Assessing the Potential Role for Topical Melatonin in an Antiaging Skin Regimen

September 2018 | Volume 17 | Issue 9 | Original Article | 966 | Copyright © September 2018

Doris Day MD,a Cheryl M. Burgess MD,b Leon H. Kircik MDc

aNYU Langone Medical Center, New York, NY bCenter for Dermatology and Dermatologic Surgery; George Washington University School of Medicine and Health Sciences; Department of Internal Medicine/Dermatology, Georgetown University Medical Hospital, Washington, DC cIcahn School of Medicine at Mount Sinai, New York, NY; Indiana Medical Center, Indianapolis, IN; Physicians Skin Care, PLLC, Louisville, KY; DermResearch, PLLC, Louisville, KY

protective effect against UVR-induced erythema when topical melatonin was applied before exposure rather than after. All the studies used artificial UVR-sources and did not investigate pos- sible side effects.25 Most recently, an in-vitro study was performed to evaluate the relative expression of genes associated with antioxidant activ- ity for a melatonin-containing topical night-time formulation. The formulation was evaluated undiluted and topically applied on medaka eleutheroembryos (ME). Topical application of me- latonin-containing formulation significantly increased gene expression of SOD1, CAT, Nrf2 and GPx1, as demonstrated via real-time quantitative PCR (Polymerase Chain Reaction) to quantify mRNA levels. Findings confirm that topically applied melatonin behaves as an indirect antioxidant by up-regulating the gene expression of Nrf2 and antioxidant enzymes.26

Considerations for Topical Application

Although oral melatonin supplements are widely available, topical formulations are far less common. Oral administration is thought to deliver the active compound to the bloodstream via the gut. But what is the mechanism for topical delivery? Topically applied melatonin is a practical option for topical application only if it can be safely and effectively delivered to the skin with minimal systemic effect. Human skin and hair follicles express functional melatonin receptors in addition to being engaged in substantial melatonin synthesis.27 Topically applied melatonin has been shown to be safe, even with full body application, showing no effect on cognition, including measures of sleepi- ness. 25 Melatonin synthesis in the human body peaks in the evening hours,21 perhaps not surprising, given its association with regulating circadian rhythms. Since cutaneous repair processes are also thought to take place overnight, and skin permeability is at its highest at night, topical application of melatonin at nighttime may optimize the wound healing and anti-aging benefits of the compound while mimicking its endogenous effects.


There is now substantial evidence that topical melatonin, a naturally occurring hormone long used as an oral supple- ment to support sleep, may have important benefits for the skin. The compound is a strong direct antioxidant as well as an indirect antioxidant with demonstrated anti-aging benefits. Within the skin, melatonin behaves as an indirect antioxidant by upregulating the gene expression of antioxidant enzymes. It accomplishes this by upregulating the transcription factor, NRF2, which after translocating to the nucleus can induce the transcription of antioxidant enzymes, such as SOD1, GPX-1, and CAT by binding to the antioxidant response element (ARE) promoter region. As the global population continues to age, photodamage remains a significant cutaneous concern. In fact, the $46.93 Billion (USD) global cosmeceuticals market is driven primarily by demand for anti-aging skincare.28 While use of sunscreens and UV avoidance strategies are essential to mitigating skin cancer risks as well as photoaging, the potential of topical melatonin to provide anti-aging benefits through an indirect and direct antioxidant effect is appealing. With its unique antioxidant effects, melatonin should be consid- ered for topical use as an anti-aging and skin protective agent. Although the available in-vitro and in-vivo studies have demon- strated that topical melatonin is an effective anti-aging option for night-time application, more clinical studies are needed to understand the full potential of topical melatonin.


Doris Day MD has been a consultant for ISDIN. Cheryl M. Burgess MD FAAD has served on the advisory board for Aclaris Therapeutics, Inc, Revance Therapeutics, Inc., The Merz Institute of Advanced Aesthetics, Merz Pharmaceuticals, and ISDIN. Leon H. Kircik MD is a consultant and advisory board member for ISDIN. 


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Leon H. Kircik MD