A new lipophilic pro-vitamin C, tetra-isopalmitoyl ascorbic acid (VC-IP), prevents UV-induced skin pigmentation through its anti-oxidative properties

J Dermatol Sci. 2006 Oct;44(1):37-44. doi: 10.1016/j.jdermsci.2006.07.001. Epub 2006 Aug 28.


Background: Vitamin C, which is a strong anti-oxidant, plays an important role in maintaining physiological states. In dermatology, Vitamin C is used for treatment of various skin problems such as de-pigmentation of hyperpigmented spots. However, Vitamin C has limited stability and permeability, and development of a Vitamin C derivative with improved properties is needed.

Objective: We evaluated the effect of a lipophilic Vitamin C derivative, tetra-isopalmitoyl ascorbic acid (VC-IP), on ultraviolet (UV)-induced skin pigmentation, to determine its potential as a more effective form of Vitamin C.

Methods: The release of Vitamin C from VC-IP was examined using a reconstructed skin model following topical application of VC-IP. Anti-oxidative and anti-inflammatory activities of VC-IP were tested in cultured human keratinocytes. Subsequently, clinical test was done to clarify the effect of VC-IP on UVB-induced skin pigmentation.

Results: VC-IP released Vitamin C in physiological conditions and worked as pro-Vitamin C. In subsequent experiments, we found that VC-IP suppressed the elevation of intracellular peroxide after UVB irradiation, and enhanced cellular tolerance against UVB and reactive oxygen species such as hydrogen peroxide and tert-butyl hydroperoxide. Furthermore, VC-IP reduced the production of interleukin-1alpha and prostaglandin E2 in UVB-irradiated keratinocytes and suppressed melanocyte proliferation in conditioned culture medium prepared from UVB-irradiated keratinocytes. Finally, in a clinical study, topical application of a 3% VC-IP cream for 3 weeks suppressed pigmentation after UVB irradiation.

Conclusions: These results demonstrate that VC-IP is a precursor of Vitamin C, and effectively suppresses UVB-induced skin pigmentation, possibly through its anti-oxidative activity.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Antioxidants / administration & dosage*
  • Antioxidants / chemistry
  • Antioxidants / pharmacokinetics
  • Ascorbic Acid / administration & dosage
  • Ascorbic Acid / analogs & derivatives*
  • Ascorbic Acid / chemistry
  • Ascorbic Acid / metabolism
  • Ascorbic Acid / pharmacokinetics
  • Cell Division
  • Cell Line, Transformed
  • Dinoprostone / metabolism
  • Female
  • Glycolipids / administration & dosage*
  • Glycolipids / chemistry
  • Glycolipids / pharmacokinetics
  • Humans
  • Interleukin-1alpha / metabolism
  • Keratinocytes / cytology
  • Keratinocytes / drug effects*
  • Keratinocytes / radiation effects
  • Male
  • Melanocytes / drug effects
  • Melanocytes / metabolism
  • Melanocytes / radiation effects
  • Oxidative Stress / drug effects
  • Skin Pigmentation / drug effects*
  • Skin Pigmentation / radiation effects
  • Sugar Acids
  • Ultraviolet Rays


  • Antioxidants
  • Glycolipids
  • Interleukin-1alpha
  • Sugar Acids
  • tetra-isopalmitoyl ascorbic acid
  • provitamin C
  • Dinoprostone
  • Ascorbic Acid