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RETRACTED ARTICLE: Magnesium-Zinc-Calcium-Vitamin D Co-supplementation Improves Hormonal Profiles, Biomarkers of Inflammation and Oxidative Stress in Women with Polycystic Ovary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

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A Correction to this article was published on 19 November 2022

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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.

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Change history

  • 28 February 2020

    The Editors-in-Chief are currently investigating this article [Maktabi, M., Jamilian, M. & Asemi, Z. 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 (2018). https://doi.org/10.1007/s12011-017-1085-0] as concerns have been raised about integrity of the clinical trial reported here. There is also an ongoing investigation by the Iranian National Committee for Ethics in Biomedical Researches. Further editorial action will be taken as appropriate once the investigation into the concerns is complete and all parties have been given an opportunity to respond in full.

  • 19 November 2022

    A Correction to this paper has been published: https://doi.org/10.1007/s12011-022-03465-3

References

  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 89:2745–2749

    Article  CAS  Google Scholar 

  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 21:1034–1043

    Article  Google Scholar 

  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 21:1426–1431

    Article  CAS  Google Scholar 

  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 90:6014–6021

    Article  CAS  Google Scholar 

  5. Glintborg D (2016) Endocrine and metabolic characteristics in polycystic ovary syndrome. Dan Med J 63

  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 91:336–340

    Article  CAS  Google Scholar 

  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 94:3505–3512

    Article  CAS  Google Scholar 

  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 52:400–403

    Article  Google Scholar 

  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 152:9–15

    Article  CAS  Google Scholar 

  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 25:15–28

    CAS  Google Scholar 

  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 158:297–304

    Article  CAS  Google Scholar 

  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 48:446–451

    Article  CAS  Google Scholar 

  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 23:158–168

    Google Scholar 

  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 57:1798–1806

    Article  CAS  Google Scholar 

  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 17:607–614

    Google Scholar 

  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 28:965–968

    Article  CAS  Google Scholar 

  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–E2493

    Article  CAS  Google Scholar 

  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 83:888–894

    Article  CAS  Google Scholar 

  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 34:586–592

    Article  CAS  Google Scholar 

  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 46:230–237

    Article  CAS  Google Scholar 

  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 50:147–150

    Google Scholar 

  22. Sandhu MS, Casale TB (2010) The role of vitamin D in asthma. Ann Allergy Asthma Immunol 105:191–199 quiz 200-192, 217

    Article  CAS  Google Scholar 

  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 81:19–25

    Article  Google Scholar 

  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 174:91–95

    Article  Google Scholar 

  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 44:348–350

    Article  CAS  Google Scholar 

  26. Benzie IF, Strain JJ (1996) The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem 239:70–76

    Article  CAS  Google Scholar 

  27. Beutler E, Gelbart T (1985) Plasma glutathione in health and in patients with malignant disease. J Lab Clin Med 105:581–584

    CAS  Google Scholar 

  28. Janero DR (1990) Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radic Biol Med 9:515–540

    Article  CAS  Google Scholar 

  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 4:108–116

    Article  Google Scholar 

  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 30:1287–1293

    Article  CAS  Google Scholar 

  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 82:885–891

    Article  CAS  Google Scholar 

  32. Kotsa K, Yavropoulou MP, Anastasiou O, Yovos JG (2009) Role of vitamin D treatment in glucose metabolism in polycystic ovary syndrome. Fertil Steril 92:1053–1058

    Article  CAS  Google Scholar 

  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 280:559–563

    Article  Google Scholar 

  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 161:575–582

    Article  CAS  Google Scholar 

  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 60:1475–1481

    Article  CAS  Google Scholar 

  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 92:2017–2029

    Article  CAS  Google Scholar 

  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 20:227–232

    Article  CAS  Google Scholar 

  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 18:85–88

    Article  Google Scholar 

  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 119:627–632

    Article  CAS  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. doi:10.2174/1381612823666170525153605

  41. Kim J, Ahn J (2014) Effect of zinc supplementation on inflammatory markers and adipokines in young obese women. Biol Trace Elem Res 157:101–106

    Article  Google Scholar 

  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 28:194–199

    Article  CAS  Google Scholar 

  43. Jialal I, Devaraj S, Venugopal SK (2004) C-reactive protein: risk marker or mediator in atherothrombosis? Hypertension 44:6–11

    Article  CAS  Google Scholar 

  44. Wellen KE, Hotamisligil GS (2005) Inflammation, stress, and diabetes. J Clin Invest 115:1111–1119

    Article  CAS  Google Scholar 

  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 174:119–130

    Article  CAS  Google Scholar 

  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 91:1634–1641

    Article  CAS  Google Scholar 

  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 55:186–210

    CAS  Google Scholar 

  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 57:279–286

    Article  CAS  Google Scholar 

  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 23:180–184

    Article  CAS  Google Scholar 

  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 27:89–95

    Article  CAS  Google Scholar 

  51. Hyderali BN, Mala K (2015) Oxidative stress and cardiovascular complications in polycystic ovarian syndrome. Eur J Obstet Gynecol Reprod Biol 191:15–22

    Article  CAS  Google Scholar 

  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 48:84–89

    Article  CAS  Google Scholar 

  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 57:437–443

    Article  CAS  Google Scholar 

  54. Powell SR (2000) The antioxidant properties of zinc. J Nutr 130:1447S–1454S

    Article  CAS  Google Scholar 

  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–E421

    CAS  Google Scholar 

  56. Ermak G, Davies KJ (2002) Calcium and oxidative stress: from cell signaling to cell death. Mol Immunol 38:713–721

    Article  CAS  Google Scholar 

  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 437:7–11

    Article  CAS  Google Scholar 

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Acknowledgements

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

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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.

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Correspondence to Zatollah Asemi.

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Maktabi, M., Jamilian, M. & Asemi, Z. RETRACTED ARTICLE: 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 (2018). https://doi.org/10.1007/s12011-017-1085-0

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