In Depth: Exercise Physiology: Take Your Medicine at the Gym

Exercise Physiology: Take Your Medicine at the Gym

Could physical activity help us stay healthy and treat disease?

Bente Klarlund Pedersen, MD, is a clinical professor and head of the Centre of Inflammation and Metabolism and the Physical Activity Research Centre at the University of Copenhagen in Denmark. Her pioneering research has helped illuminate the biochemical pathways through which physical activity affects health and disease, pointing to enticing opportunities to use exercise as medicine. 

You’re a medical doctor. How did you get into basic research? 
When I entered medical school, I met a researcher who inspired me a lot. I started to do research with her, and when I was only about 20, I was involved in developing what is now known as the western blotting method, which is something all biomedical researchers know about. This opened a whole new world for me. Since then, I have just been in love with science. 

My medical specialty is in infectious diseases and internal medicine, and I’ve always been interested in immunology and inflammation. When I realized that the immune system had implications beyond defending infections, I thought it was very important to see how the immune system was affected by normal daily activity. 

What motivated you to study how exercise affects the body? 
In the beginning, I wasn’t that interested in exercise; I was interested in the immune system and inflammation. I decided to look at exercise because it’s a nice model—you can measure people before, during and after. We found that the immune system was very sensitive to exercise, and we looked for the mechanism and came across the molecule called interleukin-6. We realized that interleukin-6 was probably the “exercise factor” that people had been looking for for many years, and it became clear that interleukin-6 had many effects beyond the immune system. 

Other people have followed this idea, and today we know there are many—a couple of hundred—molecules released by the muscle, and some of them have systemic effects. This whole concept of muscle as an endocrine organ has many clinical implications; we could understand why exercise could impact the brain or the liver or distant organs. This became the starting point for us to establish our research center focusing on exercise as medicine. 

What are you learning, and how can it help to improve people’s health? 
To give the best exercise advice for patients, we need to understand what is happening and the mechanisms whereby exercise works so that we can better monitor the specific mode of exercise—duration, time, intensity—that works for the individual patient. 

One of my group leaders, Pernille Hojman, who unfortunately passed away a couple of years ago, found that if mice had access to a wheel and could do voluntary exercise, it meant that the tumor did not grow as fast as if the mice were inactive. She also found that the reason was that exercise stimulated natural killer cells to enter the bloodstream, and via interleukin-6, these natural killer cells would go to the tumor and limit tumor growth. Recently, we’ve taken some of this research into humans. We have unpublished data indicating that patients with cancer who exercise show several beneficial effects.

We also have a focus on how exercise influences metabolism, in patients with Type 2 diabetes, for instance. We did very intense exercise training for one year—which is very hard to do in a clinical study—and showed that 56% of patients who did the exercise training did not need antidiabetic medications any longer. We’ve described some of the mechanisms, and we further developed the study and showed that exercise training just three times per week seems to decrease the need for diabetes medicine. It shows us that exercise training really can have an impact.

This type of research can also stimulate the development of new drugs. Among many people there is a hope that they could have an exercise pill. Of course, given that there are a couple of thousand genes that are activated by exercise, and hundreds of proteins are phosphorylated and many signaling pathways are activated, it would be naïve to think that you could just get one wonder drug. But it’s very possible that in the future, for people who are paralyzed or otherwise have to be inactive, we could counteract some of the effects of physical inactivity by developing drugs inspired by exercise physiological research. 

How do you translate basic research insights into real-world impacts?
Just like any other treatment, we rely very much on solid randomized controlled studies. We should not just be exercise enthusiasts or exercise believers; we really need to have strong clinical trials to convince other MDs and the whole health community that exercise should be prescribed for patients with various diseases. We also know that many things work in a supervised setting, like in a hospital or laboratory, but day to day it may not work as well. Our research center is quite big, with around 70 people, because we need people who are molecular biologists in the lab but also people who do qualitative research close to the patients to try to understand the limitations.

For the past 10 years or so, I’ve also been involved in communicating science to lay people: writing popular books, writing a health column every Saturday, two to four public talks a week, a lot of television [appearances]. When we talk about translational research, we take it all the way from the molecules to the mouse, to healthy people, to the patients, to the municipalities, and all the way into society, hoping also that we will have an impact on decision-makers and politicians. This is part of how we define translational research. It’s not just trying to find a magic bullet in a mouse and giving it back to humans as a tablet; it’s actually trying to influence the health care system with evidence-based medicine. 

Interview conducted by Anne Frances Johnson.

This article was originally published in the September 2024 issue of The Physiologist Magazine. Copyright © 2024 by the American Physiological Society. Send questions or comments to tphysmag@physiology.org.