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The effects of melatonin supplementation on blood pressure in patients with metabolic disorders: a systematic review and meta-analysis of randomized controlled trials

Journal of Human Hypertension volume 33, pages 202–209 (2019)Cite this article

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A Correction to this article was published on 23 October 2019

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Abstract

The current systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the potential effect of melatonin supplementation on blood pressure in patients with metabolic disorders. The following databases were searched until June 2018: PubMed, MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. Two reviewers independently assessed the eligibility of retrieved studies, extracted data from included trials, and evaluated the risk of bias of included studies. Statistical heterogeneity was tested using Cochran’s Q test and I-square (I2) statistic. Data were pooled using random-effect models and standardized mean difference (SMD) was considered as the effect size. Eight RCTs, out of 743 potential citations, were eligible to be included in the current meta-analysis. The pooled findings indicated a significant reduction in systolic (SBP) (SMD = −0.42; 95% CI, −0.59, −0.25; P < 0.001; I2: 0.0) and diastolic blood pressure (DBP) (SMD = −0.50; 95% CI, −0.72, −0.27; P < 0.001; I2: 37.1) following melatonin supplementation in individuals with metabolic disorders. In summary, the current meta-analysis demonstrated that melatonin supplementation significantly decreased SBP and DBP in patients with metabolic disorders. Additional prospective studies are recommended using higher supplementation doses and longer intervention periods to confirm our findings.

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  • 23 October 2019

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

References

  1. Rodgers A, Perkovic V. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2016;374:2295.

    Article  PubMed  Google Scholar 

  2. Du X, Ninomiya T, de Galan B, Abadir E, Chalmers J, Pillai A, et al. Risks of cardiovascular events and effects of routine blood pressure lowering among patients with type 2 diabetes and atrial fibrillation: results of the ADVANCE study. Eur Heart J. 2009;30:1128–35.

    Article  PubMed  Google Scholar 

  3. Jonas M, Garfinkel D, Zisapel N, Laudon M, Grossman E. Impaired nocturnal melatonin secretion in non-dipper hypertensive patients. Blood Press. 2003;12:19–24.

    PubMed  Google Scholar 

  4. Zeman M, Dulkova K, Bada V, Herichova I. Plasma melatonin concentrations in hypertensive patients with the dipping and non-dipping blood pressure profile. Life Sci. 2005;76:1795–803.

    Article  CAS  PubMed  Google Scholar 

  5. Kurpesa M, Trzos E, Drozdz J, Bednarkiewicz Z, Krzeminska-Pakula M. Myocardial ischemia and autonomic activity in dippers and non-dippers with coronary artery disease: assessment of normotensive and hypertensive patients. Int J Cardiol. 2002;83:133–42.

    Article  PubMed  Google Scholar 

  6. Pandi-Perumal SR, Srinivasan V, Maestroni GJ, Cardinali DP, Poeggeler B, Hardeland R. Melatonin: nature’s most versatile biological signal? FEBS J. 2006;273:2813–38.

    Article  CAS  PubMed  Google Scholar 

  7. Reppert SM. Melatonin receptors: molecular biology of a new family of G protein-coupled receptors. J Biol Rhythms. 1997;12:528–31.

    Article  CAS  PubMed  Google Scholar 

  8. Reiter RJ, Tan DX, Galano A. Melatonin: exceeding expectations. Physiology (Bethesda). 2014;29:325–33.

    CAS  Google Scholar 

  9. Laposky AD, Bass J, Kohsaka A, Turek FW. Sleep and circadian rhythms: key components in the regulation of energy metabolism. FEBS Lett. 2008;582:142–51.

    Article  CAS  PubMed  Google Scholar 

  10. Kozirog M, Poliwczak AR, Duchnowicz P, Koter-Michalak M, Sikora J, Broncel M. Melatonin treatment improves blood pressure, lipid profile, and parameters of oxidative stress in patients with metabolic syndrome. J Pineal Res. 2011;50:261–6.

    Article  CAS  PubMed  Google Scholar 

  11. Nduhirabandi F, Du Toit EF, Blackhurst D, Marais D, Lochner A. Chronic melatonin consumption prevents obesity-related metabolic abnormalities and protects the heart against myocardial ischemia and reperfusion injury in a prediabetic model of diet-induced obesity. J Pineal Res. 2011;50:171–82.

    CAS  PubMed  Google Scholar 

  12. Galano A, Reiter RJ. Melatonin and its metabolites vs oxidative stress: from individual actions to collective protection. J Pineal Res. 2018;65:e12514.

    Article  PubMed  Google Scholar 

  13. Romo-Nava F, Alvarez-Icaza Gonzalez D, Fresan-Orellana A, Saracco Alvarez R, Becerra-Palars C, Moreno J, et al. Melatonin attenuates antipsychotic metabolic effects: an eight-week randomized, double-blind, parallel-group, placebo-controlled clinical trial. Bipolar Disord. 2014;16:410–21.

    Article  CAS  PubMed  Google Scholar 

  14. Grossman E, Laudon M, Zisapel N. Effect of melatonin on nocturnal blood pressure: meta-analysis of randomized controlled trials. Vasc Health Risk Manag. 2011;7:577–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Cardinali DP, Cano P, Jimenez-Ortega V, Esquifino AI. Melatonin and the metabolic syndrome: physiopathologic and therapeutical implications. Neuroendocrinology. 2011;93:133–42.

    Article  CAS  PubMed  Google Scholar 

  16. Kadhim HM, Ismail SH, Hussein KI, Bakir IH, Sahib AS, Khalaf BH, et al. Effects of melatonin and zinc on lipid profile and renal function in type 2 diabetic patients poorly controlled with metformin. J Pineal Res. 2006;41:189–93.

    Article  CAS  PubMed  Google Scholar 

  17. Lusardi P, Piazza E, Fogari R. Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine: a 24-hour study. Br J Clin Pharmacol. 2000;49:423–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Armijo-Olivo S, Stiles CR, Hagen NA, Biondo PD, Cummings GG. Assessment of study quality for systematic reviews: a comparison of the Cochrane Collaboration Risk of Bias Tool and the Effective Public Health Practice Project Quality Assessment Tool: methodological research. J Eval Clin Pract. 2012;18:12–8.

    Article  PubMed  Google Scholar 

  19. Modabbernia A, Heidari P, Soleimani R, Sobhani A, Roshan ZA, Taslimi S, et al. Melatonin for prevention of metabolic side-effects of olanzapine in patients with first-episode schizophrenia: randomized double-blind placebo-controlled study. J Psychiatr Res. 2014;53:133–40.

    Article  PubMed  Google Scholar 

  20. Grossman E, Laudon M, Yalcin R, Zengil H, Peleg E, Sharabi Y, et al. Melatonin reduces night blood pressure in patients with nocturnal hypertension. Am J Med. 2006;119:898–902.

    Article  CAS  PubMed  Google Scholar 

  21. Agahi M, Akasheh N, Ahmadvand A, Akbari H, Izadpanah F. Effect of melatonin in reducing second-generation antipsychotic metabolic effects: a double blind controlled clinical trial. Diabetes Metab Syndr. 2018;12:9–15.

    Article  PubMed  Google Scholar 

  22. Brugger P, Marktl W, Herold M. Impaired nocturnal secretion of melatonin in coronary heart disease. Lancet. 1995;345:1408.

    Article  CAS  PubMed  Google Scholar 

  23. Yaprak M, Altun A, Vardar A, Aktoz M, Ciftci S, Ozbay G. Decreased nocturnal synthesis of melatonin in patients with coronary artery disease. Int J Cardiol. 2003;89:103–7.

    Article  PubMed  Google Scholar 

  24. Arangino S, Cagnacci A, Angiolucci M, Vacca AM, Longu G, Volpe A, et al. Effects of melatonin on vascular reactivity, catecholamine levels, and blood pressure in healthy men. Am J Cardiol. 1999;83:1417–9.

    Article  CAS  PubMed  Google Scholar 

  25. Cagnacci A, Arangino S, Angiolucci M, Maschio E, Melis GB. Influences of melatonin administration on the circulation of women. Am J Physiol. 1998;274:R335–8.

    CAS  PubMed  Google Scholar 

  26. Scheer FA, Van Montfrans GA, van Someren EJ, Mairuhu G, Buijs RM. Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension. Hypertension. 2004;43:192–7.

    Article  CAS  PubMed  Google Scholar 

  27. Cavallo A, Daniels SR, Dolan LM, Bean JA, Khoury JC. Blood pressure-lowering effect of melatonin in type 1 diabetes. J Pineal Res. 2004;36:262–6.

    Article  CAS  PubMed  Google Scholar 

  28. Lusardi P, Preti P, Savino S, Piazza E, Zoppi A, Fogari R. Effect of bedtime melatonin ingestion on blood pressure of normotensive subjects. Blood Press Monit. 1997;2:99–103.

    CAS  PubMed  Google Scholar 

  29. Anderson G, Maes M. Melatonin: an overlooked factor in schizophrenia and in the inhibition of anti-psychotic side effects. Metab Brain Dis. 2012;27:113–9.

    Article  CAS  PubMed  Google Scholar 

  30. Rasmussen DD, Boldt BM, Wilkinson CW, Yellon SM, Matsumoto AM. Daily melatonin administration at middle age suppresses male rat visceral fat, plasma leptin, and plasma insulin to youthful levels. Endocrinology. 1999;140:1009–12.

    Article  CAS  PubMed  Google Scholar 

  31. Terron MP, Delgado-Adamez J, Pariente JA, Barriga C, Paredes SD, Rodriguez AB. Melatonin reduces body weight gain and increases nocturnal activity in male Wistar rats. Physiol Behav. 2013;118:8–13.

    Article  CAS  PubMed  Google Scholar 

  32. Bartness TJ, Wade GN. Photoperiodic control of seasonal body weight cycles in hamsters. Neurosci Biobehav Rev. 1985;9:599–612.

    Article  CAS  PubMed  Google Scholar 

  33. Raygan F, Ostadmohammadi V, Bahmani F, Reiter RJ, Asemi Z. 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. 2017. https://doi.org/10.1016/j.clnu.2017.12.004.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  35. Rechcinski T, Trzos E, Wierzbowska-Drabik K, Krzeminska-Pakula M, Kurpesa M. Melatonin for nondippers with coronary artery disease: assessment of blood pressure profile and heart rate variability. Hypertens Res. 2010;33:56–61.

    Article  CAS  PubMed  Google Scholar 

  36. Goyal A, Terry PD, Superak HM, Nell-Dybdahl CL, Chowdhury R, Phillips LS, et al. Melatonin supplementation to treat the metabolic syndrome: a randomized controlled trial. Diabetol Metab Syndr. 2014;6:124.

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

The research grant was provided by Research Deputy of Shiraz University of Medical Sciences (SUMS).

Author contributions

ZA, MA, VO, NM, K-BL, RT and ZK contributed in conception, design, statistical analysis, and drafting of the manuscript. RJR reviewed the manuscript and offered critical comments.

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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, Iran

    Vahidreza Ostadmohammadi & Zatollah Asemi

  3. School of Public Health, University of Saskatchewan, Saskatoon, SK, Canada

    Naghmeh Mirhosseini

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

    Kamran B. Lankarani

  5. Community Health Nursing Department, Community Based Psychiatric Care Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Zahra Keshtkaran

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

    Russel J. Reiter

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  1. Maryam Akbari
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  2. Vahidreza Ostadmohammadi
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Correspondence to Zatollah Asemi.

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Akbari, M., Ostadmohammadi, V., Mirhosseini, N. et al. The effects of melatonin supplementation on blood pressure in patients with metabolic disorders: a systematic review and meta-analysis of randomized controlled trials. J Hum Hypertens 33, 202–209 (2019). https://doi.org/10.1038/s41371-019-0166-2

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