| Summary: | A body of epidemiological evidence suggests beneficial cardiovascular (CV) effects of dietary citrus flavanones. However, as systematically reviewed, there is currently only limited supporting evidence from randomised controlled trials (RCT); in particular, relatively little is known about which flavanone-derived circulating metabolites might be the underlying mediators of potential beneficial CV effects of flavanones. In an acute crossover RCT, male participants at a mild to moderate CV disease (CVD) risk received dietary interventions (in random order): orange juice (hesperidin dose: 320 mg) or control, whereby both were matched for sugar and vitamin C. Markers of CVD risk and plasma concentrations of previously identified and novel flavanone / phenolic metabolites were simultaneously assessed at baseline and 5 h post dietary intervention (5 h is the anticipated time of peak plasma concentration of flavanone metabolites). At 5 h post intervention, the orange juice intervention resulted in significantly elevated plasma concentrations of 8 flavanone metabolites (mean ± SD: 1.60 ± 1.33 μM and 0.02 ± 0.01 μM, respectively; P < 0.0001) and 15 phenolic acid metabolites (mean ± SD: 19.59 ± 7.46 μM and 5.69 ± 1.70 μM, respectively; P < 0.0001) compared with the control intervention. However, these elevated metabolite plasma concentrations did not result in acute improvements in digital endothelial function, central arterial stiffness, CV autonomic function, platelet activation, nitric oxide production and NADPH oxidase gene expression. In summary, relatively high plasma concentrations of metabolites (predominantly phenolic acids metabolites) were detected 5 h after a single dose of flavanones in men at a mild to moderate CVD risk. Simultaneously assessed markers of CVD risk were not beneficially affected and further acute RCTs with a longer time course (up to 24 h) and short-term to chronic (weeks up to years) RCTs are required to determine the potential beneficial CV effects of dietary flavanones.
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