Melatonin (N-acetyl-5-methoxytryptamine) is a hormone produced naturally by the pineal gland in humans. Production of the hormone is stimulated by beta-adrenergic receptors. Research in recent years has offered some intriguing and in some cases promising results that may one day be utilized for dermatologic treatments and products.
Also found in various animal and plant species, melatonin is probably best known for its daily fluctuations in circulating levels that play an important role in circadian rhythms. In recent years, melatonin has been gaining increased attention in antiaging medicine and dermatology because it has been found to exert antioxidant activity, particularly against hydroxyl radicals (Hautarzt. 1999;50:5-11), the most harmful of free radicals. Melatonin levels are known to decrease with age. In addition to its antioxidative and regulatory roles, including in seasonal reproduction control, melatonin modulates the immune system and inhibits inflammation (J. Pineal Res. 2009;47:324-9).
Melatonin and UV-Induced Erythema
In 1996, Bangha et al. conducted a randomized double-blind study with 20 healthy volunteers to examine the efficacy of topically applied melatonin in hindering UV-induced erythema. Each subject was irradiated with UVB (0.099 J/cm2) on 4-cm2 areas on the lower back, and then treated with different concentrations of melatonin. The investigators observed a dose-response relationship between melatonin concentration and the degree of erythema, with significantly less redness found in the areas treated with 0.5% melatonin, compared with melatonin 0.05% or just the vehicle gel (Arch. Dermatol. Res. 1996;288:522-9).
The next year, Bangha et al. performed another randomized double-blind study on topical melatonin and its antierythema effect, this time to ascertain the role of the application time in exerting the effect. Again using 20 volunteers, the researchers treated small areas of the lower back with 0.6 mg/cm2 melatonin 15 minutes before or 1, 30, or 240 minutes after simulated UVA and UVB irradiation at twice the individual minimal erythema dose. The authors found that post-treatment with melatonin imparted no protective effect but pretreatment 15 minutes prior to irradiation yielded significant protection against erythema (Dermatology 1997;195:248-52). That same year, Bangha et al. also studied the penetration kinetics of topical melatonin in six healthy volunteers between the ages of 26 and 34 years, and found that melatonin has the potential to accumulate in the stratum corneum with extended release into the bloodstream through cutaneous delivery (Skin Pharmacol. 1997;10:298-302).
In 1998, Dreher et al. conducted a randomized double-blind study in 12 healthy adults (6 women and 6 men, all white, ranging in age from 29 to 49 years). The researchers looked at the short-term photoprotective effects of topically applied vitamin C; vitamin E; and melatnonin; alone or in combination. All formulations were applied 30 minutes after UV exposure. A dose-dependent photoprotective effect was associated with melatonin, with modest effects seen with the vitamins alone. Photoprotective activity was clearly enhanced when melatonin was combined with vitamins C and E (Br. J. Dermatol. 1998;139:332-9).
The following year, Dreher et al. performed a similar experiment to assess the short-term photoprotective effects of the same compounds. This placebo-controlled, randomized double-blind human study entailed the topical use of each antioxidant alone or in combination after UV exposure in a single application (immediately or 30 minutes after UV exposure) or in multiple applications 30 minutes, 1 hour, and 2 hours after UV exposure (totaling three applications).
Interestingly, no photoprotective effects were observed regardless of the number of applications of antioxidants. The investigators concluded that given the speed of damage to skin from UV radiation, antioxidants probably must be delivered at the appropriate site in sufficient concentrations at the outset of and during active oxidative insult (Dermatology 1999;198:52-5).
Similarly, in 2006 Howes et al. studied the effects of topical melatonin applied after solar-simulated UV exposure in 16 healthy Mantoux-positive volunteers, and found that melatonin imparted no protection against sunburn or immune suppression (Photodermatol. Photoimmunol. Photomed. 2006;22:267-9).
Antioxidant Properties
Morganti et al. conducted an 8-week placebo-controlled, randomized double-blind study on 30 xerotic female volunteers (between ages 48 and 59 years) to determine the effects of topical and systemic antioxidant-enriched formulation administration on the skin. Subjects applied a nanocolloidal gel twice daily and/or took two capsules per day of an oral diet supplement. The antioxidant-enriched formulations included vitamins C and E, alpha-lipoic acid, emblica, and melatonin.
Investigators found that oxidative stress and lipid peroxidation declined 30%-40% in the blood serum of all participants who used the topical or systemic antioxidant formulation. Those treated with the antioxidants also showed reductions in free radicals recovered in blood serum and on skin, as well as decreases in reactive oxygen species engendered by UVB irradiation of leukocytes (in vitro). The researchers concluded that the tested compounds indeed exerted topical and systemic photoprotection and represent promising ingredients for combating oxidative stress and photoaging (Int. J. Cosmet. Sci. 2002;24:331-9).
Uses of Melatonin for Skin Lesions