By Areej Mir

Graphic design by Laura Wu

Until recently, people living with multiple sclerosis (MS) were advised against exercise. This caution is largely attributed to Uhthoff’s phenomenon, in which physical exertion raises body temperature and temporarily worsens neurological symptoms. While these symptoms mimic disease activity, they are reversible once body temperature normalizes, distinguishing them from a true MS relapse.¹ Historically, symptom flares during exercise were interpreted as evidence that exercise might be harmful for people with MS. 

MS is an autoimmune-mediated disease of the central nervous system (CNS) that impacts vision, sensation, coordination, and cognition.² The site and severity of CNS damage vary between patients, meaning that MS can affect people differently. Many people are first diagnosed with relapsing-remitting MS, where symptoms flare and then partly or fully improve, while others develop a more progressive course over time.³ 

Recently, clinical researchers have begun to separate temporary, exercise-related symptoms from actual disease worsening.  This distinction has prompted a re-evaluation of exercise in MS and challenged the assumption that physical activity worsens disease. A 2023 review of the safety profile of exercise training in multiple sclerosis suggests that exercise is safe, with no clear increase in relapse risk, adverse events, or serious adverse events compared with not exercising.⁴ Despite initial assumptions, emerging evidence shows that when appropriately prescribed, exercise is beneficial for people with MS.^5,6,7 

In MS, immune cells attack myelin, the fatty sheath that protects our nerves and ensures that  signals travel efficiently. When myelin is damaged, signals from the brain to the body slow or become blocked. During MS disease activity, immune cells in the CNS release inflammatory molecules, called cytokines and chemokines, that can further injure myelin. They may also limit the ability of the brain to initiate repair.⁶ This damage is especially impactful for motor function. The motor cortex may send a command to lift the foot, grip an object, or stabilize the trunk, but the message may arrive late or inconsistently. While the body’s muscles remain intact, the nervous system cannot always recruit them with precision.^6,7 Critically, heat can worsen this by disrupting signalling in demyelinated fibres. The increase in body temperature associated with exercise leads to temporarily exacerbated symptoms, but exercise itself is harmless.¹ Importantly, while some medications can slow MS activity, there is no cure for MS. As the assumptions surrounding MS and exercise have shifted, researchers are now turning to exercise as a possible strategy to improve motor function and plasticity. ⁸

Part of the benefits of exercise for MS lie in the muscles’ ability to release hormones and signaling molecules.⁹ In the last two decades, researchers have found that contracting muscles release hormones called myokines. Myokines act locally or distally via the bloodstream and can travel into the CNS.¹⁰ In the CNS, myokines perform two critical functions: they act as “peacekeepers” to calm the immune system, and they stimulate the brain’s native repair cells.^3,11 Specifically, muscle-derived myokines like Interleukin-6 (IL-6) shift the immune environment toward a resting state by stimulating anti-inflammatory mediators (such as IL-10) and suppressing inflammatory factors like tumour necrosis factor (TNF).^3,10 Myokines reduce the biological pressure that impedes natural repair by silencing the immune cells that normally attack myelin. 

Resistance training may be particularly beneficial because it puts muscles under mechanical tension. That tension triggers intracellular pathways, resulting in a coordinated burst of exercise-induced signals, known as exerkines.³ Beyond regulating inflammation, specific exerkines such as Brain-Derived Neurotrophic Factor (BDNF), irisin, and Insulin-like Growth Factor 1 (IGF-1) actively support nervous system adaptation.^3,11 BDNF promotes neuronal survival and repair, and helps the brain adjust and rewire synaptic connections after damage. Irisin facilitates muscle-brain communication, while IGF-1 is heavily involved in cellular growth, including the survival of the cells responsible for producing new myelin.³

In MS, chronic neuroinflammation leads to the breakdown of the blood-brain barrier, which controls what cells enter the CNS.¹² During inflammatory activity, hyperactive immune cells cross into the CNS and contribute to demyelination. The release of beneficial exerkines during exercise helps mitigate this effect by changing the behavior of nearby circulating immune cells and blood vessels before they even reach the brain.¹² While one lifting session may not block an MS flare, repeated training helps create a less inflammatory systemic environment, which reduces stress on vulnerable neural tissue.

Additionally, in a 2018 clinical trial, participants with relapsing-remitting MS completed 24 weeks of progressive resistance training.¹³ The trial demonstrated that resistance training improved strength and function, and MRI findings suggested increased cortical thickness in several regions. Cortical thickness refers to the thickness of the brain’s outer layer, which supports movement, sensation, cognition, and other functions. Because cortical thinning in MS can reflect neurodegeneration, preserved or increased cortical thickness after training may suggest a protective effect of exercise on brain structure.¹³ While cortical thickness is not direct evidence of remyelination, it is a surrogate measure that may suggest improvement in these patients.

Importantly, these new findings do not suggest a “train harder at any cost” approach; MS is a diverse disease that requires personalized treatments. Many factors, such as heat sensitivity, fatigue, and medication effects, should shape the type of training program utilized. What appears most beneficial is structured, progressive resistance training. This approach targets major muscle groups and promotes planned progression with adequate rest. Cooling strategies can be employed to mitigate increased body temperature, and supervision is advised when balance impairments or disability make training riskier.

Weightlifting is not a “universal remedy” for MS, nor is it a substitute for neurologic care or disease-modifying treatment. Its importance is likely additive to existing treatment options. Resistance training takes advantage of the muscle’s ability to act as a signaling organ that regulates inflammation, supports neuroplasticity, and creates a favourable environment for myelin repair.

MS damages communication between the brain and the body. Exercise asks that system to communicate again, repeatedly, under a controlled load. While resistance training cannot reverse the disease on its own, these repeated signals may help engage biological pathways involved in repair and adaptation. In that sense, strength training may represent more than rehabilitation—it may help create the conditions necessary for neurological recovery. 

References

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2. National Institute of Neurological Disorders and Stroke. Multiple sclerosis (MS) [Internet]. Bethesda: National Institute of Neurological Disorders and Stroke; 2025 [cited 2026 Apr 27]. Available from: https://www.ninds.nih.gov/health-information/disorders/multiple-sclerosis-ms
3. National Multiple Sclerosis Society. Immune-mediated disease and MS [Internet]. New York: National Multiple Sclerosis Society; [date unknown] [cited 2026 Apr 27]. Available from: https://www.nationalmssociety.org/understanding-ms/what-is-ms/how-ms-affects-the-brain/immune-mediated-disease
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