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Antioxidant Therapy for the Enhancement of Male Reproductive Health: A Critical Review of the Literature

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Male Infertility

Abstract

Oxidative stress is a well-established cause of male infertility. Reactive oxygen species (ROS) are present at higher concentrations in infertile men’s semen and have been conclusively shown to impair sperm function through oxidative damage to the sperm membrane and paternal DNA. It, therefore, would appear logical that amelioration of oxidative stress through the use of antioxidant therapy could improve infertile men’s sperm function, potentially leading to better reproductive performance. In this chapter, we critically analyse the published studies that have used in vivo antioxidant therapy to treat male infertility. Overall, there is reasonably good evidence that some antioxidant therapies can significantly reduce oxidative damage to sperm DNA and improve sperm membrane function (motility and sperm fertilization capacity). However, what is more contentious is whether these improvements in sperm quality actually translate into an increase in pregnancy rates or an improvement in pregnancy outcomes for infertile couples. While a few small studies have shown antioxidant therapy to assist both in vivo and in vitro conception, larger more definitive studies will be required before antioxidant therapy becomes established medical practice for infertile males.

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References

  1. Carlsen E, Giwercman A, Keiding N, Skakkebaek NE. Evidence for decreasing quality of semen during past 50 years. BMJ. 1992;305(6854):609–13.

    Article  PubMed  CAS  Google Scholar 

  2. Auger J, Kunstmann JM, Czyglik F, Jouannet P. Decline in semen quality among fertile men in Paris during the past 20 years. N Engl J Med. 1995;332(5):281–5.

    Article  PubMed  CAS  Google Scholar 

  3. MacLeod J. The role of oxygen in the metabolism and motility of human spermatozoa. Am J Physiol. 1943;138:512–8.

    CAS  Google Scholar 

  4. Tremellen K. Oxidative stress and male infertility—a clinical perspective. Hum Reprod Update. 2008;14(3):243–58.

    Article  PubMed  CAS  Google Scholar 

  5. Agarwal A, Nallella KP, Allamaneni SS, Said TM. Role of antioxidants in treatment of male infertility: an overview of the literature. Reprod Biomed Online. 2004;8(6):616–27.

    Article  PubMed  CAS  Google Scholar 

  6. Lanzafame FM, La Vignera S, Vicari E, Calogero AE. Oxidative stress and medical antioxidant treatment in male infertility. Reprod Biomed Online. 2009;19(5):638–59.

    Article  PubMed  CAS  Google Scholar 

  7. Panel of Dietary Antioxidants and Related Compounds, Food and Nutrition Board, Institute of Medicine. Dietary reference intakes for vitamin C, vitamin E, selenium and crotenoids. Washington, DC: National Academy Press; 2000.

    Google Scholar 

  8. Miller 3rd ER, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005;142(1):37–46.

    PubMed  CAS  Google Scholar 

  9. Geva E, Bartoov B, Zabludovsky N, Lessing JB, Lerner-Geva L, Amit A. The effect of antioxidant treatment on human spermatozoa and fertilization rate in anin vitro fertilization program. Fertil Steril. 1996;66(3):430–4.

    PubMed  CAS  Google Scholar 

  10. Suleiman SA, Ali ME, Zaki ZM, el-Malik EM, Nasr MA. Lipid peroxidation and human sperm motility: protective role of vitamin E. J Androl. 1996;17(5):530–7.

    PubMed  CAS  Google Scholar 

  11. Kessopoulou E, Powers HJ, Sharma KK, Pearson MJ, Russell JM, Cooke ID, Barratt CL. A double-blind randomized placebo cross-over controlled trial using the antioxidant vitamin E to treat reactive oxygen species associated male infertility. Fertil Steril. 1995;64(4):825–31.

    PubMed  CAS  Google Scholar 

  12. Moilanen J, Hovatta O. Excretion of alpha-tocopherol into human seminal plasma after oral administration. Andrologia. 1995;27(3):133–6.

    Article  PubMed  CAS  Google Scholar 

  13. Giovenco P, Amodei M, Barbieri C, Fasani R, Carosi M, Dondero F. Effects of kallikrein on the male reproductive system and its use in the treatment of idiopathic oligozoospermia with impaired motility. Andrologia. 1987;19:238–41.

    Article  PubMed  Google Scholar 

  14. Jacob RA, Pianalto FS, Agee RE. Cellular ascorbate depletion in healthy men. J Nutr. 1992;122(5):1111–8.

    PubMed  CAS  Google Scholar 

  15. Wayner DD, Burton GW, Ingold KU. The antioxidant efficiency of vitamin C is concentration-dependent. Biochim Biophys Acta. 1986;884(1):119–23.

    Article  PubMed  CAS  Google Scholar 

  16. Dawson EB, Harris WA, Rankin WE, Charpentier LA, McGanity WJ. Effect of ascorbic acid on male fertility. Ann N Y Acad Sci. 1987;498:312–23.

    Article  PubMed  CAS  Google Scholar 

  17. Dawson EB, Harris WA, Teter MC, Powell LC. Effect of ascorbic acid supplementation on the sperm quality of smokers. Fertil Steril. 1992;58(5):1034–9.

    PubMed  CAS  Google Scholar 

  18. Rolf C, Cooper TG, Yeung CH, Nieschlag E. Antioxidant treatment of patients with asthenozoospermia or moderate oligoasthenozoospermia with high-dose vitamin C and vitamin E: a randomized, placebo-controlled, double-blind study. Hum Reprod. 1999;14(4):1028–33.

    Article  PubMed  CAS  Google Scholar 

  19. Greco E, Iacobelli M, Rienzi L, Ubaldi F, Ferrero S, Tesarik J. Reduction of the incidence of sperm DNA fragmentation by oral antioxidant treatment. J Androl. 2005;26(3):349–53.

    Article  PubMed  CAS  Google Scholar 

  20. Greco E, Romano S, Iacobelli M, Ferrero S, Baroni E, Minasi MG, Ubaldi F, Rienzi L, Tesarik J. ICSI in cases of sperm DNA damage: beneficial effect of oral antioxidant treatment. Hum Reprod. 2005;20(9):2590–4.

    Article  PubMed  CAS  Google Scholar 

  21. Kodama H, Yamaguchi R, Fukuda J, Kasai H, Tanaka T. Increased oxidative deoxyribonucleic acid damage in the spermatozoa of infertile male patients. Fertil Steril. 1997;68(3):519–24.

    Article  PubMed  CAS  Google Scholar 

  22. Ménézo YJ, Hazout A, Panteix G, Robert F, Rollet J, Cohen-Bacrie P, Chapuis F, Clément P, Benkhalifa M. Antioxidants to reduce sperm DNA fragmentation: an unexpected adverse effect. Reprod Biomed Online. 2007;14(4):418–21.

    Article  PubMed  Google Scholar 

  23. Omu AE, Al-Azemi MK, Kehinde EO, Anim JT, Oriowo MA, Mathew TC. Indications of the mechanisms involved in improved sperm parameters by zinc therapy. Med Princ Pract. 2008;17(2):108–16.

    Article  PubMed  CAS  Google Scholar 

  24. Lewin A, Lavon H. The effect of coenzyme Q10 on sperm motility and function. Mol Aspects Med. 1997;18(Suppl):S213–9.

    Article  PubMed  CAS  Google Scholar 

  25. Safarinejad MR. Efficacy of coenzyme Q10 on semen parameters, sperm function and reproductive hormones in infertile men. J Urol. 2009;182(1):237–48.

    Article  PubMed  CAS  Google Scholar 

  26. Bleau G, Lemarbre J, Faucher G, Roberts KD, Chapdelaine A. Semen selenium and human fertility. Fertil Steril. 1984;42(6):890–4.

    PubMed  CAS  Google Scholar 

  27. Iwanier K, Zachara BA. Selenium supplementation enhances the element concentration in blood and seminal fluid but does not change the spermatozoal quality characteristics in subfertile men. J Androl. 1995;16(5):441–7.

    PubMed  CAS  Google Scholar 

  28. Scott R, MacPherson A, Yates RW, Hussain B, Dixon J. The effect of oral selenium supplementation on human sperm motility. Br J Urol. 1998;82(1):76–80.

    Article  PubMed  CAS  Google Scholar 

  29. Safarinejad MR, Safarinejad S. Efficacy of selenium and/or N-acetyl-cysteine for improving semen parameters in infertile men: a double-blind, placebo controlled, randomized study. J Urol. 2009;181(2):741–51.

    Article  PubMed  CAS  Google Scholar 

  30. Lenzi A, Culasso F, Gandini L, Lombardo F, Dondero F. Placebo-controlled, double-blind, cross-over trial of glutathione therapy in male infertility. Hum Reprod. 1993;8(10):1657–62.

    PubMed  CAS  Google Scholar 

  31. Lenzi A, Picardo M, Gandini L, Lombardo F, Terminali O, Passi S, Dondero F. Glutathione treatment of dyspermia: effect on the lipoperoxidation process. Hum Reprod. 1994;9(11):2044–50.

    PubMed  CAS  Google Scholar 

  32. Costa M, Canale D, Filicori M, D’lddio S, Lenzi A. l-carnitine in idiopathic asthenozoospermia: a multicenter study. Italian Study Group on Carnitine and Male Infertility. Andrologia. 1994;26(3):155–9.

    Article  PubMed  CAS  Google Scholar 

  33. Lenzi A, Lombardo F, Sgrò P, Salacone P, Caponecchia L, Dondero F, Gandini L. Use of carnitine therapy in selected cases of male factor infertility: a double-blind crossover trial. Fertil Steril. 2003;79(2):292–300.

    Article  PubMed  Google Scholar 

  34. Vicari E, La Vignera S, Calogero AE. Antioxidant treatment with carnitines is effective in infertile patients with prostatovesiculoepididymitis and elevated seminal leukocyte concentrations after treatment with nonsteroidal anti-inflammatory compounds. Fertil Steril. 2002;78(6):1203–8.

    Article  PubMed  Google Scholar 

  35. Paradiso Galatioto G, Gravina GL, Angelozzi G, Sacchetti A, Innominato PF, Pace G, Ranieri G, Vicentini C. May antioxidant therapy improve sperm parameters of men with persistent oligospermia after retrograde embolization for varicocele? World J Urol. 2008;26(1):97–102.

    Article  PubMed  CAS  Google Scholar 

  36. Ciftci H, Verit A, Savas M, Yeni E, Erel O. Effects of N-acetylcysteine on semen parameters and oxidative/antioxidant status. Urology. 2009;74(1):73–6.

    Article  PubMed  Google Scholar 

  37. Comhaire FH, El Garem Y, Mahmoud A, Eertmans F, Schoonjans F. Combined conventional/antioxidant “Astaxanthin” treatment for male infertility: a double blind, randomized trial. Asian J Androl. 2005;7(3):257–62.

    Article  PubMed  CAS  Google Scholar 

  38. Gupta NP, Kumar R. Lycopene therapy in idiopathic male infertility—a preliminary report. Int Urol Nephrol. 2002;34(3):369–72.

    Article  PubMed  CAS  Google Scholar 

  39. Keskes-Ammar L, Feki-Chakroun N, Rebai T, Sahnoun Z, Ghozzi H, Hammami S, Zghal K, Fki H, Damak J, Bahloul A. Sperm oxidative stress and the effect of an oral vitamin E and selenium supplement on semen quality in infertile men. Arch Androl. 2003;49(2):83–94.

    Article  PubMed  CAS  Google Scholar 

  40. Piomboni P, Gambera L, Serafini F, Campanella G, Morgante G, De Leo V. Sperm quality improvement after natural anti-oxidant treatment of asthenoteratospermic men with leukocytospermia. Asian J Androl. 2008;10(2):201–6.

    Article  PubMed  Google Scholar 

  41. Comhaire FH, Christophe AB, Zalata AA, Dhooge WS, Mahmoud AM, Depuydt CE. The effects of combined conventional treatment, oral antioxidants and essential fatty acids on sperm biology in subfertile men. Prostaglandins Leukot Essent Fatty Acids. 2000;63(3):159–65.

    Article  PubMed  CAS  Google Scholar 

  42. Gil-Villa AM, Cardona-Maya W, Agarwal A, Sharma R, Cadavid A. Role of male factor in early recurrent embryo loss: do antioxidants have any effect? Fertil Steril. 2009;92(2):565–71.

    Article  PubMed  Google Scholar 

  43. Tunc O, Thompson J, Tremellen K. Improvement in sperm DNA quality using an oral antioxidant therapy. Reprod Biomed Online. 2009;18(6):761–8.

    Article  PubMed  CAS  Google Scholar 

  44. Tremellen K, Miari G, Froiland D, Thompson J. A randomised control trial examining the effect of an antioxidant (Menevit) on pregnancy outcome during IVF-ICSI treatment. Aust N Z J Obstet Gynaecol. 2007;47(3):216–21.

    Article  PubMed  Google Scholar 

  45. Tunc O, Tremellen K. Oxidative DNA damage impairs global sperm DNA methylation in infertile men. J Assist Reprod Genet. 2009;26(9–10):537–44.

    Article  PubMed  Google Scholar 

  46. Zini A, Boman JM, Belzile E, Ciampi A. Sperm DNA damage is associated with an increased risk of pregnancy loss after IVF and ICSI: systematic review and meta-analysis. Hum Reprod. 2008;23(12):2663–8.

    Article  PubMed  CAS  Google Scholar 

  47. Aitken RJ, Koopman P, Lewis SE. Seeds of concern. Nature. 2004;432(7013):48–52.

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. School of Pharmacy and Medical Sciences, University of South Australia, Repromed, 180 Fullarton Road, Dulwich, SA, 5065, Australia

    Kelton Tremellen MBBS (Hons.), PhD, FRANZCOG, CREI

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  1. Kelton Tremellen MBBS (Hons.), PhD, FRANZCOG, CREI
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Correspondence to Kelton Tremellen MBBS (Hons.), PhD, FRANZCOG, CREI .

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Editors and Affiliations

  1. University of Florida, Director, Robotic Surgery, Winter Haven Hospital &, 200 Avenue F. N.E., Winter Haven, 33881, Florida, USA

    Sijo J. Parekattil

  2. Center for Reproductive Medicine, Department of Urology, Cleveland Clinic, Euclid Avenue 9500, Cleveland, 44195, Ohio, USA

    Ashok Agarwal

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Tremellen, K. (2012). Antioxidant Therapy for the Enhancement of Male Reproductive Health: A Critical Review of the Literature. In: Parekattil, S., Agarwal, A. (eds) Male Infertility. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3335-4_37

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  • DOI: https://doi.org/10.1007/978-1-4614-3335-4_37

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  • Print ISBN: 978-1-4614-3334-7

  • Online ISBN: 978-1-4614-3335-4

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