Redox Status and Exercise Training-induced Adaptations

December 9, 2025 updated by: Dimitrios Draganidis, University of Thessaly

Effects of N-acetylcysteine on Biological Responses to High-intensity Interval Training in Adults With Overweight/Obesity

Excess fat accumulation is a key feature of overweight and obesity that is mainly driven by nutrient overload and insufficient physical activity. White adipose tissue displays lipid overload and hypertrophy accompanied by macrophages infiltration, hypoxia, inflammation and excess production of reactive oxygen species (ROS). An inflammatory response and ROS production are also evident in other metabolism regulating tissues and organs such as skeletal muscle, liver, pancreas and hypothalamus, contributing to a chronic inflammatory state, redox status disturbances and metabolic complications. There is overwhelming evidence showing that adults with overweight/obesity exhibit lower glutathione (GSH) levels in blood erythrocytes, skeletal muscle cells and subcutaneous and visceral adipose tissue cells. GSH, a tripeptide consisting of the amino acids glutamate, cysteine and glycine, is the most abundant thiol-containing antioxidant in the human body and has been, recently, characterized as a novel therapeutic target for the treatment of numerous chronic diseases, due to its potent intracellular redox buffering capacity. Interestingly, lower GSH levels have been associated with diet-induced weight loss resistance, while enhancement of GSH levels through N-acetylcysteine (NAC) supplementation reduces markers of oxidative stress, inflammation, insulin resistance, hypertension, endothelia dysfunction and improves vitamin D metabolism. NAC is a thiol donor that elicits antioxidant effects by (i) directly scavenging ROS and (ii) providing reduced cysteine through deacetylation, which supports the biosynthesis of endogenous GSH via the activity of γ-glutamylcysteine synthase. The aim of this study is to investigate whether NAC supplementation can enhance the exercise training-induced improvements on physical fitness and metabolic health in adult men and women with overweight/obesity.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Forty adults with overweight/obesity (both males and females, aged 35-45 years) who will meet the inclusion criteria will be randomly assigned to a Placebo (Pla, n=20, will be supplemented with 2 placebo pills daily over a 12-week period) or a NAC (NAC, n=20 will be supplemented with 2 pills x 600 mg N-acetylcysteine daily over a 12-week period) group. Both groups will participate in 3 multicomponent high-intensity interval training (m-HIIT) sessions per week over a 12-week period. At baseline, 6 weeks and 12 weeks participants will undergo assessment of their (i) anthropometrics (body weight, waist and hip circumferences) (ii) body composition (through total body DXA scan), (iii) fat liver content (via high-resolution ultrasound), (iv) cardiorespiratory fitness (determination of VO2max), (v) muscle strength (upper and lower body), (vi) habitual physical activity level (via accelerometry) and (vii) daily dietary intake (via dietary recalls). In addition, at the same time-points (Baseline, 6 weeks, 12 weeks), resting blood samples will be collected for the determination of (viii) blood redox status [reduced glutathione (GSH), oxidized glutathione (GSSH), GSH/GSSG, glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT)], (ix) peripheral blood mononuclear cells antioxidant levels and markers of oxidative stress and inflammation (catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, malondialdehyde, TNF-α and Interleukin-6), (x) low-grade systemic inflammation [C-reactive protein (CRP) and Interleukin-6 (IL-6)], (xi) lipidemic profile (triglycerides, total cholesterol, HDL, LDL) and (xii) liver function (SGPT, SGOT, γ-GT, ALP, Fetuin-A), and (xiii) an oral glucose tolerance test (using 75g glucose loading) will be performed.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

  • Name: Ioannis G. Fatouros, PhD
  • Phone Number: +30 2431047047
  • Email: ifatouros@uth.gr

Study Locations

  • Greece
    • Karies
      • Trikala, Karies, Greece, 42100
        • Recruiting
        • Department of Physical Education and Sport Science, University of Thessaly
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • BMI 25-35 kg/m2
  • Free of musculoskeletal injuries
  • Free of chronic non-communicable diseases
  • Do not receive any drug therapy
  • Do not receive dietary supplements
  • Normal menstrual cycle (for females)
  • Non smokers

Exclusion Criteria:

  • NAC intolerance
  • Bleeding disorders
  • Kidney disease
  • Asthma
  • Usage of blood thinners and/or angina medication

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: N-acetylcysteine
Oral N-acetylcysteine supplementation for 12 weeks (2 x 600 mg capsules/day)
Dietary supplement: N Acetyl L Cysteine
Participants will participate in 3 multicomponent high-intensity interval training (m-HIIT) sessions per week over a 12-week period while receiving daily 1200 mg N-acetylcysteine (2 pills x 600 mg/day ).
Placebo Comparator: Placebo
Oral placebo supplementation for 12 weeks (2 placebo capsules/day)
Dietary supplement: Placebo
Participants will participate in 3 multicomponent high-intensity interval training (m-HIIT) sessions per week over a 12-week period while receiving daily 2 placebo pills/day.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in body weight (kg)
Time Frame: At baseline, 6 weeks and 12 weeks
At baseline, 6 weeks and 12 weeks
Change in waist circumference
Time Frame: At baseline, 6 weeks and 12 weeks
At baseline, 6 weeks and 12 weeks
Change in hip circumference
Time Frame: At baseline, 6 weeks and 12 weeks
At baseline, 6 weeks and 12 weeks
Change in fat mass (kg)
Time Frame: At baseline, 6 weeks and 12 weeks
Fat mass will be assessed through dual energy X-ray absorptiometry (DXA)
At baseline, 6 weeks and 12 weeks
Change in body fat percent (%)
Time Frame: At baseline, 6 weeks and 12 weeks
Body fat percent will be assessed through dual energy X-ray absorptiometry (DXA)
At baseline, 6 weeks and 12 weeks
Change in fat free mass (kg)
Time Frame: At baseline, 6 weeks and 12 weeks
Fat free mass will be assessed through dual energy X-ray absorptiometry (DXA)
At baseline, 6 weeks and 12 weeks
Change in lean body mass (kg)
Time Frame: At baseline, 6 weeks and 12 weeks
Lean body mass will be assessed through dual energy X-ray absorptiometry (DXA)
At baseline, 6 weeks and 12 weeks
Change in liver fat infiltration
Time Frame: At baseline and 12 weeks
Liver fat infiltration will be assessed through ultrasound elastography
At baseline and 12 weeks
Change in cardiorespiratory fitness
Time Frame: At baseline, 6 weeks and 12 weeks
Maximal oxygen consumption (VO2max) will be estimated during a single stage treadmill test (Ebbeling single stage test)
At baseline, 6 weeks and 12 weeks
Change in lower body muscle strength
Time Frame: At baseline, 6 weeks and 12 weeks
Maximal concentric peak torque will be assessed on an isokinetic dynamometer
At baseline, 6 weeks and 12 weeks
Change in upper body muscle strength
Time Frame: At baseline, 6 weeks and 12 weeks
Upper body muscle strength will be assessed through the abdominal strength test and the push-up test
At baseline, 6 weeks and 12 weeks
Change in reduced glutathione (GSH) concentration
Time Frame: At baseline, 6 weeks and 12 weeks
GSH concentration will be determined in blood erythrocytes and peripheral blood mononuclear cells
At baseline, 6 weeks and 12 weeks
Change in oxidized glutathione (GSSG) concentration
Time Frame: At baseline, 6 weeks and 12 weeks
GSSG concentration will be determined in blood erythrocytes and peripheral blood mononuclear cells
At baseline, 6 weeks and 12 weeks
Change in glutathione peroxidase (GPx) activity
Time Frame: At baseline, 6 weeks and 12 weeks
GPx activity will be determined in blood erythrocytes and peripheral blood mononuclear cells
At baseline, 6 weeks and 12 weeks
Change in glutathione reductase (GR) activity
Time Frame: At baseline, 6 weeks and 12 weeks
GR activity will be determined in blood erythrocytes and peripheral blood mononuclear cells
At baseline, 6 weeks and 12 weeks
Change in catalase activity
Time Frame: At baseline, 6 weeks and 12 weeks
Catalase activity will be determined in blood erythrocytes and peripheral blood mononuclear cells
At baseline, 6 weeks and 12 weeks
Change in superoxide dismutase (SOD) activity
Time Frame: At baseline, 6 weeks and 12 weeks
SOD activity will be determined in blood erythrocytes and peripheral blood mononuclear cells
At baseline, 6 weeks and 12 weeks
Change in C-reactive protein (CRP) concentration
Time Frame: At baseline, 6 weeks and 12 weeks
At baseline, 6 weeks and 12 weeks
Change in TNF-α concentration
Time Frame: At baseline, 6 weeks and 12 weeks
TNF-α concentration will be determined in blood and peripheral blood mononuclear cells
At baseline, 6 weeks and 12 weeks
Change in interleukin-6 (IL-6) concentration
Time Frame: At baseline, 6 weeks and 12 weeks
IL-6 concentration will be determined in blood and peripheral blood mononuclear cells
At baseline, 6 weeks and 12 weeks
Change in HDL cholesterol concentration
Time Frame: At baseline, 6 weeks and 12 weeks
HDL cholesterol concentration will be determined in blood
At baseline, 6 weeks and 12 weeks
Change in LDL cholesterol concentration
Time Frame: At baseline, 6 weeks and 12 weeks
LDL cholesterol concentration will be determined in blood
At baseline, 6 weeks and 12 weeks
Change in total cholesterol concentration
Time Frame: At baseline, 6 weeks and 12 weeks
Total cholesterol concentration will be determined in blood
At baseline, 6 weeks and 12 weeks
Change in triglycerides concentration
Time Frame: At baseline, 6 weeks and 12 weeks
Triglycerides concentration will be determined in blood
At baseline, 6 weeks and 12 weeks
Change in serum glutamic-oxaloacetic transaminase (SGOT/AST) concentration
Time Frame: At baseline, 6 weeks and 12 weeks
SGOT concentration will be determined in blood
At baseline, 6 weeks and 12 weeks
Alanine Aminotransferase (SGPT/ALT) concentration
Time Frame: At baseline, 6 weeks and 12 weeks
SGPT concentration will be determined in blood
At baseline, 6 weeks and 12 weeks
Change in Gamma-glutamyl transpeptidase (γ-GT) concentration
Time Frame: At baseline, 6 weeks and 12 weeks
γ-GT concentration will be determined in blood
At baseline, 6 weeks and 12 weeks
Change in fetuin-A concentration
Time Frame: At baseline, 6 weeks and 12 weeks
Fetuin-A concentration will be determined in blood
At baseline, 6 weeks and 12 weeks
Change in alkaline phosphatase (ALP) concentration
Time Frame: At baseline, 6 weeks and 12 weeks
ALP concentration will be determined in blood
At baseline, 6 weeks and 12 weeks
Change in glucose concentration
Time Frame: At baseline, 6 weeks and 12 weeks
Glucose concentration will be determined in blood
At baseline, 6 weeks and 12 weeks
Change in glycated hemoglobin (HbA1c) concentration
Time Frame: At baseline, 6 weeks and 12 weeks
HbA1c concentration will be determined in blood
At baseline, 6 weeks and 12 weeks
Change in insulin concentration
Time Frame: At baseline, 6 weeks and 12 weeks
Insulin concentration will be determined in blood
At baseline, 6 weeks and 12 weeks
Change in malondialdehyde concentration
Time Frame: At baseline, 6 weeks and 12 weeks
Malondialdehyde concentration will be determined in peripheral blood mononuclear cells
At baseline, 6 weeks and 12 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in dietary intake
Time Frame: At baseline, 6 weeks and 12 weeks
Dietary intake will be monitored through diet recalls
At baseline, 6 weeks and 12 weeks
Change in total number of steps
Time Frame: At baseline, 6 weeks and 12 weeks
Total number of steps performed per day will be assessed by using accelerometers
At baseline, 6 weeks and 12 weeks
Change in time spent in moderate-to-vigorous physical activity
Time Frame: At baseline, 6 weeks and 12 weeks
The time spent in moderate-to-vigorous physical activity per day will be assessed by using accelerometers
At baseline, 6 weeks and 12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Thessaly

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Anastasia Rosvoglou, PhDc, University of Thessaly, Department of Physical Education and Sport Science
  • Study Director: Dimitrios Draganidis, PhD, University of Thessaly, Department of Physical Education and Sport Science

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 22, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 19, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 19, 2025

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 29, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 16, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 9, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • UTH-2568_2.4.2025

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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