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Although epidemiological studies have associated the consumption of sugary beverages with adverse health effects, experimental studies have demonstrated that the metabolic response of the human body to fruit juice as compared to artificial beverages is substantially different. Fruit juices do not just provide sugars and related calories, but they are rich sources of bioactive compounds. Flavanones are specifically and abundantly found in citrus fruits, with hesperidin being the major compound in orange. Dietary intake of flavanones has been associated with a lower incidence of mortality by cardiovascular disease (CVD), with a slowdown in atherosclerosis development and with vascular protective effects. Randomized, controlled clinical trials to corroborate the suggested vasculo-protective effects of orange juice presumably mediated by the flavanones are scarce, not allowing to draw firm conclusions about their efficacy.

The goal of the HESPER-HEALTH project is to provide robust clinical evidence of the efficacy of an acute and a sub-chronic (6 weeks) consumption of orange juice in improving vascular function in subjects at risk of CVD and to evaluate the contribution of hesperidin in these effects. To reach this goal, we will perform a double-blind, randomized, controlled, crossover study with three 6-week periods of consumption of 250 mL/d of orange juice, control sugary drink and control sugary drink supplemented with hesperidin. At the beginning and at the end of each intervention period, vascular function (flow-mediated dilatation (FMD), microvascular endothelial reactivity, blood pressure, arterial stiffness, cerebral blood flow) will be assessed in fasted conditions and endothelial function will also be measured in postprandial state after consumption of study products together with a challenge meal known to induce a transient endothelial dysfunction. Hesperidin bioavailability in biofluids will be measured and correlated with the vascular response and with changes in systemic biomarkers associated to vascular health and CVD risk. This study will also allow the identification of the underpinning molecular mechanisms of the vascular responsiveness (through nutrigenomic analysis, oxylipins profiling), and of new bioactive compounds (beyond flavanones) of potential interest for vascular health (through food metabolome profiling), as well as of changes in the gut microbiota composition. The generated data will allow to reveal correlations between the gut microbiota composition, the metabolism of hesperidin, the food metabolome profiles and the vascular response. In brief, HESPER-HEALTH will provide further and original insights into the role of hesperidin-rich foods like orange juice as part of healthy diets.

Partners

• French National Research Institute for Agriculture, Food and Environment (INRAE) – Human Nutrition Unit, Clermont-Ferrand, France - Dragan Milenkovic (coordination), UMR454 MEDiS Pascale Mosoni & Pierre Peyret (partners)
• Geisenheim University – Department of Beverage Research, Chair of Analysis & Technology of Plant-based Foods, Germany - Ralf Schweiggert (Joint lead tenderer)
• Clinical Investigation Center (CIC) - Inserm 1405 - University hospital of Clermont-Ferrand, France - Gisèle Pickering & Claude Dubray (Joint lead tenderer)