N-Acetylcysteine in Handgrip Exercise: Plasma Thiols and Adverse Reactions

Article (PDF Available)inInternational journal of sport nutrition and exercise metabolism 21(2):146-54 · April 2011with51 Reads
DOI: 10.1123/ijsnem.21.2.146 · Source: PubMed
N-acetylcysteine (NAC) is a thiol donor with antioxidant properties that has potential use as an ergogenic aid. However, NAC is associated with adverse reactions that limit its use in humans. The authors evaluated NAC efficacy as a thiol donor before handgrip exercise, measuring changes in serum cysteine and glutathione status and recording adverse reactions in adult subjects across a range of doses. Healthy individuals ingested NAC capsules (9 ± 2 or 18 ± 4 mg/kg) or solution (0, 35, 70, or 140 mg/kg). Venous blood samples were collected and subjects answered a questionnaire about adverse reactions. Low doses of NAC (capsules) did not affect plasma cysteine or glutathione or cause adverse reactions. Adverse reactions to NAC solution were predominantly mild and gastrointestinal (GI). Intensity of GI reactions to 140 mg/kg NAC was significantly higher than placebo (in a.u., 0.67 ± 0.16 vs. 0.07 ± 0.04; p < .05). Plasma cysteine concentration increased with NAC dose from 9.3 ± 0.7 μM (placebo) to 65.3 ± 6.7 μM (140 mg/kg); however, there was no difference (p > .05) in plasma cysteine for 70 mg/kg vs. 140 mg/kg. Similar increases were observed for the ratio of cysteine to total cysteine, which was directly related to handgrip exercise performance. Plasma glutathione was elevated and oxidized glutathione diminished (p < .05) with NAC 140 mg/kg vs. placebo. NAC effects on plasma thiols are maximized by oral administration of 70 mg/kg, a dose that does not cause significant adverse reactions.

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Available from: Kenneth Scott Campbell, Dec 23, 2013
    • "For whole-body exercise performance, NAC appears to be more effective in endurance-trained subjects (Medved et al. 2004a,b), but the role of training status during small muscle mass exercise is unknown. Recently, Ferreira et al. (2011) using the same dosage reported a relationship between exercise performance and preexercise CySH:tCyS levels. Interestingly, we did not observe any relationships between preexercise plasma redox balance values and exercise performance. "
    [Show abstract] [Hide abstract] ABSTRACT: N-acetylcysteine (NAC; antioxidant and thiol donor) supplementation has improved exercise performance and delayed fatigue, but the underlying mechanisms are unknown. One possibility isNACsupplementation increases limb blood flow during severe-intensity exercise. The purpose was to determine ifNACsupplementation affected exercising arm blood flow and muscle oxygenation characteristics. We hypothesized thatNACwould lead to higher limb blood flow and lower muscle deoxygenation characteristics during severe-intensity exercise. Eight healthy nonendurance trained men (21.8 ± 1.2 years) were recruited and completed two constant power handgrip exercise tests at 80% peak power until exhaustion. Subjects orally consumed either placebo (PLA) orNAC(70 mg/kg) 60 min prior to handgrip exercise. Immediately prior to exercise, venous blood samples were collected for determination of plasma redox balance. Brachial artery blood flow (BABF) was measured via Doppler ultrasound and flexor digitorum superficialis oxygenation characteristics were measured via near-infrared spectroscopy. FollowingNACsupplementaiton, plasma cysteine (NAC: 47.2 ± 20.3 μmol/L vs.PLA: 9.6 ± 1.2 μmol/L;P = 0.001) and total cysteine (NAC: 156.2 ± 33.9 μmol/L vs.PLA: 132.2 ± 16.3 μmol/L;P = 0.048) increased. Time to exhaustion was not significantly different (P = 0.55) betweenNAC(473.0 ± 62.1 sec) andPLA(438.7 ± 58.1 sec). RestingBABFwas not different (P = 0.79) withNAC(99.3 ± 31.1 mL/min) andPLA(108.3 ± 46.0 mL/min).BABFwas not different (P = 0.42) during exercise or at end-exercise (NAC: 413 ± 109 mL/min;PLA: 445 ± 147 mL/min). Deoxy-[hemoglobin+myoglobin] and total-[hemoglobin+myoglobin] were not significantly different (P = 0.73 andP = 0.54, respectively) at rest or during exercise between conditions. We conclude that acuteNACsupplementation does not alter oxygen delivery during exercise in men.
    Full-text · Article · Apr 2016
    • "This novel oral NAC supplementation loading protocol was used (i) to ensure sufficient delivery to the active tissues considering the lower bioavailability (9%) of orally ingested NAC compared with intravenous administration (Olsson et al. 1988) and (ii) because under the WADA code, athletes are not permitted to receive intravenously administered substances. Each separate dose of NAC (100 mg·kg body mass −1 ) used in this study was less than the highest acute oral dose given previously (140 mg·kg body mass −1 ) (Ferreira et al. 2011), and only one subject reported an adverse effect (mild GI upset). "
    [Show abstract] [Hide abstract] ABSTRACT: 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 (V̇O2peak, 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 × 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.
    Full-text · Article · Dec 2013
    • "N-acetylcysteine, a drug currently approved and commonly used in treatment of paracetamol overdose could be beneficial. N-acetylcysteine promotes GSH synthesis by increasing the availability of cysteine, which is rate-limiting for GSH biosynthesis (Ferreira et al., 2011). Addition of GSH to skeletal muscle homogenate, even in the presence of oxidizing peroxynitrate, prevented cardiolipin oxidation (Pope et al., 2008). "
    [Show abstract] [Hide abstract] ABSTRACT: Mitochondrial diseases are an unusually genetically and phenotypically heterogeneous group of disorders, which are extremely challenging to treat. Currently, apart from supportive therapy, there are no effective treatments for the vast majority of mitochondrial diseases. Huge scientific effort, however, is being put into understanding the mechanisms underlying mitochondrial disease pathology and developing potential treatments. To date, a variety of treatments have been evaluated by randomized clinical trials, but unfortunately, none of these has delivered breakthrough results. Increased understanding of mitochondrial pathways and the development of many animal models, some of which are accurate phenocopies of human diseases, are facilitating the discovery and evaluation of novel prospective treatments. Targeting reactive oxygen species has been a treatment of interest for many years; however, only in recent years has it been possible to direct antioxidant delivery specifically into the mitochondria. Increasing mitochondrial biogenesis, whether by pharmacological approaches, dietary manipulation or exercise therapy, is also currently an active area of research. Modulating mitochondrial dynamics and mitophagy and the mitochondrial membrane lipid milieu have also emerged as possible treatment strategies. Recent technological advances in gene therapy, including allotopic and transkingdom gene expression and mitochondrially targeted transcription activator-like nucleases, have led to promising results in cell and animal models of mitochondrial diseases, but most of these techniques are still far from clinical application. Linked Articles This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue-8
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