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

• ClinicalTrials.gov Identifier: NCT01138774
• Recruitment Status: Completed
• First Posted: June 7, 2010
• Last Update Posted: May 28, 2015
• Sponsor: Clinica Universidad de Navarra, Universidad de Navarra
• Information provided by (Responsible Party): Clinica Universidad de Navarra, Universidad de Navarra

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Obesity; Body Fat; Insulin Resistance	Dietary Supplement: Double blind dietary intervention with EPA and lipoic acid	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 103 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Cellular and Molecular Effects of Lipoic Acid and Eicosapentaenoic Acid (EPA) on Adipose Tissue: Potential Application in Human Obesity
• Study Start Date: January 2010
• Actual Primary Completion Date: December 2011
• Actual Study Completion Date: December 2012

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Control group; 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; 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).
Experimental: EPA group; 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; 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).
Experimental: Lipoic acid group; 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; 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).
Experimental: EPA+LA group; 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; 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).

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Blood Pressure and Cardiovascular Risk biomarkers [ Time Frame: Baseline ]
   Blood pressure, PAI-1 and VEGF will be measured.
2. Blood Pressure and Cardiovascular Risk biomarkers [ Time Frame: Week 10 (end of treatment) ]
   Blood pressure, PAI-1 and VEGF will be measured.
3. Energy expenditure [ Time Frame: Baseline ]
   Energy expenditure will be estimated by indirect calorimetry, and T3, T4 and TSH levels will be analysed by ELISA kits
4. Energy expenditure [ Time Frame: Week 10 (end of treatment) ]
   Energy expenditure will be estimated by indirect calorimetry, and T3, T4 and TSH levels will be analysed by ELISA kits
5. Satiety [ Time Frame: Baseline ]
   Satiety will be estimated by using a VAS questionnaire
6. Satiety [ Time Frame: Week 10 (end of treatment) ]
   Satiety will be estimated by using a VAS questionnaire
7. Serum inflammation biomarkers [ Time Frame: Baseline ]
   TNF-alpha, IL-6, C-reactive protein, serum A-amiloid, Leptin, Adiponectin, Visfatin
8. Serum inflammation biomarkers [ Time Frame: Week 10 (end of treatment) ]
   TNF-alpha, IL-6, C-reactive protein, serum A-amiloid, Leptin, Adiponectin, Visfatin
9. Serum oxidative stress biomarkers [ Time Frame: Baseline ]
   Total and Reduced Glutathione, Glutathione Peroxidase, MDA, Superoxide Dismutase-2 (Mn-SOD).
10. Serum oxidative stress biomarkers [ Time Frame: Week 10 (end of treatment) ]
    Total and Reduced Glutathione, Glutathione Peroxidase, MDA, Superoxide Dismutase-2 (Mn-SOD).
11. Adipose tissue gene profile and function analysis [ Time Frame: Week 10 (end of treatment) ]
    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.
12. Metabolomic and lipidomic profile [ Time Frame: Baseline ]
    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).
13. Metabolomic and lipidomic profile [ Time Frame: Week 10 (end of treatment) ]
    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).

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 45 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

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)

Contacts and Locations

Locations

Spain

Department of Nutrition, Food Science, Physiology and Toxicology. University of Navarra

Pamplona, Navarra, Spain, 31008

Sponsors and Collaborators

Clinica Universidad de Navarra, Universidad de Navarra

Investigators

• Principal Investigator: Maria J Moreno-Aliaga, PhD; University of Navarra
• Study Director: Alfredo Martínez, PhD; University of Navarra
• Study Chair: Santiago Navas-Carretero, PhD; University of Navarra

More Information

Additional Information:

Department of Nutrition, Food Science, Physiology and Toxicology 

European Master´s Degree in Feeding, Nutrition and Metabolism 

Publications:

Prieto-Hontoria PL, Pérez-Matute P, Fernández-Galilea M, Barber A, Martínez JA, Moreno-Aliaga MJ. Lipoic acid prevents body weight gain induced by a high fat diet in rats: effects on intestinal sugar transport. J Physiol Biochem. 2009 Mar;65(1):43-50.

Lorente-Cebrián S, Bustos M, Marti A, Martinez JA, Moreno-Aliaga MJ. Eicosapentaenoic acid up-regulates apelin secretion and gene expression in 3T3-L1 adipocytes. Mol Nutr Food Res. 2010 May;54 Suppl 1:S104-11. doi: 10.1002/mnfr.200900522.

Lorente-Cebrián S, Bustos M, Marti A, Martinez JA, Moreno-Aliaga MJ. Eicosapentaenoic acid stimulates AMP-activated protein kinase and increases visfatin secretion in cultured murine adipocytes. Clin Sci (Lond). 2009 Aug 14;117(6):243-9. doi: 10.1042/CS20090020.

Pérez-Echarri N, Pérez-Matute P, Marcos-Gómez B, Marti A, Martínez JA, Moreno-Aliaga MJ. Down-regulation in muscle and liver lipogenic genes: EPA ethyl ester treatment in lean and overweight (high-fat-fed) rats. J Nutr Biochem. 2009 Sep;20(9):705-14. doi: 10.1016/j.jnutbio.2008.06.013. Epub 2008 Sep 30.

Pérez-Echarri N, Pérez-Matute P, Marcos-Gómez B, Baena MJ, Marti A, Martínez JA, Moreno-Aliaga MJ. Differential inflammatory status in rats susceptible or resistant to diet-induced obesity: effects of EPA ethyl ester treatment. Eur J Nutr. 2008 Oct;47(7):380-6. doi: 10.1007/s00394-008-0738-3. Epub 2008 Sep 18.

Pérez-Echarri N, Pérez-Matute P, Marcos-Gómez B, Martínez JA, Moreno-Aliaga MJ. Effects of eicosapentaenoic acid ethyl ester on visfatin and apelin in lean and overweight (cafeteria diet-fed) rats. Br J Nutr. 2009 Apr;101(7):1059-67. doi: 10.1017/S0007114508048307. Epub 2008 Aug 28.

Pérez-Matute P, Pérez-Echarri N, Martínez JA, Marti A, Moreno-Aliaga MJ. Eicosapentaenoic acid actions on adiposity and insulin resistance in control and high-fat-fed rats: role of apoptosis, adiponectin and tumour necrosis factor-alpha. Br J Nutr. 2007 Feb;97(2):389-98.

Marrades MP, Martínez JA, Moreno-Aliaga MJ. Differences in short-term metabolic responses to a lipid load in lean (resistant) vs obese (susceptible) young male subjects with habitual high-fat consumption. Eur J Clin Nutr. 2007 Feb;61(2):166-74. Epub 2006 Aug 9.

Marrades MP, Milagro FI, Martínez JA, Moreno-Aliaga MJ. Differential expression of aquaporin 7 in adipose tissue of lean and obese high fat consumers. Biochem Biophys Res Commun. 2006 Jan 20;339(3):785-9. Epub 2005 Nov 22.

Ramel A, Martinéz A, Kiely M, Morais G, Bandarra NM, Thorsdottir I. Beneficial effects of long-chain n-3 fatty acids included in an energy-restricted diet on insulin resistance in overweight and obese European young adults. Diabetologia. 2008 Jul;51(7):1261-8. doi: 10.1007/s00125-008-1035-7. Epub 2008 May 20.

Parra D, Ramel A, Bandarra N, Kiely M, Martínez JA, Thorsdottir I. A diet rich in long chain omega-3 fatty acids modulates satiety in overweight and obese volunteers during weight loss. Appetite. 2008 Nov;51(3):676-80. doi: 10.1016/j.appet.2008.06.003. Epub 2008 Jun 14.

Ramel A, Martinez JA, Kiely M, Bandarra NM, Thorsdottir I. Moderate consumption of fatty fish reduces diastolic blood pressure in overweight and obese European young adults during energy restriction. Nutrition. 2010 Feb;26(2):168-74. doi: 10.1016/j.nut.2009.04.002. Epub 2009 May 31.

Navas-Carretero S, Pérez-Granados AM, Schoppen S, Vaquero MP. An oily fish diet increases insulin sensitivity compared to a red meat diet in young iron-deficient women. Br J Nutr. 2009 Aug;102(4):546-53. doi: 10.1017/S0007114509220794. Epub 2009 Feb 12.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Romo-Hualde A, Huerta AE, González-Navarro CJ, Ramos-López O, Moreno-Aliaga MJ, Martínez JA. Untargeted metabolomic on urine samples after α-lipoic acid and/or eicosapentaenoic acid supplementation in healthy overweight/obese women. Lipids Health Dis. 2018 May 9;17(1):103. doi: 10.1186/s12944-018-0750-4.

Huerta AE, Prieto-Hontoria PL, Sáinz N, Martínez JA, Moreno-Aliaga MJ. Supplementation with α-Lipoic Acid Alone or in Combination with Eicosapentaenoic Acid Modulates the Inflammatory Status of Healthy Overweight or Obese Women Consuming an Energy-Restricted Diet. J Nutr. 2015 Apr 1;146(4):889S-896S. doi: 10.3945/jn.115.224105.

• Responsible Party: Clinica Universidad de Navarra, Universidad de Navarra
• ClinicalTrials.gov Identifier: NCT01138774
• Other Study ID Numbers: OBEPALIP
• First Posted: June 7, 2010
• Last Update Posted: May 28, 2015
• Last Verified: February 2012

Keywords provided by Clinica Universidad de Navarra, Universidad de Navarra:

Obesity; Calorie restriction; Eicosapentaenoic acid (EPA); Lipoic acid; Weight loss; Insulin sensitivity; Lipid metabolism; Adipokines; Inflammation; Oxidative stress; Adipose tissue gene profile; Metabolomic profile

Additional relevant MeSH terms:

Obesity; Insulin Resistance; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Thioctic Acid; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Vitamin B Complex; Vitamins; Micronutrients; Nutrients; Growth Substances