Performance and Side Effects of Supplementation with N-Acetylcysteine: A Systematic Review and Meta-Analysis

N-Acetylcysteine (NAC) is a promising antioxidant supplement with potential as an acute strategy to enhance performance in elite sport, but there are concerns about its side effects with high doses.

To review the current literature and evaluate the effects of NAC supplementation on sport performance and the risk of adverse effects.

The literature up to May 2016 was searched on MEDLINE (PubMed), EMBASE, SPORTDiscus, Google Scholar and Scopus databases to identify all studies investigating the effects of NAC supplementation on exercise performance and/or side effects experienced. Performance outcomes from each study were converted to the percent effect equivalent to mean power output in a time trial. All pooled analyses were based on random-effects models generated by Review Manager (RevMan) [Computer program], version 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, 2014).

A total of seven studies met criteria for inclusion in the sport performance meta-analysis, and 17 for inclusion in the side effects meta-analysis. The typical daily dose of NAC reported was 5.8 g·d^-1; with a range between 1.2 and 20.0 g·d^-1. The mean increase in performance was 0.29% (95% confidence interval -0.67 to 1.25). The difference in the odds ratio of side effects on NAC compared with placebo was 1.11 (95% confidence interval 0.88-1.39). The sub-analysis of NAC dose suggested an increase in side effects as the dosage of NAC increased; however, this observation requires further investigation.

Despite initial research publications reporting positive performance effects with NAC, at this stage it cannot be recommended further. The risk of side effects from NAC supplementation also remains unclear owing to significant variations in effects. Suboptimal reporting and documentation in the literature creates difficulties when meta-analysing outcomes and generating conclusions.