Punicalagin and Hydroxytyrosol Mixture on Different Inflammatory Markers

Study Overview
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Brief Summary
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A crossover trial was carried out in healthy volunteers aged 45-70 years and BMI <30 kg/m2. Subjects consumed a Antioxidant Supplement (AS) containing 65 mg of punicalagin mixed with 3.3 mg of hydroxytyrosol 3 times daily or a Control Supplement (CS) with maltodextrin for an 8 wk each phase with 4-wk rest period. Supplementation order was randomly assigned and the consumption of derivative products of punicalagin and/or hydroxytyrosol restricted. The endothelial function parameters (brachial artery flow-mediated dilation (FMD), biochemical markers), inflammatory markers and nutritional status were evaluated before and after each phase. Previously a pilot study was completed with no placebo (n=30) to determinate the effective dose of Functional Supplement.

Official Title
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Effects of Punicalagin and Hydroxytyrosol Mixture on Different Inflammatory Markers Related With Cardiovascular Disease: a Crossover Study in Healthy Middle-aged Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Dietary Supplement: punicalagin and hydroxytyrosol mixture
* Dietary Supplement: Control supplement (maltodextrin)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women from 45 to 75 years old; Signed informed consent Exclusion Criteria: Individuals with cardiovascular risk factors on drug treatment (dyslipidemia, hypertension, Diabetes Mellitus); Individuals with Metabolic Syndrome; Individuals with familiar background of premature cardiovascular disease; Individuals with BMI ≥ 30 kg/m2; Women that still maintain your menstrual cycle; Individuals with increased alcohol consumption 30g/day; Individuals that stop smoking in the next 20 weeks (during the study); Individuals that consume antioxidant supplement, drugs, ω-3 supplements, vitamins, minerals, prebiotics or/and probiotics; Women that consume oral contraceptive; Individuals with mental disease or low cognitive function; Individuals with severe diseases (hepatic, kidney, cancer…); Individuals with drugs or supplements consumption to weight lost; Pregnant women or lactating; Individuals with intensive physical activity; Individuals with physical problems complying with the recommendations of physical activity and diet general recommendations.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 75 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Antioxidant supplement<br>Treatment consist of consuming 65g of punicalagin and 3,3g of hydroxytyrosol (plus 331,7g of maltodextrin) three times daily, during 8 weeks. | Dietary Supplement: punicalagin and hydroxytyrosol mixture<br>* Antioxidant Supplement (punicalagin and hydroxytyrosol mixture) During one period of crossover study (I or II) volunteers consume daily of functional supplement during 8 weeks. Additionally, volunteers must follow guidelines for healthy diet and physical activity.<br>* Other names: Punicalagin and hydroxytyrosol;|
| Placebo Comparator: Control supplement<br>Treatment consist of consuming 400g of maltodextrin three times daily, during 8 weeks. | Dietary Supplement: Control supplement (maltodextrin)<br>* During one period of crossover study (I or II) volunteers consume daily of functional supplement during 8 weeks. Additionally, volunteers must follow guidelines for healthy diet and physical activity.<br>* Other names: Maltodextrin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Inflammatory markers after 8 weeks treatment | Inflammatory markers (Fibrinogen, gelsolin, thrombospondin, interleukin 6 and PCR) will be measured at week 0 and 8 for phase I, and at week 12 and 20 for phase II | 0, 8, 12 and 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Oxidative Stress Parameters | Parameters measured were: plasma antioxidant capacity (FRAP, ferric reducing antioxidant power) and lipidic peroxidation (TBARS, thiobarbituric acid reactive substances assay), oxidized LDL, paraoxonase 1, F2-isoprostanes. Will be measured at week 0 and 8 for phase I, and at week 12 and 20 for phase II. | 0, 8, 12 and 20 weeks | 
| Change in Glucose Metabolism | Parameters measured were: glucose, basal insulin, HbA1c (in diabetic patients), HOMA (homeostasis model assessment ) index (glycemic insulin sensitivity index was calculated using the formula: HOMA-IR ( (homeostasis model assessment insulin resistance) = fasting glucose (mmol/l)/fasting immunoreactive insulin (mU/ml)/22•5).Will be measured at week 0 and 8 for phase I, and at week 12 and 20 for phase II | 0, 8, 12 and 20 weeks | 
| Change in Lipid profile | Parameters measured were: Cholesterol, LDL-Cholesterol, HDL-Cholesterol, Triglycerides. Will be measured at week 0 and 8 for phase I, and at week 12 and 20 for phase II | 0, 8, 12 and 20 weeks | 
| Change in Endothelial function | Parameters measured were: Brachial artery flow-mediated dilation (FMD), blood pressure, eNOS, vascular endothelial cell adhesion molecule -1 and p-selectin. Will be measured at week 0 and 8 for phase I, and at week 12 and 20 for phase II | 0, 8, 12 and 20 weeks | 
| Change in Coagulation markers | Parameters measured were: Prothrombin time and activity, INR. Will be measured at week 0 and 8 for phase I, and at week 12 and 20 for phase II | 0, 8, 12 and 20 weeks | 
| Change in Anthropometric and body composition parameters | Parameters measured were: Weight, Height and waist circumference, muscle mass percentage (MM%), fat mass percentage (FM%), free fat mass percentage(FM%). Will be measured at week 0 and 8 for phase I, and at week 12 and 20 for phase II | 0, 8, 12 and 20 weeks | 
| Adverse effects | Parameters measured were: transaminases and creatinine. Will be evaluated during all the study visits | 0 to 20 weeks | 
| Adherence and Tolerance Parameters | Parameters measured were: adherence and tolerance to the products. Will be evaluated during all study visits. | 0 to 20 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cross-over studies, Antioxidants, Hydroxytyrosol, Punicalagin, Treatment outcome, Inflammatory markers, Endothelial function, Humans, Adults, volunteers