Study title
The FLAvonoids and Vascular function
Template
Intervention/Observation study
title
The FLAvonoids and Vascular function
description
The essential research question addressed the optimal quantity and types of F&Vs required to promote vascular health and modify other established and putative cardiovascular risk markers. We hypothesized that flavonoid-rich F&Vs have a greater protective effect than flavonoid-poor F&Vs on micro- and macrovascular function
startDate
2007-12-01 00:00:00.0
Study type
Human Intervention
Principle Investigator
Julie Lovegrove
Primary endpoint
From Metabolomics part: Valerolactones, phenolic acids and their derivatives were among sixteen biomarkers related to the high flavonoid dietary exposure. Four biomarkers related to the low flavonoid diet belonged to the family of phenolic acids.
Objectives
The essential research question addressed the optimal quantity and types of F&Vs required to promote vascular health and modify other established and putative cardiovascular risk markers. We hypothesized that flavonoid-rich F&Vs have a greater protective effect than flavonoid-poor F&Vs on micro- and macrovascular function
Central conclusion
In FLAVURS, the hypothesis that higher intakes of F&Vs would reduce specific CVD risk markers was confirmed. The modest improvements in CVD risk markers (which may reflect the relatively short-term intervention compared with life-long consumption) were not wholly consistent with a dose-dependent effect. Benefit was observed when increasing F&V intake from 3.9 portions/d to w6–7 portions/d, with little additional benefit thereafter. Increases in vascular stiffness were attenuated with consumption of w7 portions of F&Vs, irrespective of flavonoid content. In the FLAVURS men, after an additional 2.4 portions of HF F&Vs (a total of w6 portions F&Vs/d), CVD risk reduction appeared to be mediated in part by an improvement in microvascular reactivity associated with lower inflammatory cytokines. These data support recommendations to increase F&V intake to $6 portions daily, with additional benefit from F&Vs that are rich in flavonoids. These important findings require confirmation in further independent studies.
Main health-related outcome
In men, the HF F&V diet increased endothelium-dependent microvascular reactivity (P = 0.017) with 12 portions/d (at 6 wk) and reduced C-reactive protein (P = 0.001), E-selectin (P = 0.0005), and vascular cell adhesion molecule (P = 0.0468) with +4 portion
Exclusion criteria
Key exclusion criteria: previous stroke or myocardial infarction; clinically diagnosed diabetes, liver, or renal disease; drug treatment for lipid reduction or hypertension; antiinflammatory medication; and pregnancy or lactation.
Inclusion criteria
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
Using 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).
Institute
1) Hugh Sinclair Unit of Human Nutrition and the Institute for Cardiovascular and Metabolic Research (ICMR), Department
of Food and Nutritional Sciences, University of Reading, Whiteknights, PO Box 226, Reading RG6 6AP, UK
2) Department of Food Quality and Nutrition, Research and
Innovation Centre, Fondazione Edmund Mach (FEM), Via Mach 1, 38010 San Michele all’Adige, TN, Italy
Country (for multicentre study overall PI)
UK
Funding body
For the main study: Foods Standards Agency (UK) (ref: N02R0001). For the metabolomic study: the ADP2014 project, funded by the Autonomous Province of Trento, Italy.
Study weblink
http://link.springer.com/article/10.1007/s11306-015-0935-z
Clinicaltrials.gov or similar number
ISRCTN47748735
Was the study approved by an ethics committee?
Yes
Ethical approval number
Ethical approval for the study was obtained from the Local Research Ethics Committee of the Isle of Wight, Portsmouth and South East Hampshire (REC: 07/H0501/81), and the University of Reading’s Research (REC: 07/22) Ethics Committee
Did the individuals providing data sign informed consent?
Yes
Study design
Case-control
Description of "Start groups"
Parallel
Type of controls
control group consisted in participants that maintained their habitual diet throughout the study
Blinding method
Before baseline measures, all 3 treatment groups were blinded to the interventions after assignment; during the study, only the dietary intervention groups continued to be blinded. Researchers performing sample and vascular analyses were blinded to group
Compliance assessment (for each treatment)
In brief, compliance to the target numbers
and types of F&Vs was broadly met and verified by dietary
records and plasma and urinary biomarkers.
Number of factors (for factorial designs only)
5
Total number of arms (Give number of distinct treatments in study)
3
Explanatory text (Give a textual account of the overall design leading to the total number of groups) or provide the study protocol.
2 sequentially increasing dose-response dietary treatments containing high-flavonoid (HF) and low-flavonoid (LF) F&Vs and a control group in which participants maintained their habitual diet
Treatments (Number and types of foods, drugs or other treatments compared)
At week 0, participants were given individualised dietary advice and a handbook detailing information on the
study and the diets to which they were randomly assigned.
Low Flavonoid diet was compared to High Flavonoid diet, and to Control diet.
In this study, Low Flavonoid fruits and vegetables (LF F&V) were defined as
those containing a total flavonoid content of
< 5 mg/100 g., while High flavonoid were defined as those containing a total flavonoid content of >15 mg/100 g. See details in DOI 10.1007/s00394-012-0343-3
Number of volunteers screened N(M:xx, F: xx)
307 (M:94, F: 212)
Number of volunteers enrolled N(M:xx, F: xx)
221(M:74, F:147)
Number of subjects (Male; Female)
154(M:60, F:94)
Start of recruitment (Start year or date)
2007-12-01 00:00:00.0
End of recruitment (End year or date)
2009-01-01 00:00:00.0
