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Powers, Scott K. Ph.D., Ed.D., FACSM; Min, Kisuk M.S.; Nelson, W. Bradley M.S.; Kavazis, Andreas N. Ph.D.

ACSM'S Health & Fitness Journal: May/June 2010 - Volume 14 - Issue 3 - pp 11-14
doi: 10.1249/FIT.0b013e3181dad10a

LEARNING OBJECTIVES: After reading this review, you should understand the following:

• The definitions of free radicals, antioxidants, and oxidative stress

• The risks and benefits of antioxidant supplementation

• The current recommendation about antioxidant supplementation

Although exercise increases radical production in active skeletal muscles, current evidence does not support the concept that active people should supplement a well-balanced diet with high levels of antioxidants. Find out more in this feature.

Scott K. Powers, Ph.D., Ed.D., FACSM, is a professor in the Department of Applied Physiology and Kinesiology at the University of Florida.

Kisuk Min, M.S., is a graduate student in the Department of Applied Physiology and Kinesiology at the University of Florida.

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W. Bradley Nelson, M.S., is a graduate student in the Department of Applied Physiology and Kinesiology at the University of Florida.

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Andreas N. Kavazis, Ph.D., is a postdoctoral fellow in the Department of Applied Physiology and Kinesiology at the University of Florida.

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Reports about the dangers of free radicals and their negative impact on human health are common in the news media today. This increased public awareness of the role that free radicals play in human aging and disease has prompted many health-minded individuals to supplement their diet with commercially available antioxidant supplements. It follows that this widespread public interest in antioxidant supplements has motivated supplement suppliers to release an avalanche of antioxidant products into the marketplace. Promotional claims for these products are numerous and include the assertion that antioxidant supplements slow the aging process and decrease the risk of heart disease and cancer. Moreover, some proponents of antioxidant supplementation suggest that exercise training increases the requirements for antioxidants. However, does scientific research support the need for additional antioxidants beyond those contained in a well-balanced diet? This brief article will address this issue by summarizing the current literature on this topic. We begin with an introduction to free radicals and antioxidants.

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Free radicals (hereafter referred to as radicals) are chemical species or molecules that contain an unpaired electron in their outer orbit (4). Because of this unpaired electron, radicals are highly reactive and can interact with cellular components to promote damage to proteins, membranes, and DNA. In extreme cases, radical-mediated damage to cellular components can lead to cellular dysfunction and even cell death.

It is important to understand that radicals are constantly produced in low levels in all cells within the body (4). Therefore, it is not surprising that cells contain a network of molecules that neutralize radicals (i.e., antioxidants) and protect against radical-mediated injury. In general, these cellular antioxidants can be divided into two broad groups. The first set of antioxidants is produced within cells of the body (i.e., endogenous antioxidants), whereas the second group is derived from the diet (i.e., exogenous antioxidants). To provide maximum protection against radicals, these two antioxidant groups work as a team to neutralize radicals and prevent cellular damage.

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The term oxidative stress refers to radical-mediated damage to cells. Oxidative stress results from a cellular imbalance between antioxidants and radicals; this occurs when radical production exceeds the antioxidant capacity. It follows that high levels of radical production in cells and/or low levels of antioxidants in cells would favor oxidative stress. In contrast, high levels of antioxidants in cells would protect against radical-mediated damage and therefore prevent oxidative stress.

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Most articles about radicals in newspapers or popular health magazines discuss the damaging role that radicals can play in promoting unhealthy aging and disease. In general, research indicates that continuous and high levels of radical production in cells can promote many diseases, including atherosclerosis and cancer (4). Furthermore, scientific evidence that links radicals to the aging process has accumulated steadily during the past several decades. Indeed, the free radical theory of aging was first proposed more than 50 years ago and predicts that, over time, radical-mediated damage to cellular constituents leads to a steady decline of cellular function that is the hallmark of aging.

Although high levels of radicals in cells are potentially harmful, it also is important to appreciate that low levels of radical production are required to maintain healthy cells. Indeed, all cells produce radicals during normal metabolism, and small increases in radical production can serve as chemical messengers to stimulate cellular adaptation to various stimuli (e.g., physical exercise). In fact, removal of these radical messengers from cells can be potentially harmful. Therefore, whether radicals are "bad guys" or "good guys" depends upon the level of radicals present in the cell.

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Interestingly, although regular physical exercise provides many health benefits, exercise results in increased production of radicals. Indeed, abundant evidence indicates that exercise induces radical production, and contracting skeletal muscles are a major source of these radicals (8). The magnitude of exercise-induced radical production is influenced by several factors, including the intensity and duration of exercise, along with the environmental conditions. For example, skeletal muscle radical production increases as a function of both the exercise intensity and duration. Furthermore, skeletal muscles produce more radicals during exercise in hot environments and at high altitudes (i.e., >5,000 feet) (8). Therefore, the magnitude of exercise-induced radical production in muscles can range from relatively low to high levels, depending upon the exercise conditions.

Although contracting skeletal muscles produce radicals, exercise bouts do not always result in oxidative stress to muscles. Indeed, low- to moderate-intensity exercise does not generally promote oxidative stress in skeletal muscles. Furthermore, individuals who exercise regularly have well-adapted endogenous antioxidant systems in their skeletal muscles that resist exercise-induced oxidative stress. Therefore, whether an exercise session results in oxidative stress is dependent upon several factors, including the intensity and duration of exercise, as well as the fitness status of the individual.

So, if exercise generates radicals and high levels of radicals are associated with an increased risk of disease, is regular exercise a health risk? The short answer to this question is no. In fact, regular physical activity is the only known intervention that has been shown to reduce all-cause mortality in humans (2). Therefore, the low level of radical production that occurs during regular bouts of submaximal exercise is not detrimental to health.

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Given that exercise promotes the production of radicals in skeletal muscles, does this increased radical production warrant antioxidant supplementation? Unfortunately, the answer to this question remains a highly debated topic, and arguments exist for and against antioxidant supplementation. On the pro side, a plausible argument for antioxidant supplementation is that exercise training results in increased radical production in skeletal muscles, and therefore, to avoid oxidative damage to muscle fibers, an increased dietary intake of supplemental antioxidants is required. It could be argued that this may be particularly true for athletes engaged in extreme exercise events (e.g., 100-mile races). Another argument for taking antioxidant supplements is that many people may not consume well-balanced diets, and therefore these individuals could be deficient in antioxidant intake.

In contrast to the arguments supporting antioxidant supplementation, several lines of reasoning against antioxidant supplements also exist. For instance, regular exercise training promotes a training adaptation that increases endogenous antioxidants in muscle fibers, resulting in improved protection against exercise-induced radical production (9). Therefore, because of this training-induced enhancement in endogenous antioxidants, antioxidant supplementation may not be required to protect the exercising muscles from radical-mediated damage. Furthermore, if an active individual maintains a well-balanced isocaloric diet that contains antioxidant-rich fruits and vegetables, it can be argued that this individual does not require supplementary antioxidants above those contained in the diet.

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Perhaps the two strongest arguments against antioxidant supplementation are the following. First, recent studies suggest that high doses of antioxidant supplementation can prevent important exercise-induced adaptations in skeletal muscle. Specifically, research indicates that exercise-induced radical production serves as a required signal to trigger the exercising muscle to produce numerous proteins, including antioxidant enzymes and proteins involved in energy production (8). Importantly, two recent human studies revealed that antioxidant supplementation with high doses of vitamins E and C (e.g., ∼16 times higher than the recommended dietary allowance [RDA] for adults) can blunt the training adaptation to aerobic exercise (3,10). A second key argument against antioxidant supplementation is that the available evidence does not support the idea that antioxidant supplementation is beneficial to human health. For example, a recent review of 68 randomized antioxidant supplement trials concluded that dietary supplementation with beta carotene, vitamin A, and vitamin E does not increase human life span and may actually increase mortality (1). Furthermore, these authors also concluded that the roles of vitamin C and selenium on human mortality are unclear and require further study (1).

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It is well established that exercise promotes radical production in active skeletal muscles, and prolonged or intense exercise can promote oxidative stress. In this regard, this exercise-induced radical production may be an important signal to promote skeletal muscle adaptation to exercise. To protect against radical-mediated damage, muscle fibers contain endogenous antioxidants to scavenge radicals. Moreover, dietary antioxidants cooperate with endogenous antioxidants to form a supportive network of cellular protection against radicals.

The matter of whether active adults should take antioxidant supplements remains an important and highly debated issue. Arguments for and against antioxidant supplementation exist, and future research will be required to firmly establish the types and optimal levels of antioxidants that promote health in active adults. Unfortunately, this is a complicated issue that will be difficult to investigate. Therefore, it seems likely that the question of whether antioxidant supplementation is required for active individuals or athletes engaged in intense exercise training will remain controversial for years to come. However, based on current information, the conclusion that there is no convincing evidence that active adults or athletes require antioxidant supplementation above those found in a well-balanced diet has been reached by several major reviews on this topic (5-7,11). Furthermore, evolving evidence suggests that high levels of antioxidant supplementation (>16 times RDA) might be detrimental to both health and exercise-induced training effects in skeletal muscle. Therefore, the decision to begin a high-dose antioxidant supplement program should be made with caution and only after consultation with a nutritionist and other qualified health care providers.

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Although exercise increases radical production in active skeletal muscles, current evidence does not support the concept that active people should supplement a well-balanced diet with high levels of antioxidants. In fact, supplementation with high levels of antioxidants could prove detrimental by retarding exercise-induced training adaptations.

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1. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA. 2007;297:842-57.
2. Blair SN, Morris JN. Healthy hearts and the universal benefits of being physically active: physical activity and health. Ann Epidemiol. 2009;19:253-6.
3. Gomez-Cabrera MC, Domenech E, Romagnoli M, et al. Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adaptations in endurance performance. Am J Clin Nutr. 2008;87:142-9.
4. Halliwell B, Gutteridge J. Free Radicals in Biology and Medicine. Oxford, UK: Oxford Press; 2007. p. 936.
5. Margaritis I, Rousseau AS. Does physical exercise modify antioxidant requirements? Nutr Res Rev. 2008;21:3-12.
6. Powers SK, DeRuisseau KC, Quindry J, Hamilton KL. Dietary antioxidants and exercise. J Sports Sci. 2004;22:81-94.
7. Powers SK, Hamilton K. Antioxidants and exercise. Clin Sports Med. 1999;18:525-36.
8. Powers SK, Jackson MJ. Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production. Physiol Rev. 2008;88:1243-76.
9. Powers SK, Ji LL, Leeuwenburgh C. Exercise training-induced alterations in skeletal muscle antioxidant capacity: a brief review. Med Sci Sports Exerc. 1999;31:987-97.
10. Ristow M, Zarse K, Oberbach A, et al. Antioxidants prevent health-promoting effects of physical exercise in humans. Proc Natl Acad Sci U S A. 2009;106:8665-70.
11. Urso ML, Clarkson PM. Oxidative stress, exercise, and antioxidant supplementation. Toxicology. 2003;189:41-54.

Free Radicals; Oxidative Stress; Exercise; Nutritional Supplements; Skeletal Muscle

© 2010 American College of Sports Medicine