Study Objectives: Melatonin is an important neurohormone, which mediates circadian rhythms and the sleep cycle. As such, it is a popular and readily available supplement for the treatment and prevention of sleep-related disorders including insomnia and jet lag. This study quantified melatonin in 30 commercial supplements, comprising different brands and forms and screened supplements for the presence of serotonin. Methods: A total of 31 supplements were analyzed by ultraperformance liquid chromatography with electrochemical detection for quantification of melatonin and serotonin. Presence of serotonin was confirmed through analysis by ultraperformance liquid chromatography with mass spectrometry detection. Results: Melatonin content was found to range from −83% to +478% of the labelled content. Additionally, lot-to-lot variable within a particular product varied by as much as 465%. This variability did not appear to be correlated with manufacturer or product type. Furthermore, serotonin (5-hydroxytryptamine), a related indoleamine and controlled substance used in the treatment of several neurological disorders, was identified in eight of the supplements at levels of 1 to 75 µg. Conclusions: Melatonin content did not meet label within a 10% margin of the label claim in more than 71% of supplements and an additional 26% were found to contain serotonin. It is important that clinicians and patients have confidence in the quality of supplements used in the treatment of sleep disorders. To address this, manufacturers require increased controls to ensure melatonin supplements meet both their label claim, and also are free from contaminants, such as serotonin. Commentary: A commentary on this article appears in this issue on page 163. Keywords: contaminant, degradation, label claim, natural health product, stability Citation: Erland LA, Saxena PK. Melatonin natural health products and supplements: presence of serotonin and significant variability of melatonin content. J Clin Sleep Med. 2017;13(2):275-281.
I NTRO DUCTI O NMelatonin (N-acetyl-5-methoxytryptamine) is an indoleamine, produced by the mammalian pineal gland as a neurohormone, but has since been found in almost all clades of life encompassing both vertebrate and invertebrate animals, bacteria, fungi, algae and plants. 1,2 In all kingdoms melatonin is produced from the aromatic amino acid tryptophan. In the mammalian system, biosynthesis then proceeds via hydroxylation to 5-hydroxytryptophan followed by decarboxylation to form serotonin (5-hydroxytryptamine).3 In the plant system the hydroxylation and decarboxylation steps are reversed and serotonin synthesis proceeds via the metabolic intermediate tryptamine. 4 Though several alternative routes have been identified, the primary biosynthetic pathway for melatonin then proceeds from serotonin to N-acetylserotonin to melatonin and involves addition of a methoxy and N-acetyl group to serotonin. [3][4][5] The primary role of melatonin in vertebrates is regulation of circadian rhythms, and for humans in particular t...