Exercise increases oxygen consumption to generate energy, with a corresponding increase in reactive oxygen species (ROS), including free radicals, which are normal by-products of oxygen metabolism. Fortunately, exercise also stimulates the activities of a complex network of antioxidants that scavenge and dissipate ROS before they can cause cellular damage. Exercise-induced oxidative stress is a temporary condition in which ROS production exceeds the production of antioxidants. Over time, routine physical exercise reduces the likelihood of oxidative stress by increasing both the efficiency of oxygen metabolism and the basal activity of the antioxidant network.
Aerobic and endurance exercise can increase the body's total oxygen consumption by as much as 10-fold–20-fold over the resting state. Oxygen consumption in skeletal muscle may increase by as much as 100-fold–200-fold. This increased oxygen consumption is a major source of ROS, especially superoxide anion (O2—).
ROS have important roles in a range of physiologic functions, especially cellular signaling, but ROS can also inflict serious damage to muscles and other tissues. Damage to proteins, lipids, and DNA in muscle and blood cells from exercise-induced oxidative stress has been implicated in muscle fatigue and injury. Excess ROS can adversely affect muscle contraction and performance. Over time, ROS play a role in aging and in the initiation of cardiovascular disease, Parkinson's and Alzheimer's diseases, and cancer.
The body's complex network of antioxidants deactivates and removes ROS, minimizing their reactions with cellular components. The activities of the antioxidant network increase significantly during exercise. Among the many benefits of regular physical exercise and increased aerobic capacity are an overall decrease in oxidative stress and enhancement of antioxidant defense. However, if ROS generation exceeds the capacity of the antioxidant network, the result is exercise-induced oxidative stress. Decreasing the amount of oxidative stress to which cells are exposed and minimizing detrimental effects from oxidative stress associated with intense and/or unaccustomed exercise may improve health and athletic performance. However, exercise-induced oxidative stress also may have benefits; it appears to help break down muscle so that physical training can rebuild stronger muscle.
Although free radicals were first identified in cells in 1954, exercise-induced oxidative stress was not recognized until 1978. Since then, it has been shown that both short-duration and prolonged high-intensity exercise increase free-radical production in working skeletal muscle, which leads to oxidized proteins and lipids. Oxidative stress is also associated with diabetes, obesity, and cardiovascular complications, such as atherosclerosis and heart disease, in the elderly. Oxidative stress and the antioxidant network are very complex processes that are integrated with various other cellular processes. Both depend on numerous factors that make them difficult to study in humans.
Normal oxygen metabolism produces small amounts of ROS, including free radicals and peroxides, that are readily neutralized by the body's antioxidant defenses, including vitamins C and E. Endurance exercise may cause much higher levels of ROS. Exercise-induced oxidative stress occurs when the production of ROS from increased oxygen consumption overwhelms the body's antioxidant-defense system.
One class of antioxidants, known as scavengers, convert ROS to less reactive molecules. Other antioxidants prevent the conversion of less reactive oxygen species into more damaging forms, for example, by preventing the conversion of hydrogen peroxide to hydroxyl radical. Antioxidants may themselves be oxidized in the process of reducing ROS to less reactive forms. These antioxidants must then be reduced or recycled back to their active forms, often by other antioxidants. Thus, antioxidants work together in complex ways both inside and outside of cells.
Muscle cells employ a particularly complex network of antioxidants. Interleukin-6 (IL-6) stimulates exercise-induced antioxidant defenses, as well as other acute exercise-induced responses, and IL-6 production is regulated, in part, by oxidative stress. Regular exercise appears to enhance these antioxidant defenses and protect against exercise-induced oxidative damage. This enhancement develops gradually over time, along with other adaptations to exercise.
ENDOGENOUS ANTIOXIDANTS. Endogenous antioxidants are small molecules and enzymes that are produced by the body. Glutathione is a small sulfurcontaining peptide that is abundant in muscle cells and has multiple roles in antioxidant defense. It directly scavenges radicals by donating hydrogen atoms (protons) to the free electrons of ROS. It also works with other antioxidants, including the enzyme glutathione peroxidase, to remove ROS. Different types of physical training programs have specific effects on glutathione metabolism in different tissues. Oxidized glutathione in the blood is a marker for exerciseinduced oxidative stress. Although glutathione can be obtained in the diet, it is broken down to its constituent amino acids by the digestive system; thus, ingested glutathione is not an antioxidant.
Reduced ubiquinones are small lipid-soluble antioxidants. They react with ROS to prevent lipid peroxidation in membranes and other structures. Some ubiquinones are also important for recycling vitamin E during oxidative stress. Ubiquinone-10, or coenzyme Q, occurs in virtually all cells of the body, primarily within the mitochondria. It can be obtained in the diet from soybean oil, meat, fish, nuts, wheat germ, and vegetables such as beans, garlic, spinach, and cabbage.
Uric acid is an end-product of metabolism that accounts for about 66% of the antioxidant activity in the blood. As more calories are burned during exercise, more uric acid is produced.
Enzymatic antioxidants in the body include:
DIETARY ANTIOXIDANTS. Vitamin E, which is soluble in fat, is the most important antioxidant in cell membranes. It converts superoxide, hydroxyl radical, and lipid peroxyl radicals to less reactive forms. It can halt lipid-peroxidation chain reactions in cell membranes. Vitamin E scavenging of radicals results in the formation of vitamin E radicals, which reduces the available vitamin E. Thus, oxidative stress decreases vitamin E concentrations in tissue. Vitamin E is converted back to its antioxidant form by glutathione, vitamin C, or alpha-lipoic acid. Plant oils, avocados, almonds, peanuts, sunflower and sesame seeds, wheat germ, and whole grains are the best sources of vitamin E.
Vitamin C (ascorbic acid) directly scavenges superoxide, hydroxyl radical, and lipid hydroperoxide radicals, and recycles vitamin E to its reduced or antioxidant form. Vitamin C is converted to a radical in the process and can be recycled back to its reduced form by an enzyme or by glutathione or dihydrolipoic acid (DHLA). Five daily servings of fruits and vegetables easily provide enough vitamin C to saturate body tissues. Citrus fruits, broccoli, peppers, and strawberries are among the best sources of vitamin C. In the presence of metals such as iron or copper, vitamin C can itself become an oxidizing agent, calling into question the advisability of highdose vitamin C supplementation.
Beta-carotene and other carotenoids primarily scavenge superoxide and peroxyl radicals in cell membranes. Carrots, spinach, sweet potatoes, kale, apricots, and cantaloupe are among the best sources of carotenoids.
Although alpha-lipoic acid is an endogenous antioxidant, it is normally bound to enzymes and so is unavailable. Supplemental alpha-lipoic acid is reduced to DHLA, which is a potent antioxidant against all major ROS. Under oxidative stress, DHLA can substitute for glutathione and can reduce vitamin C radicals back to vitamin C. In the process, DHLA is converted to alpha-lipoic acid, which is enzymatically reduced back to DHLA.
Trace minerals, which are usually plentiful in a well-balanced diet, are required cofactors for antioxidant enzymes:
Acute exhaustive aerobic or anaerobic exercise can increase reactive oxygen and nitrogen species with the potential to cause oxidative stress. ROS damage to cells appears to be independent of the absolute intensity of exercise, but exercise that is exhaustive and prolonged, especially in hot weather, increases the likelihood of oxidative stress. Avoiding or overcoming potential oxidative stress is of particular concern to athletes; however, people who exercise irregularly or only occasionally are at significantly increased risk for exercise-induced oxidation stress.
Aging is associated with increased oxidative stress throughout the body, and the rate of free-radical formation increases in aging muscle. Therefore, exerciseinduced oxidative stress may be more damaging in older adults, especially postmenopausal women. However, age-related increases in exercise-induced oxidative stress appear to be accompanied by increased antioxidant defenses, providing overall health benefits.
Obesity appears to significantly increase susceptibility to exercise-induced oxidative stress. Obesity is associated with lower levels of antioxidants, such as vitamin E and beta-carotene, in the blood and with lower activities of antioxidant enzymes in red blood cells.
Many factors affect exercise-induced oxidative stress, including physical fitness, intensity and duration of exercise, and diet. In general, five daily servings of fruits and vegetables, as part of a well-balanced diet, supply high levels of antioxidants and the micronutrients essential for enzymatic antioxidants, without additional supplementation.
Individuals who are generally sedentary, but engage in occasional vigorous exercise, are perhaps at greatest risk for exercise-induced oxidative stress. They may lack the enhanced antioxidant defense network that comes with regular exercise. As a result, their antioxidant defenses may be overwhelmed, leading to ROS damage. People whose exercise regimen is interrupted for several weeks also can be affected by exercise-induced oxidative stress.
Obesity is a risk factor for exercise-induced oxidative stress, especially among older women. Obese individuals tend to have lower blood levels of antioxidants, such as vitamin E and glutathione, and lower antioxidant enzyme activities. Loss of hormones after menopause is associated with decreased glutathione levels and increased peroxide formation in tissues. Women, however, generally appear to have higher resting antioxidant levels than men. Although some antioxidants and enzyme activities decrease with age, others have been reported to increase. Blood markers of oxidative stress that are chronically elevated in patients with cardiovascular disease, diabetes, and other medical conditions may increase during prolonged exercise but diminish soon afterward.
Some evidence indicates that high doses of supplemental antioxidants can cause reductive stress—the opposite of oxidative stress. Reductive stress occurs when antioxidants outnumber oxidants inside cells. Reductive stress may impair muscle contraction and exercise performance.
Regular exercise boosts the body's antioxidant defenses and reduces the likelihood and/or consequences of exercise-induced oxidative stress. These benefits are lost if regular exercise is discontinued.
Quindry, John C., Andreas N. Kavazis, and Scott K. Powers. “Exercise-Induced Oxidative Stress: Are Supplemental Antioxidants Warranted?” In Sports Nutrition, edited by Ron J. Maughan, pp. 263–76. Chichester, UK: Wiley, 2014.
Paschalis, Vassilis, et al. “Low Vitamin C Values Are Linked with Decreased Physical Performance and Increased Oxidative Stress: Reversal by Vitamin C Supplementation.” European Journal of Nutrition 55, no. 1 (February 2016): 45–53.
Pingitore A., et al. “Exercise and Oxidative Stress: Potential Effects of Antioxidant Dietary Strategies in Sports.”Nutrition 31, nos. 7–8 (July–August 2015): 916–22. http://www.nutritionjrnl.com/article/S0899-9007(15)00073-8/fulltext (accessed March 1, 2017).
Powers, Scott K., Zsolt Radak, and Li Li Ji. “ExerciseInduced Oxidative Stress: Past, Present and Future.” Journal of Physiology 594 (2016): 5081–92.
Stea, Tonje Holte, et al. “Effect of Omega-3 and Vitamins E þ C Supplements on the Concentration of Serum B-Vitamins and Plasma Redox Aminothiol Antioxidant Status in Elderly Men after Strength Training for Three Months.” Annals of Nutrition and Metabolism 68, no. 2 (February 2016): 145–55.
Yavari, Abbas, et al. “Exercise-Induced Oxidative Stress and Dietary Antioxidants.” Asian Journal of Sports Medicine 6, no. 1 (March 2015): e24898. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393546 (accessed March 1, 2017).
MedlinePlus. “Antioxidants.” US National Library of Medicine, National Institutes of Health. https://medlineplus.gov/antioxidants.html (accessed March 1, 2017).
Academy of Nutrition and Dietetics, 120 South Riverside Plz., Ste. 2000, Chicago, IL, 60606-6995, (312) 899-0040, (800) 877-1600, http://www.eatright.org .
American College of Sports Medicine (ACSM), 401 W. Michigan St., Indianapolis, IN, 46202-3233, (317) 6379200, Fax: (317) 634-7817, http://www.acsm.org .
Margaret Alic, PhD