Abstract
Inflammation is involved in the pathogenesis of insulin resistance, atherosclerosis, neurodegeneration, and tumor growth, and low-grade chronic inflammation appears as a key player in the pathogenesis of several chronic diseases, including type 2 diabetes, cardiovascular disease, cancer and Alzheimer’s disease. Given that regular exercise offers protection against all causes of mortality, primarily by protection against atherosclerosis and insulin resistance, we suggest that exercise may exert some of its beneficial health effects by inducing anti-inflammatory actions. During exercise, skeletal muscles release IL-6 into the circulation and muscle-derived IL-6 mediates anti-inflammatory effects. Supplementation with antioxidative vitamins attenuates the systemic IL-6 response to exercise primarily via inhibition of the IL-6 protein release from contracting skeletal muscle per se. Apparently, antioxidants attenuate some of the normal physiological responses to nondamaging exercise. Therefore, the use of antioxidant supplementation may be less desirable from a long-term health perspective. This point of view is partly supported by large-scale studies showing no effect, or even a detrimental effect, of antioxidant supplementation on morbidity and mortality and by studies showing that antioxidants may blunt some of the metabolic effects of regular exercise.
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References
Alessio HM. Exercise-induced oxidative stress. Med Sci Sports Exerc 1993; 25(2):218–224.
Sobal J, Marquart LF. Vitamin/mineral supplement use among athletes: a review of the literature. Int J Sport Nutr 1994; 4(4):320–334.
Rodriguez NR, Di Marco NM, Langley S. American College of Sports Medicine position stand. Nutrition and athletic performance. Med Sci Sports Exerc 2009; 41(3):709–731.
Meydani M, Evans WJ, Handelman G et al. Protective effect of vitamin E on exercise-induced oxidative damage in young and older adults. Am J Physiol 1993; 264(5 Pt 2):R992–R998.
Irrcher I, Ljubicic V, Hood DA. Interactions between ROS and AMP kinase activity in the regulation of PGC-1alpha transcription in skeletal muscle cells. Am J Physiol Cell Physiol 2009; 296(1):C116–C123.
Ji LL, Gomez-Cabrera MC, Vina J. Exercise and hormesis: activation of cellular antioxidant signaling pathway. Ann N Y Acad Sci 2006; 1067:425-35.:425–435.
Jackson MJ, Papa S, Bolanos J et al. Antioxidants, reactive oxygen and nitrogen species, gene induction and mitochondrial function. Mol Aspects Med 2002; 23(1-3):209–285.
Sen CK, Packer L. Antioxidant and redox regulation of gene transcription. FASEB J 1996; 10(7):709–720.
Higuchi M, Cartier LJ, Chen M, Holloszy JO. Superoxide dismutase and catalase in skeletal muscle: adaptive response to exercise. J Gerontol 1985; 40(3):281–286.
Oh-ishi S, Kizaki T, Nagasawa J et al. Effects of endurance training on superoxide dismutase activity, content and mRNA expression in rat muscle. Clin Exp Pharmacol Physiol 1997; 24(5):326–332.
Jackson MJ. Muscle damage during exercise: possible role of free radicals and protective effect of vitamin E. Proc Nutr Soc 1987; 46(1):77–80.
Howald H, Segesser B, Korner WF. Ascorbic acid and athletic performance. Ann NY Acad Sci 1975; 258:458-64.:458–464.
Gey GO, Cooper KH, Bottenberg RA. Effect of ascorbic acid on endurance performance and athletic injury. JAMA 1970; 211(1):105.
Lawrence JD, Bower RC, Riehl WP, Smith JL. Effects of alpha-tocopherol acetate on the swimming endurance of trained swimmers. Am J Clin Nutr 1975; 28(3):205–208.
Petersen EW, Ostrowski K, Ibfelt T et al. Effect of vitamin supplementation on cytokine response and on muscle damage after strenuous exercise. Am J Physiol Cell Physiol 2001; 280(6):C1570–C1575.
Warren JA, Jenkins RR, Packer L, Witt EH, Armstrong RB. Elevated muscle vitamin E does not attenuate eccentric exercise-induced muscle injury. J Appl Physiol 1992; 72(6):2168–2175.
Kaikkonen J, Kosonen L, Nyyssonen K et al. Effect of combined coenzyme Q10 and d-alpha-tocopheryl acetate supplementation on exercise-induced lipid peroxidation and muscular damage: a placebo-controlled double-blind study in marathon runners. Free Radic Res 1998; 29(1):85–92.
McBride JM, Kraemer WJ, Triplett-McBride T, Sebastianelli W. Effect of resistance exercise on free radical production. Med Sci Sports Exerc 1998; 30(1):67–72.
Sumida S, Tanaka K, Kitao H, Nakadomo F. Exercise-induced lipid peroxidation and leakage of enzymes before and after vitamin E supplementation. Int J Biochem 1989; 21(8):835–838.
Rokitzki L, Logemann E, Sagredos AN, Murphy M, Wetzel-Roth W, Keul J. Lipid peroxidation and antioxidative vitamins under extreme endurance stress. Acta Physiol Scand 1994; 151(2):149–158.
Pedersen BK, Febbraio MA. Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol Rev 2008; 88(4):1379–1406.
Fischer CP. Interleukin-6 in acute exercise and training: what is the biological relevance? Exerc Immunol Rev 2006; 12:6-33.:6–33.
Bruunsgaard H, Galbo H, Halkjaer-Kristensen J, Johansen TL, MacLean DA, Pedersen BK. Exercise-induced increase in serum interleukin-6 in humans is related to muscle damage. J Physiol 1997; 499(Pt 3):833–841.
Nieman DC, Nehlsen-Cannarella SL, Fagoaga OR et al. Influence of mode and carbohydrate on the cytokine response to heavy exertion. Med Sci Sports Exerc 1998; 30(5):671–678.
Nehlsen-Cannarella SL, Fagoaga OR, Nieman DC et al. Carbohydrate and the cytokine response to 2.5 h of running. J Appl Physiol 1997; 82(5):1662–1667.
Ullum H, Haahr PM, Diamant M, Palmo J, Halkjaer-Kristensen J, Pedersen BK. Bicycle exercise enhances plasma IL-6 but does not change IL-1 alpha, IL-1 beta, IL-6, or TNF-alpha pre-mRNA in BMNC. J Appl Physiol 1994; 77(1):93–97.
Moldoveanu AI, Shephard RJ, Shek PN. Exercise elevates plasma levels but not gene expression of IL-1beta, IL-6, and TNF-alpha in blood mononuclear cells. J Appl Physiol 2000; 89(4):1499–1504.
Starkie RL, Angus DJ, Rolland J, Hargreaves M, Febbraio MA. Effect of prolonged, submaximal exercise and carbohydrate ingestion on monocyte intracellular cytokine production in humans. J Physiol 2000; 528(Pt 3):647–655.
Croisier JL, Camus G, Venneman I et al. Effects of training on exercise-induced muscle damage and interleukin 6 production. Muscle Nerve 1999; 22(2):208–212.
Steensberg A, van HG, Osada T, Sacchetti M, Saltin B, Klarlund PB. Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6. J Physiol 2000; 529 Pt 1:237-42.:237–242.
Thompson D, Williams C, McGregor SJ et al. Prolonged vitamin C supplementation and recovery from demanding exercise. Int J Sport Nutr Exerc Metab 2001; 11(4):466–481.
Vassilakopoulos T, Karatza MH, Katsaounou P, Kollintza A, Zakynthinos S, Roussos C. Antioxidants attenuate the plasma cytokine response to exercise in humans. J Appl Physiol 2003; 94(3):1025–1032.
Kosmidou I, Vassilakopoulos T, Xagorari A, Zakynthinos S, Papapetropoulos A, Roussos C. Production of interleukin-6 by skeletal myotubes: role of reactive oxygen species. Am J Respir Cell Mol Biol 2002; 26(5):587–593.
Fischer CP, Hiscock NJ, Penkowa M et al. Supplementation with vitamins C and E inhibits the release of interleukin-6 from contracting human skeletal muscle. J Physiol 2004; 558(Pt 2):633–645.
Pedersen BK. Edward F. Adolph distinguished lecture: muscle as an endocrine organ: IL-6 and other myokines. J Appl Physiol 2009; 107(4):1006–1014.
Vivekananthan DP, Penn MS, Sapp SK, Hsu A, Topol EJ. Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet 2003; 361(9374):2017–2023.
Pedersen BK. The Diseasome of Physical Inactivity- and the role of myokines in muscle-fat cross talk. J Physiol 2009.
Plomgaard P, Nielsen AR, Fischer CP et al. Associations between insulin resistance and TNF-alpha in plasma, skeletal muscle and adipose tissue in humans with and without type 2 diabetes. Diabetologia 2007; 50(12):2562–2571.
Plomgaard P, Keller P, Keller C, Pedersen BK. TNF-alpha, but not IL-6, stimulates plasminogen activator inhibitor-1 expression in human subcutaneous adipose tissue. J Appl Physiol 2005; 98(6):2019–2023.
Lin WW, Karin M. A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest 2007; 117(5):1175–1183.
Handschin C, Spiegelman BM. The role of exercise and PGC1alpha in inflammation and chronic disease. Nature 2008; 454(7203):463–469.
Plomgaard P, Fischer CP, Ibfelt T, Pedersen BK, van HG. Tumor necrosis factor-alpha modulates human in vivo lipolysis. J Clin Endocrinol Metab 2008; 93(2):543–549.
van HG, Steensberg A, Sacchetti M et al. Interleukin-6 stimulates lipolysis and fat oxidation in humans. J Clin Endocrinol Metab 2003; 88(7):3005–3010.
Starkie R, Ostrowski SR, Jauffred S, Febbraio M, Pedersen BK. Exercise and IL-6 infusion inhibit endotoxin-induced TNF-alpha production in humans. FASEB J 2003; 17(8):884–886.
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(1):142–149.
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(21):8665–8670.
Wray DW, Uberoi A, Lawrenson L, Bailey DM, Richardson RS. Oral antioxidants and cardiovascular health in the exercise-trained and untrained elderly: a radically different outcome. Clin Sci (Lond) 2009; 116(5):433–441.
J Physiol. 2009 Dec 1;587(Pt 23):5559-68. Epub 2009 Sep 14. The diseasome of physical inactivity--and the role of myokines in muscle--fat cross talk. Pedersen BK.
Acknowledgment
The Centre of Inflammation and Metabolism is supported by a grant from the Danish National Research Foundation (DG 02-512-555). In addition, support was obtained from the Danish Medical Research Council, and the Commission of the European Communities (contract no. LSHM-CT-2004-005272 EXGENESIS).
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Yfanti, C., Nielsen, S., Scheele, C., Pedersen, B.K. (2011). Exercise as a Model to Study Interactions Between Oxidative Stress and Inflammation. In: Basu, S., Wiklund, L. (eds) Studies on Experimental Models. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-956-7_25
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DOI: https://doi.org/10.1007/978-1-60761-956-7_25
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