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 Mar;99(3):479-89. doi: 10.3945/ajcn.113.074237. Epub 2014 Jan 22.


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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Biomarkers / blood
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / immunology
  • Cardiovascular Diseases / physiopathology
  • Cardiovascular Diseases / prevention & control*
  • Cohort Studies
  • Cytokines / antagonists & inhibitors
  • Cytokines / blood
  • England / epidemiology
  • Female
  • Flavonoids / therapeutic use*
  • Fruit / chemistry*
  • Humans
  • Hypertension / etiology
  • Hypertension / prevention & control
  • Male
  • Microvessels / immunology
  • Microvessels / physiology*
  • Microvessels / physiopathology
  • Middle Aged
  • Risk Factors
  • Sex Characteristics
  • Single-Blind Method
  • Vascular Resistance*
  • Vascular Stiffness
  • Vegetables / chemistry*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Biomarkers
  • Cytokines
  • Flavonoids

Associated data

  • ISRCTN/ISRCTN47748735