Melatonin for the prevention and treatment of jet lag Herxheimer A, Petrie kj

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Melatonin for the prevention and treatment of 

jet lag 

Herxheimer A, Petrie KJ 

Cover sheet












Tables & Graphs


This review should be cited as: Herxheimer A, Petrie KJ. Melatonin for the prevention 

and treatment of jet lag (Cochrane Review). In: The Cochrane Library, Issue 4, 2001. 

Oxford: Update Software.  

A substantive amendment to this systematic review was last made on 22 August 2000. 

Cochrane reviews are regularly checked and updated if necessary.  

Background: : Jet-lag commonly affects air travellers who cross several time zones. It 

results from the body's internal rhythms being out of step with the day-night cycle at the 

destination. Melatonin is a pineal hormone that plays a central part in regulating bodily 

rhythms and has been used as a drug to re-align them with the outside world.  

Objectives: : To assess the effectiveness of oral melatonin taken in different dosage 

regimens for alleviating jet-lag after air travel across several time zones.  

Search strategy: : We searched the Cochrane Controlled Trials Register, MEDLINE, 

EMBASE, PsychLit and Science Citation Index electronically, and the journals 

'Aviation, Space and Environmental Medicine' and 'Sleep' by hand. We searched citation 

lists of relevant studies for other relevant trials. We asked principal authors of relevant 

studies to tell us about unpublished trials. Reports of adverse events linked to melatonin 

use outside randomised trials were searched for systematically in 'Side Effects of 

Drugs' (SED) and SED Annuals, 'Reactions Weekly', MEDLINE, and the adverse drug 

reactions databases of the WHO Uppsala Monitoring Centre (UMC) and the US Food & 

Drug Administration.  

Selection criteria: : Randomised trials in airline passengers, airline staff or military 

personnel given oral melatonin, compared with placebo or other medication. Outcome 

measures should consist of subjective rating of jet-lag or related components, such as 

subjective wellbeing, daytime tiredness, onset and quality of sleep, psychological 

functioning, duration of return to normal, or indicators of circadian rhythms.  

Data collection and analysis: : Ten trials met the inclusion criteria. All compared 

melatonin with placebo; one in addition compared it with a hypnotic, zolpidem. Nine of 

the trials were of adequate quality to contribute to the assessment, one had a design fault 

and could not be used in the assessment. 

Reports of adverse events outside trials were found through MEDLINE, 'Reactions 

Weekly', and in the WHO UMC database. 


Main results: : Nine of the ten trials found that melatonin, taken close to the target 

bedtime at the destination (10pm to midnight), decreased jet-lag from flights crossing 

five or more time zones. Daily doses of melatonin between 0.5 and 5mg are similarly 

effective, except that people fall asleep faster and sleep better after 5mg than 0.5mg. 

Doses above 5mg appear to be no more effective. The relative ineffectiveness of 2mg 

slow-release melatonin suggests that a short-lived higher peak concentration of 

melatonin works better. Based on the review, the number needed to treat (NNT) is 2. 

The benefit is likely to be greater the more time zones are crossed, and less for westward 


The timing of the melatonin dose is important: if it is taken at the wrong time, early in 

the day, it is liable to cause sleepiness and delay adaptation to local time.  

The incidence of other side effects is low. Case reports suggest that people with 

epilepsy, and patients taking warfarin may come to harm from melatonin.  

Reviewers' conclusions: : Melatonin is remarkably effective in preventing or reducing 

jet-lag, and occasional short-term use appears to be safe. It should be recommended to 

adult travellers flying across five or more time zones, particularly in an easterly 

direction, and especially if they have experienced jet-lag on previous journeys. 

Travellers crossing 2-4 time zones can also use it if need be.  

The pharmacology and toxicology of melatonin needs systematic study, and routine 

pharmaceutical quality control of melatonin products must be established.  

The effects of melatonin in people with epilepsy, and a possible interaction with 

warfarin, need investigation. 


Jet-lag is a common complaint of travellers who fly across a number of time zones (Winget 84). The 


of jet-lag are primarily daytime fatigue and sleep disturbance, but also include loss of mental 

efficiency , weakness  

and irritability (Comperatore 90). Jet-lag is caused by desynchronisation between the body's 


system and the new day-night cycle at the traveller's destination. The sleep loss caused by the travel 

itself often  

contributes to jet-lag. After a flight through six or more time zones most travellers will take 4-6 days 

to re-establish  

a normal sleeping pattern and not to feel tired during the day. The severity of jet-lag symptoms 

largely depends on  

the number of time zones crossed and the direction of travel. They are worse the greater the number 

of zones crossed.  

Westbound travel generally causes less disruption, as it is easier to lengthen than to shorten the 

natural circadian cycle. 

Melatonin is a hormone released by the pineal gland during darkness. Exposure to bright light cuts 

off melatonin release;  

the onset of dim light triggers resumption of release. It seems to play a key role in regulating the 

body's circadian rhythms 

and has been used therapeutically to re-entrain disturbed circadian rhythms. Exogenous melatonin 

tends to produce a  

phase advance when it is taken in the late afternoon (Lewy 92, 95), since its effect is additive with 

that of endogenous  

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