AbstractA higher intake of food rich in flavonoids such as quercetin can reduce the risk of CVD. Enzymatically modified isoquercitrin (EMIQ^®) has a bioavailability 17-fold higher than quercetin aglycone and has shown potential CVD moderating effects in animal studies. The present study aimed to determine whether acute ingestion of EMIQ^® improves endothelial function, blood pressure (BP) and cognitive function in human volunteers at risk of CVD. Twenty-five participants (twelve males and thirteen females) with at least one CVD risk factor completed this randomised, controlled, crossover study. In a random order, participants were given EMIQ^® (2 mg aglycone equivalent)/kg body weight or placebo alongside a standard breakfast meal. Endothelial function, assessed by flow-mediated dilatation (FMD) of the brachial artery was measured before and 1·5 h after intervention. BP, arterial stiffness, cognitive function, BP during cognitive stress and measures of quercetin metabolites, oxidative stress and markers of nitric oxide (NO) production were assessed post-intervention. After adjustment for pre-treatment measurements and treatment order, EMIQ^® treatment resulted in a significantly higher FMD response compared with the placebo (1·80 (95 % CI 0·23, 3·37) %; P = 0·025). Plasma concentrations of quercetin metabolites were significantly higher (P < 0·001) after EMIQ^® treatment compared with the placebo. No changes in BP, arterial stiffness, cognitive function or biochemical parameters were observed. In this human intervention study, the acute administration of EMIQ^® significantly increased circulating quercetin metabolites and improved endothelial function. Further clinical trials are required to assess whether health benefits are associated with long-term EMIQ^® consumption.