Ultramarathon Running Mechanically Damages Red Blood Cells in Ways That Persist After the Race

Red blood cells are the body's oxygen couriers - small, flexible discs that squeeze through capillaries narrower than themselves, delivering oxygen to tissues and carrying carbon dioxide away. Their flexibility is not incidental; it is essential to function. A red blood cell that becomes rigid fails to navigate the microvasculature and cannot do its job. It also ages faster and gets removed from circulation sooner, reducing the total count available for oxygen transport.

A study published in Blood Red Cells and Iron, the American Society of Hematology's journal devoted to red blood cell research, examined what extreme endurance running does to these cells. The answer, drawn from a detailed molecular analysis of 23 runners before and after two major races, is that it damages them substantially - and that the damage worsens with race distance in ways that may have implications for both athletic performance and the science of blood storage.

Two Races, Two Damage Profiles

The research team analyzed blood samples collected immediately before and after athletes completed the Martigny-Combes a Chamonix race (40 kilometers, approximately 25 miles) and the Ultra Trail de Mont Blanc race (171 kilometers, approximately 106 miles). For each sample, they measured thousands of proteins, lipids, metabolites, and trace elements in both the plasma and within the red blood cells themselves - described by the authors as the most comprehensive molecular map of exercise-induced red blood cell changes produced to date.

Red blood cells from both races showed consistent evidence of two types of damage. Mechanical damage - physical deformation and disruption of cell membranes - resulted from the fluctuating fluid pressure red blood cells experience as blood circulates through a body in motion, with the impact of each footfall creating pressure waves that stress cell membranes. Molecular damage reflected inflammation and oxidative stress: when the body's antioxidant defenses are outpaced by reactive oxygen species generated during sustained exercise, those molecules attack proteins, lipids, and other cellular components.

Both damage signatures were clearly present after 40-kilometer races. After 171-kilometer races, they were amplified. The researchers interpret this as evidence that damage accumulates with distance rather than saturating at some threshold: longer runs mean more total exposure to the mechanical and oxidative stressors that harm red blood cells.

Reduced Flexibility After Long Races

A key functional consequence identified in the study was reduced red blood cell deformability - the cells became less flexible after races. This matters because flexible cells can squeeze through small capillaries to deliver oxygen to muscle tissue; stiffer cells struggle to reach the most demanding tissues and are also removed from circulation more quickly by the spleen, which filters out damaged or rigid cells.

"Participating in events like these can cause general inflammation in the body and damage red blood cells," said lead author Travis Nemkov, 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."

What Remains Unknown

The study's central limitation is that blood samples were collected immediately before and after races. The duration of the damage - how long red blood cells remain compromised after extreme exercise, and how quickly the body replenishes its normal red blood cell population - was not measured. Some recovery may be rapid; some effects may persist for weeks.

"At some point between marathon and ultra-marathon distances, the damage really starts to take hold," Nemkov said. "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."

The study was further limited by its small sample of 23 runners and lack of racial diversity - acknowledged by the researchers as constraints that future, larger studies will need to address. Blood samples were collected at only two time points per race, which means the trajectory of changes during the race itself and in the immediate recovery period is not captured.

Connections to Blood Storage Science

The research team draws an explicit parallel to a different problem: stored blood. Blood in transfusion banks begins to degrade after collection, developing similar molecular signatures to the exercise-induced damage documented in this study. After about six weeks, stored red blood cells become unsuitable for transfusion. Understanding the molecular mechanisms of red blood cell aging and damage - whether induced by extreme exercise or by storage - could inform strategies to extend the shelf life of stored blood or improve transfusion outcomes.

"The mechanisms driving red blood cell aging during storage in blood banks mirror those we observe in the blood of ultramarathon runners during extreme exercise," Nemkov noted. "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."