Nutritional Intervention With Black Garlic

Study Overview
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Brief Summary
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A controlled clinical intervention study is proposed to determine the effect of black garlic consumption on biomarkers of cardiovascular function and associated pathologies in a healthy population at risk for cardiovascular disease. Black garlic is the result of a fermentation process of common white garlic in which the temperature and humidity are kept constant over a long period of time. Black garlic is particularly rich in phenolic compounds such as S-allylcysteine or S-allyl-mercaptocysteine, with antioxidant action. It also provides vitamin C and other valuable antioxidant substances such as flavonoids.

Detailed Description
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A parallel, controlled clinical trial will be performed to assess the effect of garlic on mild hypercholesterolemia. The study will conducted in two groups of volunteer: healthy and at cardiovascular risk (hypercholesterolemic subjects), consuming black garlic, with each individual acting as its own control. The study will have a total duration of 18 weeks, divided in two stages: Stage 1: basal or washout stage of 2 weeks, in which volunteer follow their usual diet with restrictions Stage 2: intervention stage of 16 weeks, in which volunteer consume black garlic Sixty healthy volunteers (men and women) between 40-65 years old and BMI between 24.9-29.9 kg/m2 will be recruited. From the total of volunteer, 30 will correspond to the Healthy Group, which should have total blood cholesterol levels less than 200 mg/dL and LDL-cholesterol less than 135 mg/dL. The other 30 volunteers correspond to the Cardiovascular Risk Group, which should have total cholesterol levels between 200-300 mg/dL and LDL-cholesterol levels between 135-175 mg/dL. Other inclusion criteria established for all volunteers are: no acute or chronic pathology, (except hypercholesterolemia for the risk group), no taking drugs, hormones or dietary supplements, no smoking, no pregnancy, no vegetarianism. The study has been approved by the Ethical Committee of Catholic University of Murcia (UCAM) and will be carried out in accordance with the Helsinki Declaration of Human Studies. Recruitment will take place at various Health Centers and at UCAM. All participants will be informed on the characteristics of the study and, after signing the informed consent, a routine analysis will be requested to classify the volunteer in the healthy or cardiovascular risk group. To avoid bias due to gender, the number of women and men recruited in both groups will be balanced. The size of the study population has been estimated taking total blood cholesterol level as the main variable and taking into account that the study design is randomized and parallel. Considering a statistical power of 80%, a statistical significance level of 5% (one tail), a standard deviation of 6.5, aiming to estimate a difference of 2.5, the number of volunteers required is 25 for each group, rising to 30 in anticipation of dropouts. This number, being two study groups, will allow obtaining results with statistical significance in other biochemical parameters that would be determined as secondary variables of the study and that would inform on the effect of black garlic consumption on cardiovascular function and associated dysfunctions (inflammation, hypertension, endothelial function, diabetes, etc.). After an initial washout (basal) stage common to all groups, in which the volunteers will consume their usual diet with restriction in the consumption of fresh garlic and garlic products, the intervention will start, with the consumption of black garlic for 12 weeks. Volunteers will be provided with black garlic and they will ensure that no other type of garlic or culinary seasoning is used. Dietary and physical activity questionnaire according to the Global Physical Activity Questionnarie (GPAQ) will be compiled in order to collect information on habits and lifestyle, as well as to ensure the compliance of food restrictions. During the study, visits will be scheduled on the first day and last day of each stage. The subjects will come to the Unit on fasting conditions and will provide the first morning urine. Blood sample will be taken, plasma aliquoted and stored at -80°C until analysis.

Official Title
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Clinical Trial to Evaluate the Efficacy of Black Garlic in Reducing Cardiovascular Risk in Subjects With Hypercholesterolemia

Conditions
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Hypercholesterolemia, Hypertension, Hyperlipidemias, Inflammation, Endothelial Dysfunction

Intervention / Treatment
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* Dietary Supplement: black garlic


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Group: Total blood cholesterol levels of less than 200 mg/dL LDL-cholesterol levels of less than 135 mg/dL Not suffer from any other pathology. No drugs, hormones or dietary supplements, no smoking, no pregnancy, no vegetarianism, etc. Cardiovascular Risk Group: Total cholesterol levels between 200-300 mg/dL LDL-cholesterol levels between 135-175 mg/dL. No acute or chronic pathology, except hypercholesterolemia No drugs, hormones or dietary supplements, no smoking, no pregnancy, no vegetarianism, etc.). Exclusion Criteria: Failure to meet any of the inclusion criteria

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 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: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A controlled clinical intervention study is proposed to determine the effect of black garlic consumption on biomarkers of cardiovascular function and associated pathologies in a healthy population at risk for cardiovascular disease.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy Group,<br>Daily consumption of 4 cloves of black garlic, not cooked, during 12 weeks | Dietary Supplement: black garlic<br>* Daily consumption of 4 cloves of black garlic, not cooked, during 12 weeks<br>|
| Experimental: Hypercholesterolemia<br>Daily consumption of 4 cloves of black garlic, not cooked, during 12 weeks | Dietary Supplement: black garlic<br>* Daily consumption of 4 cloves of black garlic, not cooked, during 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact on blood pressure | Blood pressure (diastolic, systolic) | changes observed from baseline at day 0 compared to 12 weeks. | 
| Impact on lipid profile | Plasma levels of total cholesterol, HDL, LDL, VLDL (very low-density lipoprotein), triglycerides, apolipoproteins A1 and B. | changes observed from baseline at day 0 compared to 12 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact on blood cells (Hematology) | Blood counts | changes observed from baseline at day 0 compared to 12 weeks. | 
| evaluation of liver function to determine product safety | Hepatic enzymes (GOT, GPT) | changes observed from baseline at day 0 compared to 12 weeks. | 
| Changes in cytokine levels | Plasma levels of pro-inflammatory: IL-1β, IL6 , TNF-α (tumor necrosis factor) and anti-inflammatory (IL-10, IL-17) cytokines. | changes observed from baseline at day 0 compared to 12 weeks. | 
| Changes in chemokine MCP-1 (monocyte chemotactic protein) | Plasma levels of chemokine MCP-1 | changes observed from baseline at day 0 compared to 12 weeks. | 
| Changes in C reactive protein | Plasma levels of C reactive protein | changes observed from baseline at day 0 compared to 12 weeks. | 
| Impact on endothelial function | Plasma levels of nitric oxide, adhesion molecules VCAM-1 (vascular endothelial cell adhesion molecule), ICAM-1 (intercellular adhesion molecule), chemokines as markers of endothelium (E-selectin) and platelet (P-selectin) activation. | changes observed from baseline at day 0 compared to 12 weeks. | 
| Impact on glucose levels | Plasma levels of glucose | changes observed from baseline at day 0 compared to 12 weeks. | 
| Impact on glycosylated hemoglobin (HbA1c) | Plasma levels of glycosylated hemoglobin | changes observed from baseline at day 0 compared to 12 weeks. | 
| Impact in hormones related to metabolism | Plasma levels of thyroid hormones (TSH, T3, T4). | changes observed from baseline at day 0 compared to 12 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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endothelial dysfunction, black garlic, sulphur bioactive compounds, hypercholesterolemia, hyperlipemia, inflammation