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Male Infertility pp 845–854Cite as

Harmful Effects of Antioxidant Therapy

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Abstract

Oxidative stress has an integral role in the pathophysiology of most human diseases. With a rapidly aging population, increased attention and study have been directed toward the use of antioxidant therapy. The appeal is that these agents are considered “natural” substances and are associated with a healthy diet. The hypothesis has been that decreasing oxidative stress may prevent disease processes such as cancer or coronary heart disease. Since much of the general population are relatively healthy patients, it is critically important that these supplements are free of toxicity and side effects. While initial studies of antioxidant supplementation suggested a beneficial role in disease prevention, more recent clinical trials and a meta-analysis have questioned the benefit of these therapies. Several studies have suggested that excess supplementation may in fact be harmful. Recent attention has also focused on the use of antioxidants for the treatment of male infertility. The focus of this chapter is the potentially harmful effects of antioxidant therapy.

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References

  1. Halliwell B. Antioxidant defense mechanisms: from the beginning to the end (of the beginning). Free Radic Res. 1999;31:261–72.

    Article  CAS  PubMed  Google Scholar 

  2. Willcox JK, Ash SL, Catignani GL. Antioxidants and prevention of chronic disease. Crit Rev Food Sci Nutr. 2004;44:275–95.

    Article  CAS  PubMed  Google Scholar 

  3. Bjelakovic G, Nikolova D, Gluud LL, et al. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA. 2007;297:842–57.

    Article  CAS  PubMed  Google Scholar 

  4. Bjelakovic G, Nikolova D, Simonetti RG, Gluud C. Antioxidant supplements for preventing gastrointestinal cancers. Cochrane Database Syst Rev. 2004;1(4):CD004183.

    Google Scholar 

  5. Bjelakovic G, Nikolova D, Simonetti RG, Gluud C. Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet. 2004;364:1219–28.

    Article  CAS  PubMed  Google Scholar 

  6. Stanner SA, Hughes J, Kelly CN, Buttriss J. A review of the epidemiological evidence for the “antioxidant hypothesis”. Public Health Nutr. 2004;7:407–22.

    Article  CAS  PubMed  Google Scholar 

  7. Bjelakovic G, Nikolova D, Gluud LL, et al. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev. 2012;(3):CD007176. https://doi.org/10.1002/14651858.CD007176.pub2.

  8. Busetto GM, Agarwal A, Virmani A et al. Effect of metabolic and antioxidant supplementation on sperm parameters in oligo-astheno-teratozoospermia, with and without varicocele: a double-blind placebo-controlled study. Andrologia. 2018;50(3). doi: https://doi.org/10.1111/and.12927.

  9. Wang CC, Rogers MS. Oxidative stress and fetal hypoxia. In: Laszlo G, editor. Reactive oxygen species and disease. Trivandrum: Research Signpost; 2007. p. 257–82.

    Google Scholar 

  10. Halliwell B, Gutteridge JMC. Free radicals in biology and medicine. 2nd ed. Oxford: Clarendon Press; 1989.

    Google Scholar 

  11. Cadenas E. Biochemistry of oxygen toxicity. Annu Rev Biochem. 1989;58:79–110.

    Article  CAS  PubMed  Google Scholar 

  12. Boveris A, Chance B. The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen. Biochem J. 1973;134:707–16.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Chance B, Sies H, Boveris A. Hydroperoxide metabolism in mammalian organs. Physiol Rev. 1979;59:527–605.

    Article  CAS  PubMed  Google Scholar 

  14. Filomeni G, Rotilio G, Ciriolo MR. Disulfide relays and phosphorylative cascades: partners in redox-mediated signaling pathways. Cell Death Differ. 2005;12:1555–63.

    Article  CAS  PubMed  Google Scholar 

  15. Kalyanaraman B. Teaching the basics of redox biology to medical and graduate students: oxidants, antioxidants and disease mechanisms. Redox Biol. 2013;1:244–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. de Lamirande E, Gagnon C. A positive role for the superoxide anion in triggering hyperactivation and capacitation of human spermatozoa. Int J Androl. 1993;16:21–5.

    Article  PubMed  Google Scholar 

  17. O'Flaherty C, de Lamirande E, Gagnon C. Positive role of reactive oxygen species in mammalian sperm capacitation: triggering and modulation of phosphorylation events. Free Radic Biol Med. 2006;41:528–40.

    Article  CAS  PubMed  Google Scholar 

  18. Rehman I, Ahmad G, Alshahrani S. Lifestyle, environment, and male reproductive health: a lesson to learn. In: Sikka SC, WJG H, editors. Bioenvironmental issues affecting men's reproductive and sexual health. London, San Diego, Cambridge, Oxford: Academic Press; 2018. p. 157–71.

    Chapter  Google Scholar 

  19. Agarwal A, Prabakaran SA. Mechanism, measurement, and prevention of oxidative stress in male reproductive physiology. Indian J Exp Biol. 2005;43:963–74.

    CAS  PubMed  Google Scholar 

  20. Sikka SC. Relative impact of oxidative stress on male reproductive function. Curr Med Chem. 2001;8:851–62.

    Article  CAS  PubMed  Google Scholar 

  21. Garrido N, Meseguer M, Simon C, et al. Pro-oxidative and anti-oxidative imbalance in human semen and its relation with male fertility. Asian J Androl. 2004;6:59–65.

    CAS  PubMed  Google Scholar 

  22. Sies H. Oxidative stress: introductory remarks. In: Sies H, editor. Oxidative stress. London: Academic Press; 1985. p. 1–8.

    Google Scholar 

  23. Burcham PC. Genotoxic lipid peroxidation products: their DNA damaging properties and role in formation of endogenous DNA adducts. Mutagenesis. 1998;13:287–305.

    Article  CAS  PubMed  Google Scholar 

  24. Esterbauer H. Cytotoxicity and genotoxicity of lipid-oxidation products. Am J Clin Nutr. 1993;57(5 Suppl):779S–86S.

    Article  CAS  PubMed  Google Scholar 

  25. Luczaj W, Skrzydlewska E. DNA damage caused by lipid peroxidation products. Cell Mol Biol Lett. 2003;8:391–413.

    CAS  PubMed  Google Scholar 

  26. Sikka SC, Rajasekaran M, Hellstrom WJ. Role of oxidative stress and antioxidants in male infertility. J Androl. 1995;16:464–8.

    CAS  PubMed  Google Scholar 

  27. Riffo MS, Parraga M. Study of the acrosome reaction and the fertilizing ability of hamster epididymal cauda spermatozoa treated with antibodies against phospholipase A2 and/or lysophosphatidylcholine. J Exp Zool. 1996;275:459–68.

    Article  CAS  PubMed  Google Scholar 

  28. Makker K, Agarwal A, Sharma R. Oxidative stress & male infertility. Indian J Med Res. 2009;129:357–67.

    CAS  PubMed  Google Scholar 

  29. Wright C, Milne S, Leeson H. Sperm DNA damage caused by oxidative stress: modifiable clinical, lifestyle and nutritional factors in male infertility. Reprod Biomed Online. 2014;28:684–703.

    Article  CAS  PubMed  Google Scholar 

  30. Bisht S, Faiq M, Tolahunase M, Dada R. Oxidative stress and male infertility. Nat Rev Urol. 2017;14:470–85.

    Article  CAS  PubMed  Google Scholar 

  31. Agarwal A, Rana M, Qiu E, et al. Role of oxidative stress, infection and inflammation in male infertility. Andrologia. 2018;50(11):e13126. https://doi.org/10.1111/and.13126.

    Article  CAS  PubMed  Google Scholar 

  32. Greco E, Iacobelli M, Rienzi L, et al. Reduction of the incidence of sperm DNA fragmentation by oral antioxidant treatment. J Androl. 2005;26:349–53.

    Article  CAS  PubMed  Google Scholar 

  33. Abad C, Amengual MJ, Gosalvez J, et al. Effects of oral antioxidant treatment upon the dynamics of human sperm DNA fragmentation and subpopulations of sperm with highly degraded DNA. Andrologia. 2013;45:211–6.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  36. Ahmadi S, Bashiri R, Ghadiri-Anari A, Nadjarzadeh A. Antioxidant supplements and semen parameters: an evidence based review. Int J Reprod Biomed (Yazd). 2016;14:729–36.

    CAS  Google Scholar 

  37. Showell MG, Brown J, Yazdani A, et al. Antioxidants for male subfertility. Cochrane Database Syst Rev. 2011;(1):CD007411. https://doi.org/10.1002/14651858.CD007411.pub2.

  38. Huang C, Cao X, Pang D, et al. Is male infertility associated with increased oxidative stress in seminal plasma? A-meta analysis. Oncotarget. 2018;9:24494–513.

    PubMed  PubMed Central  Google Scholar 

  39. Garg H, Kumar R. An update on the role of medical treatment including antioxidant therapy in varicocele. Asian J Androl. 2016;18:222–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Majzoub A, Agarwal A. Antioxidant therapy in idiopathic oligoasthenoteratozoospermia. Ind J Urol. 2017;33:207–14.

    Article  Google Scholar 

  41. Alahmar AT. The effects of oral antioxidants on the semen of men with idiopathic oligoasthenoteratozoospermia. Clin Exp Reprod Med. 2018;45:57–66.

    Article  PubMed  PubMed Central  Google Scholar 

  42. 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;14:1028–33.

    Article  CAS  PubMed  Google Scholar 

  43. Silver EW, Eskenazi B, Evenson DP, et al. Effect of antioxidant intake on sperm chromatin stability in healthy nonsmoking men. J Androl. 2005;26:550–6.

    Article  CAS  PubMed  Google Scholar 

  44. Stenqvist A, Oleszczuk K, Leijonhufvud I, Giwercman A. Impact of antioxidant treatment on DNA fragmentation index: a double-blind placebo-controlled randomized trial. Andrology. 2018;6:811–6.

    Article  CAS  PubMed  Google Scholar 

  45. Kahn BE, Brannigan RE. Obesity and male infertility. Curr Opin Urol. 2017;27:441–5.

    Article  PubMed  Google Scholar 

  46. Mathur PP, D'Cruz SC. The effect of environmental contaminants on testicular function. Asian J Androl. 2011;13:585–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Sharma R, Biedenharn KR, Fedor JM, Agarwal A. Lifestyle factors and reproductive health: taking control of your fertility. Reprod Biol Endocrinol. 2013;11:66.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Poljsak B, Suput D, Milisav I. Achieving the balance between ROS and antioxidants: when to use the synthetic antioxidants. Oxidative Med Cell Longev. 2013;2013:956792. https://doi.org/10.1155/2013/956792.

    Article  CAS  Google Scholar 

  49. Miller ER 3rd, Pastor-Barriuso R, Dalal D, et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005;142:37–46.

    Article  CAS  PubMed  Google Scholar 

  50. ATBC Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. New Engl J Med. 1994;330:1029–35.

    Article  Google Scholar 

  51. Fraga CG, Motchnik PA, Shigenaga MK, et al. Ascorbic acid protects against endogenous oxidative DNA damage in human sperm. Proc Natl Acad Sci U S A. 1991;88:11003–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Aruoma OI, Halliwell B, Gajewski E, Dizdaroglu M. Copper-ion-dependent damage to the bases in DNA in the presence of hydrogen peroxide. Biochem J. 1991;273:601–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Halliwell B. The antioxidant paradox. Lancet. 2000;355:1179–80.

    Article  CAS  PubMed  Google Scholar 

  54. de Lamirande E, Gagnon C. Impact of reactive oxygen species on spermatozoa: a balancing act between beneficial and detrimental effects. Hum Reprod. 1995;10(Suppl 1):15–21.

    Article  CAS  PubMed  Google Scholar 

  55. Kothari S, Thompson A, Agarwal A, du Plessis S. Free radicals: their beneficial and detrimental effects on sperm function. Indian J Exp Biol. 2010;48:425–35.

    CAS  PubMed  Google Scholar 

  56. Henkel R. Leukocytes and oxidative stress: dilemma for sperm function and male fertility. Asian J Androl. 2011;13:43–52.

    Article  CAS  PubMed  Google Scholar 

  57. Agarwal A, Makker K, Sharma R. Clinical relevance of oxidative stress in male factor infertility: an update. Am J Reprod Immunol. 2008;59:2–11.

    Article  CAS  PubMed  Google Scholar 

  58. Wendel A. Measurement of in vivo lipid peroxidation and toxicological significance. Free Radic Biol Med. 1987;3:355–8.

    Article  CAS  PubMed  Google Scholar 

  59. Castagne V, Lefevre K, Natero R, et al. An optimal redox status for the survival of axotomized ganglion cells in the developing retina. Neurosci. 1999;93:313–20.

    Article  CAS  Google Scholar 

  60. Klein EA, Thompson IM Jr, Tangen CM, et al. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2011;306:1549–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Rajasekaran NS, Connell P, Christians ES, et al. Dysregulation of glutathione homeostasis causes oxidoreductive stress and cardiomyopathy in R120GCryAB mice. Cell. 2007;130:427–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Brewer A, Banerjee Mustafi S, Murray TV, et al. Reductive stress linked to small HSPs, G6PD and NRF2 pathways in heart disease. Antioxid Redox Signal. 2013;18:1114–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Fisher D, Mentor S. Antioxidant-induced reductive stress has untoward consequences on the brain microvasculature. Neural Regen Res. 2017;12:743–4.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Mentor S, Fisher D. Aggressive antioxidant reductive stress impairs brain endothelial cell angiogenesis and blood brain barrier function. Curr Neurovasc Res. 2017;14:71–81.

    Article  CAS  PubMed  Google Scholar 

  65. Lloret A, Fuchsberger T, Giraldo E, Vina J. Reductive stress: a new concept in Alzheimer's disease. Curr Alzheimer Res. 2016;13:206–11.

    Article  CAS  PubMed  Google Scholar 

  66. Ufer C, Wang CC, Borchert A, et al. Redox control in mammalian embryo development. Antioxid Redox Signal. 2010;13:833–75.

    Article  CAS  PubMed  Google Scholar 

  67. Harvey AJ, Kind KL, Thompson JG. REDOX regulation of early embryo development. Reproduction. 2002;123:479–86.

    Article  CAS  PubMed  Google Scholar 

  68. Bouayed J, Bohn T. Exogenous antioxidants—double-edged swords in cellular redox state: health beneficial effects at physiologic doses versus deleterious effects at high doses. Oxidative Med Cell Longev. 2010;3:228–37.

    Article  Google Scholar 

  69. Menezo YJ, Hazout A, Panteix G, et al. Antioxidants to reduce sperm DNA fragmentation: an unexpected adverse effect. Reprod Biomed Online. 2007;14:418–21.

    Article  CAS  PubMed  Google Scholar 

  70. Giustarini D, Dalle-Donne I, Colombo R, et al. Is ascorbate able to reduce disulfide bridges? A cautionary note. Nitric Oxide. 2008;19:252–8.

    Article  CAS  PubMed  Google Scholar 

  71. Lenzi A, Lombardo F, Sgro P, et al. Use of carnitine therapy in selected cases of male factor infertility: a double-blind crossover trial. Fertil Steril. 2003;79:292–300.

    Article  PubMed  Google Scholar 

  72. Nadjarzadeh A, Sadeghi MR, Amirjannati N, et al. Coenzyme Q10 improves seminal oxidative defense but does not affect on semen parameters in idiopathic oligoasthenoteratozoospermia: a randomized double-blind, placebo controlled trial. J Endocrinol Invest. 2011;34:e224–8.

    CAS  PubMed  Google Scholar 

  73. Nadjarzadeh A, Shidfar F, Amirjannati N, et al. Effect of Coenzyme Q10 supplementation on antioxidant enzymes activity and oxidative stress of seminal plasma: a double-blind randomised clinical trial. Andrologia. 2014;46:177–83.

    Article  CAS  PubMed  Google Scholar 

  74. Omu AE, Dashti H, Al-Othman S. Treatment of asthenozoospermia with zinc sulphate: andrological, immunological and obstetric outcome. Eur J Obstet Gynecol Reprod Biol. 1998;79:179–84.

    Article  CAS  PubMed  Google Scholar 

  75. Wong WY, Merkus HMWM, Thomas CMG, et al. Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled trial. Fertil Steril. 2002;77:491–8.

    Article  PubMed  Google Scholar 

  76. Safarinejad MR. Effect of pentoxifylline on semen parameters, reproductive hormones, and seminal plasma antioxidant capacity in men with idiopathic infertility: a randomized double-blind placebo-controlled study. Int Urol Nephrol. 2011;43:315–28.

    Article  CAS  PubMed  Google Scholar 

  77. Akmal M, Qadri JQ, Al-Waili NS, et al. Improvement in human semen quality after oral supplementation of vitamin C. J Med Food. 2006;9:440–2.

    Article  CAS  PubMed  Google Scholar 

  78. Cardoso JP, Cocuzza M, Elterman D. Optimizing male fertility: oxidative stress and the use of antioxidants. World J Urol. 2019;37(6):1029–34. https://doi.org/10.1007/s00345-019-02656-3.

    Article  PubMed  Google Scholar 

  79. Kumar A, Goyal R, Prakash A. Possible GABAergic mechanism in the protective effect of allopregnenolone against immobilization stress. Eur J Pharmacol. 2009;602:343–7.

    Article  CAS  PubMed  Google Scholar 

  80. Valko M, Leibfritz D, Moncol J, et al. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007;39:44–84.

    Article  CAS  PubMed  Google Scholar 

  81. Bouayed J, Rammal H, Soulimani R. Oxidative stress and anxiety: relationship and cellular pathways. Oxidative Med Cell Longev. 2009;2:63–7.

    Article  Google Scholar 

  82. Souza CG, Moreira JD, Siqueira IR, et al. Highly palatable diet consumption increases protein oxidation in rat frontal cortex and anxiety-like behavior. Life Sci. 2007;81:198–203.

    Article  CAS  PubMed  Google Scholar 

  83. Decker EA. Phenolics: prooxidants or antioxidants? Nutr Rev. 1997;55:396–8.

    Article  CAS  PubMed  Google Scholar 

  84. Galati G, O'Brien PJ. Potential toxicity of flavonoids and other dietary phenolics: significance for their chemopreventive and anticancer properties. Free Radic Biol Med. 2004;37:287–303.

    Article  CAS  PubMed  Google Scholar 

  85. Hurrell RF. Influence of vegetable protein sources on trace element and mineral bioavailability. J Nutr. 2003;133:2973S–7S.

    Article  PubMed  Google Scholar 

  86. Hunt JR. Bioavailability of iron, zinc, and other trace minerals from vegetarian diets. Am J Clin Nutr. 2003;78(3 Suppl):633S–9S.

    Article  CAS  PubMed  Google Scholar 

  87. Gibson RS, Perlas L, Hotz C. Improving the bioavailability of nutrients in plant foods at the household level. Proc Nutr Soc. 2006;65:160–8.

    Article  CAS  PubMed  Google Scholar 

  88. Kelsay JL. Effect of oxalic acid on bioavailability of calcium. In: Kies C, editor. Nutritional bioavailability of calcium. Washington D.C.: American Chemical Society; 1985.

    Google Scholar 

  89. Mosha TC, Gaga HE, Pace RD, et al. Effect of blanching on the content of antinutritional factors in selected vegetables. Plant Foods Hum Nutr. 1995;47:361–7.

    Article  CAS  PubMed  Google Scholar 

  90. Hallberg L, Brune M, Rossander L. Iron absorption in man: ascorbic acid and dose-dependent inhibition by phytate. Am J Clin Nutr. 1989;49:140–4.

    Article  CAS  PubMed  Google Scholar 

  91. Beecher GR. Overview of dietary flavonoids: nomenclature, occurrence and intake. J Nutr. 2003;133:3248S–54S.

    Article  CAS  PubMed  Google Scholar 

  92. Brune M, Rossander L, Hallberg L. Iron absorption and phenolic compounds: importance of different phenolic structures. Eur J Clin Nutr. 1989;43:547–57.

    CAS  PubMed  Google Scholar 

  93. Omenn GS, Goodman GE, Thornquist MD, et al. Risk factors for lung cancer and for intervention effects in CARET, the beta-carotene and retinol efficacy trial. J Natl Cancer Inst. 1996;88:1550–9.

    Article  CAS  PubMed  Google Scholar 

  94. Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med. 1994;330:1029–35.

    Article  Google Scholar 

  95. Bjelakovic G, Nagorni A, Nikolova D, et al. Meta-analysis: antioxidant supplements for primary and secondary prevention of colorectal adenoma. Aliment Pharmacol Ther. 2006;24:281–91.

    Article  CAS  PubMed  Google Scholar 

  96. Moher D, Pham B, Jones A, et al. Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses? Lancet. 1998;352:609–13.

    Article  CAS  PubMed  Google Scholar 

  97. Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias: dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA. 1995;273:408–12.

    Article  CAS  PubMed  Google Scholar 

  98. Kjaergard LL, Villumsen J, Gluud C. Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses. Ann Intern Med. 2001;135:982–9.

    Article  CAS  PubMed  Google Scholar 

  99. Cortes-Jofre M, Rueda JR, Corsini-Munoz G, et al. Drugs for preventing lung cancer in healthy people. Cochrane Database Syst Rev. 2012;10:CD002141.

    PubMed  Google Scholar 

  100. Vivekananthan DP, Penn MS, Sapp SK, et al. Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet. 2003;361:2017–23.

    Article  CAS  PubMed  Google Scholar 

  101. Hercberg S, Galan P, Preziosi P, et al. The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch Intern Med. 2004;164:2335–42.

    Article  CAS  PubMed  Google Scholar 

  102. Halliwell B. Free radicals, antioxidants, and human disease: curiosity, cause, or consequence? Lancet. 2000;344:721–4.

    Article  Google Scholar 

  103. Salganik RI. The benefits and hazards of antioxidants: controlling apoptosis and other protective mechanisms in cancer patients and the human population. J Am Coll Nutr. 2001;20(5 Suppl):464S–75S.

    Article  CAS  PubMed  Google Scholar 

  104. Simon HU, Haj-Yehia A, Levi-Schaffer F. Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis. 2000;5:415–8.

    Article  CAS  PubMed  Google Scholar 

  105. Kimura H, Sawada T, Oshima S, et al. Toxicity and roles of reactive oxygen species. Curr Drug Targets Inflamm Allergy. 2005;4:489–95.

    Article  CAS  PubMed  Google Scholar 

  106. Bast A, Haenen GR. The toxicity of antioxidants and their metabolites. Environ Toxicol Pharmacol. 2002;11:251–8.

    Article  CAS  PubMed  Google Scholar 

  107. Ratnam DV, Ankola DD, Bhardwaj V, et al. Role of antioxidants in prophylaxis and therapy: a pharmaceutical perspective. J Control Release. 2006;113:189–207.

    Article  CAS  PubMed  Google Scholar 

  108. Seifried HE, McDonald SS, Anderson DE, et al. The antioxidant conundrum in cancer. Cancer Res. 2003;63:4295–8.

    CAS  PubMed  Google Scholar 

  109. Lawenda BD, Kelly KM, Ladas EJ, et al. Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy? J Natl Cancer Inst. 2008;100:773–83.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. American Center for Reproductive Medicine, Department of Urology, Cleveland Clinic, Cleveland, OH, USA

    Ralf Henkel

  2. Department of Medical Biosciences, University of the Western Cape, Bellville, South Africa

    Ralf Henkel

  3. American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA

    Ashok Agarwal

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  1. Ralf Henkel
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  1. PUR Clinic, University of Central Florida (UCF), Clermont, FL, USA

    Sijo J. Parekattil

  2. ANDROFERT and State University of Campinas (UNICAMP), Campinas, Brazil

    Sandro C. Esteves

  3. Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA

    Ashok Agarwal

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Henkel, R., Agarwal, A. (2020). Harmful Effects of Antioxidant Therapy. In: Parekattil, S., Esteves, S., Agarwal, A. (eds) Male Infertility. Springer, Cham. https://doi.org/10.1007/978-3-030-32300-4_68

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