Brain Repair in Action: What Runners, Myelin, and MS Teach Us About Brain Health

Your brain is consuming itself right now.

Not dramatically. Not destructively. But under the right conditions, it will quietly burn through one of its most important structural materials just to keep you moving. And then, if you are healthy, it will rebuild.

A 2025 study published in Nature Metabolism showed this happening in real time inside the brains of marathon runners. The finding has implications far beyond sport. It changes how researchers think about brain energy, myelin repair and the central puzzle of multiple sclerosis.

Here is what the science says and why it matters for anyone who wants their brain to keep working at full capacity past 45.

Myelin is a fatty sheath that wraps around nerve fibres in the brain and spinal cord. Think of it as the insulation around an electrical cable. Without it, signals slow down, degrade or fail to reach their target.

Around 70 to 80 percent of myelin's composition is lipid, which is fat. The remaining 20 to 30 percent is protein, which compacts and stabilises the layered structure. This lipid-rich construction is what makes myelin unusual among brain tissues and relevant to the runner story below.

Myelin is produced by specialised cells called oligodendrocytes. Each oligodendrocyte can wrap its processes around multiple axons simultaneously, forming the protective sheath. When oligodendrocytes fail or are destroyed, the axons underneath become vulnerable.

Signal conduction slows first. Then, without the metabolic support myelin provides, the axons begin to degrade. Brain function follows.

In 2025, researchers from the University of the Basque Country and CIC biomaGUNE in Spain recruited ten experienced marathon runners: eight men and two women, aged 45 to 73. They scanned the runners' brains using a specialised MRI technique 24 to 48 hours before and after a 42-kilometre race, and then again at two weeks and two months post-race.

The technique measured myelin water fraction (MWF), a reliable imaging biomarker that detects water trapped within the myelin sheath layers. High MWF signals healthy, dense myelin. Low MWF signals reduced myelin content.

The result: every single runner showed a significant drop in myelin in specific brain regions immediately after the race. The average reduction was approximately 28 percent. The affected areas included motor coordination pathways, sensory processing regions and circuits involved in emotional regulation.

The recovery was equally striking. Myelin levels began returning within two weeks and were fully restored across all affected regions within two months.

The researchers named this process metabolic myelin plasticity. The hypothesis is that when glycogen, the brain's primary fuel, runs out during extreme endurance exercise, the brain begins to metabolise the lipid components of myelin as a backup energy source. Once the acute demand passes, oligodendrocytes rebuild the sheath.

It is the first direct human evidence that myelin serves as a metabolic reserve, not just a structural one.

Multiple sclerosis (MS) is an autoimmune disease that attacks the myelin sheath. The immune system treats myelin as a foreign target, progressively destroying it across the central nervous system. Over 2.9 million people worldwide live with the condition.

The core problem in MS is not simply that myelin is destroyed. It is that the brain's repair mechanisms eventually fail to keep pace. Oligodendrocyte precursor cells (OPCs), which exist in the brain specifically to generate new myelin-producing cells, become dysfunctional. The signals that would normally trigger remyelination are blocked by inflammatory byproducts in the lesion environment.

This is where the runner study connects.

If a healthy brain can deplete 28 percent of myelin under metabolic stress and then fully rebuild it within two months, it means the oligodendrocyte repair system is capable of rapid, substantial work under the right conditions. Understanding what those conditions are, and why the same process stalls in MS, is a direct research target.

Carlos Matute, the lead researcher on the marathon study, stated that understanding how myelin in runners recovers quickly may provide clues for developing treatments for demyelinating diseases, where the disappearance of myelin and its energy contribution facilitates structural damage and degeneration.

This is not a peripheral insight. It is pointing at the mechanism.

In a healthy brain, oligodendrocyte precursor cells migrate into damaged areas and differentiate into mature, myelin-producing cells. This process works efficiently after acute metabolic events, as the marathon runners demonstrate.

In MS, the same precursor cells are present in lesion sites, but they are prevented from completing their differentiation. One of the primary culprits is hyaluronan, a large molecule that is part of the structural matrix outside cells. In MS lesions, inflammation breaks hyaluronan into smaller fragments, and those fragments activate inhibitory receptors on oligodendrocytes, effectively locking them in a non-functional state.

The cells are there. The capacity is there. The repair signal is being blocked.

A 2024 study published in the journal Cell identified a small molecule compound called ESI1 that reversed this silencing in both mouse models of MS and human brain organoid tissue. Treated cells began producing myelin sheaths again and treated mice showed improved neurological function. The researchers were explicit that this represents a proof of concept only and that human clinical trials require further work.

No remyelination therapy is approved as of 2025. But the research direction is clear: the goal is to unblock the repair machinery that is already present, not to introduce something entirely new.

Myelin loss is not exclusive to MS. It is part of normal ageing.

Myelin content in the brain peaks in midlife and declines gradually from there. The decline follows a loosely predictable trajectory but accelerates under conditions of chronic stress, poor sleep, inflammatory diet and low physical activity. As myelin thins, processing speed slows, working memory becomes less reliable and the coordination between brain regions becomes noisier.

This is one of the primary structural reasons why cognitive decline in ageing is not simply about neuron death. The wiring between neurons degrades first.

The marathon study adds an important nuance here. The researchers noted that using and replenishing myelin as an energy reserve may actually be beneficial, because this process exercises the brain's metabolic machinery. The analogy is similar to intermittent fasting for metabolic flexibility: a controlled, recoverable stress may strengthen the system's capacity to respond and rebuild.

This metabolic framing aligns with work by Dr. Chris Palmer, Harvard psychiatrist and author of Brain Energy, who has argued that the brain's ability to shift between fuel sources is central to long-term neurological health. When that metabolic flexibility breaks down, cognitive and psychiatric symptoms follow. The marathon study suggests myelin itself may be part of that flexible energy architecture. I have had the chance to meet Chris in person and he is one of the most generous thinkers in this space, genuinely interested in the conversation and remarkably open with his time and knowledge. If you have not read Brain Energy yet, it belongs on the short list.

This remains a hypothesis at the population level. Controlled human trials on the long-term effects of endurance exercise on myelin content and cognitive outcomes are needed. But the mechanism is plausible and the direction of effect is consistent with existing research showing that aerobic exercise supports white matter integrity in ageing adults.

The practical takeaway from this science is not to run marathons. The study involved ten people and the cognitive implications of the myelin reduction during the event are not fully characterised.

The practical takeaway is about understanding the conditions under which myelin is maintained, stressed and repaired.

Myelin production depends on the availability of specific building blocks, including B vitamins, phospholipids and the metabolic infrastructure to produce and maintain fatty tissue in the brain. Chronic deficiency in B12 is one of the best-documented causes of demyelination outside of MS. Deficiencies in B1 and B9 impair the metabolic processes that support oligodendrocyte function. Phosphatidylserine, a phospholipid concentrated in neuronal membranes, is a structural component of the myelin-adjacent membrane environment.

Sleep is also critical. Oligodendrocyte precursor cell proliferation increases during sleep, and myelin repair is thought to be partially sleep-dependent. Chronic sleep deprivation is consistently associated with reduced white matter integrity.

Chronic systemic inflammation is the antagonist in all of this. It mimics, at a lower intensity, the same inflammatory environment in MS lesions that blocks oligodendrocyte differentiation. Reducing inflammatory load through diet, sleep and stress management removes one of the primary obstacles to the brain's own repair capacity. You can read more about how inflammation affects the brain's maintenance systems in our article on brain homeostasis and inflammation.

Primary study: Ramos-Cabrer et al., "Reversible reduction in brain myelin content upon marathon running." Nature Metabolism, 2025. DOI: 10.1038/s42255-025-01244-7

Supporting research: ESI1 remyelination compound (Lu et al., Cell, 2024); hyaluronan-TLR2 inhibition pathway (Weill Cornell Medicine Myelin Regeneration Project); cortical remyelination and clinical progression in MS (Lazzarotto et al., Brain, 2024)

Confidence rating: High. Core claims are sourced directly from peer-reviewed literature. The 28% MWF reduction figure comes from the primary Nature Metabolism paper. The absence of approved remyelination therapies is accurate as of publication date.

Limitations noted in source material: The marathon study included only ten participants. Follow-up timepoints were incomplete, with two runners scanned at two weeks and six at two months. MWF is a surrogate imaging biomarker, not histological confirmation. Brain oedema from extreme exercise was identified as a potential confounding factor, though the standard marathon format was considered unlikely to produce significant oedema compared to ultra-endurance events.

Does running a marathon damage your brain?

No. A 2025 study in Nature Metabolism found that marathon runners experience a temporary reduction in brain myelin content during a race, averaging around 28 percent, but levels fully recovered within two months. Researchers described this as a form of metabolic plasticity, not damage.

What is myelin and why does it matter for brain health?

Myelin is the fatty insulating sheath that wraps around nerve fibres in the brain and spinal cord. It enables fast, efficient signal transmission between neurons. Myelin loss, whether from disease, ageing or metabolic stress, slows cognition and eventually compromises axon integrity.

Can the brain repair myelin on its own?

In healthy individuals, yes. The brain contains oligodendrocyte precursor cells that migrate to areas of myelin loss and rebuild the sheath. This process is efficient in healthy ageing but breaks down in conditions like multiple sclerosis, where inflammation blocks the repair signal.

What supplements support myelin health?

Myelin production depends on B vitamins, particularly B1, B6, B9 and B12, as well as phospholipids such as phosphatidylserine, and a low-inflammatory metabolic environment. Deficiency in B12 is a documented cause of demyelination independent of disease.

Axolt is a nutrition brand. This article is for informational purposes only and does not constitute medical advice.