Performance and Side Effects of Supplementation with N-Acetylcysteine: A Systematic Review and Meta-Analysis
- 386 Downloads
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.
Compliance with Ethical Standards
No sources of funding were used to assist in the preparation of this article.
Conflict of interest
Kate Rhodes and Andrea Braakhuis declare they have no conflicts of interest relevant to the content of this review.
- 7.Sen C, Packer L, Hänninen O. Handbook of Oxidants and Antioxidants in Exercise. Amsterdam, The Netherlands: Elsevier Science; 2000.Google Scholar
- 8.Leelarungrayub D, Khansuwan R, Pothongsunun P, et al. N-Acetylcysteine supplementation controls total antioxidant capacity, creatine kinase, lactate, and tumor necrotic factor-alpha against oxidative stress induced by graded exercise in sedentary men. Oxid Med Cell Longev. 2011;2011:329643.Google Scholar
- 9.Maughan RJ. The Encyclopaedia of Sports Medicine: an IOC Medical Commission publication. The Olympic Textbook of Science in Sport. West Sussex, UK: Wiley; 2009.Google Scholar
- 11.Medved I, Brown MJ, Bjorksten AR, et al. N-Acetylcysteine enhances muscle cysteine and glutathione availability and attenuates fatigue during prolonged exercise in endurance-trained individuals. J Appl Physiol (1985). 2004;97(4):1477–85.Google Scholar
- 12.Sen CK, Rankinen T, Vaisanen S, et al. Oxidative stress after human exercise: effect of N-acetylcysteine supplementation. J Appl Physiol (1985). 1994;76(6):2570–7.Google Scholar
- 21.Ferreira LF, Reid MB. Muscle-derived ROS and thiol regulation in muscle fatigue. J Appl Physiol (1985). 2008;104(3):853–60.Google Scholar
- 23.Natural Medicines. N-Acetyl cysteine. 2015. Available from: https://naturalmedicines.therapeuticresearch.com. Accessed 29 June 2015.
- 24.Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from https://www.handbook.cochrane.org.
- 27.Miltenberger MR, Zipp G, Parasher R, et al. The acute effect of n-acetylcysteine supplementation on repeat sprint performance in recreationally active males. Int J Exerc Sci Conf Proc. 2015;9(3):Article 65.Google Scholar
- 31.Hopkins WG. Sample sizes for magnitude-based inferences about clinical, practical or mechanistic significance. Med Sci Sports Exerc. 2006;38(5):S528.Google Scholar
- 34.Silva LA, Silveira PC, Pinho CA, et al. N-Acetylcysteine supplementation and oxidative damage and inflammatory response after eccentric exercise. Int J Sport Nutr. 2008;18(4):379.Google Scholar
- 37.Medved I, Brown MJ, Bjorksten AR, et al. Effects of intravenous N-acetylcysteine infusion on time to fatigue and potassium regulation during prolonged cycling exercise. J Appl Physiol (1985). 2004;96(1):211–7.Google Scholar
- 38.Medved I, Brown MJ, Bjorksten AR, et al. N-Acetylcysteine infusion alters blood redox status but not time to fatigue during intense exercise in humans. J Appl Physiol (1985). 2003;94(4):1572–82.Google Scholar
- 39.Petersen DJ, Alexander GR. Needs assessment in public health: a practical guide for students and professionals. New York, US: Springer Science & Business Media; 2001.Google Scholar
- 46.Patton KT, Thibodeau GA. Anatomy & Physiology. Missouri, US: Elsevier Health Sciences; 2014.Google Scholar
- 48.Reid MB. Invited review: redox modulation of skeletal muscle contraction: what we know and what we don’t. J Appl Physiol (1985). 2001;90(2):724–31.Google Scholar
- 51.McArdle WD, Katch FI, Katch VL. Essentials of Exercise Physiology. Philadelphia, US: Lippincott Williams & Wilkins; 2006.Google Scholar
- 53.Kerksick CM, Roberts MD, Dalbo VJ, et al. Changes in skeletal muscle proteolytic gene expression after prophylactic supplementation of EGCG and NAC and eccentric damage. Food Chem Toxicol. 2013;61:47–52.Google Scholar