Condition category
Circulatory System
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting
Publication status

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Dr Julie Lovegrove


Contact details

Hugh Sinclair Human Nutrition Unit
School of Chemistry
Food Biosciences and Pharmacy
University of Reading
United Kingdom

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

Impact of increasing doses of flavonoid-rich and flavonoid-poor fruit and vegetables on cardiovascular risk factors in an ‘at risk’ group



Study hypothesis

To determine the impact of different amounts and types (flavonoid-rich versus flavonoid-poor) of fruit and vegetables on heart disease risk factors in an 'at risk' group.

Ethics approval

Ethics approval received from the Isle of Wight, Portsmouth and South East Hampshire Research Ethics Committee on 6th November 2007 (REC no.: 07/H0501/81).

Study design

A single-blind, single-centre, randomised, controlled dietary intervention study with three parallel treatment arms (one control and two intervention groups)

Primary study design


Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Quality of life

Patient information sheet


Cardiovascular disease


After a three week run-in period following a habitual (low fruit and vegetable) diet, 180 participants, selected on the basis of their increased risk of developing cardiovascular disease, will be randomly assigned to either the habitual diet (control) or one of two intervention groups, which involves the increased intake of flavonoid-rich or flavonoid-poor fruits and vegetables. In both intervention groups, participants will be asked to sequentially increase their fruit and vegetable intake by 2, 4 and 6 portions, with a 6-week duration for each dose increase. The intervention phase will last for 18-weeks. Due to the duration of the study, a parallel design is adopted to minimise burden on the participants. The control group is necessary to control for the impact of study participation and seasonal effects on the outcomes of the study.

Intervention type



Not Specified

Drug names

Primary outcome measure

Each subject has to attend four intervention visits in total for the study. The following primary outcome measures will be taken at each visit:
1. Changes in endothelial function measured by vascular reactivity and arterial stiffness using Laser Doppler Imaging with iontophoresis and Pulse Wave Analysis measurement respectively
2. Plasma biomarkers of endothelial function (e.g. nitric oxide, Vascular Cell Adhesion Molecule [VCAM], Intercellular Adhesion Molecule [ICAM], E-selectin, von Willebrand factor, microalbumin) - fasting bloods will be taken at each visit to measure these outcomes

Secondary outcome measures

1. Fasting bloods will be taken during each intervention visit to measure the following outcomes:
1.1. Fasting lipids (total, Low Density Lipoprotein [LDL] cholesterol, HDL cholesterol, triglycerides and non-esterified fatty acids)
1.2. Indices of insulin resistance
1.3. Haemostatic factors (Plasminogen Activator Inhibitor 1 [PAI-1], fibrinogen)
1.4. Inflammatory biomarkers (C-Reactive Protein [CRP], Tumour Necrotising Factor [TNF]-alpha and Interleukin-6 [IL6])
2. The following will be measured during the 6-week intervention periods between visits:
2.1. 24-hour ambulatory blood pressure
2.2. Dietary intake assessed by 24 hour dietary recalls and biomarkers of fruit and vegetable intake (24 hour urinary flavonoid metabolites, urinary potassium, plasma ascorbic acid)
3. Faecal samples will be collected at each intervention visit to perform quantitative and qualitative analysis of faecal microflora and estimation of faecal water genotoxicity and mucosal integrity
4. Changes in cognitive performance will be measured during each intervention visits using computer tests

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. Men and women between the ages of 30 - 70 years
2. At above average risk of developing heart disease
3. Meet one or more of the following criteria:
3.1. Overweight
3.2. High total cholesterol (but not on medication)
3.3. Low High Density Lipoprotein (HDL) cholesterol
3.4. High blood pressure (but not on medication)
3.5. Cigarette smoker

For the specific range of inclusion for each risk factor, we have come up with a scoring system, adapted mainly from the Framingham study. Volunteers who have an above average risk of developing heart disease (RR 1.5) would be included in the study. Volunteers who have risk factor/s at a very high risk level would be excluded. Participants should also have a low intake of fruit and vegetable (i.e. less than or equal to 3 portions per day).

Participant type


Age group




Target number of participants


Participant exclusion criteria

1. Who have diabetes, heart disease (previous stroke/myocardial infarction), renal or bowel or liver diseases and hormone abnormalities
2. On drug treatment for hyperlipidemia, hypertension, inflammation or hypercoagulation
3. Taking dietary supplements (e.g. vitamins and minerals, fish oils)
4. Who drink more than 15 units of alcohol per week
5. Who are pregnant, lactating or if of reproductive age and not using a reliable form of contraception (including abstinence)
6. Who are regularly undertaking vigorous exercise or fitness training
7. Who are on a weight-reducing regime
8. Who consume over 3 portions of fruit and vegetables per day

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

Hugh Sinclair Human Nutrition Unit
United Kingdom

Sponsor information


Foods Standards Agency (UK)

Sponsor details

Aviation House
125 Kingsway
United Kingdom

Sponsor type




Funder type


Funder name

Foods Standards Agency (UK) (ref: N02R0001)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

1. 2009 results published as a poster at ICPH 2009: Yorkshire 7th December-11th December
2. 2013 results in:
3. 2014 results in:
4. 2014 results in:

Publication citations

  1. Results

    Chong MF, George TW, Alimbetov D, Jin Y, Weech M, Macready AL, Spencer JP, Kennedy OB, Minihane AM, Gordon MH, Lovegrove JA, Impact of the quantity and flavonoid content of fruits and vegetables on markers of intake in adults with an increased risk of cardiovascular disease: the FLAVURS trial., Eur J Nutr, 2013, 52, 1, 361-378, doi: 10.1007/s00394-012-0343-3.

  2. Results

    Macready AL, George TW, Chong MF, Alimbetov DS, Jin Y, Vidal A, Spencer JP, Kennedy OB, Tuohy KM, Minihane AM, Gordon MH, Lovegrove JA, , Flavonoid-rich fruit and vegetables improve microvascular reactivity and inflammatory status in men at risk of cardiovascular disease--FLAVURS: a randomized controlled trial., Am. J. Clin. Nutr., 2014, 99, 3, 479-489, doi: 10.3945/ajcn.113.074237.

  3. Results

    Jin Y, Gordon MH, Alimbetov D, Chong MF, George TW, Spencer JP, Kennedy OB, Tuohy K, Minihane AM, Lovegrove JA; FLAVURS Study Group, A novel combined biomarker including plasma carotenoids, vitamin C, and ferric reducing antioxidant power is more strongly associated with fruit and vegetable intake than the individual components, J Nutr, 2014, 144, 11, 1866-1872, doi: 10.3945/jn.114.192856.

Additional files

Editorial Notes