Please note this is a comparison between Version 2 by Vivi Li and Version 1 by Asli Devrim Lanpir.
Exercise frequently alters the metabolic processes of oxidative metabolism in athletes, including exposure to extreme reactive oxygen species impairing exercise performance. Therefore, both researchers and athletes have been consistently investigating the possible strategies to improve metabolic adaptations to exercise-induced oxidative stress. N-acetylcysteine (NAC) has been applied as a therapeutic agent in treating many diseases in humans due to its precursory role in the production of hepatic glutathione, a natural antioxidant.
N-acetylcysteine
mitochondrial adaptation
skeletal adaptation
hormesis
oxidative stress
Please wait, diff process is still running!
References
Hawley, J.A.; Hargreaves, M.; Joyner, M.J.; Zierath, J.R. Integrative biology of exercise. Cell 2014, 159, 738–749.
Powers, S.K.; Jackson, M.J. Exercise-induced oxidative stress: Cellular mechanisms and impact on muscle force production. Physiol. Rev. 2008, 88, 1243–1276.
Ji, L.L.; Gomez-Cabrera, M.C.; Vina, J. Exercise and hormesis: Activation of cellular antioxidant signaling pathway. In Proceedings of the Annals of the New York Academy of Sciences; Blackwell Publishing Inc.: Hoboken, NJ, USA, 2006; Volume 1067, pp. 425–435.
Powers, S.K.; Radak, Z.; Ji, L.L. Exercise-induced oxidative stress: Past, present and future. J. Physiol. 2016, 594, 5081–5092.
Webb, R.; Hughes, M.G.; Thomas, A.W.; Morris, K. The ability of exercise-associated oxidative stress to trigger redox-sensitive signalling responses. Antioxidants 2017, 6, 63.
Merry, T.L.; Ristow, M. Mitohormesis in exercise training. Free Radic. Biol. Med. 2016, 98, 123–130.
Powers, S.K.; Ji, L.L.; Kavazis, A.N.; Jackson, M.J. Reactive oxygen species: Impact on skeletal muscle. Compr. Physiol. 2011, 1, 941–969.
Vitale, K.; Getzin, A. Nutrition and supplement update for the endurance athlete: Review and recommendations. Nutrients 2019, 11, 1289.
Pingitore, A.; Lima, G.P.P.; Mastorci, F.; Quinones, A.; Iervasi, G.; Vassalle, C. Exercise and oxidative stress: Potential effects of antioxidant dietary strategies in sports. Nutrition 2015, 31, 916–922.
Azeredo, H.M.C. Betalains: Properties, sources, applications, and stability a review. Int. J. Food Sci. Technol. 2009, 44, 2365–2376.
Somerville, V.; Bringans, C.; Braakhuis, A. Polyphenols and Performance: A Systematic Review and Meta-Analysis. Sport. Med. 2017, 47, 1589–1599.
Peternelj, T.T.; Coombes, J.S. Antioxidant supplementation during exercise training: Beneficial or detrimental? Sport. Med. 2011, 41, 1043–1069.
Michailidis, Y.; Karagounis, L.G.; Terzis, G.; Jamurtas, A.Z.; Spengos, K.; Tsoukas, D.; Chatzinikolaou, A.; Mandalidis, D.; Stefanetti, R.J.; Papassotiriou, I.; et al. Thiol-based antioxidant supplementation alters human skeletal muscle signaling and attenuates its inflammatory response and recovery after intense eccentric exercise. Am. J. Clin. Nutr. 2013, 98, 233–245.
Radak, Z.; Zhao, Z.; Koltai, E.; Ohno, H.; Atalay, M. Oxygen consumption and usage during physical exercise: The balance between oxidative stress and ROS-dependent adaptive signaling. Antioxid. Redox Signal. 2013, 18, 1208–1246.
Mcleay, Y.; Stannard, S.; Houltham, S.; Starck, C. Dietary thiols in exercise: Oxidative stress defence, exercise performance, and adaptation. J. Int. Soc. Sports Nutr. 2017, 14, 12.
Zembron-Lacny, A.; Slowinska-Lisowska, M.; Szygula, Z.; Witkowski, Z.; Szyszka, K. Modulatory effect of N-acetylcysteine on pro-antioxidant status and haematological response in healthy men. J. Physiol. Biochem. 2010, 66, 15–21.
Medved, I.; Brown, M.J.; Bjorksten, A.R.; Murphy, K.T.; Petersen, A.C.; Sostaric, S.; Gong, X.; McKenna, M.J. N-acetylcysteine enhances muscle cysteine and glutathione availability and attenuates fatigue during prolonged exercise in endurance-trained individuals. J. Appl. Physiol. 2004, 97, 1477–1485.
Šalamon, Š.; Kramar, B.; Marolt, T.P.; Poljšak, B.; Milisav, I. Medical and dietary uses of n-acetylcysteine. Antioxidants 2019, 8, 111.
Kerksick, C.; Willoughby, D. The Antioxidant Role of Glutathione and N-Acetyl-Cysteine Supplements and Exercise-Induced Oxidative Stress. J. Int. Soc. Sports Nutr. 2005, 2, 38.
Yavari, A.; Javadi, M.; Mirmiran, P.; Bahadoran, Z. Exercise-induced oxidative stress and dietary antioxidants. Asian J. Sports Med. 2015, 6, 24898.
Aquilano, K.; Baldelli, S.; Ciriolo, M.R. Glutathione: New roles in redox signalling for an old antioxidant. Front. Pharmacol. 2014, 5, 196.
Rhodes, K.; Braakhuis, A. Performance and Side Effects of Supplementation with N-Acetylcysteine: A Systematic Review and Meta-Analysis. Sport Med. 2017, 47, 1619–1636.
Lee, R.; West, D.; Phillips, S.M.; Britz-McKibbin, P. Differential metabolomics for quantitative assessment of oxidative stress with strenuous exercise and nutritional intervention: Thiol-specific regulation of cellular metabolism with N-acetyl-L-cysteine pretreatment. Anal. Chem. 2010, 82, 2959–2968.
Medved, I.; Brown, M.J.; Bjorksten, A.R.; Leppik, J.A.; Sostaric, S.; McKenna, M.J. N-acetylcysteine infusion alters blood redox status but not time to fatigue during intense exercise in humans. J. Appl. Physiol. 2003, 94, 1572–1582.
Sen, C.K.; Rankinen, T.; Vaisanen, S.; Rauramaa, R. Oxidative stress after human exercise: Effect of N-acetylcysteine supplementation. J. Appl. Physiol. 1994, 76, 2570–2577.
Zembron-Lacny, A.; Slowinska-Lisowska, M.; Szygula, Z.; Witkowski, K.; Szyszka, K. The Comparison of Antioxidant and Hematological Properties of N-Acetylcysteine and α-Lipoic Acid in Physically Active Males. Physiol. Res. 2009, 58, 855.
Leelarungrayub, D.; Khansuwan, R.; Pothongsunun, P.; Klaphajone, J. N-acetylcysteine supplementation controls total antioxidant capacity, creatine kinase, lactate, and tumor necrotic factor-alpha against oxidative stress induced by graded exercise in sedentary men. Oxid. Med. Cell. Longev. 2011, 2011.
Slattery, K.M.; Dascombe, B.; Wallace, L.K.; Bentley, D.J.; Coutts, A.J. Effect of N-acetylcysteine on cycling performance after intensified training. Med. Sci. Sports Exerc. 2014, 46, 1114–1123.
Matuszczak, Y.; Farid, M.; Jones, J.; Lansdowne, S.; Smith, M.A.; Taylor, A.A.; Reid, M.B. Effects of N-acetylcysteine on glutathione oxidation and fatigue during handgrip exercise. Muscle Nerve 2005, 32, 633–638.
Mihm, S.; Galter, D.; Dröge, W. Modulation of transcription factor NFχB activity by intracellular glutathione levels and by variations of the extracellular cysteine supply. FASEB J. 1995, 9, 246–252.
Oka, S.I.; Kamata, H.; Kamata, K.; Yagisawa, H.; Hirata, H. N-Acetylcysteine suppresses TNF-induced NF-κB activation through inhibition of IκB kinases. FEBS Lett. 2000, 472, 196–202.
Gaston, B. Nitric oxide and thiol groups. Biochim. Biophys. Acta Bioenerg. 1999, 1411, 323–333.
Xiong, Y.; Uys, J.D.; Tew, K.D.; Townsend, D.M. S-Glutathionylation: From molecular mechanisms to health outcomes. Antioxid. Redox Signal. 2011, 15, 233–270.
Stowe, D.F.; Camara, A.K.S. Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function. Antioxid. Redox Signal. 2009, 11, 1373–1414.
Ezeriņa, D.; Takano, Y.; Hanaoka, K.; Urano, Y.; Dick, T.P. N-Acetyl Cysteine Functions as a Fast-Acting Antioxidant by Triggering Intracellular H 2 S and Sulfane Sulfur Production. Cell Chem. Biol. 2018, 25, 447–459.
Christensen, P.M.; Bangsbo, J. N-Acetyl cysteine does not improve repeated intense endurance cycling performance of well-trained cyclists. Eur. J. Appl. Physiol. 2019, 119, 1419–1429.
Nielsen, H.B.; Kharazmi, A.; Bolbjerg, M.L.; Poulsen, H.E.; Pedersen, B.K.; Secher, N.H. N-acetylcysteine attenuates oxidative burst by neutrophils in response to ergometer rowing with no effect on pulmonary gas exchange. Int. J. Sports Med. 2001, 22, 256–260.
de Moraes, A.d.J.P.; Andreato, L.V.; Branco, B.H.M.; da Silva, E.L.; Gonçalves, M.A.; dos Santos, R.Z.; Becker, A.M.; da Silveira Cavalcante, L.; da Silva Casagrande, F.; Benetti, M. Effects of N-acetylcysteine supplementation on cellular damage and oxidative stress indicators in volleyball athletes. J. Exerc. Rehabil. 2018, 14, 802–809.
Trewin, A.J.; Lundell, L.S.; Perry, B.D.; Patil, K.V.; Chibalin, A.V.; Levinger, I.; McQuade, L.R.; Stepto, N.K. Effect of N-acetylcysteine infusion on exercise-induced modulation of insulin sensitivity and signaling pathways in human skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 2015, 309, E388–E397.
Childs, A.; Jacobs, C.; Kaminski, T.; Halliwell, B.; Leeuwenburgh, C. Supplementation with vitamin C and N-acetyl-cysteine increases oxidative stress in humans after an acute muscle injury induced by eccentric exercise. Free Radic. Biol. Med. 2001, 31, 745–753.
Ferreira, L.F.; Campbell, K.S.; Reid, M.B. N-acetylcysteine in handgrip exercise: Plasma thiols and adverse reactions. Int. J. Sport Nutr. Exerc. Metab. 2011, 21, 146–154.
Silva, L.A.; Silveira, P.C.L.; Pinho, C.A.; Tuon, T.; Pizzol, F.D.; Pinho, R.A. N-acetylcysteine supplementation and oxidative damage and inflammatory response after eccentric exercise. Int. J. Sport Nutr. Exerc. Metab. 2008, 18, 379–388.
Paschalis, V.; Theodorou, A.A.; Margaritelis, N.V.; Kyparos, A.; Nikolaidis, M.G. N-acetylcysteine supplementation increases exercise performance and reduces oxidative stress only in individuals with low levels of glutathione. Free Radic. Biol. Med. 2018, 115, 288–297.
Cobley, J.N.; McGlory, C.; Morton, J.P.; Close, G.L. N-acetylcysteine’s attenuation of fatigue after repeated bouts of intermittent exercise: Practical implications for tournament situations. Int. J. Sport Nutr. Exerc. Metab. 2011, 21, 451–461.
Bailey, S.J.; Winyard, P.G.; Blackwell, J.R.; Vanhatalo, A.; Lansley, K.E.; DiMenna, F.J.; Wilkerson, D.P.; Campbell, I.T.; Jones, A.M. Influence of N-acetylcysteine administration on pulmonary O2 uptake kinetics and exercise tolerance in humans. Respir. Physiol. Neurobiol. 2011, 175, 121–129.
Medved, I.; Brown, M.J.; Bjorksten, A.R.; McKenna, M.J. Effects of intravenous N-acetylcysteine infusion on time to fatigue and potassium regulation during prolonged cycling exercise. J. Appl. Physiol. 2004, 96, 211–217.
Miltenberger, M.; Zipp, G.; Parasher, R.; Lombardi, V.; Davis, S. The Acute Effects of N-Acetylcysteine Supplementation on Repeat Sprint Performance in Recreationally Active Males. Med. Sci. Sport. Exerc. 2015, 47, 337–338.
Kelly, M.K.; Wicker, R.J.; Barstow, T.J.; Harms, C.A. Effects of N-acetylcysteine on respiratory muscle fatigue during heavy exercise. Respir. Physiol. Neurobiol. 2009, 165, 67–72.
Merry, T.L.; Wadley, G.D.; Stathis, C.G.; Garnham, A.P.; Rattigan, S.; Hargreaves, M.; McConell, G.K. N-Acetylcysteine infusion does not affect glucose disposal during prolonged moderate-intensity exercise in humans. J. Physiol. 2010, 588, 1623–1634.
Kerksick, C.M.; Kreider, R.B.; Willoughby, D.S. Intramuscular adaptations to eccentric exercise and antioxidant supplementation. Amino Acids 2010, 39, 219–232.
McKenna, M.J.; Medved, I.; Goodman, C.A.; Brown, M.J.; Bjorksten, A.R.; Murphy, K.T.; Petersen, A.C.; Sostaric, S.; Gong, X. N-acetylcysteine attenuates the decline in muscle Na+, K+-pump activity and delays fatigue during prolonged exercise in humans. J. Physiol. 2006, 576, 279–288.
Petersen, A.C.; McKenna, M.J.; Medved, I.; Murphy, K.T.; Brown, M.J.; Della Gatta, P.; Cameron-Smith, D. Infusion with the antioxidant N-acetylcysteine attenuates early adaptive responses to exercise in human skeletal muscle. Acta Physiol. 2012, 204, 382–392.
Sakelliou, A.; Fatouros, I.G.; Athanailidis, I.; Tsoukas, D.; Chatzinikolaou, A.; Draganidis, D.; Jamurtas, A.Z.; Liacos, C.; Papassotiriou, I.; Mandalidis, D.; et al. Evidence of a Redox-Dependent Regulation of Immune Responses to Exercise-Induced Inflammation. Oxid. Med. Cell. Longev. 2016, 2016.
Faghfouri, A.H.; Zarezadeh, M.; Tavakoli-Rouzbehani, O.M.; Radkhah, N.; Faghfuri, E.; Kord-Varkaneh, H.; Tan, S.C.; Ostadrahimi, A. The effects of N-acetylcysteine on inflammatory and oxidative stress biomarkers: A systematic review and meta-analysis of controlled clinical trials. Eur. J. Pharmacol. 2020, 884, 173368.
Halliwell, B. The antioxidant paradox. Lancet 2000, 355, 1179–1180.
Margolis, L.M.; Rivas, D.A. Potential Role of MicroRNA in the Anabolic Capacity of Skeletal Muscle With Aging. Exerc. Sport Sci. Rev. 2018, 46, 86–91.
Lira, V.A.; Benton, C.R.; Yan, Z.; Bonen, A. PGC-1α regulation by exercise training and its influences on muscle function and insulin sensitivity. Am. J. Physiol. Endocrinol. Metab. 2010, 299, E145.
Cook, S.J.; Stuart, K.; Gilley, R.; Sale, M.J. Control of cell death and mitochondrial fission by ERK1/2 MAP kinase signalling. FEBS J. 2017, 284, 4177–4195.
Sahlin, K.; Shabalina, I.G.; Mattsson, C.M.; Bakkman, L.; Fernström, M.; Rozhdestvenskaya, Z.; Enqvist, J.K.; Nedergaard, J.; Ekblom, B.; Tonkonogi, M. Ultraendurance exercise increases the production of reactive oxygen species in isolated mitochondria from human skeletal muscle. J. Appl. Physiol. 2010, 108, 780–787.
Chambers, J.W.; LoGrasso, P.V. Mitochondrial c-Jun N-terminal Kinase (JNK) signaling initiates physiological changes resulting in amplification of reactive oxygen species generation. J. Biol. Chem. 2011, 286, 16052–16062.
Dunning, S.; Ur Rehman, A.; Tiebosch, M.H.; Hannivoort, R.A.; Haijer, F.W.; Woudenberg, J.; Van Den Heuvel, F.A.J.; Buist-Homan, M.; Faber, K.N.; Moshage, H. Glutathione and antioxidant enzymes serve complementary roles in protecting activated hepatic stellate cells against hydrogen peroxide-induced cell death. Biochim. Biophys. Acta Mol. Basis Dis. 2013, 1832, 2027–2034.
Pacagnelli, F.L.; Aguiar, A.F.; Campos, D.H.S.; Castan, E.P.; de Souza, R.W.A.; de Almeida, F.L.A.; Carani, F.; Carvalho, R.F.; Cicogna, A.C.; Silva, M.D.P. Training improves the oxidative phenotype of muscle during the transition from cardiac hypertrophy to heart failure without altering MyoD and myogenin. Exp. Physiol. 2016, 101, 1075–1085.
Merry, T.L.; Steinberg, G.R.; Lynch, G.S.; McConell, G.K. Skeletal muscle glucose uptake during contraction is regulated by nitric oxide and ROS independently of AMPK. Am. J. Physiol. Endocrinol. Metab. 2010, 298.
Sandström, M.E.; Zhang, S.J.; Bruton, J.; Silva, J.P.; Reid, M.B.; Westerblad, H.; Katz, A. Role of reactive oxygen species in contraction-mediated glucose transport in mouse skeletal muscle. J. Physiol. 2006, 575, 251–262.
Askari, M.; Faryabi, R.; Mozaffari, H.; Darooghegi Mofrad, M. The effects of N-Acetylcysteine on serum level of inflammatory biomarkers in adults. Findings from a systematic review and meta-analysis of randomized clinical trials. Cytokine 2020, 135, 155239.
He, F.; Li, J.; Liu, Z.; Chuang, C.-C.; Yang, W.; Zuo, L. Redox Mechanism of Reactive Oxygen Species in Exercise. Front. Physiol. 2016, 7, 486.
Rhodes, K.M.; Baker, D.F.; Smith, B.T.; Braakhuis, A.J. Acute Effect of Oral N-Acetylcysteine on Muscle Soreness and Exercise Performance in Semi-Elite Rugby Players. J. Diet. Suppl. 2019, 16, 443–453.
World Anti-Doping Agency Prohibited List Documents|World Anti-Doping Agency. Available online: https://www.wada-ama.org/en/resources/science-medicine/prohibited-list-documents (accessed on 20 January 2021).
Reid, M.B. Redox interventions to increase exercise performance. J. Physiol. 2016, 594, 5125–5133.
Crum, E.M.; Barnes, M.J.; Stannard, S.R. Multiday pomegranate extract supplementation decreases oxygen uptake during submaximal cycling exercise, but cosupplementation with n-acetylcysteine negates the effect. Int. J. Sport Nutr. Exerc. Metab. 2018, 28, 586–592.
Gould, R.L.; Pazdro, R. Impact of Supplementary Amino Acids, Micronutrients, and Overall Diet on Glutathione Homeostasis. Nutrients 2019, 11, 1056.
Paschalis, V.; Theodorou, A.A.; Kyparos, A.; Dipla, K.; Zafeiridis, A.; Panayiotou, G.; Vrabas, I.S.; Nikolaidis, M.G. Low vitamin C values are linked with decreased physical performance and increased oxidative stress: Reversal by vitamin C supplementation. Eur. J. Nutr. 2016, 55, 45–53.
Parker, L.; Trewin, A.; Levinger, I.; Shaw, C.S.; Stepto, N.K. Exercise-intensity dependent alterations in plasma redox status do not reflect skeletal muscle redox-sensitive protein signaling. J. Sci. Med. Sport 2018, 21, 416–421.
Victor, V.M.; De la Fuente, M. N-acetylcysteine improves in vitro the function of macrophages from mice with endotoxin-induced oxidative stress. Free Radic. Res. 2002, 36, 33–45.