Vitamin C and
flavonoids,
polyphenols with uncertain function, are abundant in fruits and vegetables. We postulated that
flavonoids have a novel regulatory action of delaying or inhibiting absorption of
vitamin C and
glucose, which are structurally similar. From six structural classes of
flavonoids, at least 12 compounds were chosen for studies. We investigated the effects of selected
flavonoids on the intestinal
vitamin C transporter SVCT1(h) by transfecting and overexpressing SVCT1(h) in Chinese hamster ovary cells.
Flavonoids reversibly inhibited
vitamin C transport in transfected cells with IC(50) values of 10-50 microm, concentrations expected to have physiologic consequences. The most potent inhibitor class was
flavonols, of which
quercetin is most abundant in foods. Because Chinese hamster ovary cells have endogenous
vitamin C transport, we expressed SVCT1(h) in Xenopus laevis oocytes to study the mechanism of transport inhibition.
Quercetin was a reversible and non-competitive inhibitor of ascorbate transport; K(i) 17.8 microm.
Quercetin was a potent non-competitive inhibitor of GLUT2 expressed in Xenopus oocytes; K(i) 22.8 microm. When diabetic rats were administered
glucose with
quercetin,
hyperglycemia was significantly decreased compared with administration of
glucose alone.
Quercetin also significantly decreased ascorbate absorption in normal rats given ascorbate plus
quercetin compared with rats given ascorbate alone.
Quercetin was a specific transport inhibitor, because it did not inhibit intestinal
sugar transporters GLUT5 and SGLT1 that were injected and expressed in Xenopus oocytes.
Quercetin inhibited but was not transported by SVCT1(h). Considered together, these data show that
flavonoids modulate
vitamin C and
glucose transport by their respective intestinal transporters and suggest a new function for
flavonoids.