PHYSICAL ACTIVITY AS A NON-PHARMACOLOGICAL ADJUNCT THERAPY IN THE MANAGEMENT OF RELAPSING-REMITTING MULTIPLE SCLEROSIS: A NARRATIVE REVIEW OF CURRENT EVIDENCE
DOI:
https://doi.org/10.31435/ijitss.2(50).2026.5820Keywords:
Multiple Sclerosis; RRMS; Physical Activity; BDNF; Neuroprotection; DMT Adjunct; Exercise RehabilitationAbstract
Background: Historically, patients with Relapsing-Remitting Multiple Sclerosis (RRMS) were advised to avoid physical exertion to prevent symptom exacerbation. However, recent evidence has catalyzed a paradigm shift, positioning physical activity as a critical disease-modifying intervention.
Objective: This narrative review aims to summarize the current state of knowledge regarding the role of physical activity as a non-pharmacological adjunct therapy in RRMS, focusing on its biological mechanisms, symptomatic impact, and clinical safety.
Methods: An analysis of contemporary literature was conducted, focusing on the molecular, structural, and psychosocial effects of exercise in individuals with RRMS.
Results: Physical activity modulates the central nervous system by upregulating neurotrophic factors, such as Brain-Derived Neurotrophic Factor (BDNF), which support synaptic plasticity and axonal survival. It induces a favorable systemic cytokine shift, reducing pro-inflammatory markers (TNF-α, IL-17). Clinically, structured exercise—comprising aerobic training, progressive resistance training, and mind-body interventions—effectively mitigates pathological fatigue, improves mobility, and supports cognitive processing speed. High-intensity protocols and task-oriented circuit training have shown potential neuroprotective effects, including the preservation of gray matter volume. Modern management of thermal sensitivity (Uhthoff’s phenomenon) and personalized intensity based on the Expanded Disability Status Scale (EDSS) ensure a high safety profile.
Conclusion: Physical activity acts in synergy with Disease-Modifying Therapies (DMTs), creating a "dual-track" strategy that addresses both inflammatory activity and neurodegenerative decline. Initiating exercise within the "Window of Opportunity" early after diagnosis is essential to maximize the preservation of neurological reserve. Physical activity should be considered a fundamental pillar of multidisciplinary MS care, vital for functional independence and improved quality of life.
References
Thompson, A. J., Banwell, B. L., Barkhof, F., Carroll, W. M., Coetzee, T., Comi, G., et al. (2018). Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. The Lancet Neurology, 17(2), 162–173. https://doi.org/10.1016/S1474-4422(17)30470-2
Lublin, F. D., Reingold, S. C., Cohen, J. A., Cutter, G. R., Sørensen, P. S., Thompson, A. J., et al. (2014). Defining the clinical course of multiple sclerosis: The 2013 revisions. Neurology, 83(3), 278–286. https://doi.org/10.1212/WNL.0000000000000560
Motl, R. W., & Pilutti, L. A. (2012). The benefits of exercise training in multiple sclerosis. Nature Reviews Neurology, 8(9), 487–497. https://doi.org/10.1038/nrneurol.2012.136
Panginikkod, S., Rayi, A., Rocha Cabrero, F., & Rukmangadachar, L. A. (2026). Uhthoff phenomenon. In StatPearls. StatPearls Publishing. Retrieved April 1, 2026, from http://www.ncbi.nlm.nih.gov/books/NBK470244/
Dalgas, U., Langeskov-Christensen, M., Stenager, E., Riemenschneider, M., & Hvid, L. G. (2019). Exercise as medicine in multiple sclerosis—Time for a paradigm shift: Preventive, symptomatic, and disease-modifying aspects and perspectives. Current Neurology and Neuroscience Reports, 19(11), 88. https://doi.org/10.1007/s11910-019-1002-3
Andreu-Caravaca, L., Ramos-Campo, D. J., Moncada-Jiménez, J., Abellán-Aynés, O., & Rubio-Arias, J. Á. (2025). Immediate and short-term effect of physical exercise on BDNF in multiple sclerosis patients: A systematic review and meta-analysis. Scientific Reports, 15(1), 19696. https://doi.org/10.1038/s41598-025-04675-0
Riemenschneider, M., Hvid, L. G., Stenager, E., & Dalgas, U. (2018). Is there an overlooked “window of opportunity” in MS exercise therapy? Perspectives for early MS rehabilitation. Multiple Sclerosis Journal, 24(7), 886–894. https://doi.org/10.1177/1352458518777377
Diechmann, M. D., Campbell, E., Coulter, E., Paul, L., Dalgas, U., & Hvid, L. G. (2021). Effects of exercise training on neurotrophic factors and subsequent neuroprotection in persons with multiple sclerosis—A systematic review and meta-analysis. Brain Sciences, 11(11), 1499. https://doi.org/10.3390/brainsci11111499
Farajnia, S., Rajabi, H., Ghaffari, M., Beladi-Moghadam, N., & Fayazmilani, R. (2025). Impact of cognitive-aerobic exercise training on brain-derived neurotrophic factor, dual-tasking abilities, and mood state in individuals with multiple sclerosis. Physiology & Behavior, 290, 114756. https://doi.org/10.1016/j.physbeh.2024.114756
Süleymanoğulları, M., Tekin, A., Ceylan, H. İ., Bayraktar, G., Altuğ, T., Muntean, R. I., et al. (2026). Effects of regular exercise on peripheral brain-derived neurotrophic factor in neurological and non-neurological populations: A meta-analysis with meta-regression. Brain Sciences, 16(1), 39. https://doi.org/10.3390/brainsci16010039
Hejazi, K., Rahimi, G. R. M., & Hofmeister, M. (2026). Effects of exercise training on some cytokine profiles in patients with multiple sclerosis: A systematic review and meta-analysis of randomized controlled trials. Multiple Sclerosis and Related Disorders, 107, 106951. https://doi.org/10.1016/j.msard.2025.106951
Sun, Z. X., Xie, F., Zhao, Y., Wang, X., Sun, Z. W., Qian, L. J., et al. (2025). Exercise and the blood-brain barrier: Mechanistic insights and therapeutic implications. Neurobiology of Disease, 217, 107166. https://doi.org/10.1016/j.nbd.2025.107166
Motl, R. W., & Sandroff, B. M. (2015). Benefits of exercise training in multiple sclerosis. Current Neurology and Neuroscience Reports, 15(9), 62. https://doi.org/10.1007/s11910-015-0585-6
Dalgas, U., & Stenager, E. (2012). Exercise and disease progression in multiple sclerosis: Can exercise slow down the progression of multiple sclerosis? Therapeutic Advances in Neurological Disorders, 5(2), 81–95. https://doi.org/10.1177/1756285611430719
Abal del Blanco, J., & Taboada-Iglesias, Y. (2021). Effects of resistance exercise in patients with spasticity: Systematic review. Apunts Sports Medicine, 56(212), 100356. https://doi.org/10.1016/j.apunsm.2021.100356
Rooney, S., Albalawi, H., & Paul, L. (2020). Exercise in the management of multiple sclerosis relapses: Current evidence and future perspectives. Neurodegenerative Disease Management, 10(2), 103–115. https://doi.org/10.2217/nmt-2019-0029
Sandroff, B. M., & Motl, R. W. (2025). Exercise and cognition in multiple sclerosis in 2025: Forward momentum or going nowhere fast? Current Neurology and Neuroscience Reports, 25(1), 61. https://doi.org/10.1007/s11910-025-01450-6
Kyriakatis, G. M., Besios, T., & Lykou, P. M. (2022). The effect of therapeutic exercise on depressive symptoms in people with multiple sclerosis—A systematic review. Multiple Sclerosis and Related Disorders, 68, 104407. https://doi.org/10.1016/j.msard.2022.104407
Afkar, A., Ashouri, A., Rahmani, M., & Emami Sigaroudi, A. (2017). Effect of exercise therapy on quality of life of patients with multiple sclerosis in Iran: A systematic review and meta-analysis. Neurological Sciences, 38(11), 1901–1911. https://doi.org/10.1007/s10072-017-3047-x
Flores, V. A., Šilić, P., DuBose, N. G., Zheng, P., Jeng, B., & Motl, R. W. (2023). Effects of aerobic, resistance, and combined exercise training on health-related quality of life in multiple sclerosis: Systematic review and meta-analysis. Multiple Sclerosis and Related Disorders, 75, 104746. https://doi.org/10.1016/j.msard.2023.104746
Lin, C. C., Kinnett-Hopkins, D., Alawamleh, A., Siemen, M., Lane, A., & Abou, L. (2024). Physical activity improves cardiovascular fitness and reduces cardiovascular risk factors in adults with multiple sclerosis: A systematic review and meta-analysis. Multiple Sclerosis and Related Disorders, 92, 106170. https://doi.org/10.1016/j.msard.2024.106170
Petajan, J. H., Gappmaier, E., White, A. T., Spencer, M. K., Mino, L., & Hicks, R. W. (1996). Impact of aerobic training on fitness and quality of life in multiple sclerosis. Annals of Neurology, 39(4), 432–441. https://doi.org/10.1002/ana.410390405
Campbell, E., Coulter, E. H., & Paul, L. (2018). High intensity interval training for people with multiple sclerosis: A systematic review. Multiple Sclerosis and Related Disorders, 24, 55–63. https://doi.org/10.1016/j.msard.2018.06.005
Youssef, H., Gönül, M. N., Sobeeh, M. G., Akar, K., Feys, P., Cuypers, K., et al. (2024). Is high-intensity interval training more effective than moderate continuous training in rehabilitation of multiple sclerosis: A comprehensive systematic review and meta-analysis. Archives of Physical Medicine and Rehabilitation, 105(8), 1545–1558. https://doi.org/10.1016/j.apmr.2023.12.012
Kjølhede, T., Vissing, K., & Dalgas, U. (2012). Multiple sclerosis and progressive resistance training: A systematic review. Multiple Sclerosis Journal, 18(9), 1215–1228. https://doi.org/10.1177/1352458512437418
Andreu-Caravaca, L., Ramos-Campo, D. J., Chung, L. H., Martínez-Rodríguez, A., & Rubio-Arias, J. Á. (2023). Effects and optimal dosage of resistance training on strength, functional capacity, balance, general health perception, and fatigue in people with multiple sclerosis: A systematic review and meta-analysis. Disability and Rehabilitation, 45(10), 1595–1607. https://doi.org/10.1080/09638288.2022.2069295
Kjølhede, T., Siemonsen, S., Wenzel, D., Stellmann, J. P., Ringgaard, S., Pedersen, B. G., et al. (2018). Can resistance training impact MRI outcomes in relapsing-remitting multiple sclerosis? Multiple Sclerosis Journal, 24(10), 1356–1365. https://doi.org/10.1177/1352458517722645
Buttolph, L., Bruton, A. M., Filbin, P., Wexler, R. S., Gray, O., Mazure, T., et al. (2026). Effects of mind-body movement interventions for managing symptoms in people with multiple sclerosis: An overview of reviews. Current Neurology and Neuroscience Reports, 26(1), 10. https://doi.org/10.1007/s11910-025-01478-8
Mooventhan, A., & Nivethitha, L. (2017). Evidence based effects of yoga in neurological disorders. Journal of Clinical Neuroscience, 43, 61–67. https://doi.org/10.1016/j.jocn.2017.05.012
Straudi, S., Martinuzzi, C., Pavarelli, C., Sabbagh Charabati, A., Benedetti, M. G., Foti, C., et al. (2014). A task-oriented circuit training in multiple sclerosis: A feasibility study. BMC Neurology, 14, 124. https://doi.org/10.1186/1471-2377-14-124
Ozkul, C., Guclu-Gunduz, A., Eldemir, K., Apaydin, Y., Gulsen, C., Yazici, G., et al. (2020). Effect of task-oriented circuit training on motor and cognitive performance in patients with multiple sclerosis: A single-blinded randomized controlled trial. NeuroRehabilitation, 46(3), 343–353. https://doi.org/10.3233/NRE-203029
Frohman, A. N., Okuda, D. T., Beh, S., Treadaway, K., Mooi, C., Davis, S. L., et al. (2015). Aquatic training in MS: Neurotherapeutic impact upon quality of life. Annals of Clinical and Translational Neurology, 2(8), 864–872. https://doi.org/10.1002/acn3.220
Shariat, A., Ghayour Najafabadi, M., Soroush Fard, Z., Nakhostin-Ansari, A., & Shaw, B. S. (2022). A systematic review with meta-analysis on balance, fatigue, and motor function following aquatic therapy in patients with multiple sclerosis. Multiple Sclerosis and Related Disorders, 68, 104107. https://doi.org/10.1016/j.msard.2022.104107
Opara, J., Brola, W., Wylegala, A., & Wylegala, E. (2016). Uhthoff’s phenomenon 125 years later—What do we know today? Journal of Medicine and Life, 9(1), 101–105.
Šilarová, A., Hvid, L. G., Hradílek, P., & Dalgas, U. (2024). Exercise-induced heat sensitivity in patients with multiple sclerosis: Definition, prevalence, etiology, and management—A scoping review. Multiple Sclerosis and Related Disorders, 90, 105827. https://doi.org/10.1016/j.msard.2024.105827
Razazian, N., Kazeminia, M., Moayedi, H., Daneshkhah, A., Shohaimi, S., Mohammadi, M., et al. (2020). The impact of physical exercise on the fatigue symptoms in patients with multiple sclerosis: A systematic review and meta-analysis. BMC Neurology, 20(1), 93. https://doi.org/10.1186/s12883-020-01654-y
Scholz, M., Haase, R., Trentzsch, K., Weidemann, M. L., & Ziemssen, T. (2021). Fear of falling and falls in people with multiple sclerosis: A literature review. Multiple Sclerosis and Related Disorders, 47, 102609. https://doi.org/10.1016/j.msard.2020.102609
Pilutti, L. A., Platta, M. E., Motl, R. W., & Latimer-Cheung, A. E. (2014). The safety of exercise training in multiple sclerosis: A systematic review. Journal of the Neurological Sciences, 343(1–2), 3–7. https://doi.org/10.1016/j.jns.2014.05.016
Learmonth, Y. C., Herring, M. P., Russell, D. I., Pilutti, L. A., Day, S., Marck, C. H., et al. (2023). Safety of exercise training in multiple sclerosis: An updated systematic review and meta-analysis. Multiple Sclerosis Journal, 29(13), 1604–1631. https://doi.org/10.1177/13524585231204459
Adamson, B. C., Adamson, M. D., Littlefield, M. M., & Motl, R. W. (2018). ‘Move it or lose it’: Perceptions of the impact of physical activity on multiple sclerosis symptoms, relapse and disability identity. Qualitative Research in Sport, Exercise and Health, 10(4), 457–475. https://doi.org/10.1080/2159676X.2017.1415221
Azzolini, F., Dolcetti, E., Bruno, A., Rovella, V., Centonze, D., & Buttari, F. (2024). Physical exercise and synaptic protection in human and pre-clinical models of multiple sclerosis. Neural Regeneration Research, 19(8), 1768–1771. https://doi.org/10.4103/1673-5374.389359
Andreu-Caravaca, L., Ramos-Campo, D. J., Moncada-Jiménez, J., Abellán-Aynés, O., & Rubio-Arias, J. Á. (2025). Immediate and short-term effect of physical exercise on BDNF in multiple sclerosis patients: A systematic review and meta-analysis. Scientific Reports, 15(1), 19696. https://doi.org/10.1038/s41598-025-04675-0
Van Hijfte, L., Loret, G., Bachmann, H., Reynders, T., Breuls, M., Deschepper, E., et al. (2022). Lifestyle factors in multiple sclerosis disability progression and silent brain damage: A cross-sectional study. Multiple Sclerosis and Related Disorders, 65, 104016. https://doi.org/10.1016/j.msard.2022.104016
Magyari, M., & Sorensen, P. S. (2020). Comorbidity in multiple sclerosis. Frontiers in Neurology, 11, 851. https://doi.org/10.3389/fneur.2020.00851
Kalb, R., Brown, T. R., Coote, S., Costello, K., Dalgas, U., Garmon, E., et al. (2020). Exercise and lifestyle physical activity recommendations for people with multiple sclerosis throughout the disease course. Multiple Sclerosis Journal, 26(12), 1459–1469. https://doi.org/10.1177/1352458520915629
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Copyright (c) 2026 Dawid Juszkiewicz, Krzysztof Kiełczewski, Agnieszka Zaręba, Magdalena Dłużewska, Barbara Fetner, Patrycja Stankowska, Zuzanna Gebert, Ivanna Ilkiv, Agata Kucharska, Konrad Adler

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