Effects of Ascorbic Acid on Gingival Melanin Pigmentation In Vitro and In Vivo

Background: Gingival melanin pigmentation may cause esthetic concerns, even if no serious medical problem is present. As an inhibitor of melanin formation, ascorbic acid is often used to treat skin melanin pigmentation. Thus, the present study investigated the effects of ascorbic acid on gingival melanin pigmentation in vitro and in vivo.Methods: The effects of ascorbic acid on melanin formation were evaluated in vitro in B16 mouse melanoma cells and three‐dimensional human skin models. In addition, a clinical trial was performed to investigate the inhibitory effects of a gel containing ascorbic acid 2‐glucoside (AS‐G gel) on gingival melanin pigmentation. This study used a double‐masked, split‐mouth design on 73 subjects with symmetric gingival melanin pigmentation. AS‐G gel was applied to one side of the gingiva for 12 weeks, whereas placebo gel was applied to the other side as a control. Luminance (L∗)‐value, which describes the lightness of gingiva, was determined by spectrophotometry to obtain an objective measure of melanin pigmentation every 4 weeks.Results: Ascorbic acid significantly inhibited tyrosinase activity and melanin formation in B16 mouse melanoma cells (P <0.01 and P <0.05, respectively). The inhibitory effects of ascorbic acid on melanin formation were also significant in three‐dimensional human skin models (P <0.01). Moreover, in the clinical trial, a significant relative change in pigmentation was seen after 4 weeks with the application of AS‐G gel compared to placebo (L∗‐value ratio).Conclusion: Ascorbic acid (AS‐G) has potential for the treatment of gingival melanin pigmentation.