In 2004, Fischer et al. conducted a clinical study in 15 healthy volunteers to consider the skin penetration activity of melatonin 0.01% in a cream and 0.01% and 0.03% in a solution. In a 24-hour time window, investigators took blood samples for melatonin measurement prior to application at 9:00 a.m., as well as 1, 4, 8, and 24 hours after application. Preapplication serum melatonin levels ranged from 0.6 to 15.9 pg/mL.
The mean serum value 24 hours after application of the 0.01% melatonin cream was 9.0 pg/mL. For the 0.01% solution group, the mean melatonin level was 12.7 pg/mL 24 hours after application. Melatonin levels also markedly increased just 1 and 8 hours later in the 0.03% solution group, with cumulative melatonin noted as 7.1 pg/mL in the 0.01% cream subjects, 8.6 pg/mL in the 0.01% solution participants, and 15.7 pg/mL in the 0.03% group. The investigators concluded that potently lipophilic melatonin penetrates the skin, with serum blood levels increasing in a dose- and galenic-dependent manner without causing increases above the physiological range (Skin Pharmacol. Physiol. 2004;17:190-4).
In a more recent study using NC/Nga mice, researchers investigated whether melatonin inhibits the development of 2,4-dinitrofluorobenzene (DNFB)-induced atopic dermatitis-like skin lesions. Topically administered melatonin hindered ear thickness increases and skin lesions engendered by DNFB treatment. Melatonin was also found to significantly inhibit interleukin (IL)-4 and interferon (IFN)-gamma secretion by activated CD4(+) T cells from the draining lymph nodes of DNFB-treated mice, and to diminish serum total IgE levels. The investigators concluded that topically administered melatonin, by lowering total IgE in serum, and IL-4 and IFN-gamma synthesis by activated CD4(+) T cells, suppresses atopic dermatitis-like skin lesion development provoked by DNFB treatment in NC/Nga mice (J. Pineal. Res. 2009;47:324-9).
In 2006, Sener et al. studied the effects of melatonin in treating pressure ulcers in rats. Animals were treated twice daily during reperfusion periods with a locally applied ointment or received intraperitoneal administration of the antioxidant.
Topical melatonin treatment was associated with suppressed malondialdehyde levels and attenuated decreases in glutathione in the skin induced by the pressure ulcers. Melatonin treatment also prevented significant increases in alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatinine, lactate dehydrogenase, and collagen levels. In addition, the researchers noted degenerative changes in the dermis and epidermis of the rats, with marked decreases in tissue injury in the animals that received topical melatonin. They concluded that melatonin, delivered topically or systemically, warrants consideration as a pressure ulcer treatment (J. Pineal Res. 2006;40:280-7).
Finally, in a 2010 study Ozler et al. compared systemic and topical administration of melatonin in chronic wound models in rats with pinealectomy that suppressed basal melatonin. The researchers found that hydroxyproline levels were significantly lower in rats that underwent pinealectomy and wound formation, compared with controls (with wound formation only), with increased wound surface areas. In addition, compared with the control group, these animals exhibited increased malondialdehyde levels and decreases in superoxide dismutase and glutathione peroxidase. However, superoxide dismutase and glutathione peroxidase enzymes increased in the groups treated with melatonin, and malondialdehyde decreased.
The researchers concluded that melatonin exerts a positive effect on wound healing, as the absence of melatonin prolonged the healing process. Topical and systemic administration methods were equally effective (Scand. J. Clin. Lab. Invest. 2010;70:447-52).
Conclusion
There is a good deal of research on the biological functions of melatonin. There is also an interesting, emerging body of evidence on the dermatologic effectiveness of the topical application of this hormone. In fact, there seem to be a wide variety of potential cutaneous uses for melatonin. However, most of the clinical studies have been extremely small, including a couple of investigations that indicated no photoprotective effect associated with melatonin.
Clearly, much more research, preferably in the form of randomized double-blind studies larger than those that have thus far appeared in the literature, is necessary. But the prospect of melatonin conferring dermatologic benefits is intriguing and more than likely promising.