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Biological Trace Element Research

, Volume 182, Issue 1, pp 21–28 | Cite as

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

  • Maryam Maktabi
  • Mehri Jamilian
  • Zatollah AsemiEmail author
Article

Abstract

Data on the effects of magnesium-zinc-calcium-vitamin D co-supplementation on hormonal profiles, biomarkers of inflammation, and oxidative stress among women with polycystic ovary syndrome (PCOS) are scarce. The objective of this study was to assess the effects of magnesium-zinc-calcium-vitamin D co-supplementation on hormonal profiles, biomarkers of inflammation, and oxidative stress in women with PCOS. Sixty PCOS women were randomized into two groups and treated with 100 mg magnesium, 4 mg zinc, 400 mg calcium plus 200 IU vitamin D supplements (n = 30), or placebo (n = 30) twice a day for 12 weeks. Hormonal profiles, biomarkers of inflammation, and oxidative stress were assessed at baseline and at end-of-treatment. After the 12-week intervention, compared with the placebo, magnesium-zinc-calcium-vitamin D co-supplementation resulted in significant reductions in hirsutism (−2.4 ± 1.2 vs. −0.1 ± 0.4, P < 0.001), serum high sensitivity C-reactive protein (−0.7 ± 0.8 vs. +0.2 ± 1.8 mg/L, P < 0.001), and plasma malondialdehyde (−0.4 ± 0.3 vs. +0.2 ± 1.0 μmol/L, P = 0.01), and a significant increase in plasma total antioxidant capacity concentrations (+46.6 ± 66.5 vs. −7.7 ± 130.1 mmol/L, P = 0.04). We failed to find any significant effect of magnesium-zinc-calcium-vitamin D co-supplementation on free androgen index, and other biomarkers of inflammation and oxidative stress. Overall, magnesium-zinc-calcium-vitamin D co-supplementation for 12 weeks among PCOS women had beneficial effects on hormonal profiles, biomarkers of inflammation, and oxidative stress.

Keywords

Supplementation Polycystic ovary syndrome Endocrine profiles Inflammation 

Notes

Acknowledgements

The current study was supported by a grant from the Vice-chancellor for Research, AUMS, and Iran.

Authors’ Contributions

ZA contributed in conception, design, statistical analysis, and drafting of the manuscript. MM and MJ contributed in data collection and manuscript drafting. ZA supervised the study.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO (2004) The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab 89:2745–2749CrossRefPubMedGoogle Scholar
  2. 2.
    Clark NM, Podolski AJ, Brooks ED, Chizen DR, Pierson RA, Lehotay DC, Lujan ME (2014) Prevalence of polycystic ovary syndrome phenotypes using updated criteria for polycystic ovarian morphology: an assessment of over 100 consecutive women self-reporting features of polycystic ovary syndrome. Reprod Sci 21:1034–1043CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Diamanti-Kandarakis E, Paterakis T, Alexandraki K, Piperi C, Aessopos A, Katsikis I, Katsilambros N, Kreatsas G, Panidis D (2006) Indices of low-grade chronic inflammation in polycystic ovary syndrome and the beneficial effect of metformin. Hum Reprod 21:1426–1431CrossRefPubMedGoogle Scholar
  4. 4.
    Puder JJ, Varga S, Kraenzlin M, De Geyter C, Keller U, Muller B (2005) Central fat excess in polycystic ovary syndrome: relation to low-grade inflammation and insulin resistance. J Clin Endocrinol Metab 90:6014–6021CrossRefPubMedGoogle Scholar
  5. 5.
    Glintborg D (2016) Endocrine and metabolic characteristics in polycystic ovary syndrome. Dan Med J 63Google Scholar
  6. 6.
    Gonzalez F, Rote NS, Minium J, Kirwan JP (2006) Reactive oxygen species-induced oxidative stress in the development of insulin resistance and hyperandrogenism in polycystic ovary syndrome. J Clin Endocrinol Metab 91:336–340CrossRefPubMedGoogle Scholar
  7. 7.
    Victor VM, Rocha M, Banuls C, Sanchez-Serrano M, Sola E, Gomez M, Hernandez-Mijares A (2009) Mitochondrial complex I impairment in leukocytes from polycystic ovary syndrome patients with insulin resistance. J Clin Endocrinol Metab 94:3505–3512CrossRefPubMedGoogle Scholar
  8. 8.
    Costello MF, Misso ML, Wong J, Hart R, Rombauts L, Melder A, Norman RJ, Teede HJ (2012) The treatment of infertility in polycystic ovary syndrome: a brief update. Aust N Z J Obstet Gynaecol 52:400–403CrossRefPubMedGoogle Scholar
  9. 9.
    Chakraborty P, Ghosh S, Goswami SK, 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 152:9–15CrossRefPubMedGoogle Scholar
  10. 10.
    Nandi A, Sinha N, Ong E, Sonmez H, Poretsky L (2016) Is there a role for vitamin D in human reproduction? Horm Mol Biol Clin Invest 25:15–28Google Scholar
  11. 11.
    Guler I, Himmetoglu O, Turp A, Erdem A, Erdem M, Onan MA, Taskiran C, Taslipinar MY, Guner H (2014) Zinc and homocysteine levels in polycystic ovarian syndrome patients with insulin resistance. Biol Trace Elem Res 158:297–304CrossRefPubMedGoogle Scholar
  12. 12.
    Razavi M, Jamilian M, Karamali M, Bahmani F, Aghadavod E, Asemi Z (2016) The effects of vitamin D-K-calcium co-supplementation on endocrine, inflammation, and oxidative stress biomarkers in vitamin D-deficient women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Horm Metab Res 48:446–451CrossRefPubMedGoogle Scholar
  13. 13.
    Nielsen FH, Johnson LK, Zeng H (2010) Magnesium supplementation improves indicators of low magnesium status and inflammatory stress in adults older than 51 years with poor quality sleep. Magnes Res 23:158–168PubMedGoogle Scholar
  14. 14.
    Asemi Z, Karamali M, Esmaillzadeh A (2014) Effects of calcium-vitamin D co-supplementation on glycaemic control, inflammation and oxidative stress in gestational diabetes: a randomised placebo-controlled trial. Diabetologia 57:1798–1806CrossRefPubMedGoogle Scholar
  15. 15.
    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 17:607–614PubMedPubMedCentralGoogle Scholar
  16. 16.
    Pal L, Berry A, Coraluzzi L, Kustan E, Danton C, Shaw J, Taylor H (2012) Therapeutic implications of vitamin D and calcium in overweight women with polycystic ovary syndrome. Gynecol Endocrinol 28:965–968CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Tabesh M, Azadbakht L, Faghihimani E, Esmaillzadeh A (2014) Calcium-vitamin D cosupplementation influences circulating inflammatory biomarkers and adipocytokines in vitamin D-insufficient diabetics: a randomized controlled clinical trial. J Clin Endocrinol Metab 99:E2485–E2493CrossRefPubMedGoogle Scholar
  18. 18.
    Foroozanfard F, Jamilian M, Bahmani F, Talaee R, Talaee N, Hashemi T, Nasri K, Asemi Z, Esmaillzadeh A (2015) Calcium plus vitamin D supplementation influences biomarkers of inflammation and oxidative stress in overweight and vitamin D-deficient women with polycystic ovary syndrome: a randomized double-blind placebo-controlled clinical trial. Clin Endocrinol 83:888–894CrossRefGoogle Scholar
  19. 19.
    Asemi Z, Foroozanfard F, Hashemi T, Bahmani F, Jamilian M, Esmaillzadeh A (2015) Calcium plus vitamin D supplementation affects glucose metabolism and lipid concentrations in overweight and obese vitamin D deficient women with polycystic ovary syndrome. Clin Nutr 34:586–592CrossRefPubMedGoogle Scholar
  20. 20.
    Almoznino-Sarafian D, Berman S, Mor A, Shteinshnaider M, Gorelik O, Tzur I, Alon I, Modai D, Cohen N (2007) Magnesium and C-reactive protein in heart failure: an anti-inflammatory effect of magnesium administration? Eur J Nutr 46:230–237CrossRefPubMedGoogle Scholar
  21. 21.
    Hajsadeghi S, Hejrati M, Moghadami S, Rismantab S, Namiranian P (2012) Dilated cardiomyopathy in two patients with xeroderma pigmentosum disease: a case report. Acta Med Iran 50:147–150PubMedGoogle Scholar
  22. 22.
    Sandhu MS, Casale TB (2010) The role of vitamin D in asthma. Ann Allergy Asthma Immunol 105:191–199 quiz 200-192, 217CrossRefPubMedGoogle Scholar
  23. 23.
    Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group (2004) Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 81:19–25Google Scholar
  24. 24.
    Ramezani Tehrani F, Minooee S, Azizi F (2014) Validation of a simplified method to assess hirsutism in the Iranian population. Eur J Obstet Gynecol Reprod Biol 174:91–95CrossRefPubMedGoogle Scholar
  25. 25.
    Tatsch E, Bochi GV, Pereira Rda S, Kober H, Agertt VA, de Campos MM, Gomes P, Duarte MM, Moresco RN (2011) A simple and inexpensive automated technique for measurement of serum nitrite/nitrate. Clin Biochem 44:348–350CrossRefPubMedGoogle Scholar
  26. 26.
    Benzie IF, Strain JJ (1996) The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem 239:70–76CrossRefPubMedGoogle Scholar
  27. 27.
    Beutler E, Gelbart T (1985) Plasma glutathione in health and in patients with malignant disease. J Lab Clin Med 105:581–584PubMedGoogle Scholar
  28. 28.
    Janero DR (1990) Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radic Biol Med 9:515–540CrossRefPubMedGoogle Scholar
  29. 29.
    Garg G, Kachhawa G, Ramot R, Khadgawat R, Tandon N, Sreenivas V, Kriplani A, Gupta N (2015) Effect of vitamin D supplementation on insulin kinetics and cardiovascular risk factors in polycystic ovarian syndrome: a pilot study. Endocr Connect 4:108–116CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Asemi Z, Samimi M, Tabassi Z, Shakeri H, Sabihi SS, Esmaillzadeh A (2014) Effects of DASH diet on lipid profiles and biomarkers of oxidative stress in overweight and obese women with polycystic ovary syndrome: a randomized clinical trial. Nutrition 30:1287–1293CrossRefPubMedGoogle Scholar
  31. 31.
    Jamilian M, Razavi M, Fakhrie Kashan Z, Ghandi Y, Bagherian T, Asemi Z (2015) Metabolic response to selenium supplementation in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Clin Endocrinol 82:885–891CrossRefGoogle Scholar
  32. 32.
    Kotsa K, Yavropoulou MP, Anastasiou O, Yovos JG (2009) Role of vitamin D treatment in glucose metabolism in polycystic ovary syndrome. Fertil Steril 92:1053–1058CrossRefPubMedGoogle Scholar
  33. 33.
    Yildizhan R, Kurdoglu M, Adali E, Kolusari A, Yildizhan B, Sahin HG, Kamaci M (2009) Serum 25-hydroxyvitamin D concentrations in obese and non-obese women with polycystic ovary syndrome. Arch Gynecol Obstet 280:559–563CrossRefPubMedGoogle Scholar
  34. 34.
    Wehr E, Pilz S, Schweighofer N, Giuliani A, Kopera D, Pieber TR, Obermayer-Pietsch B (2009) Association of hypovitaminosis D with metabolic disturbances in polycystic ovary syndrome. Eur J Endocrinol 161:575–582CrossRefPubMedGoogle Scholar
  35. 35.
    Li HW, Brereton RE, Anderson RA, Wallace AM, Ho CK (2011) Vitamin D deficiency is common and associated with metabolic risk factors in patients with polycystic ovary syndrome. Metabolism 60:1475–1481CrossRefPubMedGoogle Scholar
  36. 36.
    Pittas AG, Lau J, Hu FB, Dawson-Hughes B (2007) The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab 92:2017–2029CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Maestro B, Molero S, Bajo S, Davila N, Calle C (2002) Transcriptional activation of the human insulin receptor gene by 1,25-dihydroxyvitamin D(3). Cell Biochem Funct 20:227–232CrossRefPubMedGoogle Scholar
  38. 38.
    Firouzabadi R, Aflatoonian A, Modarresi S, Sekhavat L, Mohammad Taheri S (2012) Therapeutic effects of calcium & vitamin D supplementation in women with PCOS. Complement Ther Clin Pract 18:85–88CrossRefPubMedGoogle Scholar
  39. 39.
    Stamatiadis D, Bulteau-Portois MC, Mowszowicz I (1988) Inhibition of 5 alpha-reductase activity in human skin by zinc and azelaic acid. Br J Dermatol 119:627–632CrossRefPubMedGoogle Scholar
  40. 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. doi: 10.2174/1381612823666170525153605
  41. 41.
    Kim J, Ahn J (2014) Effect of zinc supplementation on inflammatory markers and adipokines in young obese women. Biol Trace Elem Res 157:101–106CrossRefPubMedGoogle Scholar
  42. 42.
    Dias PC, Sena-Evangelista KC, Paiva MS, Ferreira DQ, Ururahy MA, Rezende AA, Abdalla DS, Pedrosa LF (2014) The beneficial effects of rosuvastatin are independent of zinc supplementation in patients with atherosclerosis. J Trace Elem Med Biol 28:194–199CrossRefPubMedGoogle Scholar
  43. 43.
    Jialal I, Devaraj S, Venugopal SK (2004) C-reactive protein: risk marker or mediator in atherothrombosis? Hypertension 44:6–11CrossRefPubMedGoogle Scholar
  44. 44.
    Wellen KE, Hotamisligil GS (2005) Inflammation, stress, and diabetes. J Clin Invest 115:1111–1119CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Aneiros E, Philipp S, Lis A, Freichel M, Cavalie A (2005) Modulation of Ca2+ signaling by Na+/Ca2+ exchangers in mast cells. J Immunol 174:119–130CrossRefPubMedGoogle Scholar
  46. 46.
    Bao B, Prasad AS, Beck FW, Fitzgerald JT, Snell D, Bao GW, Singh T, Cardozo LJ (2010) Zinc decreases C-reactive protein, lipid peroxidation, and inflammatory cytokines in elderly subjects: a potential implication of zinc as an atheroprotective agent. Am J Clin Nutr 91:1634–1641CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Brandi L (2008) 1alpha(OH)D3 one-alpha-hydroxy-cholecalciferol—an active vitamin D analog. Clinical studies on prophylaxis and treatment of secondary hyperparathyroidism in uremic patients on chronic dialysis. Dan Med Bull 55:186–210PubMedGoogle Scholar
  48. 48.
    Bede O, Nagy D, Suranyi A, Horvath I, Szlavik M, Gyurkovits K (2008) Effects of magnesium supplementation on the glutathione redox system in atopic asthmatic children. Inflamm Res 57:279–286CrossRefPubMedGoogle Scholar
  49. 49.
    Mazani M, Argani H, Rashtchizadeh N, Ghorbanihaghjo A, Hamdi A, Estiar MA, Nezami N (2013) Effects of zinc supplementation on antioxidant status and lipid peroxidation in hemodialysis patients. J Ren Nutr 23:180–184CrossRefPubMedGoogle Scholar
  50. 50.
    Shaheen AA, el-Fattah AA (1995) Effect of dietary zinc on lipid peroxidation, glutathione, protein thiols levels and superoxide dismutase activity in rat tissues. Int J Biochem Cell Biol 27:89–95CrossRefPubMedGoogle Scholar
  51. 51.
    Hyderali BN, Mala K (2015) Oxidative stress and cardiovascular complications in polycystic ovarian syndrome. Eur J Obstet Gynecol Reprod Biol 191:15–22CrossRefPubMedGoogle Scholar
  52. 52.
    Liu YX, Guo YM, Wang Z (2007) Effect of magnesium on reactive oxygen species production in the thigh muscles of broiler chickens. Br Poult Sci 48:84–89CrossRefPubMedGoogle Scholar
  53. 53.
    Boujelben M, Ghorbel F, Vincent C, Makni-Ayadi F, Guermazi F, Croute F, El-Feki A (2006) Lipid peroxidation and HSP72/73 expression in rat following cadmium chloride administration: interactions of magnesium supplementation. Exp Toxicol Pathol 57:437–443CrossRefPubMedGoogle Scholar
  54. 54.
    Powell SR (2000) The antioxidant properties of zinc. J Nutr 130:1447S–1454SCrossRefPubMedGoogle Scholar
  55. 55.
    McCormick CC, Menard MP, Cousins RJ (1981) Induction of hepatic metallothionein by feeding zinc to rats of depleted zinc status. Am J Phys 240:E414–E421Google Scholar
  56. 56.
    Ermak G, Davies KJ (2002) Calcium and oxidative stress: from cell signaling to cell death. Mol Immunol 38:713–721CrossRefPubMedGoogle Scholar
  57. 57.
    Jain SK, Micinski D (2013) Vitamin D upregulates glutamate cysteine ligase and glutathione reductase, and GSH formation, and decreases ROS and MCP-1 and IL-8 secretion in high-glucose exposed U937 monocytes. Biochem Biophys Res Commun 437:7–11CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Endocrinology and Metabolism Research Center, Department of Gynecology and Obstetrics, School of MedicineArak University of Medical SciencesArakIran
  2. 2.Research Center for Biochemistry and Nutrition in Metabolic DiseasesKashan University of Medical SciencesKashanIran

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