Exercise and reactive oxygen species – a complicated relationship

Reactive oxygen species (ROS) are naturally occurring, volatile molecules located within our bodies and brains. They are also known as free radicals because they contain a “free” electron that is available to pair with another electron, thus giving them their volatile qualities. ROS include oxygen, peroxide, and hydrogen peroxide, to name a few. These free radicals are formed through metabolic processes and play important roles in cell signaling and homeostatic mechanisms. In other words, ROS are good and necessary things.

Though ROS form as part of regular physiological processes, certain things such as radiation, physical injury, drugs and chemicals, and contact with metals can increase ROS above normal levels. These high levels of ROS then cause damage to our proteins, fats, and DNA, which can cause cell death. The toxicity produced by ROS is called oxidative stress or oxidative damage. Indeed, ROS have been implicated in aging and neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease.

Fortunately, substances exist within our body called antioxidants that help to terminate the reactions caused by free radicals, thus limiting how much damage is done to our tissues.

Surprisingly, exercise has been shown to increase ROS (Radak et al., 2013). At first, this may sound anti-intuitive. However, when you think about the fact that exercise increases aerobic metabolism and ROS are a byproduct of this process, then this makes perfects sense.

On the other hand, exercise has been shown to improve cognitive functioning and have a protective effect on the brain, helping to delay the onset of age-related cognitive decline.

Therein lies a paradox. If we know that heightened levels of ROS can cause cognitive impairment and neurodegeneration, how does something that increases ROS do the opposite? Could the interaction between exercise and ROS have something to do with the beneficial effects of exercise on the brain? Researchers have recently begun to explore this relationship, and it turns that the interaction between exercise and ROS is quite complex.

In a study that examined this complicated relationship, rodents were randomly assigned to either remain sedentary or go for a daily swim for two months (Radak et al., 2001). After this time period, rats were tested on their ability to learn and remember an environment that was paired with a negative experience – a foot shock. Compared to the sedentary experience, exercise enabled the rats to better remember to avoid the bad situation. Additionally, these improvements in cognitive function were accompanied by a decrease of free radicals in the brain. Though one bout of exercise increases ROS, this research revealed that long-term exercise actually decreases ROS levels. Additionally, long-term exercise enhanced the body’s ability to repair tissue damaged through oxidative stress. Future interventional strategies will be needed to more directly link the changes in ROS to changes in learning and memory.

Traditionally, athletes have been concerned about exercise increasing ROS and the ability of these free radicals to induce muscle injury and fatigue and impair exercise performance (Belviranli & Okudan, 2015). To combat this issue, sportsmen often take antioxidant supplements. This is an interesting topic and one that I will be discussing in a future post. However, when it comes to the brain, research indicates that exercise actually helps regulate its “redox state” or alter the chemical reactions that are occurring in the brain. By naturally increasing ROS, exercise helps to enhance the regulatory processes associated with oxidative stress and damage. Essentially, the effects of exercise don’t stop at the level of ROS but translate into changes in the antioxidant system and the body and brain’s ability to repair itself. Radak and colleagues (2016) summarize this very complicated relationship in this figure.

All of these cellular alterations ultimately end in changes in brain plasticity or the capacity of the brain to change. These exercise-induced increases in plasticity then lead to improvements in learning and memory as was seen in the rodent study described above. Future research is needed in humans to determine the precise level of exercise that helps balance these redox reactions in favor of overall health, both at the level of the body and brain.


Belviranli, M., & Okudan, N. (2015). Well-Known Antioxidants and Newcomers in Sport Nutrition.

Radák, Z., Kaneko, T., Tahara, S., Nakamoto, H., Pucsok, J., Sasvári, M., ... & Goto, S. (2001). Regular exercise improves cognitive function and decreases oxidative damage in rat brain. Neurochemistry international, 38(1), 17-23.

Radak, Z., Marton, O., Nagy, E., Koltai, E., & Goto, S. (2013). The complex role of physical exercise and reactive oxygen species on brain. Journal of Sport and Health Science, 2(2), 87-93.

Radak, Z., Suzuki, K., Higuchi, M., Balogh, L., Boldogh, I., & Koltai, E. (2016). Physical exercise, reactive oxygen species and neuroprotection. Free Radical Biology and Medicine.

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Department of Human Nutrition, Foods, and Exercise

Virginia Tech Carilion Research Institute

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© 2016 by Julia C. Basso.