Clinical trial NCT01778309: NAC Supplementation and Skeletal Muscle Performance
Official title: Effects of NAC Supplementation on Skeletal Muscle Performance Following Aseptic Injury Induced by Exercise
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Skeletal Muscle Damage
Skeletal Muscle Performance
Intgracellular Signaling in Skeletal Muscle
Inflammatory Status
Keywords: aseptic inflammation
skeletal muscle function
exercise
Lead sponsor: Democritus University of Thrace
Sponsor class: OTHER
First posted: 2013-01-29
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief 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.

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 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

Primary outcomes:
measure: Change in reduced glutathione in blood
timeFrame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
measure: Change in reduced glutathione in muscle
timeFrame: one hour before exercise, 2 hours post-exercise, 2 days post-exercise, 8 days post-exercise
measure: Change in protein carbonyls in red blood cells and serum
timeFrame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
measure: Change in protein carbonyls in muscle
timeFrame: one hour before exercise, 2 hours post-exercise, 2 days post-exercise, 8 days post-exercise
measure: Change in thiobarbituric acid reactive substances in red blood cells and serum
timeFrame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
measure: Change in thiobarbituric acid reactive substances in muscle
timeFrame: one hour before exercise, 2 hours post-exercise, 2 days post-exercise, 8 days post-exercise
measure: Change in oxidized glutathione in red blood cells and blood
timeFrame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
measure: Change in total antioxidant capacity in serum
timeFrame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
measure: Change in oxidized glutathione in muscle
timeFrame: one hour before exercise, 2 hours post-exercise, 2 days post-exercise, 8 days post-exercise
measure: Change in catalase activity in red blood cells and serum
timeFrame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
measure: Change in glutathione peroxidase activity in red blood cells
timeFrame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
measure: Change in creatine kinase activity in plasma
timeFrame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
measure: Change in C-reactive protein in plasma
timeFrame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
measure: Change in macrophage infiltration in muscle
timeFrame: one hour before exercise, 2 hours post-exercise, 2 days post-exercise, 8 days post-exercise
measure: Change in white blood cell count in blood
timeFrame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
measure: Change in neutrophil count in blood
timeFrame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
measure: Change in fatty acid binding protein in plasma
timeFrame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
measure: Change in cortisol concentration in blood
timeFrame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
measure: Change in testosterone concentration in plasma
timeFrame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
measure: Change in cytokine concentration in plasma
timeFrame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
measure: Change in adhesion molecule concentration in blood
timeFrame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
measure: Change in intracellular signalling proteins in muscle
timeFrame: one hour before exercise, 2 hours post-exercise, 2 days post-exercise, 8 days post-exercise
measure: Change in myogenic determination factor (MyoD) protein levels in muscle
timeFrame: one hour before exercise, 2 hours post-exercise, 2 days post-exercise, 8 days post-exercise
measure: Change in tumor necrosis factor α in muscle
timeFrame: one hour before exercise, 2 hours post-exercise, 2 days post-exercise, 8 days post-exercise
Secondary outcomes:
measure: Change in muscle function of knee extensor and flexor muscle
timeFrame: one hour before exercise, 5 minutes post-exercise, 2 hours post-exercise, daily for 8 days post-exercise
measure: Body composition
timeFrame: One day before exercise
measure: Maximal aerobic capacity
timeFrame: One day before exercise
measure: Change in profile of dietary intake
timeFrame: one hour before exercise, daily for 8 days post-exercise
measure: Change in side effect occurence
timeFrame: one hour before exercise, daily for 8 days post-exercise
Other outcomes:
Locations:
city: Komotini
country: Greece
facility: Laboratory of Physical Education & Sport Performance
state: Thrace
Study officials:
affiliation: Democritus University of Thrace, Greece
name: Ioannis F Fatouros, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.