Investigating the Efficacy of Antioxidant Supplements in Treating Oxidative Stress-Induced Male Infertility: A Randomized Controlled Trial
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Background: Excessive seminal oxidative stress may impair sperm motility, membrane integrity, mitochondrial function, and DNA stability, but the therapeutic value of antioxidant supplementation remains uncertain. Objective: To determine whether combined vitamin C, vitamin E, and coenzyme Q10 supplementation improves sperm quality and oxidative-stress markers in infertile men with laboratory evidence of seminal oxidative stress. Methods: This randomized, double-blind, placebo-controlled trial enrolled 120 men aged 20–45 years at Akbar Niazi Teaching Hospital, Islamabad, Pakistan, from January to December 2025. Participants were allocated equally to receive vitamin C 500 mg, vitamin E 400 IU, and coenzyme Q10 200 mg daily or matching placebo for 12 weeks. The primary outcome was progressive sperm motility. Secondary outcomes included sperm concentration, total motility, normal morphology, DNA fragmentation index, and seminal oxidation-reduction potential. Week-12 outcomes were compared using analysis of covariance adjusted for baseline values. Results: Progressive motility increased from 25.3% to 35.0% in the antioxidant group and from 25.4% to 28.2% in the placebo group. The adjusted between-group difference was 6.90 percentage points (95% CI, 5.02–8.78; p<0.001). Antioxidant supplementation also improved sperm concentration (adjusted difference, 3.08 million/mL), total motility (6.83 percentage points), and normal morphology (0.45 percentage points) and reduced DNA fragmentation (−7.06 percentage points) and oxidation-reduction potential (−0.53 mV/10⁶ sperm/mL). No serious treatment-related adverse event occurred. Conclusion: Twelve weeks of combined antioxidant supplementation improved several semen and oxidative-stress measures, but its effect on pregnancy and live birth remains undetermined
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1. Agarwal A, Virk G, Ong C, du Plessis SS. Effect of oxidative stress on male reproduction. World J Mens Health. 2014;32(1):1–17. doi:10.5534/wjmh.2014.32.1.1.
2. Tremellen K. Oxidative stress and male infertility: a clinical perspective. Hum Reprod Update. 2008;14(3):243–258. doi:10.1093/humupd/dmn004.
3. Bisht S, Faiq M, Tolahunase M, Dada R. Oxidative stress and male infertility. Nat Rev Urol. 2017;14(8):470–485. doi:10.1038/nrurol.2017.69.
4. 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(6):684–703. doi:10.1016/j.rbmo.2014.02.004.
5. Barati E, Nikzad H, Karimian M. Oxidative stress and male infertility: current knowledge of pathophysiology and role of antioxidant therapy in disease management. Cell Mol Life Sci. 2020;77(1):93–113. doi:10.1007/s00018-019-03253-8.
6. Evans EPP, Scholten JTM, Mzyk A, Reyes-San-Martin C, Llumbet AE, Hamoh T, et al. Male subfertility and oxidative stress. Redox Biol. 2021;46:102071. doi:10.1016/j.redox.2021.102071.
7. Mannucci A, Argento FR, Fini E, Coccia ME, Taddei N, Becatti M, et al. The impact of oxidative stress in male infertility. Front Mol Biosci. 2022;8:799294. doi:10.3389/fmolb.2021.799294.
8. Wagner H, Cheng JW, Ko EY. Role of reactive oxygen species in male infertility: an updated review of literature. Arab J Urol. 2018;16(1):35–43. doi:10.1016/j.aju.2017.11.001.
9. Rehman R, Amjad S, Tariq H, Zahid N, Akhter M, Ashraf M. Oxidative stress and male infertility: a cross-sectional study. J Pak Med Assoc. 2020;70(3):461–466. doi:10.5455/JPMA.12992.
10. Shahid M, Hashmi SA, Rehman R. Oxidative stress, vitamin D deficiency and male infertility: an under-looked aspect. J Pak Med Assoc. 2021;71(2):786. doi:10.47391/JPMA.736.
11. Alam F, Farooqui N, Rehman R. Metformin, oxidative stress and male infertility: way forward. J Pak Med Assoc. 2021;71(2):781–782. doi:10.47391/JPMA.11-1318.
12. Kaltsas A. Oxidative stress and male infertility: the protective role of antioxidants. Medicina (Kaunas). 2023;59(10):1769. doi:10.3390/medicina59101769.
13. Agarwal A, Leisegang K, Majzoub A, Henkel R, Finelli R, Selvam MKP, et al. Utility of antioxidants in the treatment of male infertility: clinical guidelines based on a systematic review and analysis of evidence. World J Mens Health. 2021;39(2):233–290. doi:10.5534/wjmh.200196.
14. Smits RM, Mackenzie-Proctor R, Yazdani A, Stankiewicz MT, Jordan V, Showell MG. Antioxidants for male subfertility. Cochrane Database Syst Rev. 2019;3(3):CD007411. doi:10.1002/14651858.CD007411.pub4.
15. Dimitriadis F, Borgmann H, Struck JP, Salem J, Kuru TH. Antioxidant supplementation on male fertility: a systematic review. Antioxidants (Basel). 2023;12(4):836. doi:10.3390/antiox12040836.
16. Salvio G, Cutini M, Ciarloni A, Giovannini L, Perrone M, Balercia G. Coenzyme Q10 and male infertility: a systematic review. Antioxidants (Basel). 2021;10(6):874. doi:10.3390/antiox10060874.
17. Li KP, Yang XS, Wu T. The effect of antioxidants on sperm quality parameters and pregnancy rates for idiopathic male infertility: a network meta-analysis of randomized controlled trials. Front Endocrinol (Lausanne). 2022;13:810242. doi:10.3389/fendo.2022.810242.
18. Noegroho BS, Siregar S, Tampubolon KAG. Antioxidant supplementation on sperm DNA fragmentation and sperm parameters: a systematic review and meta-analysis. Turk J Urol. 2022;48(5):375–384. doi:10.5152/tud.2022.22058.
19. Alahmar AT. Coenzyme Q10 improves sperm motility and antioxidant status in infertile men with idiopathic oligoasthenospermia. Clin Exp Reprod Med. 2022;49(4):277–284. doi:10.5653/cerm.2022.05463.
20. Balercia G, Buldreghini E, Vignini A, Tiano L, Paggi F, Amoroso S, et al. Coenzyme Q10 treatment in infertile men with idiopathic asthenozoospermia: a placebo-controlled, double-blind randomized trial. Fertil Steril. 2009;91(5):1785–1792. doi:10.1016/j.fertnstert.2008.02.119.
21. Kopets R, Kuibida I, Chernyavska I, Cherepanyn V, Mazo R, Fedevych V, et al. Dietary supplementation with a novel L-carnitine multimicronutrient in idiopathic male subfertility involving oligo-, astheno-, teratozoospermia: a randomized clinical study. Andrology. 2020;8(5):1184–1193. doi:10.1111/andr.12805.
22. Ma L, Sun Y. Comparison of L-carnitine versus coenzyme Q10 and vitamin E for idiopathic male infertility: a randomized controlled trial. Eur Rev Med Pharmacol Sci. 2022;26(13):4698–4704. doi:10.26355/eurrev_202207_29194.
23. Steiner AZ, Hansen KR, Barnhart KT, Cedars MI, Legro RS, Diamond MP, et al. The effect of antioxidants on male factor infertility: the Males, Antioxidants, and Infertility randomized clinical trial. Fertil Steril. 2020;113(3):552–560.e3. doi:10.1016/j.fertnstert.2019.11.008.
24. 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(6):811–816. doi:10.1111/andr.12547.
25. Saleh R, Sallam H, Elsuity MA, Dutta S, Sengupta P, Nasr A. Antioxidant therapy for infertile couples: a comprehensive review of the current status and consideration of future prospects. Front Endocrinol (Lausanne). 2025;15:1503905. doi:10.3389/fendo.2024.1503905.
26. Schulz KF, Altman DG, Moher D; CONSORT Group. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ. 2010;340:c332. doi:10.1136/bmj.c332.
27. World Health Organization. WHO laboratory manual for the examination and processing of human semen. 6th ed. Geneva: World Health Organization; 2021.