Running Low on Energy? Your Brain Might Start Burning Its Own Myelin

A study of marathon runners conducted by the University of the Basque Country (UPV/EHU), CIC biomaGUNE, and IIS Biobizkaia reveals unexpected behavior in myelin.

Prolonged physical exercise forces the human body to draw on its energy reserves. During endurance activities like marathon running, the body primarily uses carbohydrates, especially glycogen, as its main fuel source. Once glycogen stores are depleted, the body begins to break down fat for energy. Myelin, the lipid-rich sheath that insulates neurons in the brain, is largely composed of fats, and previous studies in rodents suggest that under extreme metabolic stress, these lipids might be used as an alternative energy source.

A study by researchers from the UPV/EHU, CIC biomaGUNE, and IIS Biobizkaia has found that marathon runners show a temporary reduction in myelin levels in specific brain regions. However, the research, published in Nature Metabolism, also shows that these changes are fully reversed within two months after the marathon.

Carlos Matute, Professor of Anatomy and Human Embriology at the UPV/EHU and a researcher at IIS Biobizkaia, and Pedro Ramos-Cabrer, Ikerbasque Research Professor at CIC biomaGUNE, together with Alberto Cabrera-Zubizarreta, radiologist at HT Médica, used magnetic resonance imaging to obtain images of the brains of ten marathon runners (eight men and two women) before and 48 hours after the 42-kilometer race. Likewise, the researchers took images of the brains of two of the runners two weeks after the race, and of six runners two months after the race as a follow-up.

By measuring the fraction of myelin water in the brain —an indirect indicator of the amount of myelin— the authors discovered “a reduction in the myelin content in 12 areas of white matter in the brain, which are related to motor coordination and sensory and emotional integration”, explained Carlos Matute. Two weeks later, “the myelin concentrations had increased substantially, but had not yet reached pre-race levels”, added Pedro Ramos. The authors saw that the myelin content had recovered fully two months after the marathon.

Myelin, the brain’s fuel

The researchers concluded that “myelin seems to act as an energy source when other brain nutrients are depleted during endurance exercise, and that further research is needed to establish how extreme exercise is related to the amount of myelin in the brain. Trials in a larger cohort are needed”, said Ramos-Cabrer.

This study reveals that “brain energy metabolism is more complex than previously thought. The use of myelin as brain fuel opens up new insights into the brain’s energy requirements”, explained Matute. Furthermore, according to the authors, more studies are needed to assess whether these changes exert any effect on the neurophysiological and cognitive functions associated with these regions, but they point out that most of the myelin in the brain is not affected.

The results of this work break new ground in the energy role of healthy, aging, and diseased myelin in the brain.

“Understanding how the myelin in the runners recovers quickly may provide clues for developing treatments for demyelinating diseases, such as multiple sclerosis, in which the disappearance of myelin and, therefore, of its energy contribution, facilitates structural damage and degeneration,” said Matute.

At the same time, the researchers are keen to stress that running marathons is not harmful to the brain; “on the contrary, the use and replacement of myelin as an energy reserve is beneficial because this exercises the brain’s metabolic machinery.”

Reference: “Reversible reduction in brain myelin content upon marathon running” by Pedro Ramos-Cabrer, Alberto Cabrera-Zubizarreta, Daniel Padro, Mario Matute-González, Alfredo Rodríguez-Antigüedad and Carlos Matute, 24 March 2025, Nature Metabolism.
DOI: 10.1038/s42255-025-01244-7

This work is led by Carlos Matute (a UPV/EHU professor, lecturer in the UPV/EHU’s Department of Neurosciences and senior researcher at CIBERNED) and the Ikerbasque Research Professor of CIC biomaGUNE Pedro Ramos-Cabrer (specialist in biomedical imaging), together with the radiologist Alberto Cabrera-Zubizarreta of HT Médica, adjunct to the Neuroimagen Computacional group of Biobizkaia. The magnetic resonance images were obtained at Osatek, and neurology professionals from Biobizkaia and the Hospital Clinic de Barcelona also participated in the study.