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

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 )a fter muscledamaging 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 kB 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 2a nd 8da fter exercise. NAC also abolished the increase in myogenic determination factor and reduced tumor necrosis factor-a 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 clinicaltrials.gov as NCT01778309. Am J Clin Nutr doi: 10.3945/ajcn.112.049163.