S-Acetyl Glutathione and Performance Recovery in Soccer

Pharmacodynamics & Pharmacokinetics Study of S-Acetyl Glutathione in Highly Trained Soccer Players

Soccer players display elevated inflammatory and oxidative stress markers combined with reduced soccer specific performance over a 72-hour period. However, in modern soccer, players participate very often in 2 or 3 matches within a week, with a recovery period of 72 hours between successive matches, that is insufficient to restore skeletal muscle homeostasis and performance. Of note, reduced glutathione (GSH) levels, a tripeptide consisting of the amino acids cysteine, glycine and glutamic acid, are substantially reduced during the 72-hour recovery period after a match because of the trauma-related acute inflammatory and oxidative stress response. GSH availability is a crucial regulator of cellular redox status, affecting numerous intracellular and physiological processes such as redox signalling, immunoregulation and muscle metabolism. Indeed, enhanced GSH availability following muscle damaging exercise has been shown to be beneficial for skeletal muscle and performance recovery by mitigating the inflammatory and oxidative stress response. Thus, the enhancement of GSH availability through dietary interventions would be a promising strategy to accelerate skeletal muscle and performance recovery following a soccer game. S-Acetyl Glutathione (SAG) is a glutathione precursor with enhanced absorption kinetics due to chemical S-acetylation of the thiol group on the cysteinyl amino acid of GSH and oral administration of SAG has been shown to be more effective in restoring intracellular glutathione levels compared to oral glutathione. The aim of this study is to (i) perform a pharmacokinetic assessment of 200 mg/day vs 500 mg/day of SAG during a 7-day supplementation period (pre-loading) and (ii) to establish the pharmacodynamic effect of the two dosages at 24, 48 and 72h following a 90-minute official soccer match.

Study Overview

• Status: Not yet recruiting
• Conditions: Exercise-induced Inflammation; Exercise-induced Oxidative Stress; Performance Recovery
• Intervention / Treatment: Dietary supplement: 200 mg S-Acetyl Glutathione; Dietary supplement: 500 mg S-Acetyl Glutathione; Dietary supplement: Placebo Supplementation

Detailed Description

Following baseline testing [including assessment of anthropometrics, body composition (via DXA instrumentation) and physical performance (cardiorespiratory fitness, drop jump and countermovement jump performance, repeated sprint anility, isokinetic peak torque)], 20 well-trained, soccer players will participate in three trials, receiving daily (i) 200 mg SAG, (ii) 500 mg SAG or (iii) Placebo, according to a randomized, double-blind, crossover, repeated-measures design. The duration of each trial will be 11 days, including a 7-day pre-loading period (days 1 -7), a match day (day 8) and 3 consecutive recovery days after the match (days 9-11). Between trials a 3-week washout period will be implemented.

Pre-loading period: During the 7-day pre-loading period players will participate daily in training sessions according to a soccer-specific weekly training schedule, while receiving the respective supplement. Blood samples will be collected on day 1 and day 7 while daily nutrient intake (via 7-day diet recalls), physical activity level (via accelerometry) and training load (via global positioning system instrumentation during training sessions) will be monitored daily.

Match day: On match day, players will participate in an official 90-min soccer match. Field activity (total distance, average and maximum speed, high intensity running, high speed running, accelerations, decelerations) and heart rate (mean and maximum heart rate) will be continuously monitored using global positioning system (GPS) and heart rate monitors, respectively.

Recovery days: During the 3-day recovery period after the match, players will participate daily in (i) morning testing sessions and (ii) training sessions in the evening. Testing sessions will include blood sampling and performance measurements including drop jump and countermovement jump performance, repeated sprint anility, isokinetic peak torque and muscle soreness (DOMS). Dietary intake (via a 3-day diet recalls), physical activity level (via accelerometry) and training load (via GPS instrumentation during training sessions) will be monitored daily.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dimitrios Draganidis, PhD; Phone Number: +30 2431047078; Email: ddraganidis@uth.gr
• Study Contact Backup: Name: Athanasios Poulios, PhD; Phone Number: +30 2431047053; Email: athanpoul@gmail.com

Study Locations

• Greece
  • Karies
    • Trikala, Karies, Greece, 42100
      • Department of Physical Education and Sport Science, University of Thessaly
      • Contact: Ioannis G Fatouros, PhD; Phone Number: +30 2431047047; Email: ifatouros@uth.gr
      • Contact: Athanasios Z Jamurtas, PhD; Phone Number: +30 24310 47054; Email: ajamurt@uth.gr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• participation at elite (top three division leagues) for ≥ 4 years
• no recent history of febrile illness, musculoskeletal problems and metabolic diseases
• no consumption of medications and performance-enhancing supplements (including anti-inflammatory, antioxidants, vitamins and multivitamin supplements) for at least 6 months prior to the study
• participation in at least 5 training sessions and 1 match per week
• non-smokers

Exclusion Criteria:

• musculoskeletal injury
• consumption of medication and performance-enhancing supplements
• illness during the course of the study
• loss of follow-up measurements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SAG-200 Trial; Oral administration of S-Acetyl Glutathione (SAG)	Dietary supplement: 200 mg S-Acetyl Glutathione; Participants will be supplemented daily with 200 mg of S-acetyl glutathione, orally, over the 11-day experimental period.
Experimental: SAG-500 Trial; Oral administration of S-Acetyl Glutathione (SAG)	Dietary supplement: 500 mg S-Acetyl Glutathione; Participants will be supplemented daily with 500 mg of S-acetyl glutathione, orally, over the 11-day experimental period.
Placebo Comparator: Placebo Trial; Oral administration of placebo	Dietary supplement: Placebo Supplementation; Participants will be supplemented daily with placebo, orally, over the 11-day experimental period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in creatine kinase levels	Creatine kinase concentration will be measured in serum using a Clinical Chemistry Analyzer	Day 1, day 7, day 9, day 10 and day 11
Change in myoglobin levels	Myoglobin concentration will be measured in serum using a Clinical Chemistry Analyzer	Day 1, day 7, day 9, day 10 and day 11
Change in reduced glutathione	Reduced glutathione will be photometrically determined in red blood cell lysates using a spectrophotometer	Day 1, day 7, day 9, day 10 and day 11
Change in oxidized glutathione	Oxidized glutathione will be photometrically determined in red blood cell lysates using a spectrophotometer	Day 1, day 7, day 9, day 10 and day 11
Change in glutathione reductase activity	Glutathione reductase activity will be photometrically determined in red blood cell lysates using a spectrophotometer	Day 1, day 7, day 9, day 10 and day 11
Change in glutathione peroxidase activity	Glutathione peroxidase activity will be photometrically determined in red blood cell lysates using a spectrophotometer	Day 1, day 7, day 9, day 10 and day 11.
Change in catalase activity	Catalase activity will be photometrically determined in red blood cell lysates using a spectrophotometer	Day 1, day 7, day 9, day 10 and day 11
Change in superoxide dismutase activity	Superoxide dismutase activity will be photometrically determined in red blood cell lysates using a spectrophotometer	Day 1, day 7, day 9, day 10 and day 11
Change in maximal voluntary isometric contraction	Maximal voluntary isometric contraction will be assessed at a 60o knee joint angle, in both dominant and non-dominant limb, using an isokinetic dynamometer	Day 1, day 9, day 10 and day 11
Change in maximal peak torque	Maximal concentric and eccentric peak torque at 60o/s of the knee extensors and flexors in both dominant and non-dominant limb, will be assessed on an isokinetic dynamometer	Day 1, day 9, day 10 and day 11
Change in jumping performance	Countermovement jump and drop jump performance will be tested using an optical measurement system consisting of a transmitting and receiving bar	Day 1, day 9, day 10 and day11
Change in repeated sprint ability	Repeated sprint ability will be assessed by performing 5x25 m sprints interspersed by a 25-seconds recovery period using infrared photocells	Day 1, day 9, day 10 and day 11
Change in delayed onset muscle soreness (DOMS)	DOMS will be assessed using a 10-scale visual analogue scale	Day 1, day 9, day 10 and day 11

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in total distance covered	Total distance (km) covered during training and match play will be monitored using Global Positioning System (GPS)	Daily throughout the 11-day experimental period
Change in internal load	Heart rate during training sessions and the match will be monitored using heart rate monitors	Daily throughout the 11-day experimental period
Change in dietary intake	Dietary intake will be assessed using diet recalls	Daily throughout the 11-day experimental period
Change in time spent in moderate-to-vigorous physical activity	The time (minutes) spent in moderate-to-vigorous physical activity on a daily basis will be monitored using accelerometers	Daily throughout the 11-day experimental period
Change in distance covered with high-intensity running	Distance (km) covered with high-intensity running during training and match play will be monitored using Global Positioning System (GPS)	Daily throughout the 11-day experimental period
Change in distance covered with sprinting	Distance (km) covered with high-intensity sprinting during training and match play will be monitored using Global Positioning System (GPS)	Daily throughout the 11-day experimental period
Change in accelerations	The number of accelerations performed during training and match play will be monitored using Global Positioning System (GPS)	Daily throughout the 11-day experimental period
Change in decelerations	The number of decelerations performed during training and match play will be monitored using Global Positioning System (GPS)	Daily throughout the 11-day experimental period
Change in total step count	The total number of steps performed daily will be monitored using accelerometers	Daily throughout the 11-day experimental period
Change in physical activity-related energy expenditure	Energy expenditure (kcal) related to habitual physical activity will be assessed using accelerometers	Daily throughout the 11-day experimental period

Collaborators and Investigators

• Sponsor: University of Thessaly
• Collaborators: Lesaffre International
• Investigators: Principal Investigator: Dimitrios Draganidis, PhD, University of Thessaly, Department of Physical Education and Sport Science

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 20, 2026
• Study Completion (Estimated): January 20, 2027

Study Registration Dates

• First Submitted: June 9, 2026
• First Submitted That Met QC Criteria: July 1, 2026
• First Posted (Actual): July 8, 2026

Study Record Updates

• Last Update Posted (Actual): July 8, 2026
• Last Update Submitted That Met QC Criteria: July 1, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: recovery; soccer; Glutathione; S-Acetyl Glutathione
• Other Study ID Numbers: UTH-06/13.02.2026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No