A double-blind trial of melatonin as a treatment for jet lag in international cabin crew

Petrie, Keith J.; Dawson, Alexander G.; Thompson, L.; Brook, R. J.

doi:10.1016/0006-3223(93)90007-z

Cited by 192 publications

(91 citation statements)

References 6 publications

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“…20 Melatonin is used widely by the public as an over-the-counter supplement in the management of sleep disorders including insomnia and jet lag. [6][7][8]10 Though melatonin consumption is generally considered to be of little risk, there have been reports of interaction of melatonin with other botanical and medicinal products, as well as negative side effects if taken in excess in the short term. [21][22][23][24][25] In contrast with melatonin, serotonin has much more significant health concerns if taken in excess, leading to a condition known as serotonin syndrome, which ranges from very mild to fatal in its outcome, which can be exacerbated by interactions with other medications, such as selective serotonin reuptake inhibitors (SSRIs) and the analgesic tramadol.…”

Section: A B C Dmentioning

confidence: 99%

Melatonin Natural Health Products and Supplements: Presence of Serotonin and Significant Variability of Melatonin Content

Erland

Saxena

2017

Journal of Clinical Sleep Medicine

195

103

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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...

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Section: A B C Dmentioning

confidence: 99%

Melatonin Natural Health Products and Supplements: Presence of Serotonin and Significant Variability of Melatonin Content

Erland

Saxena

2017

Journal of Clinical Sleep Medicine

195

103

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“…Estimations of core body temperature minimum are based upon known relationships with respect to habitual wake time, prompting one to estimate core body temperature minimum timing either 2 or 3 hours prior to sleep offset, depending upon whether one typically sleeps up to 7 hours or more than 7 hours, respectively. [24][25][26] Travel to the west generally favors phase delays, which can be achieved in approximately 2-hour increments (reflecting the greater ease of delaying the clock), by following similar principles. In the opposite pattern, subjects expose themselves to light for approximately 3 hours prior to the core body temperature minimum and avoid light for approximately three hours thereafter (see Figure 3 as an example).…”

Section: Timed Light Exposurementioning

confidence: 99%

“…24,25 Immediate-release preparations appear to perform better than controlled-release formulations. 26 Although most studies have examined the efficacy of melatonin for jet lag occurring subsequent to eastward travel, [26][27][28][29] a single study examined its use in travel to the west and found it to be efficacious.…”

Section: Nocturnal Medication Administration For Jet Lagmentioning

confidence: 99%

“…26 Although most studies have examined the efficacy of melatonin for jet lag occurring subsequent to eastward travel, [26][27][28][29] a single study examined its use in travel to the west and found it to be efficacious. 25 Melatonin use has been studied using a variety of different dosing schedules. One regimen stipulates that subjects begin to use the supplement at the anticipated destination bed time 3 days prior to departure, en-route, and upon arrival.…”

Section: Nocturnal Medication Administration For Jet Lagmentioning

confidence: 99%

“…While there is evidence to support both schedules, a comparison study (involving westward travel) demonstrated superior outcomes with the simpler regimen. 25 The simpler regimen also has the advantage that it is more likely to be followed.…”

Section: Nocturnal Medication Administration For Jet Lagmentioning

confidence: 99%

See 2 more Smart Citations

Circadian rhythm sleep disorders

Kolla¹,

Auger²,

Morgenthaler³

2012

CPT

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Misalignment between endogenous circadian rhythms and the light/dark cycle can result in pathological disturbances in the form of erratic sleep timing (irregular sleep-wake rhythm), complete dissociation from the light/dark cycle (circadian rhythm sleep disorder, free-running type), delayed sleep timing (delayed sleep phase disorder), or advanced sleep timing (advanced sleep phase disorder). Whereas these four conditions are thought to involve predominantly intrinsic mechanisms, circadian dysrhythmias can also be induced by exogenous challenges, such as those imposed by extreme work schedules or rapid transmeridian travel, which overwhelm the ability of the master clock to entrain with commensurate rapidity, and in turn impair approximation to a desired sleep schedule, as evidenced by the shift work and jet lag sleep disorders. This review will focus on etiological underpinnings, clinical assessments, and evidence-based treatment options for circadian rhythm sleep disorders. Topics are subcategorized when applicable, and if sufficient data exist. The length of text associated with each disorder reflects the abundance of associated literature, complexity of management, overlap of methods for assessment and treatment, and the expected prevalence of each condition within general medical practice.

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In vivo microdialysis/liquid chromatography/tandem mass spectrometry for the on-line monitoring of melatonin in rat

Wong

Yoshioka

Xie

et al. 1999

Rapid Commun. Mass Spectrom.

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Liquid chromatography/tandem mass spectrometry (LC/MS/MS) has been coupled to in vivo microdialysis for on-line monitoring of melatonin in a freely moving rat for a period of 15 hours. A microdialysis probe was surgically implanted into the jugular vein of the rat, and deionized water was used as the perfusion medium at a flow rate of 1.0 microL/min. Microdialysis samples were collected in an on-line injector with sample injection every 30 minutes. Melatonin was dosed by intraperitoneal (i.p.) injection and then monitored by microdialysis/LC/MS/MS. The whole experiment, including the microdialysis sampling and sample injection into the LC/MS system, was fully automated. Metabolites of melatonin were identified off-line by LC/MSn experiments. Two metabolites were identified as 6-hydroxymelatonin and cyclic 2-hydroxymelatonin, consistent with ones found previously in the literature.

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A double-blind trial of melatonin as a treatment for jet lag in international cabin crew

Cited by 192 publications

References 6 publications

Melatonin Natural Health Products and Supplements: Presence of Serotonin and Significant Variability of Melatonin Content

Melatonin Natural Health Products and Supplements: Presence of Serotonin and Significant Variability of Melatonin Content

Circadian rhythm sleep disorders

In vivo microdialysis/liquid chromatography/tandem mass spectrometry for the on-line monitoring of melatonin in rat

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