptin and adiponectin concentrations were calculated using random effects model. Results were presented as weighted mean difference (WMD) and their 95% confidence intervals (CI). Between-study heterogeneity was examined using the I2 statistics.


Eight studies were included in systematic review and seven studies in meta-analysis. The overall effect suggested a significant decrement in serum leptin concentrations (WMD = − 3.63; 95% CI, − 5.63, − 1.64 μg/ml; I2 = 80.7%) and a significant increase in serum levels of adiponectin (WMD = 1.98 μg/ml; 95% CI, 0.92, 3.04; I2 = 95.7%). Subgroup analyses based on age showed a significant reduction in leptin levels only in younger adults, and subgroup analysis based on duration indicated in studies with a duration of more than 8 weeks adiponectin levels increased significantly and leptin levels decreased significantly.


Our results revealed ALA decreased leptin and increased adiponectin especially in studies lasted more than 8 weeks. We still need more studies with different ALA dose, intervention duration, and separately on male and female.


Alpha-lipoic acid Leptin Adiponectin Adipokines 



We are extremely grateful to the data collection team at the Isfahan University of Medical Sciences.

Financial support

We did not have any financial support for this article.


MH found keywords and searched through the databases. FH and MH found relevant RCTs, excluded irrelevant RCTs, read full text of articles and extracted data. FH and GA conducted statistical analysis. MH wrote the first version of article and FH and GA corrected the first version of the paper. Discrepancies in every part of the work were resolved through group discussions.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Ouchi N, Kihara S, Funahashi T, Matsuzawa Y, Walsh K (2003) Obesity, adiponectin and vascular inflammatory disease. Curr Opin Lipidol 14(6):561–566PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Ouchi N, Parker JL, Lugus JJ, Walsh K (2011) Adipokines in inflammation and metabolic disease. Nat Rev Immunol 11(2):85–97PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Berg AH, Scherer PE (2005) Adipose tissue, inflammation, and cardiovascular disease. Circ Res 96(9):939–949PubMedCrossRefGoogle Scholar
  4. 4.
    Lim S, Quon MJ, Koh KK (2014) Modulation of adiponectin as a potential therapeutic strategy. Atherosclerosis. 233(2):721–728PubMedCrossRefGoogle Scholar
  5. 5.
    Lekva T, Michelsen AE, Aukrust P, Henriksen T, Bollerslev J, Ueland T (2017) Leptin and adiponectin as predictors of cardiovascular risk after gestational diabetes mellitus. Cardiovasc Diabetol 16(1):5PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Paz-Filho G, Mastronardi C, Franco CB, Wang KB, Wong ML, Licinio J (2012) Leptin: molecular mechanisms, systemic pro-inflammatory effects, and clinical implications. Arq Bras Endocrinol Metabol 56(9):597–607PubMedCrossRefGoogle Scholar
  7. 7.
    Ramos-Lobo AM, Donato J Jr (2017) The role of leptin in health and disease. Temperature (Austin) 4(3):258–291CrossRefGoogle Scholar
  8. 8.
    Margetic S, Gazzola C, Pegg GG, Hill RA (2002) Leptin: a review of its peripheral actions and interactions. Int J Obes Relat Metab Disord 26(11):1407–1433PubMedCrossRefGoogle Scholar
  9. 9.
    Simpson KA, Singh MA (2008) Effects of exercise on adiponectin: a systematic review. Obesity (Silver Spring) 16(2):241–256CrossRefGoogle Scholar
  10. 10.
    Zhu W, Cheng KK, Vanhoutte PM, Lam KS, Xu A (2008) Vascular effects of adiponectin: molecular mechanisms and potential therapeutic intervention. Clin Sci (Lond) 114(5):361–374CrossRefGoogle Scholar
  11. 11.
    Gomez-Huelgas R, Ruiz-Nava J, Santamaria-Fernandez S, Vargas-Candela A, Alarcon-Martin AV, Tinahones FJ. Impact of intensive lifestyle modification on levels of adipokines and inflammatory Biomarkers in Metabolically Healthy Obese Women. 2019;2019:4165260Google Scholar
  12. 12.
    Evans JL, Goldfine ID (2000) Alpha-lipoic acid: a multifunctional antioxidant that improves insulin sensitivity in patients with type 2 diabetes. Diabetes Technol Ther 2(3):401–413PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Carbonelli MG, Di Renzo L, Bigioni M, Di Daniele N, De Lorenzo A, Fusco MA (2010) Alpha-lipoic acid supplementation: a tool for obesity therapy? Curr Pharm Des 16(7):840–846PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Huerta AE, Navas-Carretero S, Prieto-Hontoria PL, Martinez JA, Moreno-Aliaga MJ (2015) Effects of alpha-lipoic acid and eicosapentaenoic acid in overweight and obese women during weight loss. Obesity (Silver Spring) 23(2):313–321CrossRefGoogle Scholar
  15. 15.
    Miao Y, Ren J, Jiang L, Liu J, Jiang B, Zhang X (2013) Alpha-lipoic acid attenuates obesity-associated hippocampal neuroinflammation and increases the levels of brain-derived neurotrophic factor in ovariectomized rats fed a high-fat diet. Int J Mol Med 32(5):1179–1186PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Li Z, Dungan CM, Carrier B, Rideout TC, Williamson DL (2014) Alpha-lipoic acid supplementation reduces mTORC1 signaling in skeletal muscle from high fat fed, obese Zucker rats. Lipids. 49(12):1193–1201PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Golbidi S, Badran M, Laher I (2011) Diabetes and alpha lipoic acid. Front Pharmacol 2:69PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Pershadsingh HA (2007) Alpha-lipoic acid: physiologic mechanisms and indications for the treatment of metabolic syndrome. Expert Opin Investig Drugs 16(3):291–302PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Prieto-Hontoria PL, Perez-Matute P, Fernandez-Galilea M, Alfredo Martinez J, Moreno-Aliaga MJ (2013) Effects of lipoic acid on AMPK and adiponectin in adipose tissue of low- and high-fat-fed rats. Eur J Nutr 52(2):779–787PubMedCrossRefGoogle Scholar
  20. 20.
    Verhagen AP, de Vet HC, de Bie RA, Kessels AG, Boers M, Bouter LM, Knipschild PG (1998) The Delphi list: a criteria list for quality assessment of randomized clinical trials for conducting systematic reviews developed by Delphi consensus. J Clin Epidemiol 51(12):1235–1241PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Schwingshackl L, Knuppel S, Schwedhelm C, Hoffmann G, Missbach B, Stelmach-Mardas M et al (2016) Perspective: nutrigrade: a scoring system to assess and judge the meta-evidence of randomized controlled trials and cohort studies in nutrition research. Adv Nutr 7(6):994–1004PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    McKenzie JE, Herbison GP, Deeks JJ (2016) Impact of analysing continuous outcomes using final values, change scores and analysis of covariance on the performance of meta-analytic methods: a simulation study. Res Synth Methods 7(4):371–386PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Aslfalah H, Jamilian M (2019) Elevation of the adiponectin/leptin ratio in women with gestational diabetes mellitus after supplementation with alpha-lipoic acid. Gynecol Endocrinol 35(3):271–275PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Hosseinpour-Arjmand S, Amirkhizi F, Ebrahimi-Mameghani M (2019) The effect of alpha-lipoic acid on inflammatory markers and body composition in obese patients with non-alcoholic fatty liver disease: a randomized, double-blind, placebo-controlled trial. J Clin Pharm Ther 44(2):258–267PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Huerta AE, Prieto-Hontoria PL, Sainz N, Martinez JA. Supplementation with alpha-lipoic acid alone or in combination with Eicosapentaenoic acid modulates the inflammatory status of healthy overweight or obese women consuming an energy-restricted diet. 2016Google Scholar
  28. 28.
    Li N, Yan W, Hu X, Huang Y, Wang F, Zhang W, Wang Q, Wang X, Sun K (2017) Effects of oral alpha-lipoic acid administration on body weight in overweight or obese subjects: a crossover randomized, double-blind, placebo-controlled trial. Clin Endocrinol 86(5):680–687CrossRefGoogle Scholar
  29. 29.
    Manning PJ, Sutherland WH, Williams SM, Walker RJ, Berry EA, De Jong SA et al (2013) The effect of lipoic acid and vitamin E therapies in individuals with the metabolic syndrome. Nutr Metab Cardiovasc Dis 23(6):543–549PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Mantovani G, Mahboob S, Amirkhizi F, Hosseinpour-Arjmand S, Ebrahimi-Mameghani M (2019) Oral alpha-lipoic acid supplementation in patients with non-alcoholic fatty liver disease: effects on adipokines and liver histology features. Food FunctGoogle Scholar
  31. 31.
    Zhang Y, Han P, Wu N, He B, Lu Y, Li S et al (2011) Amelioration of lipid abnormalities by alpha-lipoic acid through antioxidative and anti-inflammatory effects. Obesity (Silver Spring) 19(8):1647–1653CrossRefGoogle Scholar
  32. 32.
    Tilg H, Hotamisligil GS (2006) Nonalcoholic fatty liver disease: cytokine-adipokine interplay and regulation of insulin resistance. Gastroenterology. 131(3):934–945PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Jarrar MH, Baranova A, Collantes R, Ranard B, Stepanova M, Bennett C, Fang Y, Elariny H, Goodman Z, Chandhoke V, Younossi ZM (2008) Adipokines and cytokines in non-alcoholic fatty liver disease. Aliment Pharmacol Ther 27(5):412–421PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Fatel ECS, Rosa FT, Simao ANC, Dichi I (2018) Adipokines in rheumatoid arthritis. Adv Rheumatol 58(1):25PubMedCrossRefGoogle Scholar
  35. 35.
    Kumari R, Kumar S, Kant R (2019) An update on metabolic syndrome: metabolic risk markers and adipokines in the development of metabolic syndrome. Diabetes Metab Syndr 13(4):2409–2417PubMedCrossRefGoogle Scholar
  36. 36.
    Ouchi N, Walsh K (2007) Adiponectin as an anti-inflammatory factor. Clin Chim Acta 380(1–2):24–30PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Baranova A, Gowder SJ, Schlauch K, Elariny H, Collantes R, Afendy A, Ong JP, Goodman Z, Chandhoke V, Younossi ZM (2006) Gene expression of leptin, resistin, and adiponectin in the white adipose tissue of obese patients with non-alcoholic fatty liver disease and insulin resistance. Obes Surg 16(9):1118–1125PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Soares AF, Guichardant M, Cozzone D, Bernoud-Hubac N, Bouzaidi-Tiali N, Lagarde M et al (2005) Effects of oxidative stress on adiponectin secretion and lactate production in 3T3-L1 adipocytes. Free Radic Biol Med 38(7):882–889PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Haghighatdoost F, Hariri M (2019) The effect of alpha-lipoic acid on inflammatory mediators: a systematic review and meta-analysis on randomized clinical trials. Eur J Pharmacol 849:115–123PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Packer L (1998) Alpha-lipoic acid: a metabolic antioxidant which regulates NF-kappa B signal transduction and protects against oxidative injury. Drug Metab Rev 30(2):245–275PubMedCrossRefGoogle Scholar
  41. 41.
    Durand M, Mach N (2013) Alpha lipoic acid and its antioxidant against cancer and diseases of central sensitization. Nutr Hosp 28(4):1031–1038PubMedGoogle Scholar
  42. 42.
    Huong DT, Ide T (2008) Dietary lipoic acid-dependent changes in the activity and mRNA levels of hepatic lipogenic enzymes in rats. Br J Nutr 100(1):79–87PubMedCrossRefGoogle Scholar
  43. 43.
    Kandeil MA, Amin KA, Hassanin KA, Ali KM, Mohammed ET (2011) Role of lipoic acid on insulin resistance and leptin in experimentally diabetic rats. J Diabetes Complicat 25(1):31–38PubMedCrossRefGoogle Scholar
  44. 44.
    Mantovani G, Maccio A, Madeddu C, Mura L, Gramignano G, Lusso MR et al (2003) Antioxidant agents are effective in inducing lymphocyte progression through cell cycle in advanced cancer patients: assessment of the most important laboratory indexes of cachexia and oxidative stress. J Mol Med (Berl) 81(10):664–673CrossRefGoogle Scholar
  45. 45.
    Prieto-Hontoria PL, Perez-Matute P, Fernandez-Galilea M, Martinez JA, Moreno-Aliaga MJ (2011) Lipoic acid inhibits leptin secretion and Sp1 activity in adipocytes. Mol Nutr Food Res 55(7):1059–1069PubMedCrossRefGoogle Scholar
  46. 46.
    Wang MY, Lee Y, Unger RH (1999) Novel form of lipolysis induced by leptin. J Biol Chem 274(25):17541–17544PubMedCrossRefGoogle Scholar
  47. 47.
    Song KH, Lee WJ, Koh JM, Kim HS, Youn JY, Park HS, Koh EH, Kim MS, Youn JH, Lee KU, Park JY (2005) Alpha-lipoic acid prevents diabetes mellitus in diabetes-prone obese rats. Biochem Biophys Res Commun 326(1):197–202PubMedCrossRefGoogle Scholar
  48. 48.
    Lee WJ, Song KH, Koh EH, Won JC, Kim HS, Park HS, Kim MS, Kim SW, Lee KU, Park JY (2005) Alpha-lipoic acid increases insulin sensitivity by activating AMPK in skeletal muscle. Biochem Biophys Res Commun 332(3):885–891PubMedCrossRefGoogle Scholar
  49. 49.
    Namazi N, Larijani B, Azadbakht L (2018) Alpha-lipoic acid supplement in obesity treatment: a systematic review and meta-analysis of clinical trials. Clin Nutr 37(2):419–428PubMedCrossRefGoogle Scholar
  50. 50.
    Rahimlou M, Asadi M, Banaei Jahromi N, Mansoori A (2019) Alpha-lipoic acid (ALA) supplementation effect on glycemic and inflammatory biomarkers: a systematic review and meta-analysis. Clin Nutr ESPEN 32:16–28PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Saboori S, Falahi E, Eslampour E, Zeinali Khosroshahi M, Yousefi Rad RE (2018) Effects of alpha-lipoic acid supplementation on C-reactive protein level: a systematic review and meta-analysis of randomized controlled clinical trials. Nutr Metab Cardiovasc Dis 28(8):779–786PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Salehi B, Berkay Yilmaz Y, Antika G, Boyunegme Tumer T (2019) Insights on the use of alpha-lipoic acid for therapeutic purposes. Biomolecules 9(8)PubMedCentralCrossRefGoogle Scholar
  53. 53.
    Isidori AM, Strollo F, More M, Caprio M, Aversa A, Moretti C et al (2000) Leptin and aging: correlation with endocrine changes in male and female healthy adult populations of different body weights. J Clin Endocrinol Metab 85(5):1954–1962PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Isfahan Cardiovascular Research Center, Cardiovascular Research InstituteIsfahan University of Medical SciencesIsfahanIran
  2. 2.Department of Epidemiology & Biostatistics, School of Public HealthNeyshabur University of Medical SciencesNeyshaburIran
  3. 3.Noncommunicable Diseases Research CenterNeyshabur University of Medical SciencesNeyshaburIran

Personalised recommendations