By Gavin Giovannoni on March 24, 2025
Fatigue in MS is common, but it is often not investigated or managed properly. This post highlights the complexity of MS-related fatigue and explains why and how to manage it holistically.
Key points
- The different mechanisms underlying MS-related fatigue are explained.
- The MS disease process, the burden of living with MS, and other factors such as drug side effects, comorbidities and lifestyle choices may all contribute to fatigue in MS.
- Practical guidance is provided on managing many aspects of MS-related fatigue, using a holistic and systematic approach.
- Not all fatigue is MS-related; it is important to ascertain if your fatigue could be due to another disease process.
Fatigue is one of the most disabling of all the symptoms of MS. It is the symptom that over 50% of people with MS would most like to be rid of. MS-related fatigue has several underlying mechanisms.
Fatigue caused by MS disease processes
Inflammation in the brain
Inflammatory mediators or cytokines associated with MS – in particular, interleukin-1 (IL-1) and TNF-alpha – trigger ‘sickness behaviour’. This is the response to inflammation that forces us to rest and sleep so that our body can recover. Sickness behaviour is also the body’s response to a viral infection such as flu; in fact, many people with MS describe their fatigue as being like the fatigue they experience with flu.
Sickness behaviour from an evolutionary perspective is well conserved and occurs in most animals. This type of fatigue needs to be managed by switching off ongoing inflammation in the brain. Many people with MS who take a highly effective DMT report feeling much better and free from fatigue and/or brain fog. This is why recent-onset fatigue that cannot be explained by other factors (see below) may indicate MS disease activity. At present, fatigue on its own does not constitute a relapse.
Many patients with MS who have had COVID-19 tell me that MS-related cog-fog and fatigue feel like the cog-fog and fatigue of COVID-19 and long-COVID. As many as one in four people with long-COVID experience cog-fog, which includes problems in attention, language fluency, processing speed, executive function, and memory: these are the same problems that affect people with MS.
Cog-fog related to MS and to COVID-19 could be linked to the same inflammatory mechanisms. This syndrome of systemic inflammation causing profound fatigue and cog-fog is not new. Some people with MS who have a systemic infection take weeks or months to return to normal; some patients with more advanced MS never return to their original baseline. This is why, as part of the holistic management of MS, we need to treat and prevent systemic infections as best we can.
