Submitted to: Journal of Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/6/2002
Publication Date: N/A
Interpretive Summary: Vitamin C is essential for human health. To prevent the fatal deficiency disease scurvy, humans must ingest the vitamin and transport it across the intestinal lumen. Recently, two human sodium-dependent vitamin C transporters were cloned, and one of the transporters (SVCT1) is likely responsible for vitamin C absorption. Primary food sources of vitamin C are fruits and vegetables. Fruits and vegetables are also major sources of flavonoids. Vitamin C accumulation is likely to be inhibited by flavonoids in tumor cell lines, but the affected transporters and physiologic relevance were unclear. Because the dominant vitamin C transporter for absorption is SVCT1 and because the gastrointestinal tract is exposed to high concentrations of dietary flavonoids, we investigated flavonoid inhibition of SVCT1 overexpressed in chinese hamster ovary cells and in Xenopus laevis oocytes. The data indicate that flavonols are potent non- competitive and reversible inhibitors of SVCT1 at concentrations predicted from dietary ingestion. The Food and Nutrition Board of the U.S. National Academy of Sciences recently published intake guidelines for vitamin C, including recommended dietary allowances (RDAs). The calculations of RDAs were based in part on vitamin C absorption, or bioavailability. Flavonoids may change vitamin C bioavailability by modifying its transport within the intestinal lumen. Therefore, outcomes of this study provides essential data for affecting recommendations for vitamin C intake.
Technical Abstract: Although vitamin C is readily absorbed, the effects of food components on vitamin C absorption are unknown. Flavonoids are widely abundant in plant-derived foods, and their functions are uncertain. We postulated that flavonoids have a novel regulatory function of inhibiting vitamin C absorption. We investigated the effects of flavonoids on an intestinal vitamin C transporter using Chinese hamster ovary cells overexpressing the vitamin C transporter. Flavonoids reversibly inhibited vitamin C transport in the cells at the micromolar ranges of concentrations. Because Chinese hamster ovary cells have endogenous vitamin C transport, we expressed the vitamin C transporter in Xenopus laevis oocytes to study the mechanism of transport inhibition. A flavonoid, quercetin, was a reversible, non-competitive, and specific inhibitor of ascorbate transport, because it did not inhibit other glucose transporters that were injected and expressed in Xenopus oocytes. These data show for the first time that food components modulate vitamin C transport by its specific intestinal transporter. Clinical trials will be appropriate to investigate whether flavonoids regulate vitamin C absorption in humans, and outcomes of such studies may affect recommendations for vitamin C intake.