Abstract
Background: Epidemiologic data suggest inverse associations between citrus flavanone intake and cardiovascular disease (CVD) risk. However, insufficient randomized controlled trial data limit our understanding of the mechanisms by which flavanones and their metabolites potentially reduce cardiovascular risk factors.Objective: We examined the effects of orange juice or a dose-matched hesperidin supplement on plasma concentrations of established and novel flavanone metabolites and their effects on cardiovascular risk biomarkers in men at moderate CVD risk.Design: In an acute, randomized, placebo-controlled crossover trial, 16 fasted participants (aged 51–69 y) received orange juice or a hesperidin supplement (both providing 320 mg hesperidin) or control (all matched for sugar and vitamin C content). At baseline and 5 h postintake, endothelial function (primary outcome), blood pressure, arterial stiffness, cardiac autonomic function, platelet activation, and NADPH oxidase gene expression and plasma flavanone metabolites were assessed. Before each intervention, a diet low in flavonoids, nitrate/nitrite, alcohol, and caffeine was followed, and a standardized low-flavonoid evening meal was consumed.Results: Orange juice intake significantly elevated mean ± SEM plasma concentrations of 8 flavanone (1.75 ± 0.35 μmol/L, P < 0.0001) and 15 phenolic (13.27 ± 2.22 μmol/L, P < 0.0001) metabolites compared with control at 5 h postconsumption. Despite increased plasma flavanone and phenolic metabolite concentrations, cardiovascular risk biomarkers were unaltered. After hesperidin supplement intake, flavanone metabolites were not different from the control, suggesting altered absorption/metabolism compared with the orange juice matrix.Conclusions: After single-dose flavanone intake within orange juice, circulating flavanone and phenolic metabolites collectively reached a concentration of 15.20 ± 2.15 μmol/L, but no effects were observed on cardiovascular risk biomarkers. Longer-duration randomized controlled trials are required to examine previous associations between higher flavanone intakes and improved cardiovascular health and to ascertain the relative importance of food matrix and flavanone-derived phenolic metabolites. This trial was registered at clinicaltrials.gov as NCT01530893.
Highlights
Cardiovascular disease (CVD) is a major cause of mortality worldwide, accounting for 32% of deaths in the United States and United Kingdom, with men being at a higher risk than women [1, 2]
Animal and in vitro studies have reported that flavanones improve endothelial function [principally via enhanced production or reduced NADPH oxidase-dependent elimination of endothelial nitric oxide [8, 9]] and cardiac autonomic function [10], as well as reduce blood pressure [11] and platelet reactivity [12]
When the model showed a significant intervention effect, pairwise comparisons between interventions were performed with Tukey-Kramer adjustments, and changes were considered significant at P, 0.05. In this acute intervention study, we examined whether the consumption of orange juice or a hesperidin supplement, matched for vitamin C, would result in acute effects on endothelial function and a number of previously unassessed cardiovascular risk biomarkers, including central arterial stiffness, cardiac baroreflex sensitivity, platelet reactivity, and NADPH oxidase gene expression
Summary
Cardiovascular disease (CVD) is a major cause of mortality worldwide, accounting for 32% of deaths in the United States and United Kingdom, with men being at a higher risk than women [1, 2]. Epidemiologic data suggest inverse associations between citrus flavanone intake and cardiovascular disease (CVD) risk. Objective: We examined the effects of orange juice or a dosematched hesperidin supplement on plasma concentrations of established and novel flavanone metabolites and their effects on cardiovascular risk biomarkers in men at moderate CVD risk. Longer-duration randomized controlled trials are required to examine previous associations between higher flavanone intakes and improved cardiovascular health and to ascertain the relative importance of food matrix and flavanone-derived phenolic metabolites. This trial was registered at clinicaltrials.gov as NCT01530893.
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