Redox Status and Exercise Training-induced Adaptations

Not Applicable

Recruiting

• Conditions: Overweight (BMI > 25); Obesity

• Registration Number: NCT07196852
• Lead Sponsor: University of Thessaly

Brief Summary

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.

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 Timeline

• Status Verified: 2025-09
• Study First Submitted: 2025-09-19
• Study First Submitted QC: 2025-09-19
• Last Update Submitted: 2025-09-19
• Study Start: 2025-09-22
• Study First Posted: 2025-09-29
• Last Update Posted: 2025-09-29
• Primary Completion: 2026-09-30
• Study Completion: 2026-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• BMI 25-35 kg/m2
• Free of musculoskeletal injuries
• Free of chronic non-comunicable 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Change in body weight (kg)	At baseline, 6 weeks and 12 weeks
Change in liver fat infiltration	At baseline and 12 weeks	Liver fat infiltration will be assessed through ultrasound elastography
Change in reduced glutathione (GSH) concentration	At baseline, 6 weeks and 12 weeks	GSH concentration will be determined in blood erythrocytes and peripheral blood mononuclear cells
Change in glutathione reductase (GR) activity	At baseline, 6 weeks and 12 weeks	GR activity will be determined in blood erythrocytes and peripheral blood mononuclear cells
Change in catalase activity	At baseline, 6 weeks and 12 weeks	Catalase activity will be determined in blood erythrocytes and peripheral blood mononuclear cells
Change in serum glutamic-oxaloacetic transaminase (SGOT/AST) concentration	At baseline, 6 weeks and 12 weeks	SGOT concentration will be determined in blood
Change in glucose concentration	At baseline, 6 weeks and 12 weeks	Glucose concentration will be determined in blood
Change in waist circumference	At baseline, 6 weeks and 12 weeks
Change in superoxide dismutase (SOD) activity	At baseline, 6 weeks and 12 weeks	SOD activity will be determined in blood erythrocytes and peripheral blood mononuclear cells
Change in HDL cholesterol concentration	At baseline, 6 weeks and 12 weeks	HDL cholesterol concentration will be determined in blood
Change in LDL cholesterol concentration	At baseline, 6 weeks and 12 weeks	LDL cholesterol concentration will be determined in blood
Change in Gamma-glutamyl transpeptidase (γ-GT) concentration	At baseline, 6 weeks and 12 weeks	γ-GT concentration will be determined in blood
Change in fetuin-A concentration	At baseline, 6 weeks and 12 weeks	Fetuin-A concentration will be determined in blood
Change in alkaline phosphatase (ALP) concentration	At baseline, 6 weeks and 12 weeks	ALP concentration will be determined in blood
Change in hip circumference	At baseline, 6 weeks and 12 weeks
Change in fat mass (kg)	At baseline, 6 weeks and 12 weeks	Fat mass will be assessed through dual energy X-ray absorptiometry (DXA)
Change in lean body mass (kg)	At baseline, 6 weeks and 12 weeks	Lean body mass will be assessed through dual energy X-ray absorptiometry (DXA)
Alanine Aminotransferase (SGPT/ALT) concentration	At baseline, 6 weeks and 12 weeks	SGPT concentration will be determined in blood
Change in insulin concentration	At baseline, 6 weeks and 12 weeks	Insulin concentration will be determined in blood
Change in physical activity level	At baseline, 6 weeks and 12 weeks	Physical activity level will be assessed by using accelerometers
Change in body fat percent (%)	At baseline, 6 weeks and 12 weeks	Body fat percent will be assessed through dual energy X-ray absorptiometry (DXA)
Change in fat free mass (kg)	At baseline, 6 weeks and 12 weeks	Fat free mass will be assessed through dual energy X-ray absorptiometry (DXA)
Change in upper body muscle strength	At baseline, 6 weeks and 12 weeks	Upper body muscle strength will be assessed through the abdominal strength test and the push-up test
Change in TNF-α concentration	At baseline, 6 weeks and 12 weeks	TNF-α concentration will be determined in blood and peripheral blood mononuclear cells
Change in interleukin-6 (IL-6) concentration	At baseline, 6 weeks and 12 weeks	IL-6 concentration will be determined in blood and peripheral blood mononuclear cells
Change in total cholesterol concentration	At baseline, 6 weeks and 12 weeks	Total cholesterol concentration will be determined in blood
Change in triglycerides concentration	At baseline, 6 weeks and 12 weeks	Triglycerides concentration will be determined in blood
Change in glycated hemoglobin (HbA1c) concentration	At baseline, 6 weeks and 12 weeks	HbA1c concentration will be determined in blood
Change in cardiorespiratory fitness	At baseline, 6 weeks and 12 weeks	Maximal oxygen consumption (VO2max) will be estimated during a single stage treadmill test (Ebbeling single stage test)
Change in lower body muscle strength	At baseline, 6 weeks and 12 weeks	Maximal concentric peak torque will be assessed on an isokinetic dynamometer
Change in oxidized glutathione (GSSG) concentration	At baseline, 6 weeks and 12 weeks	GSSG concentration will be determined in blood erythrocytes and peripheral blood mononuclear cells
Change in glutathione peroxidase (GPx) activity	At baseline, 6 weeks and 12 weeks	GPx activity will be determined in blood erythrocytes and peripheral blood mononuclear cells
Change in malondialdehyde consentration	At baseline, 6 weeks and 12 weeks	Malondialdehyde consentration will be determined in peripheral blood mononuclear cells
Change in C-reactive protein (CRP) concentration	At baseline, 6 weeks and 12 weeks

Secondary Outcome Measures

Name	Time	Method
Change in dietary intake	At baseline, 6 weeks and 12 weeks	Dietary intake will be monitored through diet recalls

Trial Locations

Locations (1)

Department of Physical Education and Sport Science, University of Thessaly; 🇬🇷 Trikala, Karies, Greece