NAC Supplementation and Skeletal Muscle Performance

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Skeletal Muscle Damage, Skeletal Muscle Performance, Intgracellular Signaling in Skeletal Muscle, Inflammatory Status

Intervention / Treatment
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* Dietary Supplement: n-acetylcysteine supplementation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: n-acetylcysteine/placebo supplementation<br>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<br>* 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<br>* Other names: Exercise-induced skeletal muscle damage;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aseptic inflammation, skeletal muscle function, exercise