Effects of Lipoic Acid and Eicosapentaenoic Acid (EPA) in Human Obesity

Study Overview
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Brief Summary
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The aim of the study is to analyze the effects of Lipoic acid and/or EPA supplementation on weight loss, lipid profile, insulin resistance, oxidative and inflammation parameters, metabolomic profile as well as on adipose tissue gene profile in healthy overweight/obese subjects following an energy-restricted diet.

Official Title
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Cellular and Molecular Effects of Lipoic Acid and Eicosapentaenoic Acid (EPA) on Adipose Tissue: Potential Application in Human Obesity

Conditions
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Obesity, Body Fat, Insulin Resistance

Intervention / Treatment
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* Dietary Supplement: Double blind dietary intervention with EPA and lipoic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women Ages between 20 and 45 years, and with regular menstrual cycles Body Mass Index (BMI) between 27.5 and 39.9 kg/m2 Weight unchanged (± 3 kg) for the last 3 months All subjects should have an overall physical and psychological condition that the investigator believes is in accordance with the overall aim of the study. Exclusion Criteria: Use of prescription medication To suffer from any chronic metabolic or obesity related disease, hepatic or renal systemic disease: Hypertension, dislipidemia, type 1 or 2 diabetes, thyroid function disorders, cirrhosis, fatty liver, etc. Food allergies or food intolerance expected to come up during the study Special diets (Atkins, vegetarian, etc.) prior three months the start of the study. Eating disorders Surgically treated obesity Pregnant or lactating women or planning to be pregnant in the next two months Alcohol or drug abuse (based on clinical parameters)

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control group<br>Dietary treatment with a calorie restriction of 30 % the subject's energy expenditure at baseline + placebos supplements | Dietary Supplement: Double blind dietary intervention with EPA and lipoic acid<br>* Placebo-controlled dietary intervention during 10 weeks. All groups will have a dietary treatment with a calorie restriction of 30 % the subject's energy expenditure at baseline, supplemented with eicosapentaenoic acid (EPA) and/or lipoic acid (LA).<br>|
| Experimental: EPA group<br>Dietary treatment with a calorie restriction of 30 % the subject's energy expenditure at baseline + EPA (1.3 g/day, 3 capsules of 433 mg/day) supplement (EPA Group). | Dietary Supplement: Double blind dietary intervention with EPA and lipoic acid<br>* Placebo-controlled dietary intervention during 10 weeks. All groups will have a dietary treatment with a calorie restriction of 30 % the subject's energy expenditure at baseline, supplemented with eicosapentaenoic acid (EPA) and/or lipoic acid (LA).<br>|
| Experimental: Lipoic acid group<br>Dietary treatment with a calorie restriction of 30 % the subject's energy expenditure at baseline + LA (300 mg/day, 3 capsules of 100 mg/day) supplement (LA Group) | Dietary Supplement: Double blind dietary intervention with EPA and lipoic acid<br>* Placebo-controlled dietary intervention during 10 weeks. All groups will have a dietary treatment with a calorie restriction of 30 % the subject's energy expenditure at baseline, supplemented with eicosapentaenoic acid (EPA) and/or lipoic acid (LA).<br>|
| Experimental: EPA+LA group<br>Dietary treatment with a calorie restriction of 30 % the subject's energy expenditure at baseline + EPA/LA (1.3 g /day and 300 mg/day respectively). | Dietary Supplement: Double blind dietary intervention with EPA and lipoic acid<br>* Placebo-controlled dietary intervention during 10 weeks. All groups will have a dietary treatment with a calorie restriction of 30 % the subject's energy expenditure at baseline, supplemented with eicosapentaenoic acid (EPA) and/or lipoic acid (LA).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight Loss | Volunteers will attend the Nutritional Intervention unit (University of Navarra), where their weight will be measured to the nearest 0.1 kg. | Week 0 (baseline) | 
| Weight Loss | Volunteers will attend the Nutritional Intervention unit (University of Navarra), where their weight will be measured to the nearest 0.1 kg. | Week 2 | 
| Weight Loss | Volunteers will attend the Nutritional Intervention unit (University of Navarra), where their weight will be measured to the nearest 0.1 kg. | Week 4 | 
| Weight Loss | Volunteers will attend the Nutritional Intervention unit (University of Navarra), where their weight will be measured to the nearest 0.1 kg. | week 6 | 
| Weight Loss | Volunteers will attend the Nutritional Intervention unit (University of Navarra), where their weight will be measured to the nearest 0.1 kg. | Week 8 | 
| Weight Loss | Volunteers will attend the Nutritional Intervention unit (University of Navarra), where their weight will be measured to the nearest 0.1 kg. | Week 10 (end of treatment) | 
| Body composition and Anthropometric parameters | Changes in body composition will be analyzed by Dual X-ray Absorptiometry (DXA) and by bioimpedance, and hip and waist circumferences will be measured. | Week 0 (Baseline) | 
| Body composition and anthropometric parameters | Changes in body composition will be analyzed by Dual X-ray Absorptiometry (DXA) and by bioimpedance, and hip and waist circumferences will be measured. | Week 10 (end of treatment) | 
| Glucose metabolism parameters | Fasting serum glucose, Fasting serum insulin, Oral Glucose Tolerance Test, HOMA index | Week 0 (baseline) | 
| Glucose metabolism parameters | Fasting serum glucose, Fasting serum insulin, Oral Glucose Tolerance Test, HOMA index | Week 10 (end of treatment) | 
| Lipid metabolism biomarkers | Serum total-cholesterol, HDL-cholesterol, LDL-cholesterol, triacylglycerols, free fatty acids, ketone bodies. | Week 0 (baseline) | 
| Lipid metabolism biomarkers | Serum total-cholesterol, HDL-cholesterol, LDL-cholesterol, triacylglycerols, free fatty acids, ketone bodies. | Week 10 (end of treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Pressure and Cardiovascular Risk biomarkers | Blood pressure, PAI-1 and VEGF will be measured. | Baseline | 
| Blood Pressure and Cardiovascular Risk biomarkers | Blood pressure, PAI-1 and VEGF will be measured. | Week 10 (end of treatment) | 
| Energy expenditure | Energy expenditure will be estimated by indirect calorimetry, and T3, T4 and TSH levels will be analysed by ELISA kits | Baseline | 
| Energy expenditure | Energy expenditure will be estimated by indirect calorimetry, and T3, T4 and TSH levels will be analysed by ELISA kits | Week 10 (end of treatment) | 
| Satiety | Satiety will be estimated by using a VAS questionnaire | Baseline | 
| Satiety | Satiety will be estimated by using a VAS questionnaire | Week 10 (end of treatment) | 
| Serum inflammation biomarkers | TNF-alpha, IL-6, C-reactive protein, serum A-amiloid, Leptin, Adiponectin, Visfatin | Baseline | 
| Serum inflammation biomarkers | TNF-alpha, IL-6, C-reactive protein, serum A-amiloid, Leptin, Adiponectin, Visfatin | Week 10 (end of treatment) | 
| Serum oxidative stress biomarkers | Total and Reduced Glutathione, Glutathione Peroxidase, MDA, Superoxide Dismutase-2 (Mn-SOD). | Baseline | 
| Serum oxidative stress biomarkers | Total and Reduced Glutathione, Glutathione Peroxidase, MDA, Superoxide Dismutase-2 (Mn-SOD). | Week 10 (end of treatment) | 
| Adipose tissue gene profile and function analysis | A biopsy (2 g) of subcutaneous abdominal periumbilical area adipose tissue will be obtained. In order to identify clusters/pathways of genes regulated by the supplementation of EPA and LA, microarray gene profiling will be performed in adipose tissue from the 4 groups after the nutritional intervention. If possible primary explant culture of adipose tissue biopsies will be also carried out. | Week 10 (end of treatment) | 
| Metabolomic and lipidomic profile | Samples of plasma and 24-h urine will be analysed by Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS), and Nuclear Magnetic Resonance (NMR), and Bidimensional Gas Chromatography-Mass Spectrometry (BC-MS). | Baseline | 
| Metabolomic and lipidomic profile | Samples of plasma and 24-h urine will be analysed by Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS), and Nuclear Magnetic Resonance (NMR), and Bidimensional Gas Chromatography-Mass Spectrometry (BC-MS). | Week 10 (end of treatment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Calorie restriction, Eicosapentaenoic acid (EPA), Lipoic acid, Weight loss, Insulin sensitivity, Lipid metabolism, Adipokines, Inflammation, Oxidative stress, Adipose tissue gene profile, Metabolomic profile