Clinical evidence of the vascular protective effects of grapefruit flavanones in post-menopausal women and potential molecular mechanisms involved

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Milenkovic, Dragan | Habauzit, Veronique | Monfoulet, Laurent-Emmanuel | Verny, Marie-Anne | Bayle, Dominique | Valéro, Séverine | Boby, Céline | Barber Chamoux, Nicolas | Mazur, André | Dubray, Claude | Morand, Christine

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This study was supported by a grant from the Florida Department of Citrus (FDOC), USA.
This study was supported by a grant from the Florida Department of Citrus (FDOC), USA.. Epidemiological studies reported that a high flavanone intake is associated with a reduced risk ofcardiovascular diseases (Mink et al, 2007; Cassidy et al, 2012), however clinical evidence is stilllacking. We carried out a cross-over RCT on 52 healthy post-menopausal women who have toconsumed daily and for 6-month, 340ml of grapefruit juice (providing 212mg naringenin-glycosides) orof an iso-energetic control beverage mimicking the composition of the juice but without naringenin.The aim of this trial was to evaluate the impact of GFJ consumption (i) on vascular function (bloodpressure, endothelial function and arterial stiffness) and (ii) on the gene and miRNA expression inPBMCs isolated from enrolled volunteers using microarrays.The intervention with GFJ improved pulse wave velocity (PWV), an indicator of arterial stiffness,without affecting endothelial function (FMD) or blood pressure. The nutrigenomic study showed thatthe regular intake of naringenin through GFJ consumption modulated the expression of genes andmiRNAs in PBMCs. Bioinformatic analysis of microarray data revealed that the differentially expressedgenes and the target genes of modulated miRNAs are involved in different cellular processes,including inflammatory processes, chemotaxis, migration and cell adhesion, known to regulateinteractions between vascular endothelium and circulating immune cells. The observed changes ingenes and miRNAS expression profiles suggest a lower adhesion and infiltration of immune cells intothe vascular wall. This hypothesis is strengthened by results obtained from cell studies usingnaringenin metabolites and showing their ability to reduce the adhesion of monocytes to activatedendothelial cells.This study showed that a regular consumption of grapefruit juice by healthy postmenopausal women isbeneficial for central aortic stiffness and that this effect may be related to flavanones. The molecularmechanisms showed as modulated by flavanones may be potentially involved in the beneficial effectof grapefruit naringenin on vascular health in human.

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