NAC Supplementation and Skeletal Muscle Performance

Effects of NAC Supplementation on Skeletal Muscle Performance Following Aseptic Injury Induced by Exercise

In this investigation the investigators utilized NAC administration to foster GSH availability during an 8-day period following eccentric exercise-induced muscle damage in order to test our hypotheses: i) antioxidant supplementation does not disturb performance and adaptations induced by exercise-induced muscle injury and ii) redox status perturbations in skeletal muscle are pivotal for the regulation of muscle' inflammatory response and repair.

Study Overview

• Status: Completed
• Conditions: Skeletal Muscle Performance; Skeletal Muscle Damage; Intgracellular Signaling in Skeletal Muscle; Inflammatory Status
• Intervention / Treatment: Dietary supplement: n-acetylcysteine supplementation

Detailed Description

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

Our objective was to examine how thiol-based antioxidant supplementation affects skeletal muscle's performance and redox-sensitive signalling during the inflammatory and repair phases associated with exercise-induced micro-trauma.In a double-blind, counterbalanced design, 12 men received placebo (PLA) or N-acetylcysteine (NAC, 20 mg/kg/day) following muscle-damaging exercise (300 eccentric contractions). In each trial, muscle performance was measured at baseline, post-exercise, 2h post-exercise and daily for 8 consecutive days. Muscle biopsies from vastus lateralis and blood samples were collected pre-exercise and 2h, 2d, and 8d post-exercise.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Greece
  • Thrace
    • Komotini, Thrace, Greece, 69100
      • Laboratory of Physical Education & Sport Performance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

a) recreationally trained as evidenced by their maximal oxygen consumption levels (VO2max >45 ml/kg/min), b) were engaged in systematic exercise at least three times/week for ≥12 months), c) non-smokers, d) abstained from any vigorous physical activity during the study, e)abstained from consumption of caffeine, alcohol, performance-enhancing or antioxidant supplements, and medications during the study.

Exclusion Criteria:

a) a known NAC intolerance or allergy, b) a recent febrile illness, c) history of muscle lesion, d) lower limb trauma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: n-acetylcysteine/placebo supplementation; n-acetylcysteine supplementation, orally in three daily dosages, at 20 mg/kg/day, daily for eight days after exercise placebo, orally in three daily dosages, content: 500 mL drink that contained water (375 mL), sugar-free cordial (125 ml), and 2 g of low-calorie glucose/dextrose powder.	Dietary supplement: n-acetylcysteine supplementation; n-acetylcysteine administration: 20 mg//kg/day, orally, daily for eight days following exercise placebo administration: 500 mL orally, daily for eight days following exercise; Other Names: Exercise-induced skeletal muscle damage

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in reduced glutathione in blood	Concentration of reduced glutathione in red blood cells	one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
Change in reduced glutathione in muscle	concentration of reduced glutathione in quadriceps skeletal muscle group	one hour before exercise, 2 hours post-exercise, 2 days post-exercise, 8 days post-exercise
Change in protein carbonyls in red blood cells and serum	concentration of protein carbonyls	one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
Change in protein carbonyls in muscle	protein carbonyl concentration in vastus lateralis skeletal muscle	one hour before exercise, 2 hours post-exercise, 2 days post-exercise, 8 days post-exercise
Change in thiobarbituric acid reactive substances in red blood cells and serum	thiobarbituric acid reactive substances concentration in serum and red blood cells	one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
Change in thiobarbituric acid reactive substances in muscle	thiobarbituric acid reactive substances concentration in vastus lateralis skeletal muscle	one hour before exercise, 2 hours post-exercise, 2 days post-exercise, 8 days post-exercise
Change in oxidized glutathione in red blood cells and blood	Concentration of oxidized glutathione in red blood cells and whole blood	one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
Change in total antioxidant capacity in serum		one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
Change in oxidized glutathione in muscle	concentration of oxidized glutathione in vastus lateralis skeletal muscle	one hour before exercise, 2 hours post-exercise, 2 days post-exercise, 8 days post-exercise
Change in catalase activity in red blood cells and serum		one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
Change in glutathione peroxidase activity in red blood cells		one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
Change in creatine kinase activity in plasma		one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
Change in C-reactive protein in plasma		one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
Change in macrophage infiltration in muscle		one hour before exercise, 2 hours post-exercise, 2 days post-exercise, 8 days post-exercise
Change in white blood cell count in blood		one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
Change in neutrophil count in blood		one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
Change in fatty acid binding protein in plasma		one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
Change in cortisol concentration in blood		one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
Change in testosterone concentration in plasma		one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
Change in cytokine concentration in plasma	Measurement of IL-1β, IL-4, IL-6, TNF-α, IL-8, IL-10, IL-12p70 concentrations in plasma	one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
Change in adhesion molecule concentration in blood	Measurement of ICAM-1, VCAM-1, sP-selectin, sE-selectin concentrations in plasma	one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
Change in intracellular signalling proteins in muscle	Measurement of phosphorylation levels of protein kinase B (Akt), mammalian target of rapamycin (mTOR), serine/threonine kinase (p70S6K), ribosomal protein S6 (rpS6), nuclear factor κB (NFκB), serine⁄threonine mitogen activated protein kinase (p38-MAPK) in vastus lateralis muscle.	one hour before exercise, 2 hours post-exercise, 2 days post-exercise, 8 days post-exercise
Change in myogenic determination factor (MyoD) protein levels in muscle	MyoD expression in vastus lateralis muscle	one hour before exercise, 2 hours post-exercise, 2 days post-exercise, 8 days post-exercise
Change in tumor necrosis factor α in muscle	Protein levels of TNF-α in vastus lateralis muscle	one hour before exercise, 2 hours post-exercise, 2 days post-exercise, 8 days post-exercise

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in muscle function of knee extensor and flexor muscle	assessment of muscle peak and mean torque of knee extensors and flexors on an isokinetic dynamometer at 0, 90 and 180 degrees/sec	one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
Body composition	Assessment of percent (%) lean body mass.	One day before exercise
Maximal aerobic capacity	Assessment of maximal oxygen consumption, an indice of cardiovascular conditioning	One day before exercise
Change in profile of dietary intake	Assessment of dietary intake with emphasis on antioxidant element intake	one hour before exercise, daily for 8 days post-exercise
Change in side effect occurence	The prevalence of potential side-effects (such as headaches or abdominal pain or any other discomfort) was monitored using a subjective 0-10 side-effects scale on a daily bases by an unblinded investigator (for ethical reasons).	one hour before exercise, daily for 8 days post-exercise

Collaborators and Investigators

• Sponsor: Democritus University of Thrace
• Investigators: Principal Investigator: Ioannis F Fatouros, Ph.D., Democritus University of Thrace, Greece

Publications and helpful links

General Publications

• Michailidis Y, Karagounis LG, Terzis G, Jamurtas AZ, Spengos K, Tsoukas D, Chatzinikolaou A, Mandalidis D, Stefanetti RJ, Papassotiriou I, Athanasopoulos S, Hawley JA, Russell AP, Fatouros IG. Thiol-based antioxidant supplementation alters human skeletal muscle signaling and attenuates its inflammatory response and recovery after intense eccentric exercise. Am J Clin Nutr. 2013 Jul;98(1):233-45. doi: 10.3945/ajcn.112.049163. Epub 2013 May 29.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: January 21, 2013
• First Submitted That Met QC Criteria: January 25, 2013
• First Posted (Estimate): January 29, 2013

Study Record Updates

• Last Update Posted (Estimate): January 29, 2013
• Last Update Submitted That Met QC Criteria: January 25, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: exercise; aseptic inflammation; skeletal muscle function
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: NACEXERCISE2011; CE-80739 (Other Identifier: Tzelalis Sports Medicine co.)