Effectiveness of sulfur-containing antioxidants in delaying skeletal muscle fatigue

Reactions involving thiol biochemistry seem to play a crucial role in skeletal muscle fatigue. N-acetylcysteine amide (NACA) and l-ergothioneine (ERGO) are thiol-based antioxidants available for human use that have not been evaluated for effects on muscle fatigue. Purpose: To test the hypothesis that NACA and ERGO delay skeletal muscle fatigue. Methods: We exposed mouse diaphragm fiber bundles to buffer (CTRL), NACA, ERGO, or N-acetylcysteine (NAC; positive control). Treatments were performed in vitro using 10 mM for 60 min at 37°C. After treatment, we determined the muscle force-frequency and fatigue characteristics. Results: The force-frequency relationship was shifted to the left by ERGO and to the right by NACA compared with CTRL and NAC. Maximal tetanic force was similar among groups. The total force-time integral (FTI; N•s•cm) during the fatigue trial was decreased by NACA (420 ± 35, P < 0.05), unaffected by ERGO (657 ± 53), and increased by NAC (P < 0.05) compared with CTRL (581 ± 54). The rate of contraction (dF/dtMAX) during the fatigue trial was not affected by any of the treatments tested. NAC, but not NACA or ERGO, delayed the slowing of muscle relaxation (dF/dtMIN) during fatigue. Conclusions: In summary, NACA and ERGO did not delay skeletal muscle fatigue in vitro. We conclude that these antioxidants are unlikely to improve human exercise performance.