Does melatonin have an effect on jet lag (time lag) syndrome?

Fråga: Does melatonin have an effect on jet lag (time lag) syndrome?

Sammanfattning: There is some evidence that melatonin is effective in relieving the jet lag symptoms. However, the optimal dosage, the timing of drug administration and the long-term toxicity is still unclear.

Svar: Questions about melatonin as sleeping aid have previously been answered in Drugline (1,2).

Melatonin is an endogenous hormone that is secreted by the pineal gland in the brain during the hours of darkness and is at a low concentration during daylight hours. The rhythm of melatonin secretion is synchronized to about 24 hours by the light-dark cycle acting via the retina. Meanwhile, jet lag is a common problem for air travelers after a flight through several time zones such as disturbed sleep, loss of mental efficiency and tiredness during the day. It seems to be due to the time required to resynchronize the body´s endogenous circadian rhythm to the night and day cycle of the new environment.

Several placebo-controlled field studies including cross-over design have been performed. It has been reported that both subjective and objective rhythms adapt more rapidly in the group (N=8) when treated with 5 mg of melatonin for three days before flight (18:00) and for four days after arrival (23:00) compared to the placebo group (N=9) (3). In a subsequent study with larger subject (N=52) conducted by the same group (4), significant improvement with melatonin treatment has been found compared to the placebo. Another similar study (N=37) (5) supports these findings. Moreover, it has been suggested that 5 mg of melatonin for three days prior to departure (10:00-12:00) and for four days after arrival (22:00-24:00) is superior to placebo in 20 volunteers (6). In a similar study using 52 aircrew (7), the group that received 5 mg of melatonin only after arrival has shown to decrease significantly in overall jet jag compared with those who received placebo, whereas the group that received 5 mg of melatonin prior to departure has reported worse recovery from jet lag and less energy and alertness than both the placebo group and the group that received melatonin only after arrival, though not statistically significant.

From the results of these five studies and summarized data about ten years of research of melatonin in treating jet jag (N=474) (8), melatonin appears to decrease jet lag symptoms and quicken the return of normal alertness and energy levels. Because of conflicting data, it is unclear whether melatonin should be taken before departure or only on arrival. There are also few data indicating the optimal dosage and duration of melatonin treatment in this disorder.

The Swedish Medical Products Agency has seriously questioned the use of melatonin due to the lack of scientific information (9). 1 Drugline no 13542 (year 1996) 2 Drugline no 12627 (year 1995) 3 Arendt J, Aldhous M, English J, Marks V, Arendt JH, Marks M, Folkard S: Some effects of jet-lag and their treatment by melatonin. Ergonomics 1987; 30: 1379-1393 4 Arendt J, Aldhous M: Further evaluation of the treatment of jet-lag by melatonin:a double blind crossover study. Ann Rev Chronopharmacol 1988; 5: 53-55 (Waiting reference) 5 Claustrat B, Brun J, David M, Sassolas G, Chazot G: Melatonin and jet lag: confirmatory results using a simplified protocol. Biol Psychiatry 1992; 32: 705-711 6 Petrie K, Conaglen JV, Thompson L, Chamberlain K: Effect of melatonin on jet lag after long haul flight. Br Med J 1989; 298: 705-707 7 Petrie K, Dawson AG, Thompson L, Brook R: A double-blind trial of melatonin as a treatment for jet lag in international cabin crew. Biol Psychiatry 1993; 33: 526-530 8 Arendt J, Deacon S: Treatment of circadian rhythm disorder-melatonin. Chronobiol Int 1997; 14: 185-204 9 Information från Läkemedelsverket 2:96, p. 5