Background: the topical use of vitamin C has been explored for many decades due to its antioxidant potential, whitening action, and the essential role it plays in the synthesis and maintenance of collagen. As Ascorbic Acid (AA) is unstable, derivative molecules and stabilization strategies have been explored to facilitate its incorporation into dermatological products. Even though these molecules are already for sale, there is still a shortage of scientific data regarding efficacy studies of these assets, especially in vivo. Objective: the purpose of this review was to investigate and discuss issues regarding the topical application of vitamin C and its most common derivatives, including the difficulties, biases, and prospects for future clinical studies to better elucidate its effects. Method: a literature review was carried out to select studies that evaluated the topical use of ascorbic acid and/or its derivatives. The studies which are “fully available”, “in vivo”, and “in vitro” were used as inclusion criteria. Results: due to the instability of Ascorbic Acid, it is essential to study derivative molecules that maintain or even improve their effectiveness in dermatological products. Despite this, the studies of these derivatives, presented in the scientific literature, are mostly in vitro. In recent years, it has been possible to observe an increase in in vivo efficacy tests, and this trend is expected to continue in the future. However, they present very different approaches and issues. Conclusion: studies of stability, safety, adverse reactions, and especially in vivo efficacy studies with a relevant number of subjects and standardized parameters are essential for better elucidating the effects of the topical application of vitamin C derivatives in comparison with ascorbic acid formulations for the skin.
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