Open Access Gateway
Med Princ Pract 2008;17:108–116

Indications of the Mechanisms Involved in Improved Sperm Parameters by Zinc Therapy

Omu A.E.a · Al-Azemi M.K.a · Kehinde E.O.b · Anim J.T.c · Oriowo M.A.d · Mathew T.C.e
Departments of aObstetrics and Gynaecology, bSurgery, cPathology, dPharmacology and Toxicology, and eAnatomy (Electron Microscopy Unit), Faculty of Medicine, Health Sciences Centre, Kuwait University, Kuwait
email Corresponding Author

 goto top of outline Key Words

  • Asthenozoospermia
  • Zinc therapy
  • Modulation
  • Sperm DNA

 goto top of outline Abstract

Objective: To determine possible indications of the mechanisms involved in improved sperm parameters by zinc therapy in asthenozoospermic men. Subjects and Methods: Forty-five men with asthenozoospermia (≥40% immotile sperm) were randomized into four therapy groups: zinc only: n = 11; zinc + vitamin E: n = 12 and zinc + vitamins E + C: n = 14 for 3 months, and non-therapy control group: n = 8. Semen analysis was done according to WHO guidelines. Malone dialdehyde, tumour necrosis factor-α (TNF-α), total antioxidant capacity, superoxide dismutase (SOD) and glutathione peroxidase were determined in the semen and serum. Antisperm antibodies IgG, IgM and IgA were evaluated by immunobeads. Sperm chromatin integrity was determined by acid denaturation by acridine orange and sperm apoptosis by light and electron microscopy. The effect of zinc on in vitro induced sperm oxidative stress by NADH was evaluated. Results: Asthenozoospermia was significantly associated with oxidative stress with higher seminal malone dialdehyde (8.8 vs. 1.8 mmol/l, p < 0.001) and TNF-α (60 vs. 12 pg/l, p < 0.001), and low total antioxidant capacity (1.8 vs. 8.4, p < 0.01), SOD (0.8 vs. 3.1, p < 0.01) and glutathione peroxidase (1.6 vs. 4.2, p < 0.05), compared to normozoospermia. Zinc therapy alone, in combination with vitamin E or with vitamin E + C were associated with comparably improved sperm parameters with less oxidative stress, sperm apoptosis and sperm DNA fragmentation index (DFI). On the whole, there was no difference in the outcome measures between zinc only and zinc with vitamin E and combination of vitamins E + C. In the in vitro experiment zinc supplementation resulted in significantly lower DFI (14–29%, p < 0.05) compared to zinc deficiency. Conclusion: Zinc therapy reduces asthenozoospermia through several mechanisms such as prevention of oxidative stress, apoptosis and sperm DNA fragmentation.

Copyright © 2008 S. Karger AG, Basel

 goto top of outline References
  1. Gil-Guzman E, Ollero M, Lopez MC, Sharma RK, Alvarez JG, Thomas AJ Jr, Agarwal A: Differential production of reactive oxygen species by subsets of human spermatozoa at different stages of maturation. Hum Reprod 2001;16:1922–1930.
  2. Kremer J, Jager S: The significance of antisperm antibodies for sperm-cervical mucus interaction. Hum Reprod 1992;7:781–784.
  3. Omu AE, Al-Qattan F, Abdulhadi F, Fernandes S: Seminal immune response in infertile men with leukocytospermia: effect on antioxodant activity. Eur J Obstet Gynecol Reprod Biol 1999;79:179–184.

    External Resources

  4. Oldereid NB, Thomassen Y, Purvis K: Seminal plasma lead, cadmium and zinc in relation to tobacco consumption. Int J Androl 1994;17:24–28.
  5. Omu AE, Al-Othman S, Mohammad AS, Al-Kaluwby NM, Fernandes S: Antibiotic therapy of seminal infection: effect on antioxidant activity and T helper cytokines. J Reprod Med 1998;43:857–864.
  6. Donnelly ET, McClure N, Lewis SEM: The effect of ascorbate and α-tocopherol supplementation in vitro on DNA integrity and hydrogen peroxide-induced DNA damage in human spermatozoa. Mutagenesis 1999;14:505–511.
  7. Chow CK: Vitamin E and oxidative stress. Free Radical Biol Med 1991;11:215–222.
  8. Niki E: Action of ascorbic acid as scavenger of active and stable oxygen radicals. Am J Clin Nutr 1991;54:1119S–1124S.
  9. Kobayashi T, Miyazaki T, Natori M, Nozawa S: Protective role of superoxide dismutase in human sperm motility: superoxide dismutase activity and lipid peroxide in human seminal plasma and spermatozoa. Hum Reprod 1991;6:987–991.
  10. Wong WY, Merkus HM, Thomas CM, Menkveld R, Zielhuis GA, Steegers-Theunissen RP: Effects of folic acid and zinc sulphate on male factor subfertility: a double-blinded, randomized, placebo-controlled trial. Fertil Steril 2002;77:491–498.
  11. Ebisch IM, Pierik FH, De Jong FH, Thomas CM, Steegers-Theunissen RP: Does folic acid and zinc sulphate intervention affect endocrine parameters and sperm characteristics in men. Int J Androl 2006;29:339–345.
  12. World Health Organisation: WHO Laboratory Manual for Examination of Human Semen and Semen-Cervical Mucus Interaction. Boston, Cambridge University Press, 1999, pp 2–5.
  13. Omu AE, Dashti H, Mohammed AT, Mattappallil AB: Significance of trace elements in seminal plasma of infertile men. Nutrition 1995;11:502–505.
  14. Kehinde EO, Mojiminiyi OA, Mahmoud AH, Al-Awadi KA, Al-Hunayan A, Omu AE: The significance of measuring the time course of serum malondialdehyde concentration in patients with torsion of the testis. J Urol 2003;169:2177–2180.
  15. Sikka SC: Oxidative stress and role of antioxidants in normal and abnormal sperm function. Front Biosci 1996;1:78–86.
  16. Evenson D, Jost L: Sperm chromatin structure assay is useful for fertility assessment. Methods Cell Sci 2000;22:169–189.
  17. Aitken RJ, Gordon E, Harkiss D, Twigg JP, Milne P, Jennings Z, Irvine DS: Relative impact of oxidative stress on the functional competence and genomic integrity of human spermatozoa. Biol Reprod 1998;59:1037–1046.
  18. Olmedo SB, Rawe VY, Nodar FN, Galaverna GD, Acosta AA, Chemes HE: Pregnancies established through intracytoplasmic sperm injection (ICSI) using spermatozoa with dysplasia of fibrous sheath. Asian J Androl 2000;2:125–130.
  19. Sandstead H: Is zinc deficiency a public health problem? Nutrition 1995;11:87–92.
  20. Fanzo JC, Reaves SR, Cui L, Zhu L, Lei KY: p53 protein levels, cyclin-dependent kinase inhibitor p21, bcl-2 family genes, and caspase-3 activity are altered by zinc status in aortic endothelial cells. Am J Physiol Cell Physiol 2002;283:C631–C638.
  21. Menella MRF, Jones R: Properties of superoxides in metal-ion-catalysed lipid peroxidation reaction in semen. Biochem J 1991;180:289–297.
  22. Fraker PJ: Roles for cell death in zinc deficiency. J Nutr 2005;135:359–362.
  23. Moustafa MH, Sharma RK, Thornton J, Mascha E, Abdel-Hafez M, Thomas AJ Jr, Agarwal A: Relationship between ROS production, apoptosis and DNA denaturation in spermatozoa from patients examined for infertility. Hum Reprod 2004;19:129–138.
  24. Agarwal A: Relationship between ROS production, apoptosis and DNA denaturation in spermatozoa from patients examined for infertility. Hum Reprod 2004;19:129–138.
  25. Wang X, Sharma RK, Sikka SC, Thomas AJ Jr, Falcone T, Agarwal A: Oxidative stress is associated with increased apoptosis leading to spermatozoa DNA damage in patients with male infertility. Fertil Steril 2003;80:531–535.
  26. Henkel R, Bittner J, Weber R, Huther F, Miska W: Relevance of zinc in human sperm flagella and its relation to motility. Fertil Steril 1999;6:1138–1143.

    External Resources

 goto top of outline Author Contacts

Dr. Alexander E. Omu, FRCOG
Department of Obstetrics and Gynaecology, Faculty of Medicine
HSC, Kuwait University, PO Box 24923
13110 Safat (Kuwait)
Tel. +965 498 6458, Fax +965 533 8906, E-Mail

 goto top of outline Article Information

Received: February 11, 2007
Revised: July 7, 2007
Published online: February 19, 2008
Number of Print Pages : 9
Number of Figures : 3, Number of Tables : 3, Number of References : 26

 goto top of outline Publication Details

Medical Principles and Practice (International Journal of the Kuwait University Health Sciences Centre)

Vol. 17, No. 2, Year 2008 (Cover Date: February 2008)

Journal Editor: Owunwanne, A. (Kuwait)
ISSN: 1011–7571 (Print), eISSN: 1423–0151 (Online)

For additional information:

Open Access License / Drug Dosage / Disclaimer

Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) (, applicable to the online version of the article only. Distribution permitted for non-commercial purposes only.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.