Ultrarunning Damages Cells as Much as a Severe Infection—That Might Actually Be a Good Thing

Updated March 10, 2026 02:54PM

It’s a common conundrum among committed runners: What began with the purest intentions (I’m going to start running for my health!) gets taken to an extreme. Suddenly, you find yourself at mile 22 of a marathon or three quarters of the way through a 100-miler, feeling like you’re going to die.

Is running actually good for me? You may find yourself wondering at that moment. It’s the same question scientists tried to answer in a recent study published by the American Society of Hematology’s journal Blood Red Cells & Iron.

Specifically in the study, “Long-Distance Trail Running Induces Inflammatory-Associated Protein, Lipid, and Purine Oxidation in Red Blood Cells,” researchers looked at the impact of ultra-long distance trail running on red blood cells—the tiny molecules that ferry oxygen from the heart and lungs to the vast corners of the body, including your hard-working muscles as they power you up mountains and withstand steep descents.

By testing elite runners in two races during the UTMB World Series Finals week—MCC, a 40K, and Ultra-Trail du Mont-Blanc (UTMB), the full 170K around the Mont Blanc massif, they were able to examine the cellular impact of going hard and long versus hard and very, very long.

What they found is racing a very, very long ultra like UTMB is akin to getting a severe infection when it comes to the inflammatory response within the body—the stress accelerates the aging and removal of red blood cells.

But what was surprising is how red blood cells are damaged. It’s not just from the mashing of red blood cells from pounding feet on the ground, a mechanism known as footstrike hemolysis. Rather, racing these types of events pushes red blood cells into an inflammatory, oxidative aging process, causing them to stiffen up and get kicked out of circulation.

What do these findings mean for ultrarunners? Probably not what you think. We unpacked the study and spoke to the lead author, Travis Nemkov, PhD and assistant research professor in the department of biochemistry and molecular genetics at the University of Colorado Anschutz Medical Campus, to find out.

Why Red Blood Cells Matter

A quick primer, for those who have understandably forgotten the minutiae of high school biology class: Red blood cells account for over 80% of the cells in your body. That’s 20 or 30 trillion red blood cells transporting oxygen (and returning carbon dioxide) from your lungs to your tissues at any given time.

But they don’t live forever—just 90 to 120 days on average. The National Institutes of Health reports that two to three million new cells are produced in the bone marrow every second to replace dying ones.

Each red blood cell starts its journey as a stem cell deep in the bone marrow. It goes through a maturation process called erythropoiesis, during which the cell changes from a blank slate that could become any type of blood cell to a specialized red blood cell, also called an erythrocyte.

“It’s a complicated molecular biological program that gives the cell its identity,” Nemkov says. “But in the process of maturing, the red blood cells are unique because they get rid of their nuclei and other organelles and they do this to maximize the amount of hemoglobin that they can have inside the cell while minimizing the cell volume,” he explains. These cells adopt a “specific geometry of the membrane so that they can deform very easily as they’re squeezing through the vasculature.”

TL;DR: Red blood cells lose the control center of the cell—the nucleus—so they can load up on oxygen to better serve the needs of other cells in the body. They are also bendable so they can move through tight vessels more easily, rendering them especially good at circulating throughout the body, where they often encounter changing fluid pressures, oxygen levels, and salt environments. Other cells wouldn’t be able to withstand those variables, but red blood cells are designed to stay flexible—literally and figuratively.

“It’s a very stressful life that the red blood cell lives,” Nemkov says. One reason red blood cells are able to make it to the three or four month mark is they don’t have a nucleus. But this adaptation also means the cell no longer has ribosomes, which are the particles that make proteins. And if a cell can’t make proteins, it becomes more difficult to repair itself when it gets damaged.

But red blood cells have developed a workaround; as the cell ages and becomes more damaged, it sheds that damage in extracellular vesicles. These small, membrane-bound structures are released by red blood cells as they age or undergo stress.

As the cell branches off these vesicles, it shrinks in size and the red blood cell loses some of its innate flexibility. As damage accrues, red blood cells eventually call in the clean-up crew: they release phosphatidylserine, a type of fat that summons macrophages—specialized white blood cells that are a critical component of the immune system—to clean up the aged red blood cells.

The more damage a red blood cell has, the more of that phosphatidylserine it releases, which tells the macrophage to come eliminate it. That’s where ultrarunning comes into the picture.

What the Study Found

The small study involved 23 elite runners who competed in either Martigny-Combes à Chamonix (MCC)—a 40K (25-mile) event with over 7,500 feet of elevation gain—or UTMB—a 171K (106-mile) ultramarathon with a whopping 33,000 feet of gain and descent through the French, Italian, and Swiss Alps. Eleven of those runners (five female and six male) ran MCC and 12 runners (four female and eight male) ran UTMB.

For reference, the winning 2025 MCC times were 3:40:10 (men) and 4:16:24 (women)—less than one-fifth of the winning 2025 UTMB times, which were 19:18:58 (men) and 22:56:23 (women).

The researchers took blood samples from participants before and after each race and compared the samples to see what changes occurred. They made several observations:

Increased Inflammation and Oxidative Stress

While both cohorts experienced increases in inflammation and oxidative stress after their events, the UTMB athletes had significantly more IL-6 and kynurenine increases and acute-phase protein induction. These increases signify significant inflammation and immune system activation.

They also noted profound lipid remodeling, or structural modifications and a reorganization of the lipid layer surrounding red blood cells. These are the types of changes we see with environmental stress, aging, and illness. The researchers also noted elevated levels of creatine kinase in the plasma, an indication that muscle damage has occurred, so “it’s hard to say how much of the fatigue, pain, and exhaustion arises from this red cell-specific damage,” Nemkov says.

Reduced Red Blood Cell Flexibility

In the UMTB cohort, the researchers observed significant hardening of red blood cells, which means these cells would have had more difficulty circulating as needed throughout the body.

Whether these changes are a problem is not clear yet, Nemkov notes. “That loss of deformability we observed was not pathological,” he says. The decrease was only about 3%, which isn’t enough to create a disease state.

Activation of the Lands Cycle

Red blood cells remodel and repair themselves through a process called the Lands Cycle—named for the biochemist William EM Lands who discovered the mechanism in the 1950s. The pathway restores cellular membrane function by replacing oxidized lipids and involves adenosine triphosphate and fatty acids—two different types of energy sources—to repair damage to the cells.

Changes to Hematocrit

Hematocrit (total red blood cell count) at the start of the event was typical of trained runners at about 40-45% of the total blood count.

At the finish line of UTMB, the average hematocrit had fallen slightly to about 38-40%. That reduction in red blood cell count could be in part due to the clean-up process initiated by the macrophages, but is also likely related to the expansion of plasma volume that’s typical during endurance activities.

“During these races—specifically in the UTMB—there’s actually an expansion of the plasma and so the hematocrit goes down because there’s more volume,” Nemkov explains.

Accelerated Cellular Aging

The bottom line is, the farther the runners went, the more cellular aging was noted in the red blood cell samples through the identification of increased generation of red cell derived micro-particles.

At the end of MCC, the researchers saw evidence of this natural process related to stress and aging at work. But at the end of UTMB, they noticed more micro-particles were being generated, “which tells you that there’s more shedding going on, predictably, because there’s more damage inside of the cells and they’re getting rid of more damaged components,” Nemkov says.

What It All Means

These findings all suggest that red blood cells are under a lot of pressure to perform during long-distance running events, but a very long and hard ultramarathon like UTMB seems to accelerate red blood cells aging more than “shorter” long events like MCC.

In short, the stress of an event like UTMB appears to outpace the body’s ability to recover. And that stands to reason: The farther you run, the more likely you are to develop cellular damage.

But what it all means is still a developing picture. Nemkov underscores that their observations don’t suggest that any disease process is at work, or that permanent or dangerous damage is occurring alongside these findings.

“Most people when they finish an ultramarathon are not OK, but they’re not in dire straits,” Nemkov notes. Indeed, hobbling around afterward with sore muscles and feeling an urgent need to refuel, rehydrate, and sleep are all normal outcomes of running for hours on end—and a badge of honor for some athletes. But in a couple of days, you’re back to normal and already thinking about signing up for the next adventure.

Should I Be Worried?

If you’re a 100-mile obsessive or are considering making the leap from shorter races to longer slogs, should you be worried by these findings?

“The research world is trying to disentangle exactly what type of event, how long of an event, how many of these events in a given year, and how many years [would be problematic]—so intensity and dosage—but that’s not known,” Nemkov says.

For its part, this singular paper aims to simply document the changes that were observed. “We’re not making a comment on if this is good or bad for people, because we just don’t know,” Nemkov says.

Indeed, there could, in fact, be a longer-range beneficial impact to this type of applied stressor: Damage to these cells could actually be rejuvenating.

“It’s possible that you’re keeping your blood younger” when you engage in ultra-endurance events, Nemkov says. While it’s clear that an ultramarathon will accelerate the damage in the short-term, “you’re also birthing new red cells in the process and they could rejuvenate and replenish” your system in the long run. (Get it? Long run? Ha.)

These insights could potentially have applications for prescribing activity for cancer patients undergoing treatment. For example, using the changes observed in the body during the “healthy fatigue” that’s induced during endurance exercise and comparing them to the changes that occur in people who have cancer could help reveal prescriptive exercise recommendations.

There’s also an application for transfusion medicine; the changes observed in the ultramarathoners’ samples bore some striking similarities to blood banked for transfusions. Nemkov and his team are continuing to look for ways of preventing the oxidation and loss of flexibility of red blood cells that’s common in stored blood so that donated blood stays viable in the bag longer.

It’s still early, Nemkov notes, “and I have no idea how things will shape up, but our research mission is to learn about human physiology on a molecular scale first so that we know what we’re looking at later.” Defining what’s “normal” could provide insight for solving issues that develop when something turns “abnormal.”

For now, if you enjoy ultrarunning, have at it. In time, science may have a better answer for how much is too much when it comes to your red blood cells. And with it may come a personalized training plan that balances the comparative age of your red blood cell pool with genetic and nutritional factors to optimize performance.

Ultrarunning Damages Red Blood Cells—In a Good Way?