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Effects of Selenium Supplementation on Asymmetric Dimethylarginine and Cardiometabolic Risk Factors in Patients with Polycystic Ovary Syndrome

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Abstract

Polycystic ovary syndrome (PCOS) is characterized by various reproductive and cardiometabolic disorders. Asymmetric dimethylarginine (ADMA) is associated with cardiovascular, metabolic, and hormonal status. Selenium, a micronutrient with antioxidant properties, could affect multiple physiological pathways. This study aimed to investigate the effect of selenium supplementation on ADMA, cardiometabolic risk factors, and hormonal status in women with PCOS. In this randomized, double-blind, placebo-controlled clinical trial, 66 women with PCOS, aged 18–45 years, were randomly assigned to receive either 200 μg/day selenium or placebo, for 12 weeks. Circulating concentrations of ADMA, testosterone, sex hormone-binding globulin (SHBG), lipid profiles, and glycemic parameters were assessed at baseline and following supplementation. ADMA concentration decreased significantly compared to baseline values (85.14 ± 75 to 56.4 ± 38.64 ng/l, p = 0.02) in the selenium group. This change was marginally significant compared with the placebo group (28.74 ± 68.63 vs. − 1.77 ± 52.88 ng/l, p = 0.056). Serum testosterone levels declined significantly in the intervention compared to the placebo group (0.01 ± 0.17 vs. − 0.08 ± 0.18 ng/ml, p = 0.038). Pre- to post-Apo-B100/Apo-A1 ratio declined considerably in the intervention group (0.72 ± 0.16 to 0.65 ± 0.16, p = 0.003). No further differences were observed in SHBG, lipid profiles, Apo-A1, Apo-B100, Apo-B100/Apo-A1 ratio, and glycemic control between the two groups at the end of the study. Selenium supplementation for 12 weeks had beneficial effects on reduction of circulating ADMA and total testosterone levels in women with PCOS. No significant improvements were seen in other cardiometabolic risk factors. The effects of selenium supplementation on hormonal, reproductive, and cardiometabolic disorders, considering the potential mediating role of ADMA, should be further investigated.

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References

  1. McGowan MP (2011) Polycystic ovary syndrome: a common endocrine disorder and risk factor for vascular disease. Current treatment options in cardiovascular medicine 13(4):289–301

    Article  PubMed  Google Scholar 

  2. Rojas J, Chávez M, Olivar L, Rojas M, Morillo J, Mejías J, Calvo M (2014) Bermúdez V (2014) Polycystic ovary syndrome, insulin resistance, and obesity: navigating the pathophysiologic labyrinth. International journal of reproductive medicine

  3. Orio F, Muscogiuri G, Nese C, Palomba S, Savastano S, Tafuri D, Colarieti G, La Sala G, Colao A, Yildiz BO (2016) Obesity, type 2 diabetes mellitus and cardiovascular disease risk: an update in the management of polycystic ovary syndrome. European Journal of Obstetrics & Gynecology and Reproductive Biology 207:214–219

    Article  Google Scholar 

  4. Paradisi G, Steinberg HO, Hempfling A, Cronin J, Hook G, Shepard MK, Baron AD (2001) Polycystic ovary syndrome is associated with endothelial dysfunction. Circulation 103(10):1410–1415

    Article  CAS  PubMed  Google Scholar 

  5. Sibal L, C Agarwal S, D Home P, H Boger R (2010) The role of asymmetric dimethylarginine (ADMA) in endothelial dysfunction and cardiovascular disease. Curr Cardiol Rev 6 (2):82–90

  6. Koleva D, Orbetzova M, Deneva T (2014) Asymmetric dimethylarginine in women with metabolic syndrome and polycystic ovary syndrome. Endocrinologia 19(3):154–159

    Google Scholar 

  7. Mohamadin AM, Habib FA, Al-Saggaf AA (2010) Cardiovascular disease markers in women with polycystic ovary syndrome with emphasis on asymmetric dimethylarginine and homocysteine. Annals of Saudi medicine 30(4):278–283

    Article  PubMed  PubMed Central  Google Scholar 

  8. Sciacqua A, Grillo N, Quero M, Sesti G, Perticone F (2012) Asymmetric dimethylarginine plasma levels and endothelial function in newly diagnosed type 2 diabetic patients. Int J Mol Sci 13(11):13804–13815

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kurtoglu E, Balta S, Sincer I, Altas Y, Atas H, Yılmaz M, Korkmaz H, Erdem K, Akturk E, Demirkol S (2014) Comparision of effects of rosuvastatin versus atorvastatin treatment on plasma levels of asymmetric dimethylarginine in patients with hyperlipidemia having coronary artery disease. Angiology 65(9):788–793

    Article  CAS  PubMed  Google Scholar 

  10. Mangiacapra F, Conte M, Demartini C, Muller O, Delrue L, Dierickx K, Di Sciascio G, Trimarco B, De Bruyne B, Wijns W (2016) Relationship of asymmetric dimethylarginine (ADMA) with extent and functional severity of coronary atherosclerosis. Int J Cardiol 220:629–633

    Article  PubMed  Google Scholar 

  11. Hafner F, Kieninger A, Meinitzer A, Gary T, Froehlich H, Haas E, Hackl G, Eller P, Brodmann M, Seinost G (2014) Endothelial dysfunction and brachial intima-media thickness: long term cardiovascular risk with claudication related to peripheral arterial disease: a prospective analysis. PLoS One 9(4):e93357

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Alipoor E, Hosseinzadeh FM, Hosseinzadeh-Attar MJ (2018) Adipokines in critical illness: a review of the evidence and knowledge gaps. Biomed Pharmacother 108:1739–1750

    Article  CAS  PubMed  Google Scholar 

  13. Heutling D, Schulz H, Nickel I, Kleinstein J, Kaltwasser P, Westphal S, Mittermayer F, Wolzt M, Krzyzanowska K, Randeva H (2008) Asymmetrical dimethylarginine, inflammatory and metabolic parameters in women with polycystic ovary syndrome before and after metformin treatment. The Journal of Clinical Endocrinology & Metabolism 93(1):82–90

    Article  CAS  Google Scholar 

  14. Bodis J, Várnagy A, Sulyok E, Kovács G, Martens-Lobenhoffer J, Bode-Böger S (2010) Negative association of L-arginine methylation products with oocyte numbers. Hum Reprod 25(12):3095–3100

    Article  CAS  PubMed  Google Scholar 

  15. Shukovski L, Tsafriri A (1994) The involvement of nitric oxide in the ovulatory process in the rat. Endocrinology 135(5):2287–2290

    Article  CAS  PubMed  Google Scholar 

  16. Di Tucci C, Di Feliciantonio M, Vena F, Capone C, Schiavi MC, Pietrangeli D, Muzii L, Benedetti Panici P (2018) Alpha lipoic acid in obstetrics and gynecology. Gynecol Endocrinol 34(9):729–733

    Article  PubMed  CAS  Google Scholar 

  17. Khorshidi M, Moini A, Alipoor E, Rezvan N, Gorgani-Firuzjaee S, Yaseri M, Hosseinzadeh-Attar MJ (2018) The effects of quercetin supplementation on metabolic and hormonal parameters as well as plasma concentration and gene expression of resistin in overweight or obese women with polycystic ovary syndrome. Phytother Res 32(11):2282–2289

    Article  CAS  PubMed  Google Scholar 

  18. Junior EL, Leite HP, Konstantyner T (2019) Selenium and selenoproteins: from endothelial cytoprotection to clinical outcomes. Transl Res

  19. Luo Y, Yue W, Quan X, Wang Y, Zhao B, Lu Z (2015) Asymmetric dimethylarginine exacerbates Aβ-induced toxicity and oxidative stress in human cell and Caenorhabditis elegans models of Alzheimer disease. Free Radic Biol Med 79:117–126

    Article  CAS  PubMed  Google Scholar 

  20. Landim MBP, Casella Filho A, Chagas ACP (2009) Asymmetric dimethylarginine (ADMA) and endothelial dysfunction: implications for atherogenesis. Clinics 64(5):471–478

    Article  PubMed  PubMed Central  Google Scholar 

  21. Benstoem C, Goetzenich A, Kraemer S, Borosch S, Manzanares W, Hardy G, Stoppe C (2015) Selenium and its supplementation in cardiovascular disease—what do we know? Nutrients 7(5):3094–3118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Flores-Mateo G, Navas-Acien A, Pastor-Barriuso R, Guallar E (2006) Selenium and coronary heart disease: a meta-analysis. Am J Clin Nutr 84(4):762–773

    Article  CAS  PubMed  Google Scholar 

  23. Spritzer PM, Lecke SB, Fabris VC, Ziegelmann PK, Amaral L (2017) Blood trace element concentrations in polycystic ovary syndrome: systematic review and meta-analysis. Biol Trace Elem Res 175(2):254–262

    Article  CAS  PubMed  Google Scholar 

  24. Razavi M, Jamilian M, Kashan ZF, Heidar Z, Mohseni M, Ghandi Y, Bagherian T, Asemi Z (2016) Selenium supplementation and the effects on reproductive outcomes, biomarkers of inflammation, and oxidative stress in women with polycystic ovary syndrome. Horm Metab Res 48(03):185–190

    Article  CAS  PubMed  Google Scholar 

  25. Jamilian M, Mansury S, Bahmani F, Heidar Z, Amirani E, Asemi Z (2018) The effects of probiotic and selenium co-supplementation on parameters of mental health, hormonal profiles, and biomarkers of inflammation and oxidative stress in women with polycystic ovary syndrome. Journal of ovarian research 11(1):80

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. 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(6):885–891

    Article  CAS  Google Scholar 

  27. Puchau B, Zulet MA, Urtiaga G, Navarro-Blasco Í, Martínez JA (2009) Asymmetric dimethylarginine association with antioxidants intake in healthy young adults: a role as an indicator of metabolic syndrome features. Metabolism 58(10):1483–1488

    Article  CAS  PubMed  Google Scholar 

  28. Hosseinzadeh FM, Hosseinzadeh-Attar MJ, Yekaninejad MS, Rashidi B (2016) Effects of selenium supplementation on glucose homeostasis and free androgen index in women with polycystic ovary syndrome: a randomized, double blinded, placebo controlled clinical trial. J Trace Elem Med Biol 34:56–61

    Article  CAS  Google Scholar 

  29. Zhang X, Liu C, Guo J, Song Y (2016) Selenium status and cardiovascular diseases: meta-analysis of prospective observational studies and randomized controlled trials. Eur J Clin Nutr 70(2):162

    Article  CAS  PubMed  Google Scholar 

  30. Oztürk Z, Gurpinar T, Vural K, Boyacıoglu S, Korkmaz M, Var A (2015) Effects of selenium on endothelial dysfunction and metabolic profile in low dose streptozotocin induced diabetic rats fed a high fat diet. Biotech Histochem 90(7):506–515

    Article  PubMed  CAS  Google Scholar 

  31. Leiper J, Nandi M (2011) The therapeutic potential of targeting endogenous inhibitors of nitric oxide synthesis. Nat Rev Drug Discov 10(4):277–291

    Article  CAS  PubMed  Google Scholar 

  32. Murphy R, Tommasi S, Lewis B, Mangoni A (2016) Inhibitors of the hydrolytic enzyme dimethylarginine dimethylaminohydrolase (DDAH): discovery, synthesis and development. Molecules 21(5):615

    Article  PubMed Central  CAS  Google Scholar 

  33. Fan N-C, Tsai C-M, Hsu C-N, Huang L-T (2013) Tain Y-L (2013) N-acetylcysteine prevents hypertension via regulation of the ADMA-DDAH pathway in young spontaneously hypertensive rats. Biomed Res Int

  34. Lu C-W, Lin Y, Lei Y-P, Wang L, He Z-M, Xiong Y (2017) Pyrrolidine dithiocarbamate ameliorates endothelial dysfunction in thoracic aorta of diabetic rats by preserving vascular DDAH activity. PLoS One 12(7):e0179908

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Jiang J-L, Zhang X-H, Li N-S, Rang W-Q, Hu C-P, Li Y-J, Deng H-W (2006) Probucol decreases asymmetrical dimethylarginine level by alternation of protein arginine methyltransferase I and dimethylarginine dimethylaminohydrolase activity. Cardiovasc Drugs Ther 20(4):281–294

    Article  CAS  PubMed  Google Scholar 

  36. Morales Y, Nitzel DV, Price OM, Gui S, Li J, Qu J, Hevel JM (2015) Redox control of protein arginine methyltransferase 1 (PRMT1) activity. J Biol Chem 290(24):14915–14926

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Teerlink T (2005) ADMA metabolism and clearance. Vasc med 10 (1_suppl):S73-S81

  38. Azziz R, Sanchez L, Knochenhauer E, Moran C, Lazenby J, Stephens K, Taylor K, Boots L (2004) Androgen excess in women: experience with over 1000 consecutive patients. The Journal of Clinical Endocrinology & Metabolism 89(2):453–462

    Article  CAS  Google Scholar 

  39. Kumarendran B, O’Reilly MW, Manolopoulos KN, Toulis KA, Gokhale KM, Sitch AJ, Wijeyaratne CN, Coomarasamy A, Arlt W, Nirantharakumar K (2018) Polycystic ovary syndrome, androgen excess, and the risk of nonalcoholic fatty liver disease in women: a longitudinal study based on a United Kingdom primary care database. PLoS Med 15(3):e1002542

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Coskun A, Arikan T, Kilinc M, Arikan DC, Ekerbiçer HÇ (2013) Plasma selenium levels in Turkish women with polycystic ovary syndrome. European Journal of Obstetrics & Gynecology and Reproductive Biology 168(2):183–186

    Article  CAS  Google Scholar 

  41. González F, Sia CL, Shepard MK, Rote NS, Minium J (2012) Hyperglycemia-induced oxidative stress is independent of excess abdominal adiposity in normal-weight women with polycystic ovary syndrome. Hum Reprod 27(12):3560–3568

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Dube R (2016) Does endothelial dysfunction correlate with endocrinal abnormalities in patients with polycystic ovary syndrome? Avicenna journal of medicine 6(4):91–102

    Article  PubMed  PubMed Central  Google Scholar 

  43. Diamanti-Kandarakis E, Alexandraki K, Piperi C, Protogerou A, Katsikis I, Paterakis T, Lekakis J, Panidis D (2006) Inflammatory and endothelial markers in women with polycystic ovary syndrome. Eur J Clin Investig 36(10):691–697

    Article  CAS  Google Scholar 

  44. Amiri M, Golsorkhtabaramiri M, Esmaeilzadeh S, Ghofrani F, Bijani A, Ghorbani L, Delavar MA (2014) Effect of metformin and flutamide on anthropometric indices and laboratory tests in obese/overweight PCOS women under hypocaloric diet. Journal of reproduction & infertility 15(4):205–213

    Google Scholar 

  45. Rosselli M, Keller R, Dubey RK (1998) Role of nitric oxide in the biology, physiology and pathophysiology of reproduction. Hum Reprod Update 4(1):3–24

    Article  CAS  PubMed  Google Scholar 

  46. Yin Q, Chen X, Li L, Zhou R, Huang J, Yang D (2013) Apolipoprotein B/apolipoprotein A1 ratio is a good predictive marker of metabolic syndrome and pre-metabolic syndrome in Chinese adolescent women with polycystic ovary syndrome. J Obstet Gynaecol Res 39(1):203–209

    Article  PubMed  CAS  Google Scholar 

  47. Alizadeh M, Safaeiyan A, Ostadrahimi A, Estakhri R, Daneghian S, Ghaffari A, Gargari BP (2012) Effect of L-arginine and selenium added to a hypocaloric diet enriched with legumes on cardiovascular disease risk factors in women with central obesity: a randomized, double-blind, placebo-controlled trial. Ann Nutr Metab 60(2):157–168

    Article  CAS  PubMed  Google Scholar 

  48. Rayman MP, Stranges S, Griffin BA, Pastor-Barriuso R, Guallar E (2011) Effect of supplementation with high-selenium yeast on plasma lipids: a randomized trial. Ann Intern Med 154(10):656–665

    Article  PubMed  Google Scholar 

  49. Hasani M, Djalalinia S, Sharifi F, Varmaghani M, Zarei M, Abdar ME, Asayesh H, Noroozi M, Kasaeian A, Gorabi AM (2018) Effect of selenium supplementation on lipid profile: a systematic review and meta-analysis. Horm Metab Res 50(10):715–727

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The present study was supported by Tehran University of Medical Sciences and Health Services grant 26211.

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Authors and Affiliations

  1. Vali-E-Asr Reproductive Health Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Batool Hossein Rashidi

  2. Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, No#44, Hojjatdoust St., Naderi St., Keshavarz Blvd, Tehran, 141556117, Iran

    Fatemeh Mohammad Hosseinzadeh, Somayyeh Asghari & Mohammad Javad Hosseinzadeh-Attar

  3. Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran

    Elham Alipoor

  4. Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

    Mir Saeed Yekaninejad

  5. Cardiac Primary Prevention Research Center (CPPRC), Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran

    Mohammad Javad Hosseinzadeh-Attar

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  1. Batool Hossein Rashidi
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  2. Fatemeh Mohammad Hosseinzadeh
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Correspondence to Mohammad Javad Hosseinzadeh-Attar.

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The study protocol was approved by the ethics committee of Tehran University of Medical Sciences and conducted according to the guidelines of the Declaration of Helsinki.

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Rashidi, B.H., Mohammad Hosseinzadeh, F., Alipoor, E. et al. Effects of Selenium Supplementation on Asymmetric Dimethylarginine and Cardiometabolic Risk Factors in Patients with Polycystic Ovary Syndrome. Biol Trace Elem Res 196, 430–437 (2020). https://doi.org/10.1007/s12011-019-01954-6

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