The pharmacology of vitamin C.

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Ascorbic acid, the reduced form of vitamin C, is a ubiquitous small carbohydrate. Despite decades of focused research, new metabolic functions of this universal electron donor are still being discovered and add to the complexity of our view of vitamin C in human health. Although praised as an unsurpassed water-soluble antioxidant in plasma and cells, the most interesting functions of vitamin C seem to be its roles as specific electron donor in numerous biological reactions ranging from the well-known hydroxylation of proline to cofactor for the epigenetic master regulators ten-eleven translocation enzymes and Jumonji domain-containing histone-lysine demethylases. Some of these functions may have important implications for disease prevention and treatment and have spiked renewed interest in, eg, vitamin C's potential in cancer therapy. Moreover, some fundamental pharmacokinetic properties of vitamin C remain to be established including if other mechanisms than passive diffusion governs the efflux of ascorbate anions from the cell. Taken together, there still seems to be much to learn about the pharmacology of vitamin C and its role in health and disease. This review explores new avenues of vitamin C and integrates our present knowledge of its pharmacology. SIGNIFICANCE STATEMENT: Vitamin C is involved in multiple biological reactions of which most are essential to human health. Hundreds of millions of people are considered deficient in vitamin C according to accepted guidelines, but little is known about the long-term consequences. Although the complexity of vitamin C's physiology and pharmacology has been widely disregarded in clinical studies for decades, it seems clear that a deeper understanding of particularly its pharmacology holds the key to unravel and possibly exploit the potential of vitamin C in disease prevention and therapy.