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

Arch Dermatol. 2007;143(5):606-612.

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

Author Affiliations: 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.

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