Effects of N-acetylcysteine on Biological Responses to High-intensity Interval Training in Adults With Overweight/Obesity
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Change in catalase activity
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 30 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •NAC intolerance
- •Bleeding disorders
- •Kidney disease
- •Usage of blood thinners and/or angina medication
结局指标
主要结局
Change in catalase activity
时间窗: At baseline, 6 weeks and 12 weeks
Catalase activity will be determined in blood erythrocytes and peripheral blood mononuclear cells
Change in superoxide dismutase (SOD) activity
时间窗: At baseline, 6 weeks and 12 weeks
SOD activity will be determined in blood erythrocytes and peripheral blood mononuclear cells
Change in C-reactive protein (CRP) concentration
时间窗: At baseline, 6 weeks and 12 weeks
Change in TNF-α concentration
时间窗: 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
时间窗: At baseline, 6 weeks and 12 weeks
IL-6 concentration will be determined in blood and peripheral blood mononuclear cells
Change in HDL cholesterol concentration
时间窗: At baseline, 6 weeks and 12 weeks
HDL cholesterol concentration will be determined in blood
Change in LDL cholesterol concentration
时间窗: At baseline, 6 weeks and 12 weeks
LDL cholesterol concentration will be determined in blood
Change in total cholesterol concentration
时间窗: At baseline, 6 weeks and 12 weeks
Total cholesterol concentration will be determined in blood
Change in triglycerides concentration
时间窗: At baseline, 6 weeks and 12 weeks
Triglycerides concentration will be determined in blood
Change in serum glutamic-oxaloacetic transaminase (SGOT/AST) concentration
时间窗: At baseline, 6 weeks and 12 weeks
SGOT concentration will be determined in blood
Alanine Aminotransferase (SGPT/ALT) concentration
时间窗: At baseline, 6 weeks and 12 weeks
SGPT concentration will be determined in blood
Change in Gamma-glutamyl transpeptidase (γ-GT) concentration
时间窗: At baseline, 6 weeks and 12 weeks
γ-GT concentration will be determined in blood
Change in fetuin-A concentration
时间窗: At baseline, 6 weeks and 12 weeks
Fetuin-A concentration will be determined in blood
Change in alkaline phosphatase (ALP) concentration
时间窗: At baseline, 6 weeks and 12 weeks
ALP concentration will be determined in blood
Change in glucose concentration
时间窗: At baseline, 6 weeks and 12 weeks
Glucose concentration will be determined in blood
Change in glycated hemoglobin (HbA1c) concentration
时间窗: At baseline, 6 weeks and 12 weeks
HbA1c concentration will be determined in blood
Change in insulin concentration
时间窗: At baseline, 6 weeks and 12 weeks
Insulin concentration will be determined in blood
Change in body weight (kg)
时间窗: At baseline, 6 weeks and 12 weeks
Change in waist circumference
时间窗: At baseline, 6 weeks and 12 weeks
Change in hip circumference
时间窗: At baseline, 6 weeks and 12 weeks
Change in fat mass (kg)
时间窗: At baseline, 6 weeks and 12 weeks
Fat mass will be assessed through dual energy X-ray absorptiometry (DXA)
Change in body fat percent (%)
时间窗: 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)
时间窗: At baseline, 6 weeks and 12 weeks
Fat free mass will be assessed through dual energy X-ray absorptiometry (DXA)
Change in lean body mass (kg)
时间窗: At baseline, 6 weeks and 12 weeks
Lean body mass will be assessed through dual energy X-ray absorptiometry (DXA)
Change in liver fat infiltration
时间窗: At baseline and 12 weeks
Liver fat infiltration will be assessed through ultrasound elastography
Change in cardiorespiratory fitness
时间窗: 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
时间窗: At baseline, 6 weeks and 12 weeks
Maximal concentric peak torque will be assessed on an isokinetic dynamometer
Change in upper body muscle strength
时间窗: 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 reduced glutathione (GSH) concentration
时间窗: At baseline, 6 weeks and 12 weeks
GSH concentration will be determined in blood erythrocytes and peripheral blood mononuclear cells
Change in oxidized glutathione (GSSG) concentration
时间窗: 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
时间窗: At baseline, 6 weeks and 12 weeks
GPx activity will be determined in blood erythrocytes and peripheral blood mononuclear cells
Change in glutathione reductase (GR) activity
时间窗: At baseline, 6 weeks and 12 weeks
GR activity will be determined in blood erythrocytes and peripheral blood mononuclear cells
Change in fat mass (kg)
时间窗: At baseline, 6 weeks and 12 weeks
Fat mass will be assessed through dual energy X-ray absorptiometry (DXA)
Change in C-reactive protein (CRP) concentration
时间窗: At baseline, 6 weeks and 12 weeks
Change in waist circumference
时间窗: At baseline, 6 weeks and 12 weeks
Change in hip circumference
时间窗: At baseline, 6 weeks and 12 weeks
Change in body weight (kg)
时间窗: At baseline, 6 weeks and 12 weeks
Change in body fat percent (%)
时间窗: 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)
时间窗: At baseline, 6 weeks and 12 weeks
Fat free mass will be assessed through dual energy X-ray absorptiometry (DXA)
Change in lean body mass (kg)
时间窗: At baseline, 6 weeks and 12 weeks
Lean body mass will be assessed through dual energy X-ray absorptiometry (DXA)
Change in liver fat infiltration
时间窗: At baseline and 12 weeks
Liver fat infiltration will be assessed through ultrasound elastography
Change in cardiorespiratory fitness
时间窗: 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
时间窗: At baseline, 6 weeks and 12 weeks
Maximal concentric peak torque will be assessed on an isokinetic dynamometer
Change in upper body muscle strength
时间窗: 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 reduced glutathione (GSH) concentration
时间窗: At baseline, 6 weeks and 12 weeks
GSH concentration will be determined in blood erythrocytes and peripheral blood mononuclear cells
Change in oxidized glutathione (GSSG) concentration
时间窗: 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
时间窗: At baseline, 6 weeks and 12 weeks
GPx activity will be determined in blood erythrocytes and peripheral blood mononuclear cells
Change in glutathione reductase (GR) activity
时间窗: At baseline, 6 weeks and 12 weeks
GR activity will be determined in blood erythrocytes and peripheral blood mononuclear cells
Change in catalase activity
时间窗: At baseline, 6 weeks and 12 weeks
Catalase activity will be determined in blood erythrocytes and peripheral blood mononuclear cells
Change in superoxide dismutase (SOD) activity
时间窗: At baseline, 6 weeks and 12 weeks
SOD activity will be determined in blood erythrocytes and peripheral blood mononuclear cells
Change in malondialdehyde concentration
时间窗: At baseline, 6 weeks and 12 weeks
Malondialdehyde concentration will be determined in peripheral blood mononuclear cells
Change in TNF-α concentration
时间窗: At baseline, 6 weeks and 12 weeks
TNF-α concentration will be determined in blood and peripheral blood mononuclear cells
Change in HDL cholesterol concentration
时间窗: At baseline, 6 weeks and 12 weeks
HDL cholesterol concentration will be determined in blood
Change in LDL cholesterol concentration
时间窗: At baseline, 6 weeks and 12 weeks
LDL cholesterol concentration will be determined in blood
Change in interleukin-6 (IL-6) concentration
时间窗: 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
时间窗: At baseline, 6 weeks and 12 weeks
Total cholesterol concentration will be determined in blood
Change in triglycerides concentration
时间窗: At baseline, 6 weeks and 12 weeks
Triglycerides concentration will be determined in blood
Change in serum glutamic-oxaloacetic transaminase (SGOT/AST) concentration
时间窗: At baseline, 6 weeks and 12 weeks
SGOT concentration will be determined in blood
Alanine Aminotransferase (SGPT/ALT) concentration
时间窗: At baseline, 6 weeks and 12 weeks
SGPT concentration will be determined in blood
Change in Gamma-glutamyl transpeptidase (γ-GT) concentration
时间窗: At baseline, 6 weeks and 12 weeks
γ-GT concentration will be determined in blood
Change in fetuin-A concentration
时间窗: At baseline, 6 weeks and 12 weeks
Fetuin-A concentration will be determined in blood
Change in alkaline phosphatase (ALP) concentration
时间窗: At baseline, 6 weeks and 12 weeks
ALP concentration will be determined in blood
Change in glucose concentration
时间窗: At baseline, 6 weeks and 12 weeks
Glucose concentration will be determined in blood
Change in glycated hemoglobin (HbA1c) concentration
时间窗: At baseline, 6 weeks and 12 weeks
HbA1c concentration will be determined in blood
Change in insulin concentration
时间窗: At baseline, 6 weeks and 12 weeks
Insulin concentration will be determined in blood
次要结局
- Change in dietary intake(At baseline, 6 weeks and 12 weeks)
- Change in dietary intake(At baseline, 6 weeks and 12 weeks)
- Change in total number of steps(At baseline, 6 weeks and 12 weeks)
- Change in time spent in moderate-to-vigorous physical activity(At baseline, 6 weeks and 12 weeks)
研究者
Dimitrios Draganidis
Assistant Professor
University of Thessaly