NAC Supplementation and Skeletal Muscle Performance

Democritus University of Thrace20 enrolled

Overview

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.

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

Allocation

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

Conditions

Skeletal Muscle Damage

Eligibility

Sex: MALEMin age: 18 YearsMax age: 30 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Change in reduced glutathione in blood

Concentration of reduced glutathione in red blood cells

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise

Change in macrophage infiltration in muscle

Time frame: one hour before exercise, 2 hours post-exercise, 2 days post-exercise, 8 days post-exercise

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

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

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

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

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

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

Time frame: 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

Time frame: 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.

Time frame: 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

Time frame: 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

Time frame: one hour before exercise, 2 hours post-exercise, 2 days post-exercise, 8 days post-exercise

Secondary Outcomes

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

Time frame: 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.

Time frame: One day before exercise

Maximal aerobic capacity

Assessment of maximal oxygen consumption, an indice of cardiovascular conditioning

Time frame: One day before exercise

Change in profile of dietary intake

Assessment of dietary intake with emphasis on antioxidant element intake

Time frame: 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).

Time frame: one hour before exercise, daily for 8 days post-exercise

NAC Supplementation and Skeletal Muscle Performance

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes