The Effects of Apple Derived Flavanols on Cardiovascular Disease Risk (FLAVASCULAR Study) (FLAVASCULAR)

The Effects of Apple Derived Flavanols on Cardiovascular Disease Risk

Fruit and vegetable rich diets are associated with a reduced risk of cardiovascular disease (CVD). The protective effect may be ascribed to compounds contained within these foods, called flavonoids. Flavanols (epicatechin and procyanidins) are a particular group of flavonoids and are found mostly in apples, berry fruits, dark chocolate, tea and red wine. There is evidence to suggest that ingestion of flavanol rich foods and beverages beneficially alter 'markers' of CVD risk (e.g. blood pressure). The aim of this study is to determine the acute and chronic effects of apple derived flavanols on some risk markers for CVD.

Study Overview

• Status: Completed
• Conditions: Blood Pressure
• Intervention / Treatment: Dietary supplement: Low Epicatechin and procyanidin; Dietary supplement: High Epicatechin and procyanidin; Dietary supplement: High procyanidin; Dietary supplement: Placebo

Detailed Description

This study is a single arm randomized, 4-phase crossover design.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Norfolk
    • Norwich, Norfolk, United Kingdom, NR4 7UA
      • Institute of Food Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women ≥ 50 years of age
• Systolic blood pressure 130 - 159 mmHg

Exclusion Criteria:

• History of cardiovascular events such as stroke, myocardial infarction trans- ischaemic attacks or peripheral vascular disease
• Kidney or liver disease/problems
• Diabetes
• Asthmatics (unless no medication taken for 1 year - occasional use will be assessed on an individual basis)
• Prescribed anti-hypertensive medication
• HRT (unless the participant has used the therapy for ≥ 6 months)
• Lipid lowering therapies e.g. statins
• Other medications that may affect any of the study outcome measures e.g. vasodilators (this will be assessed on a case by case basis)
• Current smoker (or stopped for less than 3 months)
• Throat surgery or neck injury
• Allergy to apples
• Consumption of fish oil supplements unless willing to discontinue them up for 4 weeks preceding the start of the study and for the duration of the study. (All other supplements will be assessed on a case by case basis)
• Gastro-intestinal diseases (excluding hiatus hernia unless symptomatic or study intervention/procedure is contra-indicated).
• Parallel participation in another research project which involves dietary intervention
• Participation in another research project which has involved blood sampling within the last four months unless the total amount of combined blood from both studies does not exceed 470 ml.
• Has donated or intends to donate blood within 16 weeks prior to or during the study period.
• Depressed or elevated blood pressure measurements (<90/50 or 95/55 if symptomatic or >160/100 (mmHg)) during the course of the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Low Epicatechin and procyanidin; Low epicatechin and procyanidin doses	Dietary supplement: Low Epicatechin and procyanidin; 70 mg epicatechin and 65 mg procyanidins once daily for 28 days
EXPERIMENTAL: High Epicatechin and procyanidin; High epicatechin and procyanidin doses	Dietary supplement: High Epicatechin and procyanidin; 140 mg epicatechin and 130 mg procyanidins once daily for 28 days
EXPERIMENTAL: High Procyanidin; High procyanidin only	Dietary supplement: High procyanidin; No epicatechin and 130 mg procyanidins once daily for 28 days
PLACEBO_COMPARATOR: Placebo; No epicatechin and procyanidin	Dietary supplement: Placebo; Placebo control once daily for 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Changes in systolic blood pressure from baseline	Baseline, 2 hours and 4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in plasma lipid profile from baseline	Baseline and 4 weeks
Change in plasma endothelin-1 from baseline	Baseline and 4 weeks
Changes in plasma nitric oxide metabolites from baseline	Baseline, 2 hours and 4 weeks
Changes in blood glucose from baseline	Baseline and 4 weeks
Changes in pulse wave velocity from baseline	Baseline, 2 hours and 4 weeks

Collaborators and Investigators

• Sponsor: Quadram Institute Bioscience
• Investigators: Principal Investigator: Paul Dr Kroon, PhD, Quadram Institute Bioscience

Publications and helpful links

General Publications

• Hollands WJ, Tapp H, Defernez M, Perez Moral N, Winterbone MS, Philo M, Lucey AJ, Kiely ME, Kroon PA. Lack of acute or chronic effects of epicatechin-rich and procyanidin-rich apple extracts on blood pressure and cardiometabolic biomarkers in adults with moderately elevated blood pressure: a randomized, placebo-controlled crossover trial. Am J Clin Nutr. 2018 Nov 1;108(5):1006-1014. doi: 10.1093/ajcn/nqy139.

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (ACTUAL): October 1, 2016
• Study Completion (ACTUAL): October 1, 2016

Study Registration Dates

• First Submitted: December 9, 2013
• First Submitted That Met QC Criteria: December 11, 2013
• First Posted (ESTIMATE): December 17, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): December 2, 2016
• Last Update Submitted That Met QC Criteria: December 1, 2016
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Cardiovascular disease; Blood pressure; Flavanols
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Protective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antioxidants; Proanthocyanidin; Procyanidin
• Other Study ID Numbers: IFR05/2013