Abstract
The pharmacokinetics of vitamin C (vitC) is indeed complex. Regulated primarily by a family of saturable sodium dependent vitC transporters (SVCTs), the absorption and elimination are highly dose-dependent. Moreover, the tissue specific expression levels and subtypes of these SVCTs result in a compartmentalized distribution pattern with a diverse range of organ concentrations of vitC at homeostasis ranging from about 0.2 mM in the muscle and heart, and up to 10 mM in the brain and adrenal gland. The homeostasis of vitC is influenced by several factors, including genetic polymorphisms and environmental and lifestyle factors such as smoking and diet, as well as diseases. Going from physiological to pharmacological doses, vitC pharmacokinetics change from zero to first order, rendering the precise calculation of dosing regimens in, for example, cancer and sepsis treatment possible. Unfortunately, the complex pharmacokinetics of vitC has often been overlooked in the design of intervention studies, giving rise to misinterpretations and erroneous conclusions. The present review outlines the diverse aspects of vitC pharmacokinetics and examines how they affect vitC homeostasis under a variety of conditions.
Highlights
Humans rely solely on dietary intake for the maintenance of the body pool of vitamin C.In contrast to the vast majority of vertebrates, in which l-gulonolactone oxidase catalyzes the final step in the biosynthesis of ascorbic acid, evolutionally conserved deletions have made the corresponding gene inactive in primates, flying mammals, guinea pigs, and some bird and fish species, thereby disabling its formation [1]
This evolutionary event may have resulted in an adaptational process where our ability to prevent vitamin C (vitC) deficiency has been improved by various measures changing the pharmacokinetics, including more efficient absorption, recycling, and renal reuptake of vitC compared to vitC synthesizing species [2,3]
The majority of intestinal uptake, tissue distribution, and renal reuptake is handled by the sodium-dependent vitC transporter (SVCT) family of proteins [4] that cotransports sodium ions and ascorbate (ASC) across membranes with the ability to generate considerable concentration gradients [5,6]. It is the differential expression, substrate affinity, and concentration dependency of the sodium dependent vitC transporters (SVCTs) between organs that gives rise to the unique compartmentalization and nonlinear pharmacokinetics of vitC at physiological levels [7]
Summary
Humans rely solely on dietary intake for the maintenance of the body pool of vitamin C (vitC). In contrast to the vast majority of vertebrates, in which l-gulonolactone oxidase catalyzes the final step in the biosynthesis of ascorbic acid, evolutionally conserved deletions have made the corresponding gene inactive in primates, flying mammals, guinea pigs, and some bird and fish species, thereby disabling its formation [1] This evolutionary event may have resulted in an adaptational process where our ability to prevent vitC deficiency has been improved by various measures changing the pharmacokinetics, including more efficient absorption, recycling, and renal reuptake of vitC compared to vitC synthesizing species [2,3]. The majority of intestinal uptake, tissue distribution, and renal reuptake is handled by the sodium-dependent vitC transporter (SVCT) family of proteins [4] that cotransports sodium ions and ascorbate (ASC) across membranes with the ability to generate considerable concentration gradients [5,6]. The present review outlines the pharmacokinetics of vitC under various conditions and discusses how it affects the vitC status
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