The prevention and treatment of jet lag

Andrew Herxheimer and Jim Waterhouse explain how melatonin might help prevent jet lag

The jet lag syndrome emerged with the rise of long haul air travel. The symptoms include disturbed sleep, increased fatigue, loss of concentration, and increased irritability during the new daytime, and yet difficulties in initiating and maintaining sleep at night. Long flights are also often tiring and uncomfortable (travel fatigue), and the dry cabin air contributes to dehydration. These effects can be distinguished from those of jet lag by comparing flights across time zones, for example from Europe to Asia, with flights of similar length along the same meridian, say to southern Africa, which cause travel fatigue but no jet lag. It is worth trying to minimise travel fatigue in its own rightfor simple practical advice see box.¹

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Jet lag is due to the desynchronisation between various body rhythms and environmental rhythms. The rhythm most noticeably affected is the cycle of sleep and activity, with the associated changes in physical and mental functioning. All the rhythms are regulated by internal and external factors that interact. For example, the “body clock” controls secretion of melatonin by the pineal gland, an important internal factor, and light turns it off. With a rapid change of time zone, it takes several days for the external factors to shift the phase of the body clock from the time zone just left to the new zone. Speeding up this adaptive shift can alleviate or prevent jet lag.

Non-drug measures maximise the external environmental cues that push the circadian phase towards the rhythm of light and dark at the destination. It may be worth trying to start this before departure. The most important cue is light: after a westward flight, to stay awake while it is daylight at the destination and to try to sleep when it gets dark; after an eastward flight, to be awake but avoid bright light in the morning, and to be outdoors as much as possible in the afternoon. Such behaviour will adjust the body clock and turn on the bodys own melatonin secretion at the right time. Other cues can reinforce this—eating modestly at the times that correspond to ones usual mealtimes, taking comfortable exercise, and seeing favourite sights at times when bright light is advised. Whether alcohol or caffeine affect adaptation is not clear and probably depends partly on what a person is used to. They seem more likely to hinder than to help adaptation and make it harder to assess.

Advice to minimise travel fatigue

Before travelling

• Plan the journey in advance
• Try to arrange for any stopover to be comfortable
• Check documentation, inoculations, visas
• Make arrangements at the destination

On the plane

• Take some roughage to eat—for example, apples
• Drink plenty of water or fruit juice (rather than tea and coffee)

After arrival at the destination

• Relax with a non-alcoholic drink
• Take a shower
• Take a brief nap if you want to

Another option is to use either melatonin or a short acting hypnotic. Melatonin taken at bedtime both shifts the phase and has a hypnotic effect, but the relative importance of these two effects has not been established. A hypnotic treats one symptom by providing sleep, but it does not shift the circadian phase. A recent Cochrane review found 10 randomised controlled trials comparing melatonin with placebo in long distance travellers²; one of the trials also included a comparison with the hypnotic zolpidem.³ No other randomised controlled trial of a hypnotic for jet lag seems to have been published. Eight of the 10 trials found a clear reduction in jet lag when melatonin had been taken. The 10 trials used different methods to assess jet lag or its components, observations were made at different times, and most results are reported as group means without data for individual participants, so that they are difficult to combine. For the five studies reporting global jet lag scores between 0 (none) and 100 (extreme), the mean score after placebo was 48, after melatonin 25. The two studies reporting individual results for a total of 46 people suggest that as many as one in two people using melatonin may benefit. Two trials found no difference: in one the participants were probably not fully in phase with the local time before their flight,⁴ in the other a group of fit sports scientists and administrators showed only a small effect of uncertain significance.⁵ These two trials assessed the different symptoms of jet lag as well as the rating of jet lag itself, and it might be that not all symptoms change at the same rate and that the time of assessment might be important—jet lag might be interpreted differently at different times of the day.

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Adverse effects have been reported rarely but have not been looked for systematically. Reports of adverse events possibly related to use of melatonin imply that two categories of people should avoid it until more is known: anyone taking warfarin or another oral anticoagulant, and people with epilepsy.²

The Cochrane review concludes that 2-5 mg melatonin taken at bedtime after arrival is effective and may be worth repeating for the next two to four days, together with the non-drug measures already mentioned. But people who have not had jet lag on a previous trip may well never need it.

Melatonin (N-acetyl-5-methoxytryptamine) is a simple substance, but no official standards of purity exist. In many countries—for example, the United States, Thailand, and Singapore—it is freely sold as a “dietary supplement” in health food stores and pharmacies. Suppliers need present no evidence of the degree of purity of the melatonin. Four of six melatonin products bought in health food shops in the United States were found to contain unidentified impurities.⁶ It seems advisable to buy it from a large reputable pharmacy chain and hope for the best. In Europe, Australia, and many other countries melatonin is regulated as a medicine and requires a licence, but no licensed preparation is marketed; only the internet offers a grey or black market.

No pharmaceutical company wants to pay for the toxicological studies and the data assembly required to obtain a product licence because it cannot have exclusivity. It seems that many people and organisations, including governments and armed forces, would benefit from the use of melatonin to reduce jet lag. If use of the drug is in the public interest then public funds should be used to get it properly tested and licensed. A finance initiative is urgently needed to solve the problem and might best begin with a cost benefit assessment.

Jim Waterhouse, senior lecturer, Research Institute for Sport and Exercise Sciences, John Moores University, Liverpool L3 2ET

Andrew Herxheimer, emeritus fellow, UK Cochrane Centre, 9 Park Crescent, London N3 2NL
Email: andrew_herxheimer@compuserve.com


studentBMJ 2003;11:43-86 March ISSN 0966-6494

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2. Herxheimer A, Petrie KJ. Melatonin for the prevention and treatment of jet lag. Cochrane Library 2002; disk issue 4:CD001520.
3. Suhner A, Schlagenhauf P, Hoefer I, Johnson R, Tschopp A, Steffen R. Efficacy and tolerability of melatonin and zolpidem for the alleviation of jet-lag. In: Suhner A. Melatonin and jet-lag. Zurich: Swiss Federal Institute of Technology, 1988:85-103. (Dissertation ETH No.12823.)
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6. Anon. Melatonin. Med Letter 1995;37:111-2