Mediation of coffee-induced improvements in human vascular function by chlorogenic acids and its metabolites: Two randomized, controlled, crossover intervention trials.

Abstract

Polyphenol intake has been linked to improvements in human vascular function, although data on hydroxycinnamates, such as chlorogenic acid (CGA) have not yet been studied. We aimed to investigate the impact of coffee intake rich in chlorogenic acid on human vascular function and whether CGAs are involved in potential effects. Two acute randomized, controlled, cross-over human intervention trials were conducted. The impact of coffee intake, matched for caffeine but differing in CGA content (89, and 310mg) on flow-mediated dilatation (FMD) was assessed in 15 healthy male subjects. In a second intervention trial conducted with 24 healthy male subjects, the impact of pure 5-caffeoylquinic acid (5-CQA), the main CGA in coffee (5-CQA; 450mg and 900mg) on FMD was also investigated. We observed a bi-phasic FMD response after low and high polyphenol, (89mg and 310mg CGA) intake, with increases at 1 (1.10±0.43% and 1.34±0.62%, respectively) and 5 (0.79%±0.32 and 1.52%±0.40, respectively) hours post coffee consumption. FMD responses to coffee intake was closely paralleled by the appearance of CGA metabolites in plasma, notably 3-, 4- and 5-feruloylquinic acid and ferulic-4'-O-sulfate at 1h and isoferulic-3'-O-glucuronide and ferulic-4'-O-sulfate at 5h. Intervention with purified 5-CQA (450mg) also led to an improvement in FMD response relative to control (0.75±1.31% at 1h post intervention, p=0.06) and concomitant appearance of plasma metabolites. Coffee intake acutely improves human vascular function, an effect, in part, mediated by 5-CQA and its physiological metabolites. The National Institutes of Health (NIH) on ClinicalTrials.govNCT01813981 and NCT01772784.