NAC Supplementation and Skeletal Muscle Performance - Full Text View

Purpose

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.

Condition	Intervention
Skeletal Muscle Damage Skeletal Muscle Performance Intgracellular Signaling in Skeletal Muscle Inflammatory Status	Dietary Supplement: n-acetylcysteine supplementation

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Double Blind (Subject, Outcomes Assessor) Primary Purpose: Basic Science
Official Title:	Effects of NAC Supplementation on Skeletal Muscle Performance Following Aseptic Injury Induced by Exercise

Resource links provided by NLM:

MedlinePlus related topics: Antioxidants Exercise and Physical Fitness

Drug Information available for: Acetylcysteine

U.S. FDA Resources

Further study details as provided by Democritus University of Thrace:

Primary Outcome Measures:

Change in reduced glutathione in blood [ Time Frame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise ] [ Designated as safety issue: No ]
Concentration of reduced glutathione in red blood cells
Change in reduced glutathione in muscle [ Time Frame: one hour before exercise, 2 hours post-exercise, 2 days post-exercise, 8 days post-exercise ] [ Designated as safety issue: No ]
concentration of reduced glutathione in quadriceps skeletal muscle group
Change in protein carbonyls in red blood cells and serum [ Time Frame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise ] [ Designated as safety issue: No ]
concentration of protein carbonyls
Change in protein carbonyls in muscle [ Time Frame: one hour before exercise, 2 hours post-exercise, 2 days post-exercise, 8 days post-exercise ] [ Designated as safety issue: No ]
protein carbonyl concentration in vastus lateralis skeletal muscle
Change in thiobarbituric acid reactive substances in red blood cells and serum [ Time Frame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise ] [ Designated as safety issue: No ]
thiobarbituric acid reactive substances concentration in serum and red blood cells
Change in thiobarbituric acid reactive substances in muscle [ Time Frame: one hour before exercise, 2 hours post-exercise, 2 days post-exercise, 8 days post-exercise ] [ Designated as safety issue: No ]
thiobarbituric acid reactive substances concentration in vastus lateralis skeletal muscle
Change in oxidized glutathione in red blood cells and blood [ Time Frame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise ] [ Designated as safety issue: No ]
Concentration of oxidized glutathione in red blood cells and whole blood
Change in total antioxidant capacity in serum [ Time Frame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise ] [ Designated as safety issue: No ]
Change in oxidized glutathione in muscle [ Time Frame: one hour before exercise, 2 hours post-exercise, 2 days post-exercise, 8 days post-exercise ] [ Designated as safety issue: No ]
concentration of oxidized glutathione in vastus lateralis skeletal muscle
Change in catalase activity in red blood cells and serum [ Time Frame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise ] [ Designated as safety issue: No ]
Change in glutathione peroxidase activity in red blood cells [ Time Frame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise ] [ Designated as safety issue: No ]
Change in creatine kinase activity in plasma [ Time Frame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise ] [ Designated as safety issue: No ]
Change in C-reactive protein in plasma [ Time Frame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise ] [ Designated as safety issue: No ]
Change in macrophage infiltration in muscle [ Time Frame: one hour before exercise, 2 hours post-exercise, 2 days post-exercise, 8 days post-exercise ] [ Designated as safety issue: No ]
Change in white blood cell count in blood [ Time Frame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise ] [ Designated as safety issue: No ]
Change in neutrophil count in blood [ Time Frame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise ] [ Designated as safety issue: No ]
Change in fatty acid binding protein in plasma [ Time Frame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise ] [ Designated as safety issue: No ]
Change in cortisol concentration in blood [ Time Frame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise ] [ Designated as safety issue: No ]
Change in testosterone concentration in plasma [ Time Frame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise ] [ Designated as safety issue: No ]
Change in cytokine concentration in plasma [ Time Frame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise ] [ Designated as safety issue: No ]
Measurement of IL-1β, IL-4, IL-6, TNF-α, IL-8, IL-10, IL-12p70 concentrations in plasma
Change in adhesion molecule concentration in blood [ Time Frame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise ] [ Designated as safety issue: No ]
Measurement of ICAM-1, VCAM-1, sP-selectin, sE-selectin concentrations in plasma
Change in intracellular signalling proteins in muscle [ Time Frame: one hour before exercise, 2 hours post-exercise, 2 days post-exercise, 8 days post-exercise ] [ Designated as safety issue: No ]
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.
Change in myogenic determination factor (MyoD) protein levels in muscle [ Time Frame: one hour before exercise, 2 hours post-exercise, 2 days post-exercise, 8 days post-exercise ] [ Designated as safety issue: No ]
MyoD expression in vastus lateralis muscle
Change in tumor necrosis factor α in muscle [ Time Frame: one hour before exercise, 2 hours post-exercise, 2 days post-exercise, 8 days post-exercise ] [ Designated as safety issue: No ]
Protein levels of TNF-α in vastus lateralis muscle

Secondary Outcome Measures:

Change in muscle function of knee extensor and flexor muscle [ Time Frame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise ] [ Designated as safety issue: No ]
assessment of muscle peak and mean torque of knee extensors and flexors on an isokinetic dynamometer at 0, 90 and 180 degrees/sec
Body composition [ Time Frame: One day before exercise ] [ Designated as safety issue: No ]
Assessment of percent (%) lean body mass.
Maximal aerobic capacity [ Time Frame: One day before exercise ] [ Designated as safety issue: No ]
Assessment of maximal oxygen consumption, an indice of cardiovascular conditioning
Change in profile of dietary intake [ Time Frame: one hour before exercise, daily for 8 days post-exercise ] [ Designated as safety issue: No ]
Assessment of dietary intake with emphasis on antioxidant element intake
Change in side effect occurence [ Time Frame: one hour before exercise, daily for 8 days post-exercise ] [ Designated as safety issue: Yes ]
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).

Enrollment:	20
Study Start Date:	January 2010
Study Completion Date:	April 2012
Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 Name: Exercise-induced skeletal muscle damage

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.

Eligibility

Ages Eligible for Study:	18 Years to 30 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01778309

Locations

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

Sponsors and Collaborators

Democritus University of Thrace

Investigators

Principal Investigator:

Ioannis F Fatouros, Ph.D.

Democritus University of Thrace, Greece

More Information

No publications provided

Responsible Party:	Ioannis G. Fatouros, Assistant Professor, Democritus University of Thrace
ClinicalTrials.gov Identifier:	NCT01778309 History of Changes
Other Study ID Numbers:	NACEXERCISE2011, CE-80739
Study First Received:	January 21, 2013
Last Updated:	January 25, 2013
Health Authority:	Greece: Institutional Review Board

Keywords provided by Democritus University of Thrace:

aseptic inflammation
skeletal muscle function
exercise

Additional relevant MeSH terms:

Acetylcysteine
N-monoacetylcystine
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Expectorants

Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes

ClinicalTrials.gov processed this record on May 19, 2013