8 Days of NAC could dentrimentally effect muscle recovery



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Thiol-based antioxidant supplementation alters human skeletal muscle signaling and attenuates its inflammatory response and recovery after intense eccentric exercise1,2,3

  1. Yannis Michailidis,
  2. Leonidas G Karagounis,
  3. Gerasimos Terzis,
  4. Athanasios Z Jamurtas,
  5. Kontantinos Spengos,
  6. Dimitrios Tsoukas,
  7. Athanasios Chatzinikolaou,
  8. Dimitrios Mandalidis,
  9. Renae J Stefanetti,
  10. Ioannis Papassotiriou,
  11. Spyros Athanasopoulos,
  12. John A Hawley,
  13. Aaron P Russell, and
  14. Ioannis G Fatouros
+ Author Affiliations

  1. 1From the Democritus University of Thrace, Department of Physical Education and Sport Sciences, Komotini, Greece (YM, AC, and IGF); the Nestlé Research Center, Nestec Ltd, Lausanne, Switzerland (LGK); the Athletics Laboratory, School of Physical Education and Sport Science, University of Athens, Athens, Greece (GT, DM, and SA); the Department of Physical Education and Sport Sciences, University of Thessaly, Karies, Trikala, Greece, and the Institute of Human Performance and Rehabilitation, Center for Research and Technology–Thessaly, Trikala, Greece (AZJ); the 1st Department of Neurology, University of Athens, School of Medicine, Eginition Hospital, Athens, Greece (KS); the Department of Toxicology, Medical School, University of Athens, Athens, Greece (DT); the Department of Clinical Biochemistry, “Aghia Sophia” Children's Hospital, Athens, Greece (IP); the Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria, Australia (RJS and APR); and the Exercise Metabolism Research Group, School of Medical Sciences, RMIT University, Bundoora, Australia (JAH and LGK).
+ Author Notes

  • 2 Supported by departmental funding, a grant received by Bodosakis Foundation (Greece) for instrument purchase, and grant funding (CE-80739). APR was supported by a National Health and Medical Research Council Career Development Award, Australia.
  • 3 Address correspondence to IG Fatouros, Department of Physical Education and Sports Sciences, University Campus, 69100, Komotini, Greece. E-mail: [email protected].

Background: The major thiol-disulfide couple of reduced glutathione (GSH) and oxidized glutathione is a key regulator of major transcriptional pathways regulating aseptic inflammation and recovery of skeletal muscle after aseptic injury. Antioxidant supplementation may hamper exercise-induced cellular adaptations.

Objective: The objective was to examine how thiol-based antioxidant supplementation affects skeletal muscle's performance and redox-sensitive signaling during the inflammatory and repair phases associated with exercise-induced microtrauma.

Design: In a double-blind, crossover design, 10 men received placebo or N-acetylcysteine (NAC; 20 mg · kg–1 · d–1) after muscle-damaging exercise (300 eccentric contractions). In each trial, muscle performance was measured at baseline, after exercise, 2 h after exercise, and daily for 8 consecutive days. Muscle biopsy samples from vastus lateralis and blood samples were collected before exercise and 2 h, 2 d, and 8 d after exercise.

Results: NAC attenuated the elevation of inflammatory markers of muscle damage (creatine kinase activity, C-reactive protein, proinflammatory cytokines), nuclear factor κB phosphorylation, and the decrease in strength during the first 2 d of recovery. NAC also blunted the increase in phosphorylation of protein kinase B, mammalian target of rapamycin, p70 ribosomal S6 kinase, ribosomal protein S6, and mitogen activated protein kinase p38 at 2 and 8 d after exercise. NAC also abolished the increase in myogenic determination factor and reduced tumor necrosis factor-α 8 d after exercise. Performance was completely recovered only in the placebo group.

Conclusion: Although thiol-based antioxidant supplementation enhances GSH availability in skeletal muscle, it disrupts the skeletal muscle inflammatory response and repair capability, potentially because of a blunted activation of redox-sensitive signaling pathways. This trial was registered at clinicaltrials.gov as NCT01778309.

  • Received August 13, 2012.
  • Accepted April 17, 2013.
Thiol-based antioxidant supplementation alters human skeletal muscle signaling and attenuates its inflammatory response and recovery after intense eccentric exercise


I will say this: 300 eccentric contractions + ~1.6g of NAC is a little excessive, but it does prove a valid point with regards to exercise adaptation


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NAC hardly has the best oral availability so 1600mg a day isn't an excessive dosage.

I strongly believe that all of the positives that NAC offers certainly outweigh any "negative" concerns that the study above poses.

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