title: Vitamin C crosses the blood-brain barrier in the oxidized form through the glucose transporters.
abstract: Vitamin C concentrations in the brain exceed those in blood by 10-fold. In both tissues, the vitamin is present primarily in the reduced form, ascorbic acid. We identified the chemical form of vitamin C that readily crosses the blood-brain barrier, and the mechanism of this process. Ascorbic acid was not able to cross the blood-brain barrier in our studies. In contrast, the oxidized form of vitamin C, dehydroascorbic acid (oxidized ascorbic acid), readily entered the brain and was retained in the brain tissue in the form of ascorbic acid. Transport of dehydroascorbic acid into the brain was inhibited by d-glucose, but not by l-glucose. The facilitative glucose transporter, GLUT1, is expressed on endothelial cells at the blood-brain barrier, and is responsible for glucose entry into the brain. This study provides evidence showing that GLUT1 also transports dehydroascorbic acid into the brain. The findings define the transport of dehydroascorbic acid by GLUT1 as a mechanism by which the brain acquires vitamin C, and point to the oxidation of ascorbic acid as a potentially important regulatory step in accumulation of the vitamin by the brain. These results have implications for increasing antioxidant potential in the central nervous system.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. d-agus@ski.mskcc.org
authors.forename: D B
authors.initials: DB
authors.lastname: Agus
authors.forename: S S
authors.initials: SS
authors.lastname: Gambhir
authors.forename: W M
authors.initials: WM
authors.lastname: Pardridge
authors.forename: C
authors.initials: C
authors.lastname: Spielholz
authors.forename: J
authors.initials: J
authors.lastname: Baselga
authors.forename: J C
authors.initials: JC
authors.lastname: Vera
authors.forename: D W
authors.initials: DW
authors.lastname: Golde
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000493:pharmacokinetics*; D001345:Autoradiography; D001812:Blood-Brain Barrier; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002199:Capillary Permeability; D003683:Dehydroascorbic Acid / Q000493:pharmacokinetics*; D003847:Deoxyglucose / Q000494:pharmacology; D051272:Glucose Transporter Type 1; D007091:Image Processing, Computer-Assisted; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D010084:Oxidation-Reduction; D011859:Radiography; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
chemical_list: D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495678:Slc2a1 protein, mouse; C495679:Slc2a1 protein, rat; D003847:Deoxyglucose; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid