“No pain, no gain.” Hard exercise has many benefits, but it also carries a risk beyond a sprained muscle or joint injury. We are talking about problems with the heart (Goodman, Burr, Banks, & Thomas, 2016; Guasch et al., 2013). So, a trade-off exists. Is there a way to know what the right balance is – realize the wonderful benefits exercise has to offer without increasing the risk of heart problems? Could the answer be lurking in blood?

A recent study published in Nature’s Scientific Reports describes how our bodies react to exercise intensity down to the molecular level (Guseh et al., 2020). Twelve men (~ 21 years old) ran 5 miles at 5 miles per hour (moderate intensity exercising) and 9 miles per hour (high intensity exercising). Blood samples were collected from the participants before and after each run, and protein changes were determined using our technology.

What defines a moderate intensity from a high intensity exercise? Pending on a person’s fitness level, running at 5 mph for an hour may be a high intensity exercise, but the research team made sure it met the criteria for moderate intensity. They looked at the cortisol levels of the participants in the samples collected. For the “moderate” intensity exercise, the cortisol levels dropped, but rose during the “high” intensity exercise. A pattern, supported by the literature, showing that indeed the activities were inducing the appropriate cortisol response for a moderate versus high intensity exercise (Davies & Few, 1973).

Upon looking at the data from our technology, the researchers found that 623 out of 1305 proteins measured responded to the exercise intensities. Of these, 159 proteins’ levels changed up or down in both types of exercises. A subset of these 159 protein responses showed a dose-response (i.e., high intensity exercise produced greater change in a protein’s level than moderate intensity exercise). For the remaining proteins, 25 protein levels changed only with moderate intensity exercise and 439 protein levels changed only with high intensity exercise.

What did all the data that the team collected and analyzed reveal about the intensity’s impact on the human body? For moderate intensity exercise, the research team found that biological pathways associated with bone growth, inflammation and fat metabolism were enhanced. With respect to high intensity exercise, neurological pathways, proteins associated with coronary artery disease (CAD), processes involving the making of free radicals, inflammation and processes involved in repairing vascular system dominated. What is remarkable is that the proteins associated with CAD (i.e., heart disease) only increased with the high intensity exercise and not the moderate intensity exercise.

It is worth noting that benefits seen in high intensity exercise can be achieved with moderate intensity exercise too. For instance, the research team saw that brain-derived neurotrophic factor (BDNF) – a protein linked to cognitive function and mood- increased in both intensity levels. The high intensity only yielded 30% more of the protein. The research team mentioned that this confirms earlier findings about how BDNF could help explain some of the benefits (improved mood and reduced dementia risk) of exercise.

This study shows the power of proteins to find potential health risks and offer a potential explanation for why the person is at risk. It is tantalizing to think that one day people would be able to know if the pain of an exercise program will eclipse any gain.



Davies, C. T., & Few, J. D. (1973). Effects of exercise on adrenocortical function. J Appl Physiol, 35(6), 887-891. doi:10.1152/jappl.1973.35.6.887

Goodman, J. M., Burr, J. F., Banks, L., & Thomas, S. G. (2016). The Acute Risks of Exercise in Apparently Healthy Adults and Relevance for Prevention of Cardiovascular Events. Can J Cardiol, 32(4), 523-532. doi:10.1016/j.cjca.2016.01.019

Guasch, E., Benito, B., Qi, X., Cifelli, C., Naud, P., Shi, Y., . . . Nattel, S. (2013). Atrial fibrillation promotion by endurance exercise: demonstration and mechanistic exploration in an animal model. J Am Coll Cardiol, 62(1), 68-77. doi:10.1016/j.jacc.2013.01.091

Guseh, J. S., Churchill, T. W., Yeri, A., Lo, C., Brown, M., Houstis, N. E., . . . Baggish, A. L. (2020). An expanded repertoire of intensity-dependent exercise-responsive plasma proteins tied to loci of human disease risk. Sci Rep, 10(1), 10831. doi:10.1038/s41598-020-67669-0