Study Finds That Extreme Exercise Carries Metabolic Consequences

by Shawna Williams for The Scientist e-zine

Healthy people put through high-intensity interval training, or HIIT, displayed  insulin resistance and mitochondrial dysfunction after working out excessively.

 As a researcher at the Swedish School of Sport and Health Sciences, Filip Larsen would hear anecdotes about the downsides of too much exercise—a common enough phenomenon that nevertheless puzzled him. “All athletes know if you train too much, something’s happening. . . . Your legs feel terrible after a while, and then if you just continue, you have these psychological disturbances too, like mood disturbances,” he says. “That hasn’t been really described in the literature—no one knows exactly what’s going on.”

To find out, Larsen and his colleagues recruited 11 healthy young people and put them through a 4-week, increasingly intense regimen of sessions on a stationary bike while monitoring their glucose tolerance and mitochondrial function. During the toughest week, the subjects displayed insulin resistance and other deleterious metabolic changes, the team reported last week (March 18) in Cell Metabolism.  

“It’s a very impressive study,” says Thijs Eijsvogels, an exercise physiology researcher at Radboud University Medical Center who was not involved in the work. Typically, cardio-metabolic health improves with greater exercise volumes, and the results indicate that there’s a point at which those benefits stop accruing, he notes.

That changed in the third week, designed to represent excessive training, during which the participants completed a grueling 152 minutes of intervals over the course of the week. After that, the subjects’ intrinsic mitochondrial respiration fell by an average of 40 percent compared with the samples taken at the end of the moderate-intensity week, the researchers report. 

It’s quite similar to the changes that you see in people that are starting to develop diabetes or insulin resistance.
—Filip Larsen, Swedish School of Sport and Health Sciences

Furthermore, the subjects’ glucose tolerance—measured by their glucose levels before and after they consumed a sweet drink—also dropped between the light-training week and the end of the excessive-training week (no oral glucose test was performed after the moderate training week). “It’s quite similar to the changes that you see in people that are starting to develop diabetes or insulin resistance,” Larsen says. 

After a recovery period, during which participants completed 53 minutes of intervals spread across the week, most measures rebounded. Oxygen consumption and power output during exercise, as measured by how hard they pedaled, were higher after recovery than at baseline or at any other point during the experiment. However, intrinsic mitochondrial respiration had not fully recovered by the end of the experiment, remaining 25% lower after recovery than it had been after the moderate week. 

In a second component of the experiment, the researchers monitored blood glucose levels in 15 elite athletes who weren’t subject to any intervention and in matched, non-athlete controls. On average, the two groups’ levels over a given 24-hour period were about the same, but the athletes spent more time with glucose levels either above or below the normal range. Eijsvogels remarked, “I think joining together all of these findings gives a really strong message of the impact of repeated and sustained bouts of intense exercise training on glucose tolerance,” he says. 

The study didn’t examine what, if any, long-term health consequences might arise from excessive exercise. Linda Pescatello, who studies the health effects of exercise at the University of Connecticut and was not involved in the study, says she suspects the findings about the effects of over-exercise do indeed have real-life ramifications, with individuals having different thresholds for over-exercise depending on their fitness levels.

She points to a 2020 review article, coauthored by Eijsvogels, that found associations between very high levels of exercise and what the authors called “potential cardiac maladaptations” such as coronary artery calcification. “I guess the bottom line is, especially for the average person, all in moderation if you want to maximize the health benefits” of exercise, she says. 

Study coauthor Mikael Flockhart, also at the Swedish School of Sport and Health Sciences, says that it’s not clear where the “tolerable limit of training” is. Knowing where that limit is, he says, would be helpful to everyone. 

Reference: M. Flockhart et al., “Excessive exercise training causes mitochondrial functional impairment and decreases glucose tolerance in healthy volunteers,” Cell Metab, doi:10.1016/j.cmet.2021.02.017, 2021.