Effect of the Intake of Corbella Extra Virgin Olive Oil on the Microbiota-gut-brain Axis in Healthy Adults (HEVOOC)

Study Overview
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Brief Summary
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The consumption of the improved extra virgin olive oil (EVOO) of the Corbella variety could have a beneficial effect on the microbiota-intestine-brain axis (MGBA). Olive oil contains polyphenols that are not present in other oils, notably oleocanthal and oleacein, which behave similarly to ibuprofen and have a protective effect on some neurodegenerative diseases. The polyphenols of the oil present prebiotic characteristics, at the level of the intestinal microbiota, which metabolizes them forming bioactive metabolites that can have a modulating effect on the MGBA, improving brain health. In this study, the researchers seek to identify the benefits of the consumption of Corbella variety EVOO on MGBA in healthy participants. The overall benefit of the study would be to achieve knowledge that would allow its future applicability to prevent and improve certain diseases and in general contribute to optimal health.

Detailed Description
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To evaluate possible effects on MGBA, a randomized, controlled, crossover nutritional trial will be conducted. Thirty healthy adult participants (between 18 and 35 years of age, with 50% male and 50% female) will be included according to the estimated sample size. Participants will consume a daily amount of 0.7 g Corbella EVOO/kg body weight plus their normal diet (experimental intervention) and 0.7 g refined olive oil (ROO)/kg body weight plus their normal diet (control intervention) for 1 month. Biological samples (plasma, peripheral blood mononuclear cells, serum, 24-hour urine, feces and saliva) will be obtained at baseline and at the end of each trial arm.

Official Title
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Development of Oil With Healthy Properties Based on Corbella Olive Variety (HEVOOC)

Conditions
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Healthy Nutrition

Intervention / Treatment
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* Other: EXTRA VIRGIN OLIVE OIL
* Other: OLIVE OIL LOW POLYPHENOL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult with Body mass index (BMI) < 30 kg/m2 Signed informed consent Exclusion Criteria: Any chronic disease (e.g. cardiovascular disease, cancer or diabetes) Mental disorders (e.g. depression, dementia, autism, etc.) Cardiovascular alterations in cholesterol,triglycerides, glucose, etc. Current smokers Repeated use of antibiotics Frequent use of corticoids, nonsteroidal anti-inflammatory drugs Repeated use of vitamins Volunteers with extreme eating habits (i.e. Atkins diet, very high protein diets, etc.) Excessive alcohol consumption (>30 g/d for males and >20 g/d for females), Pregnant, lactating, and postmenopausal women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

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: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: EXPERIMENTAL: Extra virgin olive oil (EVOO): should add 0.7 g of Corbella EVOO/ kg body weight to their usual diet per day, either raw or cooked, for one month CONTROL: Olive oil low in polyphenols (OOLP): should add 0.7 g of OOLP/ kg body weight to their usual diet per day, either raw or cooked, for one month
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EXTRA VIRGIN (intervention / control)<br>After a 3-day run in period avoiding EVOO consumption, participants will consume a daily amount of 0.7 g EVOO / kg body weight in addition to their usual diet for 1 months. They will then have 4 weeks with their usual diet and another 3-day run in period before starting the control intervention, which consists of following their usual diet plus 0.7 g olive oil low of polyphenol (OOLP)/ kg body weight daily for one month. | Other: EXTRA VIRGIN OLIVE OIL<br>* Participants will consume a daily amount of extra virgin olive oil. Can consume the oil either raw or cooked<br>Other: OLIVE OIL LOW POLYPHENOL<br>* Participants will consume a daily amount of olive oil low polyphenol. Can consume the oil either raw or cooked<br>|
| Experimental: LOW POLYPHENOL (control/intervention)<br>After a 3-day run-in period avoiding EVOO consumption, participants will consume a daily amount of 0.7 g of OOLP/ kg body weight in addition to their usual diet for 1 month. Then, they will have 4 weeks with their usual diet and another run in period of 3 days before starting the intervention which consists of following their usual diet plus 0.7 g of EVOO / kg body weight daily for one month. | Other: EXTRA VIRGIN OLIVE OIL<br>* Participants will consume a daily amount of extra virgin olive oil. Can consume the oil either raw or cooked<br>Other: OLIVE OIL LOW POLYPHENOL<br>* Participants will consume a daily amount of olive oil low polyphenol. Can consume the oil either raw or cooked<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in brain-derived neurotrophic factor (BDNF) after each intervention with EVOO and the control intervention. | Serum samples will be analysed for mature BDNF using a Mature BDNF Rapid ELISA kit. | Baseline and after completed each intervention (1 month) | 
| Changes in the gut microbiota after each intervention with EVOO and the control intervention. | Fecal samples will be collected by the volunteers using a system for easy self-collection and stabilization of microbial DNA for gut microbiome profiling (OMNIgene - GUT). The extraction of genomic DNA from fecal samples will be carried out utilizing the DNeasy Power Kit. Subsequently, microbial profiling will employ 16 S ribosomal RNA (rRNA) sequencing to investigate microbial communities, with a specific focus on bacterial phylogeny and taxonomy. | Baseline and after completed each intervention (1 month) | 
| Changes in the polyphenols and their metabolites after each intervention with EVOO and the control intervention. | Polyphenols and their metabolites derived from intestinal gut microbiota will be identified and quantified in human plasma, urine, feces, and saliva samples using high performance liquid chromatography (HPLC) - Linear Trap Quadrupole (LTQ) Orbitrap-MS/MS and HPLC-MS/MS techniques. | Baseline and after completed each intervention (1 month) | 
| Changes in carotenoids and their metabolites after each intervention with EVOO and the control intervention. | Carotenoids and their metabolites derived from intestinal gut microbiota will be identified and quantified in human plasma, urine, feces, and saliva samples using high performance liquid chromatography (HPLC) - Linear Trap Quadrupole (LTQ) Orbitrap-MS/MS and HPLC-MS/MS techniques. | Baseline and after completed each intervention (1 month) | 
| Changes in the short-chain fatty acids in plasma and feces samples after each intervention with EVOO and the control intervention. | After acidifying the fecal samples with formic acid, a quantification of short-chain fatty acids will be performed using gas chromatography by direct injection according to previously described methodology (Zhao et al., 2006). | Baseline and after completed each intervention (1 month) | 
| Changes in bile acids in plasma and feces samples after each intervention with EVOO and the control intervention. | Bile acids will be assayed using a validated liquid chromatography-mass spectrometry (LC-MS) method | Baseline and after completed each intervention (1 month) | 
| Changes in cerebrovascular function after each intervention with EVOO and the control intervention. | Cerebrovascular function will be measured using functional magnetic resonance imaging (FMRI), a non-invasive method for assessing brain activity. FMRI maps blood oxygenation levels in the brain and estimates changes in the blood flow that depends on metabolic function and is correlated with specific brain region activities | Baseline and after completed each intervention (1 month) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in body weight after each intervention with EVOO and the control intervention. | Body weight in kilograms (kg) | Baseline and after completed each intervention (1 month) | 
| Changes in body mass index (BMI) after each intervention with EVOO and the control intervention. | BMI will be calculated as body weight (kg) divided by height (m). Weight and height will be combined to report BMI in kg/m^2 | Baseline and after completed each intervention (1 month) | 
| Changes in hip circumference after each intervention with EVOO and the control intervention. | It will be measured with a tape-measure in triplicate, in centimeters (cm) | Baseline and after completed each intervention (1 month) | 
| Changes in waist circumference after each intervention with EVOO and the control intervention. | It will be measured with a tape-measure in triplicate, in centimeters (cm) | Baseline and after completed each intervention (1 month) | 
| Changes in body composition after each intervention with EVOO and the control intervention. | Body fat percentage will be measured using a bioelectrical impedance analysis monitor. | Baseline and after completed each intervention (1 month) | 
| Changes in blood pressure after each intervention with EVOO and the control intervention. | Diastolic and systolic blood pressure will be measured by a blood pressure monitor in triplicate. | Baseline and after completed each intervention (1 month) | 
| Changes in heart rate after each intervention with EVOO and the control intervention. | Heart rate (bpm) will be measured with an automatic monitor in triplicate. | Baseline and after completed each intervention (1 month) | 
| Changes in lipidic profile after each intervention with EVOO and the control intervention. | Total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides (mg/dL) will be measured by molecular absorption spectrometry. | Baseline and after completed each intervention (1 month) | 
| Changes in liver function after each intervention with EVOO and the control intervention. | Alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and albumin will be assayed by immunoenzymatic methods. | Baseline and after completed each intervention (1 month) | 
| Changes in glucose after each intervention with EVOO and the control intervention. | Glucose (mg/dL) will be measured by molecular absorption spectrometry. | Baseline and after completed each intervention (1 month) | 
| Assessing variations in inflammatory biomarkers post-intervention for both EVOO treatments and the control group. | Cytokines (pg/mL) will be assayed by immunoenzymatic methods. | Baseline and after completed each intervention (1 month) | 
| Changes in inflammatory biomarkers after each intervention with EVOO and the control intervention. | Tumor necrosis factor α (TNF-α) (pg/mL) will be assayed by immunoenzymatic methods. | Baseline and after completed each intervention (1 month) | 
| Changes in inflammatory biomarkers after each intervention with EVOO and the control intervention. | C-reactive protein (CRP) (mg/dL) will be assayed by immunoenzymatic methods. | Baseline and after completed each intervention (1 month) | 
| Changes in nutrients and energy intake after each intervention with EVOO and the control intervention. | A 7-day food recall will be used. The data will be analyzed using a software called Professional Nutritional Calculation Program (PCN Pro) | Baseline and after completed each intervention (1 month) | 
| Changes in quality of the diet after each intervention with EVOO and the control intervention. | Participants will fill the validated Mediterranean Diet Adherence Screener (MEDAS) questionnaire used in the PREDIMED study. This questionnaire has been validated for the Spanish population and assesses adherence to the Mediterranean diet.The MEDAS score can range from 0 to 17 and higher scores mean better outcome. | Baseline and after completed each intervention (1 month) | 
| Changes in physical activity after each intervention with EVOO and the control intervention. | Physical activity will be assessed with the ActiGraph® wGT3X-BT accelerometer | Baseline and after completed each intervention (1 month) | 
| Changes in sleep quality after each intervention with EVOO and the control intervention | Sleep quality will be assessed with the ActiGraph® wGT3X-BT accelerometer. | Baseline and after completed each intervention (1 month) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MGBA, Extra virgin olive oil, Microbiota, Polyphenol