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Thiol-based antioxidant supplementation alters human skeletal muscle signaling and attenuates its inflammatory response and recovery after intense eccentric exercise

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journal contribution
posted on 2013-07-01, 00:00 authored by Y Michailidis, L G Karagounis, G Terzis, A Z Jamurtas, K Spengos, D Tsoukas, A Chatzinikolaou, D Mandalidis, Renae Stefanetti, I Papassotiriou, S Athanasopoulos, J A Hawley, Aaron RussellAaron Russell, I G Fatouros
BACKGROUND: The major thiol-disulfide couple of reduced glutathione (GSH) and oxidized glutathione is a key regulator of major transcriptional pathways regulating aseptic inflammation and recovery of skeletal muscle after aseptic injury. Antioxidant supplementation may hamper exercise-induced cellular adaptations. OBJECTIVE: The objective was to examine how thiol-based antioxidant supplementation affects skeletal muscle's performance and redox-sensitive signaling during the inflammatory and repair phases associated with exercise-induced microtrauma. DESIGN: In a double-blind, crossover design, 10 men received placebo or N-acetylcysteine (NAC; 20 mg · kg(-1) · d(-1)) after muscle-damaging exercise (300 eccentric contractions). In each trial, muscle performance was measured at baseline, after exercise, 2 h after exercise, and daily for 8 consecutive days. Muscle biopsy samples from vastus lateralis and blood samples were collected before exercise and 2 h, 2 d, and 8 d after exercise. RESULTS: NAC attenuated the elevation of inflammatory markers of muscle damage (creatine kinase activity, C-reactive protein, proinflammatory cytokines), nuclear factor κB phosphorylation, and the decrease in strength during the first 2 d of recovery. NAC also blunted the increase in phosphorylation of protein kinase B, mammalian target of rapamycin, p70 ribosomal S6 kinase, ribosomal protein S6, and mitogen activated protein kinase p38 at 2 and 8 d after exercise. NAC also abolished the increase in myogenic determination factor and reduced tumor necrosis factor-α 8 d after exercise. Performance was completely recovered only in the placebo group. CONCLUSION: Although thiol-based antioxidant supplementation enhances GSH availability in skeletal muscle, it disrupts the skeletal muscle inflammatory response and repair capability, potentially because of a blunted activation of redox-sensitive signaling pathways. This trial was registered at as NCT01778309.



American journal of clinical nutrition






233 - 245


American Society for Nutrition


Bethesda, Md.







Publication classification

C Journal article; C1.1 Refereed article in a scholarly journal

Copyright notice

2013, American Society for Nutrition