Clinical trial NCT01138774: Effects of Lipoic Acid and Eicosapentaenoic Acid (EPA) in Human Obesity
Official title: Cellular and Molecular Effects of Lipoic Acid and Eicosapentaenoic Acid (EPA) on Adipose Tissue: Potential Application in Human Obesity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Body Fat
Insulin Resistance
Keywords: Obesity
Calorie restriction
Eicosapentaenoic acid (EPA)
Lipoic acid
Weight loss
Insulin sensitivity
Lipid metabolism
Adipokines
Inflammation
Oxidative stress
Adipose tissue gene profile
Metabolomic profile
Lead sponsor: Clinica Universidad de Navarra, Universidad de Navarra
Sponsor class: OTHER
First posted: 2010-06-07
Enrollment: 103
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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)

Primary outcomes:
measure: Weight Loss
timeFrame: Week 0 (baseline)
measure: Weight Loss
timeFrame: Week 2
measure: Weight Loss
timeFrame: Week 4
measure: Weight Loss
timeFrame: week 6
measure: Weight Loss
timeFrame: Week 8
measure: Weight Loss
timeFrame: Week 10 (end of treatment)
measure: Body composition and Anthropometric parameters
timeFrame: Week 0 (Baseline)
measure: Body composition and anthropometric parameters
timeFrame: Week 10 (end of treatment)
measure: Glucose metabolism parameters
timeFrame: Week 0 (baseline)
measure: Glucose metabolism parameters
timeFrame: Week 10 (end of treatment)
measure: Lipid metabolism biomarkers
timeFrame: Week 0 (baseline)
measure: Lipid metabolism biomarkers
timeFrame: Week 10 (end of treatment)
Secondary outcomes:
measure: Blood Pressure and Cardiovascular Risk biomarkers
timeFrame: Baseline
measure: Blood Pressure and Cardiovascular Risk biomarkers
timeFrame: Week 10 (end of treatment)
measure: Energy expenditure
timeFrame: Baseline
measure: Energy expenditure
timeFrame: Week 10 (end of treatment)
measure: Satiety
timeFrame: Baseline
measure: Satiety
timeFrame: Week 10 (end of treatment)
measure: Serum inflammation biomarkers
timeFrame: Baseline
measure: Serum inflammation biomarkers
timeFrame: Week 10 (end of treatment)
measure: Serum oxidative stress biomarkers
timeFrame: Baseline
measure: Serum oxidative stress biomarkers
timeFrame: Week 10 (end of treatment)
measure: Adipose tissue gene profile and function analysis
timeFrame: Week 10 (end of treatment)
measure: Metabolomic and lipidomic profile
timeFrame: Baseline
measure: Metabolomic and lipidomic profile
timeFrame: Week 10 (end of treatment)
Other outcomes:
Locations:
city: Pamplona
country: Spain
facility: Department of Nutrition, Food Science, Physiology and Toxicology. University of Navarra
state: Navarra
Study officials:
affiliation: University of Navarra
name: Maria J Moreno-Aliaga, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Navarra
name: Alfredo Martínez, PhD
role: STUDY_DIRECTOR
affiliation: University of Navarra
name: Santiago Navas-Carretero, PhD
role: STUDY_CHAIR
References:
citation: Prieto-Hontoria PL, Perez-Matute P, Fernandez-Galilea M, Barber A, Martinez 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. doi: 10.1007/BF03165968.
citation: Lorente-Cebrian 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.
citation: Lorente-Cebrian 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.
citation: Perez-Echarri N, Perez-Matute P, Marcos-Gomez B, Marti A, Martinez 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.
citation: Perez-Echarri N, Perez-Matute P, Marcos-Gomez B, Baena MJ, Marti A, Martinez 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.
citation: Perez-Echarri N, Perez-Matute P, Marcos-Gomez B, Martinez 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.
citation: Perez-Matute P, Perez-Echarri N, Martinez 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. doi: 10.1017/S0007114507207627.
citation: Marrades MP, Martinez 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. doi: 10.1038/sj.ejcn.1602500. Epub 2006 Aug 9.
citation: Marrades MP, Milagro FI, Martinez 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. doi: 10.1016/j.bbrc.2005.11.080. Epub 2005 Nov 22.
citation: Ramel A, Martinez 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.
citation: Parra D, Ramel A, Bandarra N, Kiely M, Martinez 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.
citation: 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.
citation: Navas-Carretero S, Perez-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.
citation: Romo-Hualde A, Huerta AE, Gonzalez-Navarro CJ, Ramos-Lopez O, Moreno-Aliaga MJ, Martinez JA. Untargeted metabolomic on urine samples after alpha-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.
citation: Huerta AE, Prieto-Hontoria PL, Sainz N, Martinez JA, Moreno-Aliaga MJ. Supplementation with alpha-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.