Researchers uncover a surprising side effect of marathon running—temporary loss of brain myelin—hinting that the brain may burn its own insulation for energy during extreme physical stress.
Brief Communication: Reversible reduction in brain myelin content upon marathon running. Image Credit: Real Sports Photos / Shutterstock
In a Brief Communication published in the journal Nature Metabolism, researchers demonstrated that marathon running results in a substantial but reversible reduction in myelin water fraction (MWF).
Marathon runners rely on carbohydrates as the primary source of energy during a race. Once glycogen levels decrease in the liver, muscle, brain, and other organs, fat is utilized as the energy source. Fat is more abundant than carbohydrates in the human body, providing a sustained energy source for protracted exercise.
Myelin enwraps and surrounds axons in both the peripheral nervous system (PNS) and central nervous system (CNS), providing metabolic support and electrical insulation. Myelin is primarily composed of lipids, accounting for 70% to 80% of its composition. During glucose deprivation, oligodendroglial fatty acid metabolism likely serves as an energy reserve. The authors propose that in such extreme metabolic conditions, local myelin lipid turnover may transiently support brain energy metabolism.
This concept is described as “metabolic myelin plasticity”, a novel form of myelin structural adaptation proposed to buffer energy stress in the brain.
The study and findings
Researchers evaluated whether myelin lipids contribute to brain activity. They used multi-echo T2-weighted MRI sequences processed with the DECAES algorithm to generate 3D parametric maps of MWF—a biomarker of myelin that measures water pools between myelin lamellae.
Participants included ten healthy, well-trained runners (eight men and two women, aged 45–73), from city and mountain marathons. Imaging sessions were conducted 24–48 hours before and after the marathon, as well as two weeks and two months later. Only two participants were scanned at the two-week timepoint and six at the two-month follow-up.
MWF maps taken before the marathon revealed a consistent distribution across the brain, with minor individual variations.
High-resolution MRI scans showed no significant individual variability across sessions. The consistency allowed averaging of MWF values, which matched those seen in healthy individuals of similar age.
MWF maps averaged from post-marathon sessions (24–48 hours, two weeks, and two months) revealed a decline in MWF in motor descending pathways shortly after the marathon. The brain was segmented into 56 grey matter and 50 white matter regions for further analysis.
The authors found significant and region-specific MWF decreases in 12 white matter regions, and limited changes in a few grey matter areas. However, low myelin content in grey matter limits the reliability of these findings due to current MRI spatial resolution constraints. Bilateral MWF reductions in white matter were extensive, especially in the pontine crossing tract, corticospinal tract, cerebellar and cerebral peduncles, and corona radiata.
Specifically, MWF signals were reduced by up to 26% in the corticospinal tract and 28% in the pontine crossing tract.
To rule out dehydration, partial and total CNS volumes were measured. No significant differences were found in the brain, ventricles, or other regions across sessions.
Regional water content was also assessed and showed no significant change in areas with MWF loss. While MWF values improved two weeks post-marathon, they remained below pre-marathon levels. By two months, MWF levels had fully recovered in affected regions.
Conclusions
White matter tracts in the brain experience reversible MWF loss after prolonged endurance exercise. This may reflect temporary mobilization of myelin lipids to support local neuronal metabolism under energy stress—a process termed “metabolic myelin plasticity.”
Future studies should investigate whether these changes impact neurophysiological or cognitive functions, though this study did not include such assessments.
The authors note that while MWF reductions are localized and limited, myelin is unlikely to contribute significantly to overall body energy during marathons. However, it may act as a strategic energy buffer under extreme conditions or in disease.
Limitations of the study include small sample size, especially at follow-ups, lack of a control group, difficulty measuring grey matter MWF, and limited MRI spatial resolution. Despite this, the findings suggest important links between myelin dynamics and brain energy metabolism, warranting further investigation.
Journal 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. Nature Metabolism, 2025. DOI: 10.1038/s42255-025-01244-7, https://www.nature.com/articles/s42255-025-01244-7