Clinical Studies Using Topical Melatonin

Abstract

Melatonin is ubiquitously present in all animals and plants, where it exerts a variety of physiological activities thanks to its antioxidant properties and its key role as the first messenger of extracellular signaling functions. Most of the clinical studies on melatonin refer to its widespread oral use as a dietary supplement to improve sleep. A far smaller number of articles describe the clinical applications of topical melatonin to treat or prevent skin disorders by exploiting its antioxidant and anti-inflammatory activities. This review focuses on the clinical studies in which melatonin was applied on the skin as a photoprotective, anti-aging, or hair growth-promoting agent. The methodologies and results of such studies are discussed to provide an overall picture of the state of the art in this intriguing field of research. The clinical studies in which melatonin was applied on the skin before exposure to radiation (UV, sunlight, and high-energy beams) were all characterized by an appropriate design (randomized, double-blind, and placebo-controlled) and strongly support its clinical efficacy in preventing or reducing skin damage such as dermatitis, erythema, and sunburn. Most of the studies examined in this review do not provide a clear demonstration of the efficacy of topical melatonin as a skin anti-aging or as a hair growth-promoting agent owing to limitations in their design and/or to the use of melatonin combined with extra active ingredients, except for one trial that suggests a possible beneficial role of melatonin in treating some forms of alopecia in women. Further research efforts are required to reach definitive conclusions concerning the actual benefits of topical melatonin to counteract skin aging and hair loss.

Keywords: anti-aging; clinical studies; dermatology; hair growth; melatonin; photoprotection; skin; topical applications.

Figure 1

Structure of melatonin.

Figure 2

The main mechanisms of action of melatonin underlying its antioxidant and anti-inflammatory properties (see text for details). Melatonin is represented as a green filled square; the proteins that are positively modulated or upregulated are in blue; and the proteins that are negatively modulated or downregulated are in red. The levels of the second messengers and enzymes are in blue or red to indicate, respectively, their increase or decrease. Abbreviations (listed in the same order as they are mentioned in the text): MT1: melatonin receptor 1; MT2: melatonin receptor 2; PKA: protein kinase A; CREB: cAMP responsive element-binding protein; PKC: protein kinase C; MAPK1/2: mitogen-activated protein kinases 1 and 2; Nrf2: nuclear factor erythroid 2-related factor 2; AHR: aryl hydrocarbon receptor; PPARγ: peroxisome proliferator-activated receptor γ; UPS: ubiquitin–proteasome system; ROS: reactive oxygen species; COX-2: cyclooxygenase-2; iNOS: inducible nitric oxide synthase; p300 HAT: p300 histone acetyltransferase; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; AC: adenylate cyclase; and sGC: soluble guanylate cyclase.