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

Chapter
First Online:

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.

Keywords

In vivo antioxidant therapy Male infertility Impaired sperm function Oxidative damage to sperm Reactive oxygen species Oxidative stress Antioxidant supplementation Antioxidant trials 
This is a preview of subscription content, log in to check access.

References

  1. 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.PubMedCrossRefGoogle Scholar
  2. 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.PubMedCrossRefGoogle Scholar
  3. 3.
    MacLeod J. The role of oxygen in the metabolism and motility of human spermatozoa. Am J Physiol. 1943;138:512–8.Google Scholar
  4. 4.
    Tremellen K. Oxidative stress and male infertility—a clinical perspective. Hum Reprod Update. 2008;14(3):243–58.PubMedCrossRefGoogle Scholar
  5. 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.PubMedCrossRefGoogle Scholar
  6. 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.PubMedCrossRefGoogle Scholar
  7. 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. 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.PubMedGoogle Scholar
  9. 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.PubMedGoogle Scholar
  10. 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.PubMedGoogle Scholar
  11. 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.PubMedGoogle Scholar
  12. 12.
    Moilanen J, Hovatta O. Excretion of alpha-tocopherol into human seminal plasma after oral administration. Andrologia. 1995;27(3):133–6.PubMedCrossRefGoogle Scholar
  13. 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.PubMedCrossRefGoogle Scholar
  14. 14.
    Jacob RA, Pianalto FS, Agee RE. Cellular ascorbate depletion in healthy men. J Nutr. 1992;122(5):1111–8.PubMedGoogle Scholar
  15. 15.
    Wayner DD, Burton GW, Ingold KU. The antioxidant efficiency of vitamin C is concentration-dependent. Biochim Biophys Acta. 1986;884(1):119–23.PubMedCrossRefGoogle Scholar
  16. 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.PubMedCrossRefGoogle Scholar
  17. 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.PubMedGoogle Scholar
  18. 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.PubMedCrossRefGoogle Scholar
  19. 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.PubMedCrossRefGoogle Scholar
  20. 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.PubMedCrossRefGoogle Scholar
  21. 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.PubMedCrossRefGoogle Scholar
  22. 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.PubMedCrossRefGoogle Scholar
  23. 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.PubMedCrossRefGoogle Scholar
  24. 24.
    Lewin A, Lavon H. The effect of coenzyme Q10 on sperm motility and function. Mol Aspects Med. 1997;18(Suppl):S213–9.PubMedCrossRefGoogle Scholar
  25. 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.PubMedCrossRefGoogle Scholar
  26. 26.
    Bleau G, Lemarbre J, Faucher G, Roberts KD, Chapdelaine A. Semen selenium and human fertility. Fertil Steril. 1984;42(6):890–4.PubMedGoogle Scholar
  27. 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.PubMedGoogle Scholar
  28. 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.PubMedCrossRefGoogle Scholar
  29. 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.PubMedCrossRefGoogle Scholar
  30. 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.PubMedGoogle Scholar
  31. 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.PubMedGoogle Scholar
  32. 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.PubMedCrossRefGoogle Scholar
  33. 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.PubMedCrossRefGoogle Scholar
  34. 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.PubMedCrossRefGoogle Scholar
  35. 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.PubMedCrossRefGoogle Scholar
  36. 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.PubMedCrossRefGoogle Scholar
  37. 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.PubMedCrossRefGoogle Scholar
  38. 38.
    Gupta NP, Kumar R. Lycopene therapy in idiopathic male infertility—a preliminary report. Int Urol Nephrol. 2002;34(3):369–72.PubMedCrossRefGoogle Scholar
  39. 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.PubMedCrossRefGoogle Scholar
  40. 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.PubMedCrossRefGoogle Scholar
  41. 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.PubMedCrossRefGoogle Scholar
  42. 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.PubMedCrossRefGoogle Scholar
  43. 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.PubMedCrossRefGoogle Scholar
  44. 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.PubMedCrossRefGoogle Scholar
  45. 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.PubMedCrossRefGoogle Scholar
  46. 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.PubMedCrossRefGoogle Scholar
  47. 47.
    Aitken RJ, Koopman P, Lewis SE. Seeds of concern. Nature. 2004;432(7013):48–52.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.School of Pharmacy and Medical SciencesUniversity of South AustraliaDulwichAustralia

Personalised recommendations