Cosmeceutical Critique

Melatonin update, Part 1


Found in various plant and animal species, including humans, melatonin (N-acetyl-5-methoxytryptamine) is best known for its daily fluctuations in circulating levels that regulate circadian rhythms. But this ancient serotonin derivative, stimulated by beta-adrenergic receptors, is the primary neuroendocrine product of the pineal gland (discovered as such in 1917) in humans and a dynamic compound with diverse roles in human health levels of which decrease with age.1,2 Over the last quarter of a century, we have arrived at a much greater understanding of the varied biological functions of this highly lipophilic hormone, which is now recognized as the strongest endogenous antioxidant, particularly potent against hydroxyl radicals, the most harmful of reactive oxygen species, and known to protect mitochondria and DNA from direct oxidative harm.2-4 Directly or via its circadian impact, melatonin also affects skin as well as core body temperature.1 This column is a brief review of some early studies on melatonin and some of the cutaneous conditions for which exogenous melatonin shows promise. Next month’s column will address some more of the activities of this dynamic hormone while concentrating on the interaction of melatonin and ultraviolet radiation.

Illustration of melatonin Dr_Microbe/Getty Images

Early studies

In the mid-1990s, Bangha et al. performed several studies in healthy human volunteers that demonstrated that topically applied melatonin suppressed UVB-induced erythema (with one study showing pre- and posttreatment as effective and a subsequent one showing only pretreatment as effective), and also found that melatonin appears to have the potential to accumulate in the stratum corneum with extended release into the blood system through cutaneous delivery.5-7

A randomized, double-blind study by Dreher et al. in 12 healthy adults (6 women and 6 men, all white, aged 29-49 years) considered the short-term photoprotective effects of topically applied vitamin C, vitamin E, and melatonin, alone or in combination, 30 minutes after UV exposure. A dose-dependent photoprotective effect was associated with melatonin, and photoprotective properties were enhanced when melatonin in was combined with vitamins C and E.8

The following year, Dreher et al. evaluated the short-term photoprotective effects of the same compounds in a randomized, double-blind, placebo-controlled human study. Each antioxidant was topically applied 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 seen. The researchers concluded that given the speed of cutaneous damage from UV radiation, antioxidants likely must be delivered at the appropriate site in sufficient doses at the outset of and during active oxidative harm.9

In 2004, Fischer et al. conducted a clinical study of 15 healthy volunteers to test the skin penetration activity of melatonin 0.01% in a cream and 0.01% and 0.03% in a solution. During a 24-hour period, researchers obtained blood samples for melatonin measurement prior to application at 9 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 later 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 substantially rose just 1 and 8 hours later in the 0.03% solution group, with cumulative melatonin measured as 7.1 pg/mL in the 0.01% cream group, 8.6 pg/mL in the 0.01% solution participants, and 15.7 pg/mL in the 0.03% group. The investigators concluded that as a strong lipophilic compound melatonin penetrates the skin with serum blood levels increasing in a dose- and galenic-dependent manner without prompting spikes above the physiological range.10

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