Can Endurance Exercise Be Harmful?

In 490 BC, Pheidippides (or possibly Philippides) ran from Athens to Sparta to ask for military aid against the invading Persian army, then back to Athens, then off to the battlefield of Marathon, then back to Athens to announce the army’s victory, after which he promptly died. The story, if it is to be believed (there is some doubt among historians), raises an interesting question: Are some forms of exercise dangerous?
Running a marathon is a lot of work. The “worst parade ever,” as one spectator described it, is not without its risks. As a runner myself, I know that it doesn’t take much to generate a bloody sock at the end of a long run. 
But when most people think about the risks of exercise, they mean the cardiovascular risks, such as sudden deaths during marathons, probably because of the aforementioned ancient Greek’s demise. The reality is more reassuring. An analysis of 10 years’ worth of data from US marathons and half-marathons found that out of 10.9 million runners, there were 59 cardiac arrests, an incidence rate of 0.54 per 100,000 participants. Others have found incidence rates in the same range. An analysis of the annual Marine Corps and Twin Cities marathons found a sudden death rate of 0.002%.
Marathon runners do sometimes require medical attention. In the Twin Cities cohort, 25 out of every 1000 finishers required medical attention, but 90% of their problems were mild. The majority included issues such as dehydration, vasovagal syncope, hyperthermia, and exhaustion. Musculoskeletal problems and skin abrasions made up the rest. Objectively, long distance running is fairly safe.
Then a study comes around suggesting that marathon runners have more coronary artery calcium (CAC). In 2008, German researchers compared 108 healthy male marathon runners over 50 years of age with Framingham risk–matched controls. The marathoners had a higher median CAC score (36 vs 12; P =.02), but scores across the board were quite low and not all studies were in agreement. The MESA study and another from Korea found an inverse relationship between physical activity and coronary calcium, but they compared sedentary people with vigorous exercisers, not specifically marathoners.
Two later studies, published in 2017, generally corroborated that endurance exercise was associated with higher calcium — with some caveats. A group from the Netherlands looked at lifelong exercise volume and compared men who accumulated > 2000 MET-min/week with those who exercised < 1000 MET-min/week. Again, the analysis was limited to men, and CAC scores, though statistically different, were still very low (9.4 vs 0; P =.02). Importantly, in men with coronary plaques, the more active group had less mixed plaque and more calcified plaque. 
A UK study of middle-aged masters-level athletes at low cardiovascular risk had similar findings. Most of the study population (70%) were men, and 77% were runners (not all were marathoners). Overall, the male athletes had not only more plaque but more calcified plaque than their sedentary peers, even though most male athletes (60%) had a CAC score of zero. 
The findings from these two studies were interpreted as reassuring. They confirmed that athletes are a generally low-risk group with low calcium scores, and although they might have more plaque and coronary calcium on average, it tends to be the more benign calcified type.
But the 2023 Master@Heart study challenged that assertion. It analyzed lifelong endurance athletes, late-onset endurance athletes (those who came to the game later in life), and healthy nonathletic controls. The median number of plaques and the average CAC score were the same across groups, but the plaque burden was higher in lifelong athletes compared with controls. The study also found more coronary stenoses in lifelong athletes, but the breakdown of calcified vs noncalcified vs mixed plaques was the same across groups, thus contradicting the idea that exercise exerted its protective effect by calcifying and therefore stabilizing said plaques. The silver lining was fewer vulnerable plaques in the lifelong athletes (defined via high-risk features) but these were generally rare across the entire population.
Whether Master@Heart is groundbreaking or an outlier depends on your point of view. In 2024, a study from Portugal suggested that the relationship between exercise and coronary calcification is more complicated. Among 105 male veteran athletes, a high volume of exercise was associated with more coronary atherosclerosis in those at higher cardiovascular risk, but it tended to be protective in those deemed lower risk. In fact, the high-volume exercise group had fewer individuals with a CAC score > 100 (16% vs 4%; P =.029), though again, the vast majority had low CAC scores.
A limitation of all these studies is that they had cross-sectional designs, measuring coronary calcium at a single point in time and relying on questionnaires and patient recall to determine lifelong exposure to exercise. Recall bias could have been a problem, and exercise patterns vary over time. It’s not unreasonable to wonder whether people at higher cardiovascular risk should start exercising to mitigate that risk. Granted, they might not start running marathons, but many of these studies looked only at physical activity levels. A study that measured the increase (or stability) of coronary calcium over time would be more helpful.
Prior research (in men again) showed that high levels of physical activity were associated with more coronary calcium, but not with all-cause or cardiovascular mortality. But it too looked only at a single time point. The most recent study added to the body of evidence included data on nearly 9000 men and women and found that higher exercise volume did not correlate with CAC progression over the mean follow-up of 7.8 years. The study measured physical activity of any variety and included physically taxing sports like golf (without a cart). So it was not an assessment of the dangers of endurance exercise.
Ultimately, many questions remain. Is the lack of risk seen in women a spurious finding because they are underrepresented in most studies, or might exercise affect men and women differently? Is it valid to combine studies on endurance exercise with those looking at physical activity more generally? How accurate are self-reports of exercise? Could endurance exercisers be using performance-enhancing drugs that are confounding the associations? Are people who engage in more physical activity healthier or just trying to mitigate a higher baseline cardiovascular risk? Why do they give out bananas at the end of marathons given that there are better sources of potassium? 
We have no randomized trials on the benefits and risks of endurance exercise. Even if you could get ethics approval, one imagines there would be few volunteers. In the end, we must make do with observational data and remember that coronary calcifications are a surrogate endpoint. 
When it comes to hard endpoints, an analysis of French Tour de France participants found a lower risk for both cardiovascular and cancer deaths compared with the general male population. So perhaps the most important take-home message is one that has been said many times: Beware of surrogate endpoints. And for those contemplating running a marathon, I am forced to agree with the person who wrote the sign I saw during my first race. It does seem like a lot of work for a free banana.
Christopher Labos is a cardiologist with a degree in epidemiology. He spends most of his time doing things that he doesn’t get paid for, like research, teaching, and podcasting. Occasionally he finds time to practice cardiology to pay the rent. He realizes that half of his research findings will be disproved in 5 years; he just doesn’t know which half. He is a regular contributor to the  Montreal Gazette, CJAD radio, and CTV television in Montreal and is host of the award-winning podcast The Body of Evidence.