[PHNUTR-L] Vitamin A (Retinol) Effaces Wrinkles in Naturally Aged Skin

[Kathrynne Holden]

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Vitamin A (Retinol) Effaces Wrinkles in Naturally Aged Skin
http://www.medscape.com/viewarticle/557377?src=mp

News Author: Laurie Barclay, MD


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.
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.
-- 
Kathrynne Holden, MS, RD < fivestar at nutritionucanlivewith.com >
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