*2.2. Animal Studies Involving Ascorbic Acid*

Since it can be synthesized *de novo* and is not an essential nutrient for most animals, ascorbate should not be referred to as a vitamin in these animals. Conceptually, this questions the use of most experimental animal models, in particular rats and mice, to study the role of ascorbic acid in human health and disease [50]. This echoes recent studies that have cast doubt on the pervasive use of rodent models to mimic human inflammatory responses [51]. Although genetically variant strains incapable of synthesizing ascorbic acid have been established, none of these models fully recapitulate vitamin C transport functions or the effects of vitamin C depletion and repletion observed in humans or guinea pigs [50]. Indeed, there is evidence that regulation of vitamin C transport was altered during the evolutionary loss of L-gulonolactone oxidase (GULO) expression, which does not occur in genetic knockouts. Here, we examine the current issues related to the use of animal models in ascorbate research. Overall, if animals are to be used, the limitations imposed by the model should be well understood. Animal experiments should be avoided if comparable studies can be performed in human subjects.
