I had a running injury that kept me from running consistently for the better part of 13 years. I went to running coach after running coach, chiropractors, PT specialists, orthopedists, and they all told me the same thing after treatment: “I can’t fix you.” It was an incredibly frustrating experience because I so badly wanted to get back to running, but I wasn’t able to. And specialist after specialist told me to do nearly the exact same things, and it didn’t work.
At some point, after the third or fourth specialist that I saw, my brain started to think, “Wait, this doesn’t make sense, I’ve already done this and it didn’t help.” I didn’t listen to that voice though. After all, these people made their livings fixing athletes, and surely they knew better than me, so I kept looking for another, and another, each time hearing the same thing, “I can’t fix you.”
I should’ve listened to that voice earlier, it would’ve saved me years of rehab. But I didn’t, because they were the experts and I was just a guy trying to get back on the road. I assumed that, because they were the “experts” their abilities to identify the issue was superior to mine, and perhaps I was doing something wrong and my logic was somehow flawed.
As it turns out, I wasn’t wrong, my logic wasn’t flawed. And as I was wondering about why we lose our breath at the early portions of a run when we’re first starting out, I got that same feeling. The explanation that I kept reading didn’t make sense given my history (and I started, stopped and restarted again many times during that 13-year period). Something seemed “off” in what I read time and time again and that same twinge of “Wait, this doesn’t make sense,” crept into the back of my brain.
What we read most often is that it’s because our bodies are shifting from a resting state to one of high demand, and that creates an oxygen debt. And the heart and lungs need to adjust to this demand before things can stabilize. But that didn’t make sense to me.
When we’re starting a running program, our bodies aren’t yet in a position to fully stabilize things, our bodies haven’t yet adapted to the demands of running so we simply don’t have the ability to process oxygen on a higher level, but that’s what we read, time and time again. It’s like telling someone who’s building up credit card debt not to worry, because things will stabilize eventually if they keep doing what they’re doing, without changing their spending habits. It doesn’t make sense.
The Jack Daniels “Aha!” Moment
Then, I remember reading a book by running coach Jack Daniels, Daniels’ Running Formula, who makes the argument that breathing is more about getting rid of carbon dioxide than it is bringing in fresh air. And then it clicked.
Most people think they’re gasping for more oxygen. The reality? Your ‘engine’ is just waiting for you to clear the exhaust.
Again, if lack of oxygen was the only issue, then it would mean that our bodies would need to reach a state of efficiency that, frankly, doesn’t seem plausible to me. But, if it was too much of something else, in this case carbon dioxide, then the body needing a little time to get rid of it then causing us to breathe harder for a few minutes makes perfect sense.
As it turns out, the brain is at least slightly more sensitive to carbon dioxide than it is oxygen and, as Daniels argued, our breathing is more regulated by increasing carbon dioxide levels than it is decreasing oxygen levels.
The biology of the ‘First-Mile Gasp’: Your lungs prioritizing the exit of CO2 over the entry of oxygen.
Why Your Brain is a CO2 Sensor
One of the illustrations (paraphrased) that Daniels gives is to remember a time that you were holding your breath under water. At some point, we get an urge to come up to the surface and breath — the longer we stay down, the more that urge becomes urgent. That urgency that we feel, is more about the body saying, “We’ve got way too much CO2 here, I need to clear this out before things get serious!”.
So what should you do when you start breathing heavy at the beginning of a run? Keep going, walk if you need to. Understand that your body just suddenly started requiring a lot of energy, and a byproduct of that is carbon dioxide. And that carbon dioxide has built up and needs to leave. That process of getting rid of it will happen relatively quickly, so keep moving and let it run its course.
The good news here is that, the longer we run consistently, the better our bodies become at running and the more efficiently our bodies will clear that CO2 — you’ll no longer be gasping for air a minute after you start running. This can happen in a few weeks, a few months or longer for some people. But it does improve significantly.
Just know though that those heavy breaths? They’re completely normal, nothing’s wrong. It’s a rite of passage, a badge of honor, if you will, that every runner earns once they get through this stage. Keep moving though, whatever that looks like for you. Keep lacing up, heading out and get through this stage. You probably won’t even notice that those rough starts to your runs aren’t there anymore. But one day, you’ll finish a run and think, “Wow, that was easy!”. And then it hits you.
Sources:
Physiology, Respiratory Drive – National Center for Biotechnology Information (NCBI). An in-depth look at how the body prioritizes CO2 levels to regulate breathing.
Think about that feeling of finishing a race, whether it’s a 5k or 10k, even a half marathon. For me, there’s that immediate feeling of, “it’s done, I’ve finished,” followed by a sense of accomplishment and a deep curiosity about my time. While I’m pondering how I did, the fatigue is starting to creep in. But honestly, it’s nothing that a short recovery walk with some water and a quick snack won’t fix.
But those are shorter races. How about that feeling that comes after a marathon, or the even more demanding ultra? Now we’re talking about the kind of fatigue that a short walk and some electrolytes simply can’t fix. For marathons, full recovery can take more than a few days and, for some ultramarathons, full recovery can take weeks.
Let’s talk about that.
Why These Races Take Such a Toll
We’ve always known that high endurance events such as the marathon and ultra are hard on the body. And even as early as the late 1800s, we knew that our bodies paid a price for running marathons. Until recently though, we’ve lacked the scientific ability to figure out exactly what that price was and why and how it was being paid.
In February of 2026, a study was released in the journal Blood: Red Cells & Iron, led by Travis Nemkov, PhD, an Associate Professor at the University of Colorado Anschutz Medical Campus. This study evaluated red blood cells in runners who participated in both marathon and ultramarathon distances, and the results were pretty interesting (at least I think so). And, before continuing, no, I’m not going to get all scientific here. In fact, we’ll be talking a lot about UPS trucks!
Again, this isn’t the first time that we’ve looked at red blood cells in endurance events. We’ve known for some time that red blood cells experience damage and get replaced more often post-race. But, for the first time, we now have the ability to look inside of those cells, to see what’s happening on a molecular level, evaluating things like proteins, lipids and metals to understand exactly why and how this damage is occurring.
What Red Blood Cells Do
To start off, let’s cover the basics: what do red blood cells actually do?
Simply put, they carry oxygen to every part of our body and transport things like carbon dioxide out of it. That’s it. And, keep in mind that every single organ and muscle in our bodies relies on red blood cells doing their job at a near flawless level in order to keep operating at a high level.
Imagine your body was a company who relied heavily on deliveries going in and out of your doors. Your chosen fulfillment partner is UPS. As long as those deliveries and pickups happen on schedule, everything’s going to go well. But, once there’s a hiccup in the chain, things begin to break down. That’s essentially what happens in marathons and ultras, somewhere in UPS’s system, things go awry and your business pays the price.
What the Study Looked At
Researchers tested blood before and after a marathon and an ultra — the particular events being the 40k (roughly 25 miles) Martigny-Combes à Chamonix and the 171k (or 106 miles) Ultra Trail de Mont Blanc races. To analyze the samples they used testing called multiomics, which is like a 360 degree molecular health scan. For example, if a dashboard warning light on one of the UPS trucks comes on, multiomics can take the entire truck apart and evaluate every single component to see what caused the light to go on, and figure out what else may have contributed to the warning light.
Multiomics can evaluate any number of things. For this study, they specifically looked at metabolomics (chemical byproducts), lipidomics (fats), proteomics (proteins), and metallomics (metals) that exist within our red blood cells. And with that, all of the scientific terms are officially out of the way…for the most part.
What the study found
Increased Inflammation
Inflammation is one of the body’s primary defense mechanisms, the “first responders”, if you will. When damage in the body is sensed, white blood cells are sent to localized sites to fix what’s broken. It works really well as a short-term fix. However, when inflammation persists, we run the risk of healthy tissue being compromised. It’s important to note that the inflammation that we see as a result of ultramarathons, though intense, is typically short lived and highly regulated.
In both the marathon and ultra distances, increases in inflammation were present (which makes sense). One way we measure this is by looking at two markers called IL-6 and kynurenine. Simply put: when elevated levels of both are present, it means the body is under significant stress and is switching its available resources into survival mode. Think of IL-6 as the person waving a red flag saying, “Hey, we need help here!”, while kynurenine is evidence that the body has started diverting its normal “business-as-usual” fuel into emergency repairs.
Once that IL-6 starts waving its flag, other things also start happening inside of our red blood cells.
Oxidative Stress and Molecular Damage
When endurance events push the body “off-book,” red blood cells face oxidative damage similar to a delivery fleet being driven over punishing terrain.
Let’s talk about our UPS trucks again.
When delivery vehicles are used as they’re designed to be used, they’ll last a long time and remain that reliable key component of what’s needed to run our business. Let’s say though that the drivers of these vehicles go off book and use them in ways that they’re not intended to be used. Imagine them taking these trucks through “short cuts” that involve rough dirt roads, ice, snow and a few “Here, hold my beer!”, moments. Those trucks aren’t going to last very long. Before long, we’ll see them dented with paint scratched and rusting, with what’s underneath the hood experiencing similar damage.
The study suggests that the same thing happens to our red blood cells when we run in ultramarathons.
The key thing to come out of this study was that, as a result of running that 106 mile ultramarathon, the red blood cells in the runners had appeared to “age”. Red blood cells hang around in our system for somewhere around 120 days before they’re cycled out and replaced. Because of the damage that occurred to the cells as a result of the race, a red blood cell that is, say, 20 days old, may appear as if it was 100 days old.
This happened for a number of reasons.
Firstly, the cell walls themselves became more rigid, losing their flexibility. This occurs because the cell’s skin, the “lipid layer” hardens and loses its ability to flex and bend. This matters because red blood cells need to flex in order to fit through a myriad of narrow capillaries. When those cells can’t bend, they can’t bring that much needed oxygen to organs and muscles and, just as importantly, they aren’t able to carry all of those waste products, like carbon dioxide and hydrogen ions.
This lack of flexibility happens because of oxidation, and we see oxidation everywhere in everyday life. On our delivery trucks, it shows up as rust on the body panels or hardened rubber on tires and weather stripping around windows. That exact same thing happens to cell walls and just as we perceive a rusty car as being old, those red blood cells also appear to have aged before their time.
And, while oxidation was having its way on the outside of the cell, the insides suffer as well. Imagine the brakes and suspension creaking and squealing, the welds that keep the vehicle stable, and engines eventually seizing, giving up. The proteins that live inside of these red blood cells, because of this oxidation, simply can no longer do their jobs; the ability to carry badly needed oxygen to the organs and muscles is significantly compromised, not to mention carrying out waste products like carbon dioxide and hydrogen.
Under oxidative stress, red blood cells can become misshapen and less flexible, reducing their ability to efficiently carry oxygen.
So, we get this double-whammy of damage that happens. The cell walls are stiffening, making it difficult to navigate those tight turns inside of smaller blood vessels and capillaries, and they lose the ability to carry the cargo from one place to another.
When The System Gets Overwhelmed
The body is an amazing thing though, and it has a process in place to deal with these issues. Think of this process as the repair facility that keeps all of those UPS trucks running in peak condition. In the body, it’s called the Lands cycle and its essentially a mobile repair shop that fixes the normal wear and tear that occurs in the body. During ultramarathons though, this system becomes overwhelmed and it cannot keep up with the demands that we’re asking of it.
It’s important to keep in mind that the body is always getting rid of older, lower performing red blood cells as part of its business-as-usual routine. What this study also showed is that the process of clearing out underperforming cells speeds up, citing that “there is enhanced removal of damaged cells from circulation”. The downside is that it takes time to produce these new red blood cells. And, as is the case with the Lands cycle, this system isn’t able to keep up with the demand.
We’ve spent a lot of time talking about ultramarathons, but what about marathons?
Marathon vs Ultramarathon
We see this same type of cellular damage happening in marathons, but the distance is less severe and therefore more recoverable — the body repair mechanisms appear to have the ability to keep up with the pace of what’s being asked of it. Nemkov said this, “At some point between marathon and ultra-marathon distances, the damage really starts to take hold,”. So, once you push past those 26.2 miles, the math changes.
In both the marathon and the ultramarathon groups, damage to red blood cells was evident. But it was the ultramarathon group showed that red blood cell oxidation happening — the cell walls stiffening and the internal components starting to fail.
Another Interesting Observation
Probably one of the most intriguing things to come out of this study, again for me at least, was the comparisons to red blood cells after ultramarathons and what’s seen in stored blood used for transfusions. And people like Nemkov are actively looking at ways to prevent this type of oxidation from happening so that blood can last longer in bags as it’s waiting to be used.
At the end of the day, there were no recommendations or guidance telling people that they shouldn’t run ultramarathons; that wasn’t the aim of this study. It was merely something that was tested because it was interesting — the extreme nature of ultramarathons makes the body a very unique and effective laboratory for evaluating things like this. And, it helps explain why that fatigue lasts so long after we push our bodies past that marathon distance. But that’s how science works — as we do a bunch of studies that are interesting, our knowledge base grows. And as that knowledge base grows, we gain a better understanding of what’s happening in our world. We’re then able to take all of the accumulated knowledge and come up with treatments and technologies that eventually go on to make meaningful differences in people’s lives.
For something like this, perhaps it can make the difference between life and death after someone’s been in an automobile accident. Perhaps it will mean that recovery happens just that much quicker for Olympic runners so they can train more effectively. We don’t know.
It’s been said that the best reaction that a researcher can have after a study isn’t, “That’s exactly what I expected!”, but rather, “Hmmm…that’s interesting…” And that’s what this study was, a point of interest, a thing that expands our body of knowledge about a thing that may lead to future discoveries. That’s how science works, and that’s why science is cool.
Sources:
Travis Nemkov et al. Long-distance trail running induces inflammation-associated protein, lipid, and purine oxidation in red blood cells.Blood: Red Cells & Iron, 2026. [Read the study]
American Society of Hematology. Ultramarathons may damage red blood cells and accelerate aging. Science News release, February 21, 2026. [Read the press release]
HealthDay News. Ultra-Marathon Running Depletes Athletes’ Red Blood Cells, Study Finds. February 19, 2026. [Read the article]
