NAC Supplementation and Skeletal Muscle Performance

Skeletal Muscle Damage Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01778309
• Other study ID #: NACEXERCISE2011
• Secondary ID: CE-80739
• Status: Completed
• Phase: N/A
• First received: January 21, 2013
• Last updated: January 25, 2013
• Start date: January 2010
• Est. completion date: April 2012

Study information

• Verified date: January 2013
• Source: Democritus University of Thrace
• Contact: n/a
• Is FDA regulated: No
• Health authority: Greece: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: April 2012
• Est. primary completion date: September 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 30 Years

Eligibility

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 Design

Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Inflammatory Status
• Intgracellular Signaling in Skeletal Muscle
• Skeletal Muscle Damage
• Skeletal Muscle Performance

Intervention

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

Locations

Country	Name	City	State
Greece	Laboratory of Physical Education & Sport Performance	Komotini	Thrace

Sponsors (1)

Lead Sponsor	Collaborator
Democritus University of Thrace

Country where clinical trial is conducted

Greece, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	Change in macrophage infiltration in muscle		one hour before exercise, 2 hours post-exercise, 2 days post-exercise, 8 days post-exercise	No
Primary	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	No
Primary	Change in neutrophil count in blood		one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise	No
Primary	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	No
Primary	Change in cortisol concentration in blood		one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise	No
Primary	Change in testosterone concentration in plasma		one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise	No
Primary	Change in cytokine concentration in plasma	Measurement of IL-1ß, IL-4, IL-6, TNF-a, 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	No
Primary	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	No
Primary	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 ?B (NF?B), 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	No
Primary	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	No
Primary	Change in tumor necrosis factor a in muscle	Protein levels of TNF-a in vastus lateralis muscle	one hour before exercise, 2 hours post-exercise, 2 days post-exercise, 8 days post-exercise	No
Secondary	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	No
Secondary	Body composition	Assessment of percent (%) lean body mass.	One day before exercise	No
Secondary	Maximal aerobic capacity	Assessment of maximal oxygen consumption, an indice of cardiovascular conditioning	One day before exercise	No
Secondary	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	No
Secondary	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	Yes