Ultra-endurance running may accelerate aging and breakdown of red blood cells

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Extreme endurance running damages red blood cells in ways that may affect their ability to function properly, according to a recent study. Although the duration and long-term implications of the damage are unclear, the study adds to a growing body of evidence that extreme forms of exercise may harm rather than support overall health. The work appears in the journal Blood Red Cells & Iron.

While previous studies have shown that ultramarathon runners experience breakdown of normal red blood cells during races—potentially leading to anemia—the causes of this phenomenon have remained unclear.

The new study shows that athletes’ red blood cells become less flexible after a long race, potentially reducing their ability to efficiently carry oxygen, nutrients, and waste products throughout the body. In addition, the research team was able to provide the most complex and detailed molecular map to date of how an endurance race changes red blood cells.

“Participating in events like these can cause general inflammation in the body and damage red blood cells,” said the study’s lead author, Travis Nemkov, Ph.D., associate professor in the Department of Biochemistry and Molecular Genetics at the University of Colorado Anschutz. “Based on these data, we don’t have guidance as to whether people should or should not participate in these types of events; what we can say is, when they do, that persistent stress is damaging the most abundant cell in the body.”

Inside the ultramarathon field research

The study examined markers of red blood cell health before and after athletes participated in the world-class Martigny-Combes à Chamonix race (40 kilometers or about 25 miles long) and the Ultra Trail de Mont Blanc race (171 kilometers or 106 miles long). Red blood cells transport oxygen and waste throughout the body and must be flexible enough to squeeze through small blood vessels.

In the study, researchers collected blood samples from 23 runners immediately before and after long-distance races and analyzed thousands of proteins, lipids, metabolites, and trace elements in their plasma and red blood cells. According to the results, runners’ red blood cells consistently showed evidence of damage from both mechanical (physical) and molecular drivers.

Mechanical and molecular damage explained

Mechanical damage to red blood cells likely resulted from running-induced variations in fluid pressure as blood cells circulate through the body, while molecular changes likely resulted from inflammation and oxidative stress (when the body has low levels of antioxidants, which fight off molecules that damage DNA and other components within cells).

These patterns of damage, which essentially accelerate the aging and breakdown of red blood cells, were clearly seen after 40-kilometer races and were amplified in athletes who ran 171-kilometer races. Based on this observation, researchers speculate that as the length of a run increases, athletes can expect to lose more blood cells and accumulate more damage to those remaining in circulation.

“At some point between marathon and ultra-marathon distances, the damage really starts to take hold,” said Dr. Nemkov. “We’ve observed this damage happening, but we don’t know how long it takes for the body to repair that damage, if that damage has a long-term impact, and whether that impact is good or bad.”

Potential implications for athletes and blood banking

With further study, researchers say the findings could one day help inform strategies to improve athletic performance or reduce potential negative impacts of endurance exercise through personalized training, nutrition, and recovery protocols. Researchers noted that insights into how the body responds to the extreme conditions of endurance exercise can also inform approaches to handling and preserving stored blood, which begins to break down after a few weeks of storage, rendering it unusable for transfusions after six weeks, according to U.S. Food and Drug Administration regulations.

“Red blood cells are remarkably resilient, but they are also exquisitely sensitive to mechanical and oxidative stress,” said study co-author Angelo D’Alessandro, Ph.D., professor at the University of Colorado Anschutz and member of the Hall of Fame of the Association for the Advancement of Blood and Biotherapies.

“This study shows that extreme endurance exercise pushes red blood cells toward accelerated aging through mechanisms that mirror what we observe during blood storage. Understanding these shared pathways gives us a unique opportunity to learn how to better protect blood cell function both in athletes and in transfusion medicine.”

Study limitations and next research steps

The study was limited by its small number of participants and lack of racial diversity, as well as the fact that blood samples were collected at only two time points. The researchers are planning studies with more participants and blood samples, as well as additional measurements in the post-race period. They also plan to further examine opportunities for improving the shelf life of stored blood.

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