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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| N-acetylcysteine | Experimental | Oral N-acetylcysteine supplementation for 12 weeks (2 x 600 mg capsules/day) |
|
| Placebo | Placebo Comparator | Oral placebo supplementation for 12 weeks (2 placebo capsules/day) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 ). |
| Measure | Description | Time Frame |
|---|---|---|
| Change in body weight (kg) | At baseline, 6 weeks and 12 weeks | |
| Change in waist circumference | At baseline, 6 weeks and 12 weeks | |
| Change in hip circumference | At baseline, 6 weeks and 12 weeks | |
| Change in fat mass (kg) | Fat mass will be assessed through dual energy X-ray absorptiometry (DXA) | At baseline, 6 weeks and 12 weeks |
| Change in body fat percent (%) | 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) | 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) | 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 | Liver fat infiltration will be assessed through ultrasound elastography | At baseline and 12 weeks |
| Change in cardiorespiratory fitness |
| Measure | Description | Time Frame |
|---|---|---|
| Change in dietary intake | Dietary intake will be monitored through diet recalls | At baseline, 6 weeks and 12 weeks |
| Change in total number of steps | Total number of steps performed per day will be assessed by using accelerometers |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Dimitrios Draganidis, PhD | Contact | +30 2431047078 | ddraganidis@uth.gr | |
| Ioannis G. Fatouros, PhD | Contact | +30 2431047047 | ifatouros@uth.gr |
| Name | Affiliation | Role |
|---|---|---|
| Anastasia Rosvoglou, PhDc | University of Thessaly, Department of Physical Education and Sport Science | Principal Investigator |
| Dimitrios Draganidis, PhD | University of Thessaly, Department of Physical Education and Sport Science |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Physical Education and Sport Science, University of Thessaly | Recruiting | Trikala | Karies | 42100 | Greece |
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| ID | Term |
|---|---|
| D050177 | Overweight |
| D009765 | Obesity |
| ID | Term |
|---|---|
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
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| ID | Term |
|---|---|
| D000111 | Acetylcysteine |
| ID | Term |
|---|---|
| D003545 | Cysteine |
| D000603 | Amino Acids, Sulfur |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
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Randomized clinical trial with repeated measures
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| 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. |
|
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 | Maximal concentric peak torque will be assessed on an isokinetic dynamometer | At baseline, 6 weeks and 12 weeks |
| Change in upper body muscle strength | 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 | 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 | 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 | 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 | GR activity will be determined in blood erythrocytes and peripheral blood mononuclear cells | At baseline, 6 weeks and 12 weeks |
| Change in catalase activity | 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 | SOD activity will be determined in blood erythrocytes and peripheral blood mononuclear cells | At baseline, 6 weeks and 12 weeks |
| Change in malondialdehyde concentration | Malondialdehyde concentration will be determined in peripheral blood mononuclear cells | At baseline, 6 weeks and 12 weeks |
| Change in C-reactive protein (CRP) concentration | At baseline, 6 weeks and 12 weeks |
| Change in TNF-α concentration | 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 | 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 | HDL cholesterol concentration will be determined in blood | At baseline, 6 weeks and 12 weeks |
| Change in LDL cholesterol concentration | LDL cholesterol concentration will be determined in blood | At baseline, 6 weeks and 12 weeks |
| Change in total cholesterol concentration | Total cholesterol concentration will be determined in blood | At baseline, 6 weeks and 12 weeks |
| Change in triglycerides concentration | Triglycerides concentration will be determined in blood | At baseline, 6 weeks and 12 weeks |
| Change in serum glutamic-oxaloacetic transaminase (SGOT/AST) concentration | SGOT concentration will be determined in blood | At baseline, 6 weeks and 12 weeks |
| Alanine Aminotransferase (SGPT/ALT) concentration | SGPT concentration will be determined in blood | At baseline, 6 weeks and 12 weeks |
| Change in Gamma-glutamyl transpeptidase (γ-GT) concentration | γ-GT concentration will be determined in blood | At baseline, 6 weeks and 12 weeks |
| Change in fetuin-A concentration | Fetuin-A concentration will be determined in blood | At baseline, 6 weeks and 12 weeks |
| Change in alkaline phosphatase (ALP) concentration | ALP concentration will be determined in blood | At baseline, 6 weeks and 12 weeks |
| Change in glucose concentration | Glucose concentration will be determined in blood | At baseline, 6 weeks and 12 weeks |
| Change in glycated hemoglobin (HbA1c) concentration | HbA1c concentration will be determined in blood | At baseline, 6 weeks and 12 weeks |
| Change in insulin concentration | Insulin concentration will be determined in blood | At baseline, 6 weeks and 12 weeks |
| At baseline, 6 weeks and 12 weeks |
| Change in time spent in moderate-to-vigorous physical activity | The time spent in moderate-to-vigorous physical activity per day will be assessed by using accelerometers | At baseline, 6 weeks and 12 weeks |
| D012816 |
| Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000596 |
| Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |