Article 2 (Regarding Retinol)
Dermatology Times July, 2000
Author: Cheryl Guttman

San Francisco -- Cosmeceuticals containing appropriate concentrations of stabilized retinol can yield perceivable improvement in visible signs of photoaging when used on a daily basis, and are more user-friendly than prescription retinoic acid products, Patricia Farris, M.D., said at the annual meeting of the American Academy of Dermatology.

"There remains a lot of skepticism regarding the efficacy of retinol. Clearly, this vitamin is not a facelift in a bottle, but I believe there are convincing scientific data to show it has antiaging activity. Further, in my own clinical experience, I have been impressed by its tolerability and my observations that it does work," said Dr. Farris, a private practitioner in New Orleans.

She noted that on a theoretical basis, retinol may be predicted to be effective for reversing the signs of aging skin, since vitamin A is known to be important in epidermal growth and proliferation, as well as for maintenance of dermal connective tissue integrity. Further, retinol is enzymatically converted in human skin to retinoic acid, and there is an abundance of proof regarding the antiaging efficacy of that vitamin A derivative.

Dose-related results

The results of a series of studies conducted by researchers from the University of Michigan department of dermatology provide further evidence that retinol may offer clinical benefits. In these investigations examining the biologic activity profile of retinol in skin, Sewon Kang, M.D., John Voorhees, M.D., and their colleagues found that retinol had a dose-related effect on inducing epidermal hyperplasia when applied to normal buttock skin. At the highest concentration tested, 1.6 percent, retinol mimicked the activity of retinoic acid 0.025 percent on epidermal thickening. Like retinoic acid, retinol also enhanced expression of cellular retinoic acid binding protein II and cellular retinol-binding protein. However, retinol, unlike retinoic acid, caused no clinically significant erythema, even at the 1.6 percent concentration.

Further studies demonstrated that retinol, like retinoic acid, mitigated the collagen degradation that is induced by UV light exposure.

"Irradiation of human skin with UV light leads to upregulation of c-jun and through a series of events results in upregulation of matrix metalloproteinases (MMPs) that mediate collagen degradation. Pretreatment of human skin prior to UV exposure with either retinoic acid 0.025 percent or retinol 1 percent was noted to prevent c-jun upregulation and the resultant increase of MMP activity and collagen degradation," Dr. Farris said.

Retinol-induced repair

More recently, the University of Michigan group demonstrated that retinol may induce repair of intrinsically aged skin as well. These investigations showed that the features of chronologic aging are very similar to those associated with photoaging and include decrease in interstitial fibroblasts, thinning of collagen bundles, reduced collagen formation, and increased collagen degradation.

Treatment of the intrinsically aged skin with retinol 1 percent induced epidermal hyperplasia, increased colony formation of both keratinocytes and fibroblasts, increased expression of procollagen I and III, and reduced levels of MMPs.

Dr. Farris acknowledged that the concentrations of retinol investigated in these laboratory studies are much higher than those found in any commercially available cosmeceuticals. Unfortunately, there is little to no data from double-blind, controlled studies to demonstrate the clinical efficacy of retinol-containing products, she added.

"The fact is the ability to market these OTC preparations is not dependent on producing the same type of efficacy documentation that is mandatory for prescription medications. So, there is no real incentive for manufacturers to undertake these expensive trials," Dr. Farris said.

Study shows satisfaction

Aside from her own favorable experience with retinol use, which now encompasses more than 600 patients, Dr. Farris cited the unpublished results of a study performed by Albert Kligman, M.D. In this small, industry-sponsored trial, women using a product containing 0.15 percent retinol for three months were observed to have about 50 percent improvement in surface roughness, 30 percent improvement in fine lines and wrinkles, and 35 percent improvement in lentigines, she reported.

Retinol is highly unstable to light and oxygen, and, until fairly recently, could not be incorporated in cosmetic products. However, thanks to developments in formulation technology, retinol is now stable and available in a plethora of products available at retail outlets and through office dispensing in concentrations ranging from 0.05 to 0.6 percent. (Note: Young Again's Retinol Anti-Aging Skin Cream is 1.0 or 1.0 percent)

Based on her clinical observations, Dr. Farris suggested that to achieve appreciable results, patients should probably be started on a product containing retinol at a concentration of at least 0.1 or 0.15 percent.

Better efficacy may be achieved with higher concentrations, but since there does seem to be some dose-dependent potential for irritation, the dose can be titrated to a more concentrated preparation based on tolerability.

Dr. Farris is a consultant for Advanced Polymer Systems and Bioglan, companies that market retinol products. She has also consulted in the past for Ortho.

FOR MORE INFORMATION

* Varani J, et al. J Invest Dermatol 2000;114(3):480-486.

* Kang S, et al. J Invest Dermatol 1995;105(4):549-556.