Regulation of Vitamin C Homeostasis during Deficiency

Abstract

Large cross-sectional population studies confirm that vitamin C deficiency is common in humans, affecting 5%–10% of adults in the industrialized world. Moreover, significant associations between poor vitamin C status and increased morbidity and mortality have consistently been observed. However, the absorption, distribution and elimination kinetics of vitamin C in vivo are highly complex, due to dose-dependent non-linearity, and the specific regulatory mechanisms are not fully understood. Particularly, little is known about how adaptive mechanisms during states of deficiency affect the overall regulation of vitamin C transport in the body. This review discusses mechanisms of vitamin C transport and potential means of regulation with special emphasis on capacity and functional properties, such as differences in the Km of vitamin C transporters in different target tissues, in some instances demonstrating a tissue-specific distribution.

Developmental study of vitamin C distribution in children's brainstems by immunohistochemistry

“…Humans, non-human primates (including macaque monkeys), and guinea pigs cannot synthesize ascorbate from glucose, unlike other animals that have the enzyme required for the last step in ascorbate biosynthesis. The uptake and distribution of Vit C in the body is under homeostatic control and is regulated by tissue-specific sodium-dependent Vit C co-transporters (SVCT) 1 and 2, which actively transport Vit C (Tsukaguchi et al, 1999;Fischer et al, 2004;Corti et al, 2010;Lindblad et al, 2013). In the body, Vit C displays complex non-linear pharmacokinetics, and in brain tissue the Vit C is present at higher concentrations than in other organs (Kaufman, 1966;Spector, 1977;Schreiber and Trojan, 1991;Lindblad et al, 2013).…”

“…The uptake and distribution of Vit C in the body is under homeostatic control and is regulated by tissue-specific sodium-dependent Vit C co-transporters (SVCT) 1 and 2, which actively transport Vit C (Tsukaguchi et al, 1999;Fischer et al, 2004;Corti et al, 2010;Lindblad et al, 2013). In the body, Vit C displays complex non-linear pharmacokinetics, and in brain tissue the Vit C is present at higher concentrations than in other organs (Kaufman, 1966;Spector, 1977;Schreiber and Trojan, 1991;Lindblad et al, 2013). Additionally, the brain is able to preferentially retain Vit C at the expense of other tissues during chronic states of severe deficiency, and to uphold concentrations 100-fold higher than other organs, which are readily depleted (Hughes et al, 1971;Lykkesfeldt et al, 2007).…”

Pharmacokinetic and anti-cancer properties of high dose ascorbate in solid tumours of ascorbate-dependent mice

“…The SVCTs show distinct tissue distribution, and together ensure the effective uptake and regulation of plasma and cellular ascorbate concentrations [36,35]. SVCT1 is responsible for uptake through the gut and re-absorption in the kidneys, and is thought to largely regulate plasma levels, whereas SVCT2 is concentrated in more metabolically active cells throughout the body, ensuring an adequate intracellular supply to support crucial intracellular functions [36,35]. Both SVCT1 and SVCT2 have been found in lung tissue, with SVCT1 being identified solely in the blood vessels in one study [37], and on the apical surfaces of rat lung columnar epithelial cells in another study [52], both reporting widespread distribution of SVCT2.…”

“…The SVCTs show distinct tissue distribution, and together ensure the effective uptake and regulation of plasma and cellular ascorbate concentrations [36,35]. SVCT1 is responsible for uptake through the gut and re-absorption in the kidneys, and is thought to largely regulate plasma levels, whereas SVCT2 is concentrated in more metabolically active cells throughout the body, ensuring an adequate intracellular supply to support crucial intracellular functions [36,35].…”

Poor Vitamin C Status Late in Pregnancy Is Associated with Increased Risk of Complications in Type 1 Diabetic Women: A Cross-Sectional Study

“…VitC is thought to be actively transported by SVCT transporters in the placenta [50]; however, it also shares the same transporters as glucose via the GLUT-mediated transport of dehydroascorbic acid (DHA; the oxidized form of vitC) [51]. Thus, it may be speculated that the degree of glycemic control and, consequently, the level of oxidative stress and ascorbate oxidation rate may affect the bioavailability of vitC in T1DM pregnant women through competitive inhibition of DHA transport as proposed by Mann and Newton already in 1975 [52] and supported by the NHANES study 2003–2006 data [53]; here an inverse relationship between vitC and HbA1c was reported in 7697 non-diabetic participants.…”