The Brain Can Run Too: How It Adapts and Regenerates After Great Efforts

After running a marathon, the brain can use some of its myelin, a layer that protects neurons, as an extra source of energy. Our study showed that there is a small and temporary reduction in myelin after running, but that it recovers afterwards. This reveals a new way for the brain to adapt to high-stress situations without causing permanent damage.

The human brain is one of the most energy-intensive organs, consuming around 20% of the body’s energy despite accounting for only 2% of its weight.

A crucial part of the brain are oligodendrocytes, specialized cells responsible for producing myelin, a fatty substance that forms a protective layer around the axons of neurons. This layer, called the myelin sheath, allows electrical signals between neurons to travel quickly and efficiently. Without myelin, communication in the brain would be much slower and inefficient.

Interestingly, oligodendrocytes demonstrate a surprising resilience to the lack of glucose, the body's main energy fuel, and are able to draw on alternative energy sources, especially those related to mitochondria, the cells' "power plants." This suggests that in situations where glucose supply is compromised, such as during extreme physical activity, myelinated nerves may use components of their own myelin as an emergency energy source.

Oligodendrocyte (yellow) wrapping around the axons of neurons (blue)

This ability has implications for a number of diseases. For example, in multiple sclerosis, a disease in which myelin is damaged, ongoing inflammation can disrupt the energy supply needed to repair and maintain this protective layer.

As a result, energy homeostasis, the internal balance required for normal cellular function, is disrupted, worsening disease progression.

In the context of physical exercise, this study showed that after the completion of a marathon, there was only a small but detectable reduction in the amount of myelin (measured by an MRI technique called myelin water fraction, or MWF). This makes it unlikely that, under normal conditions, the body would significantly use myelin as an energy source.

This study was observational and pilot in nature, that is, an initial investigation to generate hypotheses. Working with a small number of participants: 10 runners (8 men and 2 women) aged between 45 and 73, who participated in urban marathons (Donostia-San Sebastián and Valencia) and mountain marathons (Zegama-Aizkorri and Hiru Handiak) in the years 2022 and 2023.

None of them received financial compensation and all provided informed consent to participate, strictly following the ethical principles of the Declaration of Helsinki.

Brain MRI scans were performed 24–48 hours before and after the marathons, and in some cases additionally two weeks or two months later. Measurements focused on the myelin water fraction (MWF), a reliable proxy for estimating myelin content in the brain.

We found that reductions in myelin were most evident in areas responsible for motor coordination and sensory and emotional integration, and that these effects were reversible: after two months, myelin levels appeared to have returned to normal.

However, in even more extreme scenarios, such as more strenuous physical activity or in states of severe malnutrition, such as anorexia nervosa or during starvation, it is possible that myelin is degraded to meet energy needs. Indeed, previous studies have shown that malnutrition compromises the formation and maintenance of myelin, leading to cognitive deficits and changes in brain structure.

Sagittal, axial and coronal views of 3D MRI images acquired before and after exercise. The images did not show significant interindividual differences for the different imaging sessions. The volumes of the whole brain and structures remained unchanged.

In addition, while regular and moderate physical exercise is extremely beneficial for brain health, helping to preserve cognitive function throughout life, strenuous and repeated physical exercise may be detrimental in people genetically predisposed to certain diseases, such as amyotrophic lateral sclerosis (ALS).

Oligodendrocytes (blue) surrounding neuron axons. Hill Lab image

In vulnerable individuals, high-intensity exercise can exacerbate the risk of developing the disease by affecting areas of the brain rich in myelin, such as the corticospinal tract, which is essential for voluntary movement.

One of the mechanisms involved could be glutamate excitotoxicity, a process in which excess nervous stimulation causes cell damage or death, also affecting oligodendrocytes and their ability to maintain myelin.

It is important to emphasize that myelin is not a rigid and unchanging structure. There is something called myelin plasticity, which is the brain's ability to adjust the thickness and function of myelin sheaths in response to neuronal activity.

In other words, the brain is able to "remodel" its connections and its protections (myelin) according to need. These findings suggest that the reversible reduction of myelin after intense exercise, such as running a marathon, may represent a new form of plasticity: the body temporarily uses components of myelin to support high energy demands, and later rebuilds it.

The study has some limitations, such as the small sample size, difficulties in measuring changes in gray matter (where there is less myelin naturally), and technical limitations of the MRI itself, such as long scanning times and slight movement of participants during the scan.

In short, the myelin content in the human brain can be temporarily reduced after intense exercise, such as running a marathon, supporting the idea that, in situations of great energetic stress, myelin can function as an “energy reserve” for the brain.

This discovery expands our understanding not only of the function of myelin, but also of the brain’s incredible ability to adapt to extreme metabolic challenges.

READ MORE:

Reversible reduction in brain myelin content upon marathon running

Pedro Ramos-Cabrer, Alberto Cabrera-Zubizarreta, Daniel Padro, Mario Matute-González, Alfredo Rodríguez-Antigüedad & Carlos Matute 

Nature Metabolism (2025)

https://doi.org/10.1038/s42255-025-01244-7

Abstract

Here we use magnetic resonance imaging to study the impact of marathon running on brain structure in humans. We show that the signal for myelin water fraction—a surrogate of myelin content—is substantially reduced upon marathon running in specific brain regions involved in motor coordination and sensory and emotional integration, but recovers within two months. These findings suggest that brain myelin content is temporarily and reversibly diminished by severe exercise, a finding consistent with recent evidence from rodent studies that suggest that myelin lipids may act as glial energy reserves in extreme metabolic conditions.