Bioavailability and Vascular Effects of Apple Polyphenols (POLYMALUS)

The main purpose of this study is to determine the oral bioavailability of flavanols (polyphenolic compounds) from apple granules and an apple extract delivered in a water based beverage at two different doses. We will also investigate the effects of apple flavanols on nitric oxide production.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Other: Apple extract delivering 70 mg epicatechin; Other: Apple extract delivering 140 mg epicatechin; Other: Apple granules delivering 70 mg epicatechin; Other: Water delivering no epicatechin

Detailed Description

This study is a randomized four phase crossover trial investigating the bioavailability of apple flavanols and the effects on nitric oxide products, a surrogate marker for changes in endothelial function. Each test phase will comprise a 3 day period of intervention which will be identical in nature (except for the test product consumed) and separated by a minimum of 1 week. On days 1-3 of each test phase volunteers will consume a low flavanol diet. After consumption of the test product on the morning of day 2, blood and urine samples will be collected at regular intervals for the next 24h.

• Study Type: Interventional
• Enrollment (Actual): 12
• 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: 45 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women aged 45-70 years

Exclusion Criteria:

• Smokers (or have quit smoking less than 1 year ago)
• Regular prescribed medication (excluding some eye and skin medication that is judged not to affect study outcome)
• Non-prescribed medication that may affect the study data, e.g. aspirin. The use of non prescribed medications will be assessed on an individual basis.
• Dietary supplements or herbal remedies which may affect the study data unless the volunteer is willing to discontinue them for 1 month prior to starting study. (Please note that some supplements may not affect the study and this will be assessed on an individual basis).
• Gastro-intestinal diseases (excluding hiatus hernia unless symptomatic or study intervention/procedure is contra-indicated).
• Diabetics
• Known cardiovascular disease
• Asthmatics (unless no medication taken for 1 year)
• Lactose Intolerance
• Pregnancy or have been pregnant within the last 12 months
• 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 mls.
• 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)
• Any person related to or living with any member of the study team
• Results of the clinical screening which indicate or are judged by the HNU Medical Advisor to be indicative of a health problem which could compromise the well-being of the volunteer if they participated or which could affect the study data.
• Alcohol consumption > approximately 20 g alcohol/day (2.5 units/day)
• BMI <19.5 or > 35

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Apple flavanols	Other: Apple extract delivering 70 mg epicatechin; Delivered as a flavoured water based beverage; Other: Apple extract delivering 140 mg epicatechin; Delivered as a flavoured water based beverage; Other: Apple granules delivering 70 mg epicatechin; Delivered as a puree; Other: Water delivering no epicatechin; Delivered as flavoured water

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the plasma pharmacokinetic curve for total epicatechin	24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Additional measures of bioavailability: Plasma Cmax, Tmax, half life and urinary excretion	24 hours
Changes in levels of nitric Oxide metabolites as a surrogate measure of endothelial function after consumption of apple flavanols	24 hours

Collaborators and Investigators

• Sponsor: Quadram Institute Bioscience
• Collaborators: Danisco; Coressence LTD
• Investigators: Principal Investigator: Paul Kroon, Quadram Institute Bioscience

Publications and helpful links

General Publications

• Saha S, Hollands W, Needs PW, Ostertag LM, de Roos B, Duthie GG, Kroon PA. Human O-sulfated metabolites of (-)-epicatechin and methyl-(-)-epicatechin are poor substrates for commercial aryl-sulfatases: implications for studies concerned with quantifying epicatechin bioavailability. Pharmacol Res. 2012 Jun;65(6):592-602. doi: 10.1016/j.phrs.2012.02.005. Epub 2012 Feb 25.

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: March 31, 2010
• First Submitted That Met QC Criteria: March 31, 2010
• First Posted (Estimate): April 1, 2010

Study Record Updates

• Last Update Posted (Estimate): March 6, 2013
• Last Update Submitted That Met QC Criteria: March 5, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Healthy volunteers; bioavailability; Dietary intervention
• Other Study ID Numbers: IFR06-2009