Histological evaluation of a topically applied retinol-vitamin C combination

Skin Pharmacol Physiol. 2005 Mar-Apr;18(2):81-7. doi: 10.1159/000083708.


Two double-blind studies versus vehicle were carried out to investigate the effects of a topically applied retinol plus vitamin C combination on epidermal and dermal compartments of aged or photoaged human skin. The two studies were performed on postmenopausal women who were selected for treatment based on the mild level of elastosis of their facial skin. At completion of treatment, skin biopsies were collected and processed for classical histology and immunohistochemistry. In the first study (aged skin), 8 volunteers applied the retinol- and vitamin C-containing preparation on the ventral side of one elbow and the vehicle on the other elbow twice daily for 3 months. After the 3-month treatment we observed histological changes mainly within the epidermis. The stratum corneum was thinner with a compact pattern, whereas the epidermal proliferation increased, resulting in a thickening of the viable epidermis. Moreover, the interdigitation index was increased. In the second study (photoaged skin), 11 volunteers were divided in two groups; one applied the retinol- and vitamin C-containing preparation and the other one the vehicle on their face twice daily for 6 months. Facial skin samples presented histologic hallmarks of photoaging, i.e. accumulation of elastotic material in the papillary dermis. After the 6-month topical treatment, the observed histological changes were mainly concentrated at the dermal level. Both treated and control groups showed the same distribution pattern of type I procollagen, however, the high level of type III procollagen originally observed in photoaged skin was reduced in the retinol- and vitamin C-treated group, resulting in a lower type III-to-type I procollagen ratio. Furthermore, a wide band of eosinophilic material just beneath the epidermis, devoid of oxytalan fibers and forming the 'grenz zone', appeared more frequently and was larger in the retinol- and vitamin C-treated group. In conclusion, our results show that repeated topical application of a preparation containing both retinol and vitamin C is able to reverse, at least in part, skin changes induced by both chronologic aging and photoaging.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Cutaneous*
  • Ascorbic Acid / administration & dosage*
  • Ascorbic Acid / chemistry
  • Ascorbic Acid / pharmacokinetics
  • Ascorbic Acid / therapeutic use
  • Biopsy
  • Drug Administration Schedule
  • Drug Combinations*
  • Drug Evaluation / methods
  • Elbow / pathology
  • Face / pathology
  • Facial Dermatoses / drug therapy
  • Facial Dermatoses / etiology
  • Facial Dermatoses / pathology
  • Female
  • Humans
  • Immunohistochemistry / methods*
  • Middle Aged
  • Postmenopause
  • Skin / drug effects
  • Skin / pathology
  • Skin / ultrastructure
  • Skin Aging / drug effects*
  • Skin Aging / pathology*
  • Sunlight / adverse effects
  • Time Factors
  • Vitamin A / administration & dosage*
  • Vitamin A / chemistry
  • Vitamin A / pharmacokinetics
  • Vitamin A / therapeutic use


  • Drug Combinations
  • Vitamin A
  • Ascorbic Acid