Punicalagin and Hydroxytyrosol Mixture on Different Inflammatory Markers (PROBELTEII)

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Dietary supplement: punicalagin and hydroxytyrosol mixture; Dietary supplement: Control supplement (maltodextrin)

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28061
    • Hospital Universitario La Paz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Antioxidant supplement; 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; 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.; Other Names: Punicalagin and hydroxytyrosol
Placebo Comparator: Control supplement; Treatment consist of consuming 400g of maltodextrin three times daily, during 8 weeks.	Dietary supplement: Control supplement (maltodextrin); 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.; Other Names: Maltodextrin

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Instituto de Investigación Hospital Universitario La Paz

Publications and helpful links

Helpful Links

• Institute for Health Research IdiPAZ
• Research group in Nutrition and Functional Foods (NUTRINVEST)

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: December 27, 2013
• First Submitted That Met QC Criteria: January 20, 2014
• First Posted (Estimate): January 23, 2014

Study Record Updates

• Last Update Posted (Estimate): January 23, 2014
• Last Update Submitted That Met QC Criteria: January 20, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Antioxidants; Humans; Adults; volunteers; Endothelial function; Inflammatory markers; Treatment outcome; Hydroxytyrosol; Cross-over studies; Punicalagin
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents, Local; Anti-Infective Agents; Platelet Aggregation Inhibitors; Protective Agents; Antioxidants; Disinfectants; 3,4-dihydroxyphenylethanol; Phenylethyl Alcohol
• Other Study ID Numbers: PROBELTEII