A Systematic Review and Meta-Analysis on the Influence of Exercise-Induced Oxidative Stress on the Pathogenesis of Infectious Diseases
Subject Areas : Exercise Training and Diseases
1 - Department of Physical Education and Sport Sciences, Parand Branch, Islamic Azad University, Parand, Tehran, Iran.
Keywords: Exercise-induced oxidative stress, Immune modulation, Infectious diseases, Reactive oxygen species, Antioxidant defenses, Physical activity,
Abstract :
Background: Exercise-induced oxidative stress (EIOS) plays a pivotal role in immune modulation and the pathogenesis of infectious diseases. While moderate-intensity exercise has been shown to enhance immune defenses and redox balance, excessive or prolonged physical activity can lead to transient immunosuppression, increasing infection susceptibility. This systematic review and meta-analysis aim to evaluate the influence of EIOS on immune function and infection risk across diverse exercise protocols and populations.
Materials and Methods: A systematic search was conducted across PubMed, Scopus, and ScienceDirect databases, encompassing studies published up to 2025. Inclusion criteria were controlled trials and observational studies that assessed oxidative stress biomarkers, immune responses, and infectious disease outcomes in human participants. Out of 1,245 initially identified studies, 28 met the inclusion criteria, representing a wide range of exercise intensities and durations. Meta-analytic methods using a random-effects model quantified standardized mean differences (SMD) with 95% confidence intervals (CI). Heterogeneity was assessed via I² statistics, and subgroup analyses were conducted to explore variability by population characteristics and exercise modalities. The review protocol was registered at PROSPERO (CRD42024611777).
Results: Moderate-intensity exercise (50–70% VO2max) was associated with significant reductions in pro-oxidant markers, such as malondialdehyde (MDA; SMD: -1.08, 95% CI: -1.57 to -0.58), and enhanced antioxidant capacity, including superoxide dismutase and total antioxidant status (TAS; SMD: 1.45, 95% CI: 0.83–2.06). High-intensity exercise (≥70% VO2max) triggered elevated reactive oxygen species and pro-inflammatory cytokines, leading to a transient immune suppression. Subgroup analyses revealed that sedentary populations experienced amplified oxidative responses compared to physically active individuals. Antioxidant supplementation, particularly with compounds like resveratrol and vitamin C, showed potential in mitigating oxidative damage and improving recovery outcomes.
Conclusion: EIOS exhibits a dual nature, where moderate exercise fosters immune resilience and infection prevention, while excessive intensity compromises immune defenses. These findings emphasize the importance of tailored exercise regimens and antioxidant strategy to optimize health outcomes. Further research is needed to investigate long-term effects and develop standardized intervention protocols for at-risk populations.
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1. Paul J. Introduction to Infectious Diseases. Disease Causing Microbes: Springer; 2024. p. 1-63.
doi: 10.1007/978-3-031-28567-7_1
2. Baral B, Mamale K, Gairola S, Chauhan C, Dey A, Kaundal RK. Infectious diseases and its global epidemiology. Nanostructured Drug Delivery Systems in Infectious Disease Treatment: Elsevier; 2024. p. 1-24.
doi: B978-0-443-13337-4.00017-3
3. Shokri A, Sabzevari S, Hashemi SA. Impacts of flood on health of Iranian population: Infectious diseases with an emphasis on parasitic infections. Parasite epidemiology and control. 2020;9:e00144.
doi: 10.1016/j.parepi.2020.e00144
4. Azadnajafabad S, Mohammadi E, Aminorroaya A, Fattahi N, Rezaei S, Haghshenas R, et al. Non-communicable diseases’ risk factors in Iran; a review of the present status and action plans. Journal of Diabetes & Metabolic Disorders. 2024;23(2):1515-23.
doi: 10.1007/s40200-020-00709-8
5. Ghalichi L, Shariat SV, Naserbakht M, Taban M, Abbasi-Kangevari M, Afrashteh F, et al. National and subnational burden of mental disorders in Iran (1990–2019): findings of the Global Burden of Disease 2019 study. The Lancet Global Health. 2024;12(12):e1984-e92.
doi: 10.1016/S2214-109X(24)00342-5
6. Li X-C, Zhang Y-Y, Zhang Q-Y, Liu J-S, Ran J-J, Han L-F, et al. Global burden of viral infectious diseases of poverty based on Global Burden of Diseases Study 2021. Infectious Diseases of Poverty. 2024;13(05):53-67.
doi: 10.1186/s40249-024-01234-z
7. Baker RE, Mahmud AS, Miller IF, Rajeev M, Rasambainarivo F, Rice BL, et al. Infectious disease in an era of global change. Nature Reviews Microbiology. 2022;20(4):193-205.
doi: 10.1038/s41579-021-00639-z
8. Organization WH. Globalization, diets and noncommunicable diseases. 2003. [Accessed 15 February 2025]; Available from: https://pesquisa.bvsalud.org/portal/resource/pt/who-42609
9. Schwellnus MP, Jeans A, Motaung S, Swart J. Exercise and infections. The Olympic textbook of medicine in sport Oxford: Wiley-Blackwell. 2008:344-64.
doi: 10.1002/9781444300635
10. Guerreiro RdC, Silva A, Andrade HdA, Biasibetti IG, Vital R, Silva HGVd, et al. Was postponing the Tokyo 2020 Olympic and Paralympic Games a correct decision? Revista Brasileira de Medicina do Esporte. 2020;26(3):191-5.
doi: 10.1590/1517-8692202026030036
11. McCloskey B, Saito T, Shimada S, Ikenoue C, Endericks T, Mullen L, et al. The Tokyo 2020 and Beijing 2022 Olympic Games held during the COVID-19 pandemic: planning, outcomes, and lessons learnt. The Lancet. 2024;403(10425):493-502.
12. Neira M, Erguler K, Ahmady-Birgani H, Al-Hmoud ND, Fears R, Gogos C, et al. Climate change and human health in the Eastern Mediterranean and Middle East: Literature review, research priorities and policy suggestions. Environmental research. 2023;216:114537.
doi: 10.1016/j.envres.2022.114537
13. Takhti M, Riyahi Malayeri S, Behdari R. Comparison of two methods of concurrent training and ginger intake on visfatin and metabolic syndrome in overweight women. RJMS 2020; 27 (9) :98-111
14. Adegboye O, Adegboye M, Saffary T, Emeto T, Elfaki F. The increased risk of middle east respiratory syndrome coronavirus: Effects of the interaction between temperature variability and dromedary exposure: Int J Infect Dis. 2020 Dec;101:247-8.
doi: 10.1016/j.ijid.2020.11.081
15. Magherini F, Fiaschi T, Marzocchini R, Mannelli M, Gamberi T, Modesti PA, et al. Oxidative stress in exercise training: The involvement of inflammation and peripheral signals. Free radical research. 2019;53(11-12):1155-65.
doi: 10.1080/10715762.2019.1697438
16. Farazandeh Nia, D., Hosseini, M., Riyahi Malayeri, S., Daneshjoo, A. Effect of Eight Weeks of Swimming Training with Garlic Intake on Serum Levels of IL-10 and TNF-α in Obese Male Rats. Jundishapur Scientific Medical Journal, 2018; 16(6): 665-671.
doi: 10.22118/jsmj.2018.57830.
17. Lu Y, Wiltshire HD, Baker JS, Wang Q. Effects of high intensity exercise on oxidative stress and antioxidant status in untrained humans: A systematic review. Biology. 2021;10(12):1272.
doi: 10.3390/biology10121272
18. He F, Li J, Liu Z, Chuang C-C, Yang W, Zuo L. Redox mechanism of reactive oxygen species in exercise. Frontiers in physiology. 2016;7:486.
doi: 10.3389/fphys.2016.00486
19. Siedlik JA, Deckert J, Dunbar AJ, Bhatta A, Gigliotti NM, Chan M, et al. Acute high-intensity exercise enhances T cell proliferation compared to moderate-intensity exercise. Applied Physiology, Nutrition, and Metabolism. 2025(ja).
doi: 10.1139/apnm-2024-0420
20. Ghoochani, S., Riyahi Malayeri, S., Daneshjo, A. Short-term effect of Citrulline Malate supplement on LDH and Lactate levels and Resistance Exercise Performance. Journal of Military Medicine, 2022; 22(4): 154-162.
21. Hosseini M, Ghasem Zadeh Khorasani N, Divkan B, Riyahi Malayeri S. Interactive Effect of High Intensity Interval Training with Vitamin E Consumption on the Serum Levels of Hsp70 and SOD in Male Wistar Rats. Iranian J Nutr Sci Food Technol 2019; 13 (4) :21-28
URL: http://nsft.sbmu.ac.ir/article-1-2689-en.html
22. Zhang N, Zhai L, Wong RMY, Cui C, Law S-W, Chow SK-H, et al. Harnessing immunomodulation to combat sarcopenia: current insights and possible approaches. Immunity & Ageing. 2024;21(1):55.
doi: 10.1186/s12979-024-00458-9
23. Shephard RJ, Shek PN. Exercise training and immune function. Exercise and immune function: CRC Press; 2024. p. 93-120.
ISBN: 9781003575108
24. Suzuki K, Tominaga T, Ruhee RT, Ma S. Characterization and modulation of systemic inflammatory response to exhaustive exercise in relation to oxidative stress. Antioxidants. 2020;9(5):401.
doi: 10.3390/antiox9050401
25. Simioni C, Zauli G, Martelli AM, Vitale M, Sacchetti G, Gonelli A, et al. Oxidative stress: role of physical exercise and antioxidant nutraceuticals in adulthood and aging. Oncotarget. 2018;9(24):17181.
doi: 10.18632/oncotarget.24729
26. Silvas J. Effects of Polyphenols Supplementation on Inflammation and Oxidative Stress after Acute Exercise: A Systematic Review with Meta-Analysis: The University of Texas at San Antonio; 2020.
[Accessed 15 February 2025]; Available from: https://www.proquest.com/openview/f8b2648a4b6da9c9d0df16b4e6b8afce/1?pq-origsite=gscholar&cbl=18750&diss=y
27. Wang Y, Luo D, Jiang H, Song Y, Wang Z, Shao L, et al. Effects of physical exercise on biomarkers of oxidative stress in healthy subjects: A meta-analysis of randomized controlled trials. Open Life Sciences. 2023;18(1):20220668.
doi: 10.1515/biol-2022-0668
28. de Sousa CV, Sales MM, Rosa TS, Lewis JE, de Andrade RV, Simões HG. The antioxidant effect of exercise: a systematic review and meta-analysis. Sports medicine. 2017;47:277-93.
doi: 10.1007/s40279-016-0566-1
29. Da Rosa PC, Bertomeu JB, Royes LFF, Osiecki R. The physical exercise-induced oxidative/inflammatory response in peripheral blood mononuclear cells: signaling cellular energetic stress situations. Life Sciences. 2023;321:121440.
doi: 10.1016/j.lfs.2023.121440
30. Nieman DC, Nehlsen-Cannarella SL. Exercise and infection. Exercise and disease: CRC Press; 2020. p. 121-48.
ISBN: 9781003068853
31. Moreland G, Diaz W, Barkley LC. Infectious Disease in Sports. Current Sports Medicine Reports. 2023;22(2):47-8.
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