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Effects of Melatonin and/or Magnesium Supplementation on Biomarkers of Inflammation and Oxidative Stress in Women with Polycystic Ovary Syndrome: a Randomized, Double-Blind, Placebo-Controlled Trial

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Abstract

Magnesium and melatonin are known to exert multiple beneficial effects including anti-inflammatory and antioxidant actions. This study was designed to determine the effects of magnesium and/or melatonin supplementation on metabolic profiles in women with polycystic ovary syndrome (PCOS). This randomized double-blind, placebo-controlled trial was conducted among 84 subjects with PCOS aged 18–40 years old. Patients were randomly assigned based on the random block procedure to take magnesium, melatonin, magnesium plus melatonin, or placebo for 8 weeks. Fasting blood samples were taken at baseline and after the intervention to quantify related variables. After the 8-week intervention, an insignificant marginal difference was seen in waist circumference (WC) between groups (P = 0.085). Magnesium-melatonin co-supplementation resulted in more reductions in hirsutism compared with other groups (P < 0.001). Serum levels of tumor necrosis factor-α (TNF-α) declined significantly in the melatonin and co-supplementation groups compared to baseline (P < 0.05). Also, magnesium plus melatonin was associated with a more increase in total antioxidant capacity (TAC) levels, as compared to the other treatment groups (P = 0.001). Overall, we found a favorable effect of co-supplementation of magnesium and melatonin for 8 weeks in women with PCOS on hirsutism, serum TNF-α, and TAC levels. Furthermore, melatonin independently contributed to decreased serum values of TNF-α.

Clinical trial registration number http://www.irct.ir: IRCT20191130045556N1, January 2020

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The data gathered and analyzed during the current study are available from the corresponding author on reasonable request.

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References

  1. Glueck C, Papanna R, Wang P, Goldenberg N, Sieve-Smith L (2003) Incidence and treatment of metabolic syndrome in newly referred women with confirmed polycystic ovarian syndrome. Metabolism 52:908–915. https://doi.org/10.1016/s0026-0495(03)00104-5

    Article  CAS  PubMed  Google Scholar 

  2. Tarlatzis B, Fauser BC, Legro R et al (2008) Consensus on infertility treatment related to polycystic ovary syndrome. Hum Reprod 23:462–477. https://doi.org/10.1093/humrep/dem426

    Article  Google Scholar 

  3. Group REASPCW (Revised 2003) consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 19:41–47

  4. Artimani T, Karimi J, Mehdizadeh M et al (2018) Evaluation of pro-oxidant-antioxidant balance (PAB) and its association with inflammatory cytokines in polycystic ovary syndrome (PCOS). Gynecol Endocrinol 34:148–152. https://doi.org/10.1080/09513590.2017.1371691

    Article  CAS  PubMed  Google Scholar 

  5. Shorakae S, Teede H, de Courten B, Lambert G, Boyle J, Moran LJ (2015) The emerging role of chronic low-grade inflammation in the pathophysiology of polycystic ovary syndrome. Semin Reprod Med 33:257–269. https://doi.org/10.1055/s-0035-1556568

    Article  CAS  PubMed  Google Scholar 

  6. Repaci A, Gambineri A, Pasquali R (2011) The role of low-grade inflammation in the polycystic ovary syndrome. Mol Cell Endocrinol 335:30–41. https://doi.org/10.1016/j.mce.2010.08.002

    Article  CAS  PubMed  Google Scholar 

  7. Sathyapalan T, Atkin SL (2010, 2010) Mediators of inflammation in polycystic ovary syndrome in relation to adiposity. Mediat Inflamm. https://doi.org/10.1155/2010/758656

  8. Murri M, Luque-Ramirez M, Insenser MA, Ojeda-Ojeda M, Escobar-Morreale HF (2013) Circulating markers of oxidative stress and polycystic ovary syndrome (PCOS): a systematic review and meta-analysis. Hum Reprod Update 19:268–288. https://doi.org/10.1093/humupd/dms059

    Article  CAS  PubMed  Google Scholar 

  9. Chakraborty P, Ghosh S, Goswami S, Kabir SN, Chakravarty B, Jana K (2013) Altered trace mineral milieu might play an aetiological role in the pathogenesis of polycystic ovary syndrome. Biol Trace Elem Res 152:9–15. https://doi.org/10.1007/s12011-012-9592-5

    Article  CAS  PubMed  Google Scholar 

  10. Zhang D, Luo W-Y, Liao H, Wang C-F, Sun Y (2008) The effects of oxidative stress to PCOS. Sichuan Da Xue Xue Bao Yi Xue Ban 39:421–423

    CAS  PubMed  Google Scholar 

  11. Cagnacci A, Volpe A (2002) A role for melatonin in PCOS? Fertil Steril 77:1089. https://doi.org/10.1016/s0015-0282(02)03070-4

    Article  PubMed  Google Scholar 

  12. Cassone VM, Natesan AK (1997) Time and time again: the phylogeny of melatonin as a transducer of biological time. J Biol Rhythm 12:489–497. https://doi.org/10.1177/074873049701200602

    Article  CAS  Google Scholar 

  13. Reiter RJ, Tan D-X, Fuentes-Broto L (2010) Melatonin: a multitasking molecule. Prog Brain Res 181:127–151. https://doi.org/10.1016/s0079-6123(08)81008-4

    Article  CAS  PubMed  Google Scholar 

  14. Tan DX, Manchester LC, Sainz RM et al (2005) Interactions between melatonin and nicotinamide nucleotide: NADH preservation in cells and in cell-free systems by melatonin. J Pineal Res 39:185–194. https://doi.org/10.1111/j.1600-079x.2005.00234.x

    Article  CAS  PubMed  Google Scholar 

  15. Reiter RJ, Tan DX, Maldonado MD (2005) Melatonin as an antioxidant: physiology versus pharmacology. J Pineal Res 39:215–216. https://doi.org/10.1111/j.1600-079x.2005.00261.x

    Article  CAS  PubMed  Google Scholar 

  16. Tanavde V, Maitra A (2011) In vitro modulation of steroidogenesis and gene expression by melatonin: a study with porcine antral follicles. Endocr Res 29:399–410. https://doi.org/10.1081/erc-120026946

    Article  Google Scholar 

  17. Galano A, Tan DX, Reiter RJ (2011) Melatonin as a natural ally against oxidative stress: a physicochemical examination. J Pineal Res 51:1–16. https://doi.org/10.1111/j.1600-079x.2011.00916.x

    Article  CAS  PubMed  Google Scholar 

  18. Tamura H, Nakamura Y, Korkmaz A et al (2009) Melatonin and the ovary: physiological and pathophysiological implications. Fertil Steril 92:328–343. https://doi.org/10.1016/j.fertnstert.2008.05.016

    Article  CAS  PubMed  Google Scholar 

  19. Pacchiarotti A, Carlomagno G, Antonini G, Pacchiarotti A (2016) Effect of myo-inositol and melatonin versus myo-inositol, in a randomized controlled trial, for improving in vitro fertilization of patients with polycystic ovarian syndrome. Gynecol Endocrinol 32:69–73. https://doi.org/10.3109/09513590.2015.1101444

    Article  PubMed  Google Scholar 

  20. Jamilian M, Foroozanfard F, Mirhosseini N et al (2019) Effects of melatonin supplementation on hormonal, inflammatory, genetic, and oxidative stress parameters in women with polycystic ovary syndrome. Front Endocrinol 10:273. https://doi.org/10.3389/fendo.2019.00273

    Article  Google Scholar 

  21. Glasdam S-M, Glasdam S, Peters GH (2016) The importance of magnesium in the human body: a systematic literature review. Adv Clin Chem 73:169–193. https://doi.org/10.1016/bs.acc.2015.10.002

    Article  CAS  PubMed  Google Scholar 

  22. Rodríguez-Morán M, Mendía LES, Galván GZ, Guerrero-Romero F (2012) The role of magnesium in type 2 diabetes: a brief based-clinical review. Magnes Res 24:156–162. https://doi.org/10.1684/mrh.2011.0299

    Article  CAS  Google Scholar 

  23. Asemi Z, Esmaillzadeh A (2015) DASH diet, insulin resistance, and serum hs-CRP in polycystic ovary syndrome: a randomized controlled clinical trial. Horm Metab Res 47:232–238. https://doi.org/10.1055/s-0034-1376990

    Article  CAS  PubMed  Google Scholar 

  24. Szczuko M, Skowronek M, Zapalowska-Chwyc M, Starczewski A (2016) Quantitative assessment of nutrition in patients with polycystic ovary syndrome (PCOS). Rocz Panstw Zakl Hig 67:419–426

    PubMed  Google Scholar 

  25. Hamilton KP, Zelig R, Parker AR, Haggag A (2019) Insulin resistance and serum magnesium concentrations among women with polycystic ovary syndrome. Curr Dev Nutr 3:nzz108. https://doi.org/10.1093/cdn/nzz108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ebrahimi FA, Foroozanfard F, Aghadavod E, Bahmani F, Asemi Z (2018) The effects of magnesium and zinc co-supplementation on biomarkers of inflammation and oxidative stress, and gene expression related to inflammation in polycystic ovary syndrome: a randomized controlled clinical trial. Biol Trace Elem Res 184:300–307. https://doi.org/10.1007/s12011-017-1198-5

    Article  CAS  Google Scholar 

  27. Maktabi M, Jamilian M, Asemi Z (2018) Magnesium-zinc-calcium-vitamin D co-supplementation improves hormonal profiles, biomarkers of inflammation and oxidative stress in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Biol Trace Elem Res 182:21–28. https://doi.org/10.1007/s12011-017-1085-0

    Article  CAS  PubMed  Google Scholar 

  28. Moslehi N, Vafa M, Rahimi-Foroushani A, Golestan B (2012) Effects of oral magnesium supplementation on inflammatory markers in middle-aged overweight women. J Res Med Sci 17:607–614

    PubMed  PubMed Central  Google Scholar 

  29. Dou M, Ma AG, Wang QZ et al (2009) Supplementation with magnesium and vitamin E were more effective than magnesium alone to decrease plasma lipids and blood viscosity in diabetic rats. Nutr Res 29:519–524. https://doi.org/10.1016/j.nutres.2009.07.001

    Article  CAS  PubMed  Google Scholar 

  30. Chang W, Ma A, Wang Q, Mao R, Li C (2014) Effects of vitamin E and magnesium on glucolipid metabolism in obese rats. Wei Sheng Yan Jiu 43:713–718

    CAS  PubMed  Google Scholar 

  31. Neter J, Wasserman W, Kutner MH (1989) Applied linear regression models.

  32. Shabani A, Foroozanfard F, Kavossian E et al (2019) Effects of melatonin administration on mental health parameters, metabolic and genetic profiles in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. J Affect Disord 250:51–56. https://doi.org/10.1016/j.jad.2019.02.066

    Article  CAS  PubMed  Google Scholar 

  33. Committee IR (2005) Guidelines for data processing and analysis of the International Physical Activity Questionnaire (IPAQ)-short and long forms. http://www.ipaq.ki.se/scoring.pdf. Accessed 1 Dec 2019

  34. Hatch R, Rosenfield RL, Kim MH, Tredway D (1981) Hirsutism: implications, etiology, and management. Am J Obstet Gynecol 140:815–830. https://doi.org/10.1016/0002-9378(81)90746-8

    Article  CAS  PubMed  Google Scholar 

  35. Janero DR (1990) Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radic Biol Med 9:515–540. https://doi.org/10.1016/0891-5849(90)90131-2

    Article  CAS  PubMed  Google Scholar 

  36. Miller NJ, Rice-Evans C, Davies MJ, Gopinathan V, Milner A (1993) A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates. Clin Sci 84:407–412. https://doi.org/10.1042/cs0840407

    Article  CAS  Google Scholar 

  37. Duleba AJ, Dokras A (2012) Is PCOS an inflammatory process? Fertil Steril 97:7–12. https://doi.org/10.1016/j.fertnstert.2011.11.023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Hyderali BN, Mala K (2015) Oxidative stress and cardiovascular complications in polycystic ovarian syndrome. Eur J Obstet Gynecol Reprod Biol 191:15–22. https://doi.org/10.1016/j.ejogrb.2015.05.005

    Article  CAS  PubMed  Google Scholar 

  39. González F (2012) Inflammation in polycystic ovary syndrome: underpinning of insulin resistance and ovarian dysfunction. Steroids 77:300–305. https://doi.org/10.1016/j.steroids.2011.12.003

    Article  CAS  PubMed  Google Scholar 

  40. Simental-Mendia LE, Sahebkar A, Rodriguez-Moran M, Zambrano-Galvan G, Guerrero-Romero F (2017) Effect of magnesium supplementation on plasma C-reactive protein concentrations: a systematic review and meta-analysis of randomized controlled trials. Curr Pharm Des 23:4678–4686. https://doi.org/10.2174/1381612823666170525153605

    Article  CAS  PubMed  Google Scholar 

  41. Elin RJ (2010) Assessment of magnesium status for diagnosis and therapy. Magnes Res 23:194–198. https://doi.org/10.1684/mrh.2010.0213

    Article  CAS  Google Scholar 

  42. Alfrey AC, Miller NL (1973) Bone magnesium pools in uremia. J Clin Invest 52:3019–3027. https://doi.org/10.1172/jci107500

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Shokrpour M, Asemi Z (2019) The effects of magnesium and vitamin E co-supplementation on hormonal status and biomarkers of inflammation and oxidative stress in women with polycystic ovary syndrome. Biol Trace Elem Res 191:54–60. https://doi.org/10.1007/s12011-018-1602-9

    Article  CAS  PubMed  Google Scholar 

  44. Barbagallo M, Dominguez LJ, Galioto A et al (2003) Role of magnesium in insulin action, diabetes and cardio-metabolic syndrome X. Mol Asp Med 24:39–52. https://doi.org/10.1016/s0098-2997(02)00090-0

    Article  CAS  Google Scholar 

  45. Liu Y, Guo Y, Wang Z (2007) Effect of magnesium on reactive oxygen species production in the thigh muscles of broiler chickens. Br Poult Sci 48:84–89. https://doi.org/10.1080/00071660601148187

    Article  CAS  PubMed  Google Scholar 

  46. Boujelben M, Ghorbel F, Vincent C et al (2009) Lipid peroxidation and HSP72/73 expression in rat following cadmium chloride administration: interactions of magnesium supplementation. Exp Toxicol Pathol 57:437–443. https://doi.org/10.1016/j.etp.2006.02.012

    Article  CAS  Google Scholar 

  47. Tamura H, Takasaki A, Taketani T et al (2012) The role of melatonin as an antioxidant in the follicle. J. Ovarian Res 5:1–9. https://doi.org/10.1186/1757-2215-5-5

    Article  CAS  Google Scholar 

  48. Jain P, Jain M, Haldar C, Singh TB, Jain S (2013) Melatonin and its correlation with testosterone in polycystic ovarian syndrome. J Hum Reprod Sci 6:253. https://doi.org/10.4103/0974-1208.126295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Mojaverrostami S, Asghari N, Khamisabadi M, Khoei HH (2019) The role of melatonin in polycystic ovary syndrome: a review. Int J Reprod Biomed 17:865. https://doi.org/10.18502/ijrm.v17i12.5789

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Dokras A, Sarwer DB, Allison KC et al (2016) Weight loss and lowering androgens predict improvements in health-related quality of life in women with PCOS. J Clin Endocrinol Metab 101:2966–2974. https://doi.org/10.1210/jc.2016-1896

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Lin YW, Lee LM, Lee WJ et al (2016) Melatonin inhibits MMP-9 transactivation and renal cell carcinoma metastasis by suppressing Akt-MAPK s pathway and NF-κB DNA-binding activity. J Pineal Res 60:277–290. https://doi.org/10.1111/jpi.12308

    Article  CAS  PubMed  Google Scholar 

  52. Mohan N, Sadeghi K, Reiter RJ, Meltz ML (1995) The neurohormone melatonin inhibits cytokine, mitogen and ionizing radiation induced NF-kappa B. Int J Biochem Mol Biol 37:1063–1070

    CAS  Google Scholar 

  53. Akbari M, Ostadmohammadi V, Tabrizi R et al (2018) 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. Inflammopharmacology 26:899–907. https://doi.org/10.1007/s10787-018-0508-7

    Article  CAS  PubMed  Google Scholar 

  54. 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  Google Scholar 

  55. Karamitri A, Jockers R (2019) Melatonin in type 2 diabetes mellitus and obesity. Nat Rev Endocrinol 15:105–125. https://doi.org/10.4103/2277-9175.204593

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors wish to thank Mr. Meisam Barati, Mr. Seyed Javad Mousavi and Mrs. Marziyeh Keshizadeh for their assistance and the staff of the Diagnostic Laboratory Department at 29 Bahman Hospital (Tabriz, Iran) for their technical help. We also thank all of the study participants.

Funding

The present study was funded by the vice chancellor for research of Ahvaz Jundishapur University of Medical Science (Grant No.: NRC-9815) and Tabriz University of Medical science (Grant No.: 64999).

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Authors and Affiliations

  1. Department of Nutrition, School of Allied Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Reihaneh Mousavi

  2. Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Reihaneh Mousavi

  3. Department of Clinical Nutrition, Faculty of Nutrition and Food Science, Tabriz University of Medical Science, Tabriz, Iran

    Mohammad Alizadeh

  4. Department of Statistics and Epidemiology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran

    Mohammad Asghari Jafarabadi

  5. Road Traffic Injury Research Center, Tabriz University of Medical Science, Tabriz, Iran

    Mohammad Asghari Jafarabadi

  6. Nahal Infertility Center, Tabriz, Iran

    Lida Heidari

  7. Fertility Infertility and Perinatology Research Center, Ahvaz Jundishapur University of Medical Science, Ahvaz, Iran

    Roshan Nikbakht

  8. Hyperlipidemia Research Center, Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Science, Ahvaz, Iran

    Hossein Babaahmadi Rezaei

  9. Nutrition and Metabolic Disease Research Center, Clinical Science Research Institute, Ahvaz Jundishapur University of Medical Science, Ahvaz, Iran

    Majid Karandish

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  1. Reihaneh Mousavi
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Contributions

MK, MA, and RM were involved in the conception and design of the study. LH, RN, and HBR contributed in methodology. MAJ and RM performed the data analysis and interpretation. RM participated in the conduction of the study and manuscript drafting. MK supervised the development of the work. Mk and MA conducted the critical review. All authors read and approved the final manuscript.

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Correspondence to Majid Karandish.

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The ethical committee of Ahvaz Jundishapur University of Medical Sciences confirmed the study and the approval of the Ethics Committee was obtained (IR.AJUMS.REC.1398.637).

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Mousavi, R., Alizadeh, M., Asghari Jafarabadi, M. et al. Effects of Melatonin and/or Magnesium Supplementation on Biomarkers of Inflammation and Oxidative Stress in Women with Polycystic Ovary Syndrome: a Randomized, Double-Blind, Placebo-Controlled Trial. Biol Trace Elem Res 200, 1010–1019 (2022). https://doi.org/10.1007/s12011-021-02725-y

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