Marathon running temporarily reduces brain myelin content, but levels fully recover within two months.
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Published: March 24, 2025
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I still remember the elation I felt crossing the finish line of my first marathon – mixed with sheer exhaustion and the nagging question of how my brain was coping with the intense effort. It turns out, I wasn’t alone in wondering about the brain’s response to endurance running.
A new study conducted at the University of the Basque Country, published in Nature Metabolism, reveals that marathon running can cause a temporary reduction in brain myelin content, with levels fully recovering within two months.
Why does myelin matter for marathon runners?
Marathon running is the ultimate test of human endurance, pushing the body to its metabolic limits over a grueling distance of 42 km. During a marathon, runners predominantly rely on carbohydrates, particularly glycogen stored in their muscles, as the primary source of energy. However, as glycogen reserves become depleted over the course of the race, the body gradually shifts to utilizing fat as fuel. This metabolic transition is essential for maintaining energy levels during prolonged exercise, but it also poses a challenge for the brain – which typically relies on glucose as its primary energy source.
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Scientists are now suggesting that the brain may adapt to this energy deficit by utilizing myelin lipids as an alternative fuel. Myelin is a fatty substance that surrounds and insulates nerve fibers in the brain and spinal cord, forming a sheath that facilitates the rapid transmission of electrical signals between neurons. Composed of approximately 70–80% lipids, myelin has traditionally been understood as purely structural and insulating. However, animal studies have hinted at a dual function: under extreme metabolic stress, myelin lipids may be mobilized to sustain neural function. Yet, whether this phenomenon occurs in humans during endurance exercise has remained unclear.
Could the brain also be using myelin as a metabolic buffer during these moments of acute energy shortage? The possibility raises important questions about the potential long-term impacts of endurance training on brain health, particularly for those who regularly undertake such strenuous activities.
Such a question is especially relevant to marathon runners, who push their bodies through hours of continuous physical effort, potentially depleting glycogen stores and forcing the body to draw on fat reserves. This hypothesis led corresponding author Dr. Carlos J. Matute, a professor in the Department of Neurosciences at the University of the Basque Country, and colleagues to investigate whether intense endurance exercise – like running a marathon – could transiently reduce brain myelin content in humans. Although previous studies have explored the effects of prolonged exercise on the brain, none have specifically examined changes in myelin.
Marathon running temporarily affects brain myelin
Matute and his team used advanced magnetic resonance imaging (MRI) with a specialized technique called multicomponent relaxometry to assess the myelin water fraction (MWF) – a well-established imaging biomarker that reflects the amount of myelin in the brain – on 10 marathon runners before and after completing a 42 km race. MWF is calculated by measuring the proportion of water trapped between the lipid bilayers of the myelin sheath relative to the total water content in brain tissue. This method is particularly sensitive to subtle changes in myelin levels and is commonly used to monitor myelin integrity in neurological conditions.
Multicomponent relaxometry
An MRI technique that analyzes the relaxation times of water molecules to differentiate between different tissue components. It is commonly used to measure the MWF, which reflects the amount of myelin in the brain.
Brain scans were performed on all participants (8 men and 2 women) both before and within 48 hours after completing the race. Follow-up scans were also performed on two of the runners two weeks post-race and on six runners two months post-race to track recovery. The imaging technique generated detailed 3D parametric maps of MWF, allowing researchers to detect even minor changes in myelin content.
The study revealed a consistent reduction in MWF in 12 areas of white matter, with the most significant reductions – up to 28% and 26% – observed in the pontine crossing and corticospinal tracts, respectively. The affected areas are vital for motor function and integrating sensory and emotional inputs, highlighting a potential impact on movement and emotional regulation.
Pontine crossing tracts
White matter pathways in the brainstem that are involved in the coordination and integration of motor signals from the brain to the spinal cord.
Corticospinal tracts
Major neural pathways that transmit motor commands from the cerebral cortex to the spinal cord, playing a crucial role in voluntary motor control.
“The signal for myelin water fraction – a surrogate of myelin content – is substantially reduced upon marathon running in specific brain regions but recovers within two months. These findings suggest that brain myelin content is temporarily and reversibly diminished by severe exercise,” said the authors.
MWF levels began to rebound within two weeks and by two months post-marathon, MWF levels had fully recovered to pre-race levels.
The team examined whether the observed decrease in MWF could be attributed to dehydration, as prolonged endurance exercise often leads to fluid loss. However, analyses of brain volume and hydration status indicated that neither global nor regional dehydration was responsible for the changes in MWF. Brain volumes remained unchanged before and after the race, suggesting that the reduction in MWF truly reflected a temporary depletion of myelin content rather than changes in water distribution.
Metabolic myelin plasticity and its implications
The study introduces the concept of “metabolic myelin plasticity” – the idea that myelin may also function as a lipid reservoir during periods of metabolic stress. The idea proposes that myelin lipids could be mobilized as an energy source when common brain nutrients, like glucose, are in short supply. This concept challenges the conventional view of myelin as purely a structural entity and suggests that it may play an adaptive role in maintaining neural function during extreme endurance activities.
“Myelin plasticity is fundamental to brain adaptation to neuronal activity, as it modifies myelin structure by increasing or decreasing the thickness of the myelin sheath. Our findings strongly suggest that widespread reversible MWF reduction in endurance physical exercise represents a new form of plasticity to support brain function at the expense of myelin lipid use,” said the authors.
The ability to draw on myelin lipids may support brain function during endurance challenges, but repeated depletion and restoration of myelin could have long-term consequences, particularly in athletes who frequently engage in prolonged, strenuous activities. Individuals with neurological vulnerabilities, such as those predisposed to demyelinating diseases, might also face increased risks if myelin is routinely used as an energy reserve. While the reversible nature of MWF reduction is reassuring, it remains unclear whether repeated cycles of depletion and recovery could lead to cumulative damage or impaired remyelination over time.
Larger and more comprehensive studies are essential to validate these findings and explore their broader implications. Future research should investigate whether cognitive or neurophysiological functions are affected during or after endurance activities, particularly in those who regularly participate in marathons or ultramarathons.
Reference: Ramos-Cabrer P, Cabrera-Zubizarreta A, Padro D, Matute-González M, Rodríguez-Antigüedad A, Matute C. Reversible reduction in brain myelin content upon marathon running. Nat Metab. 2025. doi: 10.1038/s42255-025-01244-7
This article is a rework of a press release issued by Springer Nature. Material has been edited for length and content.
Meet the Author
Rhianna-lily Smith
Editorial Assistant
Rhianna-lily is an Editorial Assistant at Technology Networks. She holds an honors degree in biomedicine from the University of East Anglia and a masters degree in microbiology. Before joining Technology Networks she researched maternal health and the microbiome.
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