1. Van Wicklin, Sharon Ann PhD, RN, CNOR, CRNFA(E), CPSN-R, PLNC, FAAN, ISPAN-F

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Plastic Surgical Nursing(PSN), the official journal of the International Society of Plastic and Aesthetic Nurses (ISPAN), publishes this column to provide evidence-based answers to practice questions from plastic and aesthetic nurses.





Are over-the-counter cosmetic retinol products an effective treatment option for facial skin aging?




Over-the-counter cosmetic retinol products are not an effective treatment option for facial skin aging (Spierings, 2021). When providing treatment for patients with facial skin aging, plastic and aesthetic nurses should understand the product definitions and the differences between products that contain retinol and products that contain retinoids.


Definitions: Retinol, Retinoids, and Retinoic Acid

Retinol, also known as vitamin A, is a compound found in green and yellow vegetables, egg yolk, and fish liver oil (Spierings, 2021). It is the primary form of vitamin A that circulates throughout the body and is essential for growth and vision in dim light. Retinoids are natural or synthetic derivatives of vitamin A. Retinoid products contain retinoic acid, a metabolite of vitamin A, whereas retinol products contain retinyl esters (e.g., retinyl palmitate, retinaldehyde) that must be converted to retinoic acid. With one exception (i.e., adapalene; Galderma Laboratories LP, Fort Worth, TX), retinoids require a prescription, whereas retinols are available over-the-counter without a prescription.



Tretinoin is a synthetic retinoic acid that has been extensively investigated as a treatment option for preventing facial skin aging (Mukherjee et al., 2006). There is high-level scientific evidence, conducted over decades, demonstrating the microscopic anatomical effects of tretinoin on collagen synthesis, fibroblast activity, and the inhibition of matrix metalloproteinases (Spierings, 2021). In 2000, tretinoin 0.02% (Ortho-McNeil Pharmaceutical Corporation, Raritan, NJ) was approved by the U.S. Food and Drug Administration (FDA) as an adjunctive agent "for use in the mitigation (palliation) of fine facial wrinkles in patients who use comprehensive skin care and sunlight avoidance programs" (Ortho-McNeil Pharmaceutical Corporation, 2000, p. 2). Notably, the FDA-approved labeling states that tretinoin "does not eliminate wrinkles, repair sun damaged skin, reverse photoaging, or restore more youthful or younger skin" (p. 2). The FDA labeling further states,


In double-blinded, vehicle-controlled clinical studies, many patients in the vehicle group [i.e., the control group] achieved desired palliative effects on fine wrinkling of facial skin with the use of comprehensive skin care and sunlight avoidance programs including sunscreens, protective clothing, and non-prescription emollient creams. (p. 2)


The FDA considers an adjunctive agent to be a product that is used in combination with comprehensive skin care, sunlight avoidance, effective sunscreens (i.e., sunscreens with a minimum sun protection factor [SPF] of 15), and protective clothing (p. 2).


To determine the long-term safety and efficacy of 0.05% tretinoin emollient cream, Kang et al. (2005) conducted a 2-year, double-blind, randomized, placebo-controlled study of 204 participants between the ages of 30 and 75 years from 17 clinical sites. All participants had lightly pigmented skin (i.e., Fitzpatrick skin Type I, II, or III) with moderate to severe facial photodamage. The researchers defined facial photodamage as damage caused by repeated exposure to ultraviolet radiation from sunlight characterized by skin roughness, fine and coarse wrinkling, mottled hyperpigmentation, lentigines, and sallowness.


The researchers randomly divided the participants into two groups. The experimental group (n = 101) received 0.05% tretinoin emollient cream. The control group (n = 103) received a placebo. The researchers instructed the study participants to apply a pea-sized amount of the study cream to the entire face each night after washing with a skin cleanser, to apply a moisturizer with sunscreen daily, and to apply an additional sunscreen (SPF 30) before extended periods of exposure to ultraviolet light. The researchers conducted efficacy and safety evaluations of photodamage, cutaneous irritation, and the participants' self-assessments at 1, 2, 4, 6, 9, 12, 15, 18, 21, and 24 months. Photodamage and cutaneous irritation were graded using a 10-point scale categorized into four levels: 0 = none; 1-3 = mild; 4-6 = moderate; and 7-9 = severe.


The researchers found that compared with the placebo, treatment with tretinoin resulted in significantly greater improvement in fine and course wrinkling and mottled hyperpigmentation, lentigines, and sallowness (p = .002). The researchers also found that significant improvement was noted as early as 1 month for coarse wrinkling, 2 months for fine wrinkling, and 4 months for mottled hyperpigmentation, sallowness, and lentigines (p < .05). At 24 months, the overall severity of photodamage was significantly reduced following treatment compared with placebo (p = .006). Improvement in tactile roughness was not significant compared with placebo. There was no evidence that treatment with tretinoin for up to 24 months caused an increase in keratinocytic (i.e., cells containing the structural protein, keratin) or melanocytic (i.e., potentially malignant moles or skin spots) atypia (i.e., abnormal or irregular), dermal elastosis (i.e., degenerative changes in skin caused by deposits of elastic fibers), or untoward effects on the epidermis compared with placebo. Notably, in the placebo group, a substantial percentage of participants showed improvement in fine wrinkling (55%; n = 57) and mottled hyperpigmentation (65%; n = 67).



Retinol has been shown to be 20 times less potent than retinoic acid (Spierings, 2021). Once metabolized in the skin, retinol and retinyl esters are no longer active. When manufactured under inert atmospheric conditions and stored in aluminum tubes at less than 68 [degrees]F (20[degrees]C), retinol can remain stable for more than 6 months; however, cosmetic skin care products are generally not manufactured or stored in this manner, making it likely that the retinol in these products has very little, if any, effect when applied to the skin.


To evaluate the efficacy of retinol in the treatment of facial skin aging, Spierings (2021) conducted a systematic review of randomized, double-blind, controlled trials of over-the-counter retinol products in the treatment of facial skin aging. After conducting a PubMed search using the terms retinoid, tretinoin, retinol, retinal, retinaldehyde, and skin, the researcher identified and reviewed 432 publications and included a total of nine publications in the systematic review.


Three of the studies found there were no statistically significant differences between the retinol-containing product and the placebo (Creidi et al., 1998; Gold et al., 2013; Green et al., 1998). The remaining six studies provided weak evidence to show that retinol decreased fine facial skin wrinkles (Bellemere et al., 2009; Kikuchi et al., 2009; Kim et al., 2010; Lee et al., 2006; Randhawa et al., 2015; Tucker-Samaras et al., 2009). However, all six of these studies had major methodological flaws sufficient to call the results into question (Spierings, 2021). The researcher concluded that there was minimal trustworthy evidence to support the use of over-the-counter cosmetic retinol-containing products to improve the appearance of aged skin.


If you have a question about plastic and aesthetic nursing that you would like to see addressed in the I Have a Question! column ofPSN, or if you would like to provide an answer to a particular practice question, please contact Sharon Ann Van Wicklin, Editor-in-Chief,PSN, atmailto:[email protected].




Bellemere G., Stamatas G. N., Bruere V., Bertin C., Issachar N., Oddos T. (2009). Antiaging action of retinol: From molecular to clinical. Skin Pharmacology and Physiology, 22(4), 200-209.[Context Link]


Creidi P., Vienne M. P., Ochonisky S., Lauze C., Turlier V., Lagarde J. M., Dupuy P. (1998). Profilometric evaluation of photodamage after topical retinaldehyde and retinoic acid treatment. Journal of the American Academy of Dermatology, 39(6), 960-965.[Context Link]


Gold M. H., Kircik L. H., Bucay V. W., Kiripolsky M. G., Biron J. A. (2013). Treatment of facial photodamage using a novel retinal formulation. Journal of Drugs in Dermatology, 12(5), 533-540. [Context Link]


Green C., Orchard G., Cerio R., Hawk J. L. (1998). A clinicopathological study of the effects of topical retinyl propionate cream in skin photoageing. Clinical and Experimental Dermatology, 23(4), 162-167.[Context Link]


Kang S., Bergfeld W., Gottlieb A. B., Hickman J., Humeniuk J., Kempers S., Lebwohl M., Lowe N., Mcmichael A., Milbauer J., Phillips T., Powers J., Rodriguez D., Savin R., Shavin J., Sherer D., Silvis N., Weinstein R., Weiss J., Nyirady J. (2005). Long-term efficacy and safety of tretinoin emollient cream 0.05% in the treatment of photodamaged facial skin: A two-year, randomized, placebo-controlled trial. American Journal of Clinical Dermatology, 6(4), 245-253.[Context Link]


Kikuchi K., Suetake R., Kumasaka N., Tagami H. (2009). Improvement of photoaged facial skin in middle-aged Japanese females by topical retinal (vitamin A alcohol): A vehicle-controlled, double-blind study. Journal of Dermatological Treatment, 20(5), 276-281.[Context Link]


Kim H., Kim N., Jung S., Mun J., Kim J., Lee J., Ryoo H., Jung H. (2010). Improvement in skin wrinkles from the use of photostable retinyl retinoate: A randomized controlled trial. British Journal of Dermatology, 162(3), 497-502.[Context Link]


Lee M-S., Lee K-H., Sin H-S., Um S-J., Kim J-W., Koh B-K. (2006). A newly synthesized photostable retinol derivative (retinyl N-formyl aspartamate) for photodamages skin: Profilometric evaluation of 24-week study. Journal of the American Academy of Dermatology, 55(2), 220-224.[Context Link]


Mukherjee S., Date A., Patravale V., Korting H. C., Roeder A., Weindl G. (2006). Retinoids in the treatment of skin aging: An overview of clinical efficacy and safety. Clinical Interventions in Aging, 1(4), 327-348.[Context Link]


Ortho-McNeil Pharmaceutical Corporation. (2000). Renova (tretinoin cream) 0.02%.[Context Link]


Randhawa M., Rossetti D., Leyden J. J., Fantasia J., Zeichner J., Oana Cula G., Southall M., Tucker-Samaras S. (2015). One-year topical stabilized retinol treatment improves photodamaged skin in a double-blind, vehicle-controlled trial. Journal of Drugs in Dermatology, 14(3), 271-276. [Context Link]


Spierings K. M. (2021). Evidence for the efficacy of over-the-counter vitamin A cosmetic products in the improvement of facial skin aging: A systematic review. Journal of Clinical and Aesthetic Dermatology, 14(9), 33-40. [Context Link]


Tucker-Samaras S., Zedayko T., Cole C., Miller D., Wallo W., Leyden J. J. (2009). A stabilized 0.1% retinol facial moisturizer improves the appearance of photodamaged skin in an eight-week, double-blind, vehicle-controlled study. Journal of Drugs in Dermatology, 8(10), 932-936. [Context Link]


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