Retinol Rejuvenation

Abstract & Commentary

By Allan J. Wilke, MD, Residency Program Director, Associate Professor of Family Medicine, University of Alabama at Birmingham School of Medicine—Huntsville Regional Medical Campus, Huntsville. Dr. Wilke reports no financial relationship to this field of study.

Synopsis: Application of vitamin A to naturally aged skin reduced fine wrinkling.

Source: Kafi R, et al. Improvement of naturally aged skin with vitamin A (retinol). Arch Dermatol. 2007;143:606-612.

Aged skin is more susceptible to shearing forces, because there is flattening of the rete ridges and subsequent loss of contact between the dermis and the epidermis. In the extracellular matrix, the quantity of protein, composed primarily of collagen, is decreased. This occurs through decreased production and increased catabolism. The collagen quality is degraded. There is also a decrease in dermal microcirculation. All of these factors contribute to poor or delayed wound healing and chronic ulceration. There is "naturally aged skin" (ie, skin that is generally shielded from the sun), and then there is photo-aged skin, where aging is accelerated. Compared to naturally aged skin, photo-aged skin has less procollagen. The fine wrinkling can be reversed with topical retinoids and laser resurfacing. Both treatments increase procollagen synthesis.

Kafi and colleagues at the University of Michigan Medical School Department of Dermatology hypothesized that similar therapy directed at naturally aged skin would increase its collagen content. Because laser resurfacing and the usually prescribed retinoids (retinoic acid and tazarotene) cause large wounds and irritation, respectively, when used on naturally aged skin, they decided to use all-trans-retinol, which is a retinoic acid precursor and known to cause less irritation. They enrolled 36 subjects, average age 87 years (range 80-96), 71% female, from two senior centers, excluding those who had used topical medication in the previous 2 weeks or, for women, hormonal therapy in the previous 6 months. Thirteen subjects did not complete the trial for a variety of reasons, but only 3 quit because of skin irritation. Each subject served as his/her own control. The subjects had 4-mm punch biopsies of both arms at baseline and at the end of the study. A 0.4% retinol lotion (mixed up by one of the investigators in his lab) was applied to the sun-protected, upper, inner arm; the vehicle lotion was applied to the other arm. Which arm received the active treatment was randomized. The subjects received treatment three times weekly for 24 weeks and were evaluated at 2, 4, 8, 16, and 24 weeks. The skin was examined by two blinded dermatologists (no jokes please!) for fine wrinkling, tactile roughness, and overall severity. These attributes were scored on a 10-point scale: 0, none; 1-3, mild; 4-6 moderate, 7-9 severe. At the beginning of the study, the fine wrinkling scores for treated and untreated arms averaged slightly more than 7. At the end of the study, the retinol-treated arms averaged 5.61; the untreated arms averaged 7.14. This was statistically significant. The other measures showed similar reductions. Mild adverse reactions (erythema, peeling, pruritis, dryness, burning/stinging) were noted by most participants. Staining for procollagen of the punch biopsies showed an increase in the retinol-treated arms.


This is a nice proof-of-concept trial, but it needs to be repeated in a larger group, and then we'll need evidence that the treatment prevents skin tears and ulcers and improves healing. The dropout rate for skin irritation (8%) doesn't seem too high, but since aging skin is already susceptible to pruritis secondary to decreased sebum production ("xerosis"), this treatment won't be for everyone. Although skin injury prevention was the stated goal of this study, fine wrinkling was the primary outcome measure. Skin products containing retinol are already marketed as a cure for wrinkles. How much are you willing to pay to change fine wrinkling from severe to moderate?