When are Antioxidants Effective in Blunting the Cytokine Response to Exercise?

Abstract

Dear Editor-in-Chief: We have read with great interest the paper by Nieman et al. (6) published recently in MSSE®. These authors showed that antioxidant administration was ineffective in attenuating the IL-6 response to strenuous exercise in trained endurance athletes participating in an ultramarathon, which confirms previously published data (4,5). However, these results are different from those obtained by our group (12,13), and by Fischer et al. (1), where antioxidant supplementation was effective in attenuating the IL-6 response to exercise. What is the potential explanation for these apparently conflicting reports? Oxidative stress was not prevented in the vitamin E– supplemented group, and in fact was augmented as was the cytokine response to exercise (6). This would at a first glance lend support to the hypothesis that oxidative stress is a major stimulus for the cytokine induction secondary to exercise (12,13) since antioxidant supplementation that effectively attenuates oxidative stress downregulates the cytokine response to exercise (1,12,13). Furthermore, oxidative stress stimulates IL-6 production in cell cultures of skeletal myocytes (3) and the exercising skeletal muscles are the source of exercise-induced IL-6 (2). However, antioxidant supplementation that effectively attenuated oxidative stress did not downregulate the cytokine response to exercise in ultramarathon runners (4). When are antioxidants effective in attenuating the cytokine response to exercise? The type of exercise seems influential. In the studies where antioxidants where effective in attenuating the IL-6 response, the exercise was purely concentric (cycling (12), inspiratory resistive breathing (which is exercise-specific for the respiratory muscles (13)), two-legged knee-extensor exercise (1)), whereas the studies where antioxidants were ineffective included mixed type (concentric and eccentric) exercise, such as (ultra-) marathon (4,5), triathlon (6) and downhill running (7). Interestingly, the elevation of plasma IL-6 secondary to eccentric exercise is considerably smaller than the corresponding increase observed after concentric exercise (11), which suggests that the stimulus(i) and/or mechanism of IL-6 induction is different in the two types of exercise. It should also be noted that that a dietary supplement containing antioxidants was effective in attenuating the IL-6 response even secondary to eccentric exercise (8). However, this supplement also contained flavonoids and docosahexaenoate, which also have antiinflammatory properties and thus the effect of antioxidants cannot be isolated (8). The training status is also important. Thus, antioxidants attenuated the IL-6 response to exercise in untrained (nonathletes) healthy subjects (1,8,12,13), whereas negative results were obtained in trained endurance athletes participating in long-duration strenuous sports activities (4,5,6). Trained athletes have already augmented antioxidant defenses (9), which might partly attenuate the effect of antioxidant supplementation. Of course oxidative stress is not the sole stimulus for IL-6 induction secondary to exercise, and other stimuli such as glycogen-carbohydrate availability are also important, (2,10). This is why antioxidants blunt, but do not completely abolish the IL-6 response to concentric exercise in healthy nonathletes. Theodoros Vassilakopoulos Charis Roussos Spyros Zakynthinos Department of Critical Care and Pulmonary Services, University of Athens Medical School, Evangelismos Hospital, Athens, Greece