Vitamin A (Retinol) Effaces Wrinkles in Naturally Aged Skin from MEDSCAPE

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Vitamin A (Retinol) Effaces Wrinkles in Naturally Aged Skin

May 29, 2007 — Topical vitamin A (retinol) effaces fine wrinkles associated with natural aging, according to the results of a small randomized trial in elderly patients published in the May issue of the Archives of Dermatology.

"Because accelerated skin aging due to excessive sun exposure has marked collagen deficiency and effective treatments for photoaging promote procollagen synthesis, we hypothesized that similar therapies might also improve the collagen deficiency found in intrinsic aging," write Reza Kafi, MD, from the University of Michigan Medical School in Ann Arbor, and colleagues.

"Compared with retinoic acid, the ability of retinol to induce skin irritation is notably less, at least according to a 4-day patch test (an occlusive treatment). Thus, retinol has the potential to deliver retinoic acid–like effects to human skin with improved tolerability."

In this double-blind, vehicle-controlled, left-and-right-arm comparison study at an academic referral center, 36 elderly participants received topical 0.4% retinol lotion or its vehicle applied at each visit by study personnel to either the right or the left arm, as often as 3 times weekly for 24 weeks. Mean age was 87 years, and all patients lived in 1 of 2 senior citizen facilities.

Primary endpoints were clinical assessment using a semiquantitative scale (0, none; 9, most severe) and biochemical measurements from skin biopsy specimens obtained from treated areas. Analysis was by intent-to-treat, using the last-observation-carried-forward method.

After 24 weeks, changes in fine wrinkling scores were different between retinol-treated and vehicle-treated skin (-1.64 [95% confidence interval [CI], -2.06 to -1.22] vs -0.08 [95% CI, -0.17 to 0.01]; P < .001). In a subgroup, retinol treatment was associated with increased glycosaminoglycan expression (P = .02 [n = 6]) and procollagen I immunostaining (P = .049 [n = 4]) compared with vehicle.

The retinol preparation was relatively well tolerated.

"Topical retinol improves fine wrinkles associated with natural aging," the authors write. "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."

The Babcock Endowment for Dermatologic Research, the Merck-American Federation for Aging Research, Alpha Omega Alpha Student Research Fellowship, and the National Institutes of Health supported this study. Four of the authors have disclosed being named inventors on an issued patent application concerning methods of treating skin aging, and 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.

Arch Dermatol. 2007;143:606-612.

Learning Objectives for This Educational Activity

Upon completion of this activity, participants will be able to:

Describe skin changes associated with aging.

Identify the effects of topical retinol lotion on naturally aged skin.

Clinical Context

The skin undergoes profound changes as adults grow older. These changes are most noticeable in sun-exposed areas, but other unexposed areas change as well. Generally, skin grows thinner and more finely wrinkled with time. The epidermis and dermis become thinner, and the number of keratinocytes and fibroblasts declines. Collagen formation is therefore decreased, and, moreover, there is a qualitative fragmentation of dermal collagen fibers in the skin of older adults.

Retinoic acid can improve skin damaged by the sun, but it has not been extensively tested in skin that ages without sun exposure. The current study addresses this subject.

Study Highlights

Patients eligible for study participation were 80 years or older, in relatively good health, and free of skin diseases affecting the upper extremity. Patients who had used topical medications within 2 weeks of study entry or hormone therapy in the past 6 months were excluded from the study.

Study participants were randomized to receive topical 0.4% retinol lotion or its vehicle as often as 3 times per week for 24 weeks. Approximately 2 mL of either treatment were applied to the upper inner arm for 24 weeks. Participants who complained of skin irritation had their treatment held, and participants who had more than 2 weeks of irritation were terminated from the study.

Dermatologists blinded to study therapy assessed tactile roughness, fine wrinkling, and overall severity of aging at 2, 4, 8, 16, and 24 weeks after randomization. Participants also underwent skin biopsies at baseline and 24 weeks to assess the effects of retinol lotion on levels of glycosaminoglycans and procollagen I.

36 adults entered the study. Mean age was 87 years, and there were more than twice as many women as men. 13 individuals dropped out of the trial, with 3 of these dropouts resulting from adverse events related to retinol lotion.

Biopsy results indicated that retinol was active within the skin.

Fine wrinkling improved with retinol treatment, whereas there was little change in the control group. This benefit of retinol was evident at 4 weeks of treatment and continued through week 24.

Tactile roughness and overall severity were also improved with retinol vs placebo.

Retinol was associated with increased concentrations of glycosaminoglycans and procollagen I in biopsy specimens at 24 weeks vs placebo.

All patients in the retinol group had erythema at the application site, and most also reported peeling, pruritus, and dryness. However, most of these adverse events were classified as mild by patients.

In a subgroup of patients who were followed up after the trial, the clinical benefits of retinol therapy persisted to 12, but not 24, weeks after treatment.

Pearls for Practice

As skin ages, the epidermis and dermis become thinner, and the number of keratinocytes and fibroblasts declines. Collagen formation is therefore decreased, and there is a qualitative fragmentation of dermal collagen fibers in the skin.

The current study demonstrates that topical retinol can improve the degree of fine wrinkling, tactile roughness, and overall severity of changes in naturally aged skin unexposed to sunlight among older adults. This effect was probably mediated by increased concentrations of glycosaminoglycans and procollagen I induced by retinol treatment.