title: Effects of ascorbic acid on gingival melanin pigmentation in vitro and in vivo.
abstract: 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).
  
  
  CONCLUSIONS
  Ascorbic acid (AS-G) has potential for the treatment of gingival melanin pigmentation.
authors.affiliation: Division of Periodontology, Niigata University Graduate School of Medical and Dental Sciences, Niigata-shi, Niigata, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Shimada
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tai
authors.forename: Aya
authors.initials: A
authors.lastname: Tanaka
authors.forename: Ikuyo
authors.initials: I
authors.lastname: Ikezawa-Suzuki
authors.forename: Keiji
authors.initials: K
authors.lastname: Takagi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Yoshie
mesh_terms: D000328:Adult; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004311:Double-Blind Method; D005260:Female; D005782:Gels; D005882:Gingival Diseases / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008543:Melanins / Q000037:antagonists & inhibitors; D008548:Melanosis / Q000188:drug therapy*; D051379:Mice; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors; D012880:Skin Pigmentation; D013053:Spectrophotometry
chemical_list: D000975:Antioxidants; D005782:Gels; D008543:Melanins; C065378:ascorbic acid 2-O-glucoside; D014442:Monophenol Monooxygenase; D001205:Ascorbic Acid