Flavonoid-rich fruit and vegetables improve microvascular reactivity and inflammatory status in men at risk of cardiovascular disease—FLAVURS: a randomized controlled trial1,2,3,4,5

Anna L Macready, Trevor W George, Mary F Chong, Dauren S Alimbetov, Yannan Jin, Alberto Vidal, Jeremy PE Spencer, Orla B Kennedy, Kieran M Tuohy, Anne-Marie Minihane, Michael H Gordon, Julie A Lovegrove, for the FLAVURS Study Group
+ Author Affiliations

1From the Hugh Sinclair Unit of Human Nutrition (ALM, TWG, MFC, DSA, YJ, AV, JPES, OBK, KMT, A-MM, MHG, and JAL), and the Institute for Cardiovascular and Metabolic Research, Department of Food and Nutritional Sciences (ALM and JAL), University of Reading, Reading, Berkshire, United Kingdom.
+ Author Notes

↵2 ALM and TWG are joint first authors.


↵3 Present address: for TWG, Northumbria University, Faculty of Health and Life Sciences, Newcastle upon Tyne, United Kingdom; for KMT, Research and Innovation Centre, Fondazione Edmund Mach, San Michele all'Adige, Trento, Italy; for A-MM, Norwich Medical School, University of East Anglia, Norwich, United Kingdom; for MFC, Clinical Nutrition Research Centre, Singapore Institute for Clinical Sciences, Singapore.

↵4 Supported by the Food Standards Agency, United Kingdom (project no. N02039/F5234012). Sainsbury's PLC (supermarket retailer) provided the study foods.

↵5 Address correspondence and requests for reprints to JA Lovegrove, Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading, Reading, Berkshire RG6 6AP, United Kingdom. E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it..">This email address is being protected from spambots. You need JavaScript enabled to view it..


Background: Observed associations between increased fruit and vegetable (F&V) consumption, particularly those F&Vs that are rich in flavonoids, and vascular health improvements require confirmation in adequately powered randomized controlled trials.

Objective: This study was designed to measure the dose-response relation between high-flavonoid (HF), low-flavonoid (LF), and habitual F&V intakes and vascular function and other cardiovascular disease (CVD) risk indicators.

Design: A single-blind, dose-dependent, parallel randomized controlled dietary intervention study was conducted. Male and female low-F&V consumers who had a ≥1.5-fold increased risk of CVD (n = 174) were randomly assigned to receive an HF F&V, an LF F&V, or a habitual diet, with HF and LF F&V amounts sequentially increasing by 2, 4, and 6 (+2, +4, and +6) portions/d every 6 wk over habitual intakes. Microvascular reactivity (laser Doppler imaging with iontophoresis), arterial stiffness [pulse wave velocity, pulse wave analysis (PWA)], 24-h ambulatory blood pressure, and biomarkers of nitric oxide (NO), vascular function, and inflammation were determined at baseline and at 6, 12, and 18 wk.

Results: In men, the HF F&V diet increased endothelium-dependent microvascular reactivity (P = 0.017) with +2 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 portions/d (at 12 wk). HF F&Vs increased plasma NO (P = 0.0243) with +4 portions/d (at 12 wk) in the group as a whole. An increase in F&Vs, regardless of flavonoid content in the groups as a whole, mitigated increases in vascular stiffness measured by PWA (P = 0.0065) and reductions in NO (P = 0.0299) in the control group.

Conclusion: These data support recommendations to increase F&V intake to ≥6 portions daily, with additional benefit from F&Vs that are rich in flavonoids, particularly in men with an increased risk of CVD. This trial was registered at www.controlled-trials.com as ISRCTN47748735.

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