Chapter 62: Melatonin

INTRODUCTION

SOURCE

Melatonin (N-acetyl-5-methoxytryptamine), a tryptophan derivative, is a hormone produced naturally by the pineal gland in humans, and stimulated by β-adrenergic receptors. In addition, it is synthesized in mammals by the eyes, ovaries, bone marrow, gastrointestinal tract, lymphocytes, and skin, where it is also metabolized.^3–6 Additionally, melatonin has been recorded at significant levels in bile fluid, cerebrospinal fluid, and gastral mucosa.⁷ Also found in most animal and plant species as well as fungi and even unicellular organisms, it follows a circadian light-dependent rhythm of secretion, and is derived from tryptophan, which is present in all organisms.^8,9 That is, melatonin is secreted during the dark phase of the light/dark cycle, and also regulates seasonal biorhythms (and is often accordingly referred to as the “hormone of darkness” and the body’s chronological pacemaker).^5,9 In fact, melatonin is best known for regulating and facilitating sleep, with its “chronobiotic” characteristics justifying its use to treat sleep disorders including jet lag, shift-work sleep disruption, and insomnia in elderly and depressive patients.⁵

HISTORY

Although melatonin is a phylogenetically ancient methoxyindole, it was initially isolated from bovine pineal glands in 1958.^5,7–12 Subsequently, researchers learned that melatonin was produced nocturnally and secreted by the pineal gland and other organs in mammals including humans.⁸ Melatonin and its relations to skin function have been studied since its skin-lightening effects on frogs were observed in the late 1950s.^10,13,14 The status of melatonin as a potent free radical scavenger was uncovered in 1993.^8,15,16 That same year, the first evidence emerged of the production of melatonin in the skin.^17–19 Significantly, a melatoninergic antioxidative system that regulates cutaneous homeostasis and exhibits the potential to prevent ultraviolet (UV)-induced skin aging and skin cancer has been recently discovered.^7,8,20,21

CHEMISTRY

Melatonin is a methoxyindole produced primarily by the pineal gland. In the skin, the essential amino acid tryptophan is the precursor; it is converted by tryptophan hydroxylase to 5-OH-Trp and then to serotonin. The acetylation of serotonin leads to the formation of N-acetylserotonin, which is transformed after the hydroxyindole-O-methyltransferase into melatonin.⁹

ORAL USES

Several plants are good sources of dietary melatonin, as it appears ubiquitously in nature and is found in almost 60 herbs used in traditional Chinese medicine.⁵ Melatonin is also used as an oral supplement, primarily to restore regular sleep patterns. Prescriptions are required in some countries for melatonin supplements.