The role of zinc in male fertility

FertilityNutritionWellness
Written By Whitney Lodge

Zinc is one of the most abundant trace elements in humans and is found in high concentrations in the male reproductive organs of healthy men. A deficiency in dietary zinc impairs reproduction and fertility in both males and females. Zinc is found in high concentrations in the prostate, testes and semen highlighting its significant role in male fertility. It cannot be stored in the body and is easily lost through ejaculation, making its consumption paramount through dietary means and in some cases therapeutic supplementation.

Zinc is required for many facets of male fertility including the maturation of spermatozoa, stabilisation of sperm DNA and optimal sperm motility, count and morphology. Zinc does many things to protect and optimise a male’s reproductive potential and whilst it’s well-known as a stand-alone antioxidant that positively protects sperm from reactive oxygen species (ROS) and free radical damage, it also plays a key role in nutrient and electrolyte balance and the acrosome reaction.

A male’s sperm is said to be a direct byproduct of his diet and lifestyle and is very sensitive, for better or for worse, to nutrient and antioxidant deficiencies as well as excess ROS exposure. A systemic review and meta-analysis found that ‘seminal plasma zinc concentrations in infertile males were significantly lower than those in fertile males, and zinc supplementation could significantly increase the sperm quality of infertile males.’

When it comes to zincs role as a fertility antioxidant is plays numerous important roles. It is an essential element in more than 300 enzymes that require zinc for their function. Male idiopathic infertility has been correlated with high ROS levels and low antioxidant status in comparison to healthy fertile men. ROS drives damage of the sperm which impacts sperm motility, the ability of the sperm to fuse with the oocyte, sperm DNA and the paternal genomic contribution to the embryo. Most notably, zinc is a necessary component of antioxidant superoxide dismutase which is the most active antioxidant enzyme in semen. Zinc protects protein from oxidation, reduces binding capacity of redox metals such as iron and copper and instead redirects them to bind to metallothionein and ferritin. Research has shown that 25-40% of infertile men had higher ROS levels. 

What’s more, insufficient zinc compromises DNA repair, making sperm more susceptible to oxidative damage. Reducing oxidative damage is becoming of more importance in our modern-day world given how toxic our dietary and lifestyle practices have become. Several studies have reported that zinc deficiency is a risk factor for men with lowered semen quality. One study found that the need for zinc was higher when ROS exposure was high. For instance, men that smoke are more susceptible to zinc deficiency, likely because the lifestyle practice of smoking creates the free radical damage that zinc is so expert at ‘mopping up’. Seminal zinc was correlated significantly with sperm count (P < .01) and normal morphology (P < .001), in both smokers and nonsmokers highlighting how powerful an ROS scavenger this mineral can be.

Zinc is also integral in the form and function of the sperm. One study found that ‘zinc therapy in men with asthenozoospermia resulted in a significant increase in sperm concentration, progressive motility, sperm integrity and improved conception and pregnancy rates’. Whilst many studies have found zinc to have a positive impact on sperm density, motility, count and motility there haven’t been as many consistent studies with the same results of zinc on sperm morphology, although it is a key mineral present in the head of the sperm.

It's also important to understand how zinc can positively impact hormone function in men. This is quite commonly ignored but plays an important part in the picture as to why sperm function may not be optimal. One study indicated that men who were low in zinc had disordered testosterone synthesis in the Leydig cells. Zinc plays a leading role in the enzyme reaction that is required to transform testosterone into a bioactive form. It’s important to note that the effect that zinc has on serum testosterone is dependent on zinc dosage, form and duration of supplementation.

Zinc also stabilises cell membranes and sperm chromatin which supports the health of sperm DNA, particularly in men with diabetes. Diabetes causes unfavourable sperm parameters, chromatin efficiency and DNA integrity. One study found a statistical reduction in the amount of sperm with deformed head and neck structures when prescribing zinc sulphate supplementation (p < 0.05). Zinc sulphate supplementation also reduced abnormal morphology and DNA fragmentation in sperm of infertile diabetic men by inhibiting oxidative stress and regulating glucose homeostasis.

In addition to sperm development and structure, zinc also supports the acrosome reaction, regulates capacitation and is essential for conception and embryonic implantation. De-Yi Liu et al (2009) found that the most frequent sperm defect is a defective ZP-induced acrosome reaction. After ejaculation, zinc binds to the sperm plasma membrane stabilizing sperm DNA during sperm transportation in the female reproductive tract. The maintenance of sperm zinc levels sustains the energy and stability of the sperm plasma to enable fertilisation to take place.

Zinc also plays an important role in regulating the effects of supportive fertility nutrients such as folate, calcium, vitamin D and magnesium. Zinc is a co-factor for methionine synthesis and for betaine homocysteine methyltransferase and is required for the absorption and metabolism of folate. Animal in vivo and in vitro studies have shown that zinc deficiency decreases the absorption and metabolism of dietary folate. This is also reflective in studies that have shown folate plus zinc supplementation having a statistically higher impact on sperm health and function than either nutrient alone. Zinc is also an essential cofactor for the function of vitamin D, whereby it regulates transcription of vitamin D-dependent genes. In addition, zinc supplementation protects the oxidative damage induced by high doses of iron due to its regulation of ROS as mentioned above.

Zinc nutrient status as well as therapeutic supplementation plays a role of importance in male fertility. As a practitioner, I’d like to see a meta-analysis on zinc form, dose and duration of supplementation and its impact on different aspects of sperm function, including any important co-factors required to achieve efficient results.

 

References

  1. Ebisch, IMW. et al. (2003). ‘C677T methylenetetrahydrofolate reductase polymorphism interferes with the effects of folic acid and zinc sulfate on sperm concentration’, Fertil Steril, 80 (5), pp. 1190-4. [Online]. Available at: https://www.fertstert.org/article/S0015-0282(03)02157-5/fulltext

  2. Camejo, MI. et al. (2011). ‘Selenium, copper and zinc in seminal plasma of men with varicocele, relationship with seminal parameters’, Biol Trace Elem Res, 143 (3), pp. 1247-54. [Online]. Available at: https://link.springer.com/article/10.1007/s12011-011-8957-5

  3. Colagar, AH. Marzony, ET. Chaichi, MJ. (2009). ‘Zinc levels in seminal plasma are associated with sperm quality in fertile and infertile men’, Nutr Res, 29 (2), pp. 82-88. [Online]. Available at: https://www.sciencedirect.com/science/article/abs/pii/S0271531708002601?via%3Dihub

  4. Schisterman EF. et al. (2020). ‘Effect of Folic Acid and Zinc Supplementation in Men on Semen Quality and Live Birth Among Couples Undergoing Infertility Treatment: A Randomized Clinical Trial’, JAMA, 323 (1), pp. 35-48, pp. 35-48. [Online]. Available at: https://jamanetwork.com/journals/jama/fullarticle/2758450

  5. Riffo, M. Leiva, S. Astudillo, J. (1992). ‘Effect of zinc on human sperm motility and the acrosome reaction’, Int J Androl, 15 (3), pp. 229-37. [Online]. Available at: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2605.1992.tb01343.x?sid=nlm%3Apubmed

  6. Osadchuk, L. Kleschchev, M. Osadchuk, A. (2023). ‘Effects of cigarette smoking on semen quality, reproductive hormone levels, metabolic profile, zinc and sperm DNA fragmentation in men: results from a population-based study’, Endocrinol, 14. [Online]. Available at: https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1255304/full

  7. Nematollahi-Mahani. et al. (2013). ‘Effect of folic acid and zinc sulphate on endocrine parameters and seminal antioxidant level after varicocelectomy’, Andrologia, 46 (3), pp. 240-5. [Online]. Available at: https://onlinelibrary.wiley.com/doi/10.1111/and.12067

  8. Osadchuk, L. Kleschchev, M. Danilenko, A. (2021). ‘Impact of seminal and serum zinc on semen quality and hormonal status: A population-based cohort study of Russian young men’, J Trace Elem Med Biol, 68. [Online]. Available at: https://www.sciencedirect.com/science/article/pii/S0946672X21001450

  9. Talevi, R. et al. (2013). ‘Protective effects of in vitro treatment with zinc, d-aspartate and coenzyme q10 on human sperm motility, lipid peroxidation and DNA fragmentation’, Reprod Biol Endocrinol, 11 (81). [Online]. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC3765367/

  10. De-Yi Liu. et al. (2009). ‘Relationship between seminal plasma zinc concentration and spermatozoa-zona pellucida binding and the ZP-induced acrosome reaction in subfertile men’, Asian J Androl, 11 (4), pp. 499-507. [Online]. Available at: http://www.asiaandro.com/Abstract.asp?doi=10.1038/aja.2009.23

  11. Schisterman, EF. et al. (2020). ‘Effect of Folic Acid and Zinc Supplementation in Men on Semen Quality and Live Birth Among Couples Undergoing Infertility Treatment A Randomized Clinical Trial’, JAMA, 323 (1), pp. 35-48. [Online]. Available at: https://jamanetwork.com/journals/jama/fullarticle/2758450#:~:text=Findings%20In%20this%20randomized%20clinical,measured%206%20months%20after%20randomization

  12. Kerns, K. et al. (2020). ‘Sperm Cohort-Specific Zinc Signature Acquisition and Capacitation-Induced Zinc Flux Regulate Sperm-Oviduct and Sperm-Zona Pellucida Interactions’, Int J Mol Sci, 21 (6). [Online]. Available at: https://www.mdpi.com/1422-0067/21/6/2121

  13. Young, SS. et al. (2008). ‘The association of folate, zinc and antioxidant intake with sperm aneuploidy in healthy non-smoking men’, Hum Reprod, 23 (5), pp. 1014-22. [Online]. Available at: https://academic.oup.com/humrep/article-abstract/23/5/1014/646098?redirectedFrom=fulltext&login=false

  14. Irani, M. et al. (2017). ‘The Effect of Folate and Folate Plus Zinc Supplementation on Endocrine Parameters and Sperm Characteristics in Sub-Fertile Men: A Systematic Review and Meta-Analysis’, Urol J, 14 (5), pp. 4069-4078. [Online]. Available at: https://journals.sbmu.ac.ir/urolj/index.php/uj/article/view/3772

  15. Akbari, H. et al. (2023). ‘ The effect of zinc supplementation on improving sperm parameters in infertile diabetic men’, J Obstet Gynaecol India, 73 (4), pp. 316-321. [Online]. Available at: https://link.springer.com/article/10.1007/s13224-023-01767-7

  16. Akbari, H. Forouzandeh, H. Ghavamizadeh. M. (2020). ‘Protective Effects of Zinc Supplement on Chromatin Deficiency and Sperm Parameters in Streptozotocin-Induced Diabetic Rats’, International Medical Journal, 27 (5). Pp. 545-548. [Online]. Available at: https://seronjihou.com/wp-content/uploads/2021/06/275545.pdf

  17. Jenkins, T. et al. (2022). ‘The impact of zinc and folic acid supplementation on sperm DNA methylation: results from the folic acid and zinc supplementation randomized clinical trial (FAZST)’, Fertil Steril, 117 (1), pp. 75-85. [Online]. Available at: https://www.fertstert.org/article/S0015-0282(21)02047-1/fulltext

  18. Ebisch, IMW. et al. (2006). ‘The importance of folate, zinc and antioxidants in the pathogenesis and prevention of subfertility’, Human Reproduction Update, 13 (2). pp. 163-174. [Online]. Available at: https://academic.oup.com/humupd/article-abstract/13/2/163/661418?redirectedFrom=PDF#google_vignette 

  19. Fallah, A. Mohammad-Hasani, A. Colagar, AH. (2018). ‘Zinc is an Essential Element for Male Fertility: A Review of Zn Roles in Men's Health, Germination, Sperm Quality, and Fertilization’, J Reprod Infertil, 19 (2), pp. 69-81. [Online]. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/30009140/

  20. Irani, M. et al. (2017). ‘The Effect of Folate and Folate Plus Zinc Supplementation on Endocrine Parameters and Sperm Characteristics in Sub-Fertile Men: A Systematic Review and Meta-Analysis’, Urol J, 14 (5). pp. 4069-4078. [Online]. Available at: https://journals.sbmu.ac.ir/urolj/index.php/uj/article/view/3772

  21. Amos, A. Razzaque, MS. et al. (2022). ‘Zinc and its role in vitamin D function’, Current Research in Physiology,  5, pp. 203-207. [Online]. Available at: https://www.sciencedirect.com/science/article/pii/S2665944122000190#:~:text=Zinc%20also%20acts%20as%20a,transporters%20to%20regulate%20zinc%20homeostasis

  22. Madej, D. Pietruszka, B. Kaluza, J. (2021). ‘The effect of iron and/or zinc diet supplementation and termination of this practice on the antioxidant status of the reproductive tissues and sperm viability in rats’, J Trace Elem Med Biol, 64. [Online]. Available at: https://www.sciencedirect.com/science/article/abs/pii/S0946672X20302546

  23. Te, L. et al. (2023). ‘Correlation between serum zinc and testosterone: A systematic review’, J Trace Elem Med Biol, 76. [Online]. Available at: https://www.sciencedirect.com/science/article/abs/pii/S0946672X22002048

  24. Hechtman, L. (2019).  ‘Clinical Naturopathic Medicine’. Second Edition. Australia: Elsevier. Available at: https://bookshelf.health.elsevier.com/reader/books/9780729585750/epubcfi/6/2[%3Bvnd.vst.idref%3Did_cover]!/4/2 (Accessed 10 October 2024)

     

Whitney Lodge
Previous

The health risks associated with transferring multiple embryos for maternal and foetal health
Next

Sexual health and it’s role in conception + beyond