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NCT Number: NCT07196852

Redox Status and Exercise Training-induced Adaptations

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.

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Key information

Conditions

Overweight (BMI > 25) Body Weight Nutrition Disorders Nutritional and Metabolic Diseases Obesity Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

30 year–45 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

N Acetyl L Cysteine

Dietary Supplement

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

Dietary Supplement

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.

Primary outcomes

  1. Change in body weight (kg)

    Time frame: At baseline, 6 weeks and 12 weeks

  2. Change in waist circumference

    Time frame: At baseline, 6 weeks and 12 weeks

  3. Change in hip circumference

    Time frame: At baseline, 6 weeks and 12 weeks

  4. 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)

  5. 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)

  6. 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)

  7. 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)

  8. Change in liver fat infiltration

    Time frame: At baseline and 12 weeks

    Liver fat infiltration will be assessed through ultrasound elastography

  9. 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)

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. Change in malondialdehyde concentration

    Time frame: At baseline, 6 weeks and 12 weeks

    Malondialdehyde concentration will be determined in peripheral blood mononuclear cells

  19. Change in C-reactive protein (CRP) concentration

    Time frame: At baseline, 6 weeks and 12 weeks

  20. 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

  21. 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

  22. Change in HDL cholesterol concentration

    Time frame: At baseline, 6 weeks and 12 weeks

    HDL cholesterol concentration will be determined in blood

  23. Change in LDL cholesterol concentration

    Time frame: At baseline, 6 weeks and 12 weeks

    LDL cholesterol concentration will be determined in blood

  24. Change in total cholesterol concentration

    Time frame: At baseline, 6 weeks and 12 weeks

    Total cholesterol concentration will be determined in blood

  25. Change in triglycerides concentration

    Time frame: At baseline, 6 weeks and 12 weeks

    Triglycerides concentration will be determined in blood

  26. 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

  27. Alanine Aminotransferase (SGPT/ALT) concentration

    Time frame: At baseline, 6 weeks and 12 weeks

    SGPT concentration will be determined in blood

  28. 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

  29. Change in fetuin-A concentration

    Time frame: At baseline, 6 weeks and 12 weeks

    Fetuin-A concentration will be determined in blood

  30. Change in alkaline phosphatase (ALP) concentration

    Time frame: At baseline, 6 weeks and 12 weeks

    ALP concentration will be determined in blood

  31. Change in glucose concentration

    Time frame: At baseline, 6 weeks and 12 weeks

    Glucose concentration will be determined in blood

  32. Change in glycated hemoglobin (HbA1c) concentration

    Time frame: At baseline, 6 weeks and 12 weeks

    HbA1c concentration will be determined in blood

  33. Change in insulin concentration

    Time frame: At baseline, 6 weeks and 12 weeks

    Insulin concentration will be determined in blood

Secondary outcomes

  1. Change in dietary intake

    Time frame: At baseline, 6 weeks and 12 weeks

    Dietary intake will be monitored through diet recalls

  2. 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

  3. 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

Study contacts

Contact information is provided by the study sponsor or research team.

Dimitrios Draganidis, PhD

CONTACT

[email protected]

+30 2431047078

Ioannis G. Fatouros, PhD

CONTACT

[email protected]

+30 2431047047

Sponsors and collaborators

Lead sponsor

University of Thessaly

Other

Registry information

Official study title

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

Important dates

Study start
2025
Primary completion
2026
Study completion
2026
First posted
Sep 29, 2025
Registry last updated
Dec 16, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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