BACKGROUND: jet lag commonly affects air travelers 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 realign 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 We asked principal authors of relevant studies to tell us about unpublished trials.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 randomized trials were searched for systematically in 'Side Effects of Drugs' (SED) and SED Annuals, 'Reactions Weekly,' MEDLINE, and the adverse drug reactions data-bases of the WHO Uppsala Monitoring Centre (UMC) and the US Food & Drug Administration.SELECTION CRITERIA: Randomized trials in airline passengers, air-line 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 well being, 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 10 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 flights. 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 pre-venting or reducing jet lag, and occasional short-term use appears to be safe. It should be recommended to adult travelers flying across five or more time zones, particularly in an easterly direction, and especially if they have experienced jet lag on previous journeys. Travelers 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.
QUESTION: In people who travel by air across several time zones, can oral melatonin prevent or treat jet lag? DATA SOURCES: Studies were identified by searching the Cochrane Controlled Trials Register, Medline, EMBASE/Excerpta Medica, and PsycLIT with the terms melatonin, jet-lag, jet lag, aviation, air travel, and airtravel. SciSearch was also accessed, 2 journals (Aviation, Space and Environmental Medicine and Sleep from 1986-99) were hand searched, bibliographies of relevant studies were scanned, and authors of studies were contacted to identify further studies. Data and case reports of adverse effects of melatonin were also sought. STUDY SELECTION: Randomised controlled trials were selected if airline passengers, airline staff, or military personnel were studied; oral melatonin was compared with placebo or other medication; drugs were taken before, during, after, or a combination of times related to travel; and outcome data were provided. DATA EXTRACTION: Data were extracted on study quality and participants, timing and dose of melatonin and other study medications, flight information, and outcomes of subjective ratings of jet lag and its components (fatigue, daytime tiredness, onset of sleep at destination, onset and quality of sleep, psychological functioning, duration of return to normal, and measures indicating the phase of circadian rhythms). MAIN RESULTS: 10 trials met the inclusion criteria; 1 was not used in the analysis because the design was weak. All compared melatonin with placebo in adults. Melatonin was taken at the same clock time after arrival at the destination (close to bedtime at the destination). All trials were of treatment longer than 2 days; none examined shorter duration of treatment. All 9 trials individually showed a reduction in symptoms of jet lag. Meta-analysis of 5 trials showed that the weighted mean decrease in the global rating scale (range from 0, no jet lag, to 100, maximum jet lag) was 38 (95% CI 35 to 40) favouring melatonin. Studies comparing melatonin taken both before and after travel with melatonin taken after travel showed that the before and after treatment had no benefit over only taking melatonin after arrival. 1 study showed that jet lag was worse after eastward flights than westward flights. Both passengers and airline staff experienced benefits with melatonin. Daily doses between 0.5 and 5 mg were similarly effective, except that on the higher dose, study participants fell asleep more quickly and reported better sleep quality. Doses above 5 mg did not appear to be more effective. Slow release melatonin in a 2 mg dose was relatively ineffective. Few adverse effects occurred in healthy adults. CONCLUSION: Short term use of oral melatonin reduces jet lag in healthy adult air travellers and has few adverse effects.
jet lag commonly affects air travelers 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 realign 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 randomized trials were searched for systematically in 'Side Effects of Drugs' (SED) and SED Annuals, 'Reactions Weekly,' MEDLINE, and the adverse drug reactions data-bases of the WHO Uppsala Monitoring Centre (UMC) and the US Food & Drug Administration.
SELECTION CRITERIA:
Randomized trials in airline passengers, air-line 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 well being, 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 10 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 flights. 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 pre-venting or reducing jet lag, and occasional short-term use appears to be safe. It should be recommended to adult travelers flying across five or more time zones, particularly in an easterly direction, and especially if they have experienced jet lag on previous journeys. Travelers 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.
