Improvement of Naturally Aged Skin With Vitamin A (Retinol)

Kafi, Reza MD
Kwak, Heh Shin R. MD
Schumacher, Wendy E. BS
Cho, Soyun MD, PhD
Hanft, Valerie N. MD
Hamilton, Ted A. MS
King, Anya L. MS
Neal, Jacqueline D. BSE
Varani, James PhD
Fisher, Gary J. PhD
Voorhees, John J. MD, FRCP
Kang, Sewon MD

Department of Dermatology, University of Michigan Medical School, Ann Arbor. Drs Kafi and Kwak are now with the Department of Dermatology, Stanford Medical School, Palo Alto, Calif, and Dr Cho is now with the Department of Dermatology, Seoul National University, Seoul, South Korea.

Correspondence: Sewon Kang, MD, University of Michigan Medical School, Department of Dermatology, 1910 Taubman Center, 1500 E Medical Center Dr, Ann Arbor, MI 48109 ([email protected]).

Author Contributions:Study concept and design: Kafi, Neal, Varani, Fisher, Voorhees, and Kang. Acquisition of data: Kafi, Kwak, Schumacher, Cho, Neal, Varani, Fisher, and Kang. Analysis and interpretation of data: Kafi, Kwak, Hamilton, King, Varani, Fisher, Voorhees, and Kang. Drafting of the manuscript: Kafi, Kwak, Schumacher, Neal, and Kang. Critical revision of the manuscript for important intellectual content: Kafi, Cho, Hamilton, King, Varani, Fisher, Voorhees, and Kang. Statistical analysis: Hamilton and King. Obtained funding: Kafi, Voorhees, and Kang. Administrative, technical, and material support: Kafi, Kwak, Schumacher, Cho, King, Neal, Varani, Fisher, Voorhees, and Kang. Study supervision: Kafi, Voorhees, and Kang.

Financial Disclosure: Drs Fisher, Kang, Varani, and Voorhees are named inventors on an issued patent application concerning methods of treating skin aging. They will receive royalties under the University of Michigan's Intellectual Property Policy in the event that a commercial license is signed and a product is sold. This article describes research that was part of the basis of the approved application.

Funding/Support: This study was supported in part by grants from the Babcock Endowment for Dermatologic Research, the Merck-American Federation for Aging Research (Dr Kafi), Alpha Omega Alpha Student Research Fellowship (Dr Kafi), and the National Institutes of Health (K24, Dr Kang).

Accepted for Publication: October 19, 2006.

Archives of Dermatology 143(5):p 606-612, May 2007.

Objective

To evaluate the effectiveness of topical retinol (vitamin A) in improving the clinical signs of naturally aged skin.

Design

Randomized, double-blind, vehicle-controlled, left and right arm comparison study.

Setting

Academic referral center.

Patients

The study population comprised 36 elderly subjects (mean age, 87 years), residing in 2 senior citizen facilities.

Intervention

Topical 0.4% retinol lotion or its vehicle was applied at each visit by study personnel to either the right or the left arm, up to 3 times a week for 24 weeks.

Main Outcome Measures

Clinical assessment using a semiquantitative scale (0, none; 9, most severe) and biochemical measurements from skin biopsy specimens obtained from treated areas.

Results

After 24 weeks, an intent-to-treat analysis using the last-observation-carried-forward method revealed that there were significant differences between retinol-treated and vehicle-treated skin for changes in fine wrinkling scores (−1.64 [95% CI, −2.06 to −1.22] vs −0.08 [95% CI, −0.17 to 0.01]; P<.001). As measured in a subgroup, retinol treatment significantly increased glycosaminoglycan expression (P = .02 [n = 6]) and procollagen I immunostaining (P = .049 [n = 4]) compared with vehicle.

Conclusions

Topical retinol improves fine wrinkles associated with natural aging. Significant induction of glycosaminoglycan, which is known to retain substantial water, and increased collagen production are most likely responsible for wrinkle effacement. With greater skin matrix synthesis, retinol-treated aged skin is more likely to withstand skin injury and ulcer formation along with improved appearance.

Trial Registration

clinicaltrials.gov Identifier: NCT00272610