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The effects of melatonin supplementation on inflammatory markers among patients with metabolic syndrome or related disorders: a systematic review and meta-analysis of randomized controlled trials

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Abstract

Objective

This systematic review and meta-analysis of randomized controlled trials (RCTs) was carried out to determine the effect of melatonin supplementation on the inflammatory markers among individuals with metabolic syndrome (MetS) and related disorders.

Methods

We searched the following databases up to March 2018: PubMed, MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. Three reviewers independently assessed study eligibility, extracted data, and evaluated risk of bias of included primary studies. Statistical heterogeneity was assessed using Cochran’s Q test and I-square (I2) statistic. Data were pooled using the random effect model and standardized mean difference (SMD) was considered as the summary effect size.

Results

Six trials of 317 potential reports were identified to be suitable for our meta-analysis. The pooled results using random effects model indicated that melatonin supplementation significantly reduced C-reactive protein (CRP) (SMD = − 1.80; 95% CI − 3.27, − 0.32; P = 0.01; I2: 95.2) and interleukin 6 (IL-6) concentrations (SMD = − 2.02; 95% CI − 3.57, − 0.47; P = 0.01; I2: 91.2) among patients with MetS and related disorders; however, it did not affect tumor necrosis factor-α (TNF-α) concentrations (SMD = − 1.87; 95% CI − 3.81, 0.07; P = 0.05; I2: 94.4).

Conclusions

In summary, the current meta-analysis showed the promising effect of melatonin administration on reducing CRP and IL-6, but not TNF-α levels among patients with MetS and related disorders. Additional prospective studies are recommended using higher supplementation doses and longer intervention period.

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References

  • Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr (2009) Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; national heart, lung, and blood institute; american heart association; world heart federation; international atherosclerosis society; and international association for the study of obesity. Circulation 120:1640–1645

    Article  PubMed  CAS  Google Scholar 

  • Ballantyne CM, Nambi V (2005) Markers of inflammation and their clinical significance. Atheroscler Suppl 6:21–29

    Article  PubMed  CAS  Google Scholar 

  • Ben-Shmuel S, Rostoker R, Scheinman EJ, LeRoith D (2016) Metabolic Syndrome, type 2 diabetes, and Cancer: epidemiology and potential mechanisms. Handb Exp Pharmacol 233:355–372

    Article  PubMed  CAS  Google Scholar 

  • Bruscia EM, Bonfield TL (2016) Innate and adaptive immunity in cystic fibrosis. Clin Chest Med 37:17–29

    Article  PubMed  Google Scholar 

  • Celinski K, Konturek PC, Slomka M, Cichoz-Lach H, Brzozowski T, Konturek SJ, Korolczuk A (2014) Effects of treatment with melatonin and tryptophan on liver enzymes, parameters of fat metabolism and plasma levels of cytokines in patients with non-alcoholic fatty liver disease–14 months follow up. J Physiol Pharmacol 65:75–82

    PubMed  CAS  Google Scholar 

  • Chen YT, Chiang HJ, Chen CH, Sung PH, Lee FY, Tsai TH, Chang CL, Chen HH, Sun CK, Leu S, Chang HW, Yang CC, Yip HK (2014) Melatonin treatment further improves adipose-derived mesenchymal stem cell therapy for acute interstitial cystitis in rat. J Pineal Res 57:248–261

    Article  PubMed  CAS  Google Scholar 

  • Cichoz-Lach H, Celinski K, Konturek PC, Konturek SJ, Slomka M (2010) The effects of l-tryptophan and melatonin on selected biochemical parameters in patients with steatohepatitis. J Physiol Pharmacol 61:577–580

    PubMed  CAS  Google Scholar 

  • Cuzzocrea S, Reiter RJ (2002) Pharmacological actions of melatonin in acute and chronic inflammation. Curr Top Med Chem 2:153–165

    Article  PubMed  CAS  Google Scholar 

  • Fantuzzi G (2005) Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol 115:911–919 quiz 920

    Article  PubMed  CAS  Google Scholar 

  • Galano A, Tan DX, Reiter RJ (2013) On the free radical scavenging activities of melatonin’s metabolites, AFMK and AMK. J Pineal Res 54:245–257

    Article  PubMed  CAS  Google Scholar 

  • Javanmard SH, Heshmat-Ghahdarijani K, Mirmohammad-Sadeghi M, Sonbolestan SA, Ziayi A (2016) The effect of melatonin on endothelial dysfunction in patient undergoing coronary artery bypass grafting surgery. Adv Biomed Res 5:174

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kaptoge S, Di Angelantonio E, Lowe G, Pepys MB, Thompson SG, Collins R, Danesh J (2010) C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet 375:132–140

    Article  PubMed  CAS  Google Scholar 

  • Lee CC, Adler AI, Sandhu MS, Sharp SJ, Forouhi NG, Erqou S, Luben R, Bingham S, Khaw KT, Wareham NJ (2009) Association of C-reactive protein with type 2 diabetes: prospective analysis and meta-analysis. Diabetologia 52:1040–1047

    Article  PubMed  CAS  Google Scholar 

  • Leisegang K, Bouic PJ, Henkel RR (2016) Metabolic syndrome is associated with increased seminal inflammatory cytokines and reproductive dysfunction in a case-controlled male cohort. Am J Reprod Immunol 76:155–163

    Article  PubMed  CAS  Google Scholar 

  • Liu C, Feng X, Li Q, Wang Y, Li Q, Hua M (2016) Adiponectin, TNF-alpha and inflammatory cytokines and risk of type 2 diabetes: a systematic review and meta-analysis. Cytokine 86:100–109

    Article  PubMed  CAS  Google Scholar 

  • Maldonado MD, Garcia-Moreno H, Gonzalez-Yanes C, Calvo JR (2016) Possible involvement of the inhibition of NF-kappaB factor in anti-inflammatory actions that melatonin exerts on mast cells. J Cell Biochem 117:1926–1933

    Article  PubMed  CAS  Google Scholar 

  • Mauriz JL, Collado PS, Veneroso C, Reiter RJ, Gonzalez-Gallego J (2013) A review of the molecular aspects of melatonin’s anti-inflammatory actions: recent insights and new perspectives. J Pineal Res 54:1–14

    Article  PubMed  CAS  Google Scholar 

  • Mesri Alamdari N, Mahdavi R, Roshanravan N, Lotfi Yaghin N, Ostadrahimi AR, Faramarzi E (2015) A double-blind, placebo-controlled trial related to the effects of melatonin on oxidative stress and inflammatory parameters of obese women. Horm Metab Res 47(7):504–508

    PubMed  CAS  Google Scholar 

  • Mozos I, Malainer C, Horbanczuk J, Gug C, Stoian D, Luca CT, Atanasov AG (2017) Inflammatory markers for arterial stiffness in cardiovascular diseases. Front Immunol 8:1058

    Article  PubMed  PubMed Central  Google Scholar 

  • Nuesch E, Trelle S, Reichenbach S, Rutjes AW, Tschannen B, Altman DG, Egger M, Juni P (2010) Small study effects in meta-analyses of osteoarthritis trials: meta-epidemiological study. BMJ 341:c3515

    Article  PubMed  PubMed Central  Google Scholar 

  • Odegaard AO, Jacobs DR Jr, Sanchez OA, Goff DC Jr, Reiner AP, Gross MD (2016) Oxidative stress, inflammation, endothelial dysfunction and incidence of type 2 diabetes. Cardiovasc Diabetol 15:51

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pakravan H, Ahmadian M, Fani A, Aghaee D, Brumanad S, Pakzad B (2017) The Effects of melatonin in patients with nonalcoholic fatty liver disease: a randomized controlled trial. Adv Biomed Res 6:40

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Radogna F, Diederich M, Ghibelli L (2010) Melatonin: a pleiotropic molecule regulating inflammation. Biochem Pharmacol 80:1844–1852

    Article  PubMed  CAS  Google Scholar 

  • Raygan F, Ostadmohammadi V, Bahmani F, Reiter RJ, Asemi Z (2017) Melatonin administration lowers biomarkers of oxidative stress and cardio-metabolic risk in type 2 diabetic patients with coronary heart disease: a randomized, double-blind, placebo-controlled trial. Clin Nutr. https://doi.org/10.1016/j.clnu.2017.12.004

    Article  PubMed  Google Scholar 

  • Rodriguez C, Mayo JC, Sainz RM, Antolin I, Herrera F, Martin V, Reiter RJ (2004) Regulation of antioxidant enzymes: a significant role for melatonin. J Pineal Res 36:1–9

    Article  PubMed  CAS  Google Scholar 

  • Tabrizi R, Akbari M, Moosazadeh M, Lankarani KB, Heydari ST, Kolahdooz F, Mohammadi AA, Shabani A, Badehnoosh B, Jamilian M, Assarian A, Asemi Z (2017) The effects of selenium supplementation on glucose metabolism and lipid profiles among patients with metabolic diseases: a systematic review and meta-analysis of randomized controlled trials. Horm Metab Res. 49:826–830

    Article  PubMed  CAS  Google Scholar 

  • Tang Y, Purkayastha S, Cai D (2015) Hypothalamic microinflammation: a common basis of metabolic syndrome and aging. Trends Neurosci 38:36–44

    Article  PubMed  CAS  Google Scholar 

  • Usta A, Avci E, Bulbul CB, Kadi H, Adali E (2018) The monocyte counts to HDL cholesterol ratio in obese and lean patients with polycystic ovary syndrome. Reprod Biol Endocrinol 16:34

    Article  PubMed  PubMed Central  Google Scholar 

  • Veneroso C, Tunon MJ, Gonzalez-Gallego J, Collado PS (2009) Melatonin reduces cardiac inflammatory injury induced by acute exercise. J Pineal Res 47:184–191

    Article  PubMed  CAS  Google Scholar 

  • Willeit P, Thompson SG, Agewall S, Bergstrom G, Bickel H, Catapano AL, Chien KL, de Groot E, Empana JP, Etgen T, Franco OH, Iglseder B, Johnsen SH, Kavousi M, Lind L, Liu J, Mathiesen EB, Norata GD, Olsen MH, Papagianni A, Poppert H, Price JF, Sacco RL, Yanez DN, Zhao D, Schminke U, Bulbul A, Polak JF, Sitzer M, Hofman A, Grigore L, Dorr M, Su TC, Ducimetiere P, Xie W, Ronkainen K, Kiechl S, Rundek T, Robertson C, Fagerberg B, Bokemark L, Steinmetz H, Ikram MA, Volzke H, Lin HJ, Plichart M, Tuomainen TP, Desvarieux M, McLachlan S, Schmidt C, Kauhanen J, Willeit J, Lorenz MW, Sander D (2016) Inflammatory markers and extent and progression of early atherosclerosis: meta-analysis of individual-participant-data from 20 prospective studies of the PROG-IMT collaboration. Eur J Prev Cardiol 23:194–205

    Article  PubMed  Google Scholar 

  • Zhang J, Chen L, Delzell E, Muntner P, Hillegass WB, Safford MM, Millan IY, Crowson CS, Curtis JR (2014) The association between inflammatory markers, serum lipids and the risk of cardiovascular events in patients with rheumatoid arthritis. Ann Rheum Dis 73:1301–1308

    Article  PubMed  CAS  Google Scholar 

  • Zoccali C (2009) Overweight, obesity and metabolic alterations in chronic kidney disease. Prilozi 30:17–31

    PubMed  CAS  Google Scholar 

Download references

Acknowledgement

The authors of this study would like to appreciate Dr. Naghmeh Mirhosseini for a scientific review and edition of the paper.

Funding

The research grant (no. 97-01-106-17191) was provided by Research Deputy of Shiraz University of Medical Sciences (SUMS).

Author information

Authors and Affiliations

  1. Health Policy Research Center, Institute of Health, Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran

    Maryam Akbari & Reza Tabrizi

  2. Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Islamic Republic of Iran

    Vahidreza Ostadmohammadi, Elaheh Amirani & Zatollah Asemi

  3. Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran

    Kamran B. Lankarani & Seyed Taghi Heydari

  4. Department of Cellular and Structural Biology, University of Texas Health Science, Center, San Antonio, TX, USA

    Russel J. Reiter

Authors
  1. Maryam Akbari
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  2. Vahidreza Ostadmohammadi
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  3. Reza Tabrizi
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  4. Kamran B. Lankarani
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  5. Seyed Taghi Heydari
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  6. Elaheh Amirani
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  7. Russel J. Reiter
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  8. Zatollah Asemi
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Contributions

ZA, MA, VO and RT contributed in conception, design, statistical analysis and drafting of the manuscript. KB-L and TH contributed in conception, data collection and manuscript drafting. Dr. J. Reiter Russel reviewed the manuscript, and offered critical comments.

Corresponding author

Correspondence to Zatollah Asemi.

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The authors declare no conflict of interest.

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Akbari, M., Ostadmohammadi, V., Tabrizi, R. et al. The effects of melatonin supplementation on inflammatory markers among patients with metabolic syndrome or related disorders: a systematic review and meta-analysis of randomized controlled trials. Inflammopharmacol 26, 899–907 (2018). https://doi.org/10.1007/s10787-018-0508-7

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  • DOI: https://doi.org/10.1007/s10787-018-0508-7

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