N-acetylcysteine alters substrate metabolism during high-intensity cycle exercise in well-trained humans

We investigated the effects of N-acetylcysteine (NAC) on metabolism during fixed work rate high-intensity interval exercise (HIIE) and self-paced 10-min time-trial (TT₁₀) performance. Nine well-trained male cyclists (VO2peak, 69.4 ± 5.8 mL·kg⁻¹·min⁻¹; peak power output (PPO), 385 ± 43 W; mean ± SD) participated in a double-blind, repeated-measures, randomised crossover trial. Two trials (NAC supplementation and placebo) were performed 7 days apart consisting of 6 x 5 min HIIE bouts at 82% PPO (316 ± 40 W) separated by 1 min at 100 W, and then after 2 min of recovery at 100 W, TT₁₀ was performed. Expired gases, venous blood, and electromyographic (EMG) data were collected. NAC did not influence blood glutathione but decreased lipid peroxidation compared with the placebo (P <0.05). Fat oxidation was elevated with NAC compared with the placebo during HIIE bouts 5 and 6 (9.9 ± 8.9 vs. 3.9 ± 4.8 μmol·kg⁻¹·min⁻¹; P <0.05), as was blood glucose throughout HIIE (4.3 ± 0.6 vs. 3.8 ± 0.6 mmol·L⁻¹; P <0.05). Blood lactate was lower with NAC after TT10 (3.3 ± 1.3 vs. 4.2 ± 1.3 mmol·L⁻¹; P <0.05). Median EMG frequency of the vastus lateralis was lower with NAC during HIIE (79 ± 10 vs. 85 ± 10 Hz; P <0.05), but not TT₁₀ (82 ± 11 Hz). Finally, NAC decreased mean power output 4.9% ± 6.6% (effect size = -0.3 ± 0.4, mean ± 90% CI) during TT₁₀ (305 ± 57 W vs. 319 ± 45 W). These data suggest that NAC alters substrate metabolism and muscle fibre type recruitment during HIIE, which is detrimental to time-trial performance.