Frequent, intense training cripples mitochondrial function and reduces glucose tolerance, resulting in poorer performance and possibly illness, according to a new study examining the cellular mechanism behind fatigue, soreness and a host of other ills familiar to professional and amateur athletes alike.

The Swedish scientists who authored the paper, published March 18 in Cell Metabolism, believe their research can serve as a reminder to fitness enthusiasts of all experience levels that the body needs time to adapt to the stress of strenuous exercise.

"I think it's a call for caution that it's not better to just train harder," said lead author Mikael Flockhart, a Ph.D. student at The Swedish School of Sport and Health Sciences. "You should get a feeling for when you are too fatigued, and maybe then you should take a rest day or a day off, not try to push harder, because you don't necessarily get better —  you get worse."

Over three weeks, Flockhart and his colleagues subjected a group of people who were healthy and active but not considered athletes to an increasingly grueling regimen of high-intensity interval training on a stationary exercise cycle. The 11 volunteers began with two interval sessions totaling 36 minutes of all-out effort in the first week, ending with five totaling 152 minutes in the last week. 

For the volunteers, it wasn't all fun and fascinating findings.

"Some guy was just sitting up between intervals, screaming, 'What is happening in my legs? What is this? I feel so terrible,'" Flockhart said in an interview with The Academic Times. "That's how it would feel to be really fatigued. But yeah, they come back day after day and just struggle."

At the end of each week of training, Flockhart and his colleagues performed a glucose tolerance test on each participant after giving them a glass of sugar water and controlling their diet on training days. They also took thigh muscle biopsies, which helped reveal activity in mitochondria, the energy-producing organelles.

Intense training is known to damage mitochondria, so Flockhart hypothesized that the extreme training would break the organelles down to the point where the body could not create effective replacements. He also hypothesized that the oxidative stress produced by abnormally vigorous exercise might further damage mitochondria.

But the participants' muscle biopsies and measurements of oxidative stress proved both of these hypotheses wrong. 

Instead, Flockhart and his colleagues interpret their results as a partial shutdown of mitochondria in response to the high amounts of oxidative stress they produce when pushed too far. The mitochondria increased in number and became more densely packed in the muscle cells, creating oxidative stress, from which the body appears to try to protect itself by inhibiting some of this mitochondrial activity. 

According to Flockhart, the findings show a "mismatch" between the defense system in the muscle and the stress that is produced in the muscle. This imbalance appears to hamper the body's ability to metabolize glucose, as revealed by the weekly glucose tests at the end of the most intense training week. 

To better understand how frequent, demanding exercise affects glucose metabolism, the researchers also continuously monitored the blood sugar of 15 elite endurance athletes over two weeks and compared them to a group of 12 controls who trained less than 7 hours per week. To their surprise, they found that the athletes spent almost double the amount of time in a hyperglycemic range than the less athletic control group, and more than triple the time in a hypoglycemic range, further suggesting disturbed glucose control as a result of extreme exercise.

Overall, the endurance athletes still remained in a normal range for roughly the same amount of time, though somewhat less, as the controls. But the fluctuations were still surprising because athletes "are assumed to have high insulin sensitivity, and during aging, they show less decline in metabolic health than controls," the study authors wrote. 

Flockhart and his colleagues recommend that anyone looking to start exercising pay attention to how their body responds, and perhaps monitor their glucose, as they become more accustomed to greater stress. 

"That's why you can't go from amateur to elite and just train in the same amount of exercise," Flockhart said. "You have to get used to exercise over a long period of time to adapt and create this tolerance to training. So when we are shocking the system with this hard training, we get these negative outcomes."

Because he and his coauthors were able to discern a link between glucose tolerance and mitochondrial function, Flockhart wants to conduct similar studies using volunteers with diabetes or other metabolic diseases. 

But ultimately, with this study, Flockhart wants to make clear that exercise is still an important part of a healthy life, as his volunteers had positive health effects before their week of overtraining, and began to recover quickly during a fourth week of less intense activity. He doesn't want to scare anyone away from exercise. 

"You have to really go in hard for this lifestyle of excessive training to cause permanent damage," Flockhart said. "I think the warning bells will ring really loud before you get to that state."

The study, "Excessive exercise training causes mitochondrial functional impairment and decreases glucose tolerance in healthy volunteers," published March 18 in Cell Metabolism, was authored by Mikael Flockhart, Lina C. Nilsson, Senna Tais, Björn Ekblom and Filip J. Larsen, The Swedish School of Sport and Health Sciences; and William Apró, The Swedish School of Sport and Health Sciences and Karolinska Institutet.