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The effect of acute NAC supplementation on sport performance outcomes may depend on sex and genetic polymorphism in trained endurance adults: a randomized clinical trial

Sep 2026 · Scientific Reports · Vol 16 · 0 citations · 45 references

Abstract

The aim of this study was to assess the effects of short-term N-acetylcysteine (NAC) supplementation on sports performance among trained endurance adults and to compare the results across sex and MTHFR and GSTP1 genotype groups. Altogether 56 males and 21 females finished the randomized double-blinded placebo-controlled crossover trial. Participants received NAC or placebo for seven days in a crossover design with a 3-week washout period between two intervention phases. Body composition was measured with air-displacement plethysmography, followed by an afternoon Wingate Anaerobic Test (WAnT), and a 60-min time trial (60TT). Heart rate (HR) and ratings of perceived exertion (RPE) were monitored during 60TT. Genotyping was conducted using TaqMan probes. The distance covered during 60TT did not change after NAC in both males and females. However, RPEs were lower after NAC, but only in men. Average HR and %HRmax decreased in both sexes, however, the post hoc differences were observed only among males. NAC increased average power (AP) during WAnT in men, with a significant time × treatment × GSTP1 genotype interaction favoring G-allele carriers. In women, a time × treatment × MTHFR genotype interaction was observed for peak power, without significant post hoc effect. Short-term NAC supplementation does not improve covered distance in 60TT. However, it reduces RPE and HR and enhances AP in men. Exploratory analyses suggest that some responses may differ by sex and genotype, although these findings require confirmation.

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