Biology 103
2000 Third Web Report
On Serendip

Those who have traveled further than four time zones over a period of less than four days have probably experienced a condition commonly known as jet lag. A very brief, concise definition of it would be the interruption of digestive and behavior, especially concerning sleep. For a little more than the last ten years, melatonin in a synthetic form has been touted as a sort of miracle-cure for the problem, but the hormone's effectiveness concerning such has been surrounded by much controversy.

Melatonin is a hormone - a serotonin-derivative - produced in the pineal gland of the brain, and is thought to be responsible for the maintenance of the body's circadian system (which itself is in turn responsible for the regular maintenance of the biological processes of digestion and the sleep-wake cycle), as defined by the Journal of Travel Medicine(1), and "Go Ask Alice!", an health question-and-answer website maintained by Columbia University's Health Education Program (2). At least one of the reasons that it is thought to play such a role is because it is a light-sensitive hormone - i.e. when light is absent, it is secreted; the opposite happens when light is present. On an average nightly basis, between five and twenty-five micrograms are released into the body.

Jet-lag syndrome is a group of symptoms - including feeling tired during the day, insomnia at night, low levels of concentration, and disturbances in the digestive process - that occur when at least four time zones are crossed rapidly, according to the Life Extension Foundation (3), a nonprofit organization in Florida dedicated to scientific research concerning aging, and the Journal (1). In other words, the internal biological clock, or circadian rhythm, is disturbed by the body's slow adjustment to the new time zone, and this is displayed through the mentioned symptoms.

Ever since it was put into a synthetic form, melatonin has been praised as a sort of miracle cure for both those who suffer from chronic circadian-rhythm-related problems - i.e. blind people, since the substance is light-sensitive and regulates the sleep-wake cycle - as well as those who suffer from jet lag. However, in clinical trials that have taken place to test exactly how effective the commercial form of melatonin is, the results have been mixed; thus, it has its supporters as well as its skeptics. In its third quarter issue of 1998, the Journal of Travel Medicine reported that it knew of six such controlled trials with differing designs.

Four of the trials involved passengers on long-haul flights; one involved a cabin crew; and the last involved military personnel. The subjects of the first two trials were divided into two different types of groups: one was determined by whether they were taking melatonin or a placebo; the other was determined by which flight they were taking - either one that crossed eight time zones or twelve of them plus, for the latter, the journey back as well (1).

Passengers on both flights took either melatonin or the placebo two to three days before their flight, on the day of their flight, and for three to four days after their arrival. On the flight which crossed over eight time zones, none of the eight passengers taking melatonin experienced jet lag, whereas six of the nine that were taking the placebo did. As for the flight which included the crossing of twelve time zones and returning to the original point of departure, jet lag was reported as a score on a six-point scale, six representing severe jet lag: the subjects taking melatonin had a mean score of 2.2; those taking the placebo had a mean score of 3.4. Depending on which substance was taken, a normal circadian rhythm - observed through sleep patterns, energy levels, and absence of daytime tiredness - was established after three days of taking melatonin and three to four days of taking the placebo (1).

Passengers in the next two studies took either melatonin or the given placebo beginning the day of their departure and continued until either three or seven days after their arrival. In the first study carried out, there was no significant difference reported between the results of the melatonin group and the placebo group. In the second study, eleven of the fifteen participants taking melatonin reported that it was effective; five of those taking the placebo reported that the placebo was effective. The symptoms that are indicative of the normal maintenance of the circadian system were similar for both groups (1).

The effects of "early melatonin," or melatonin taken before the respective flight, "late melatonin," or melatonin taken after arrival, and a placebo were compared in the trial that involved the cabin crew. The participants in this study differed from those in the previous four in that their circadian rhythms had been severely off- balance for nine days before the trial. The results for jet lag for this trial were reported as mean scores on a one-hundred point scale, one-hundred being the maximum level of jet lag: those taking "early melatonin" had a score of 67; those taking "late melatonin" had a score of 38; and those taking the placebo scored 65 (1).

The last trial reported in the Journali involved military personnel, and, like the first four trials, tested simply the effects of a placebo against melatonin in counteracting jet lag. Those taking melatonin slept for longer than those participants taking the placebo. Those taking the placebo had difficulty in remaining asleep, and made more errors than the other group in a vigilance test. However, both groups reported having a similar mood and subjective fatigue (1).

OnHealth, a website associated with WebMD, reported in November 1999 a a later trial - and the largest to date (4). For six days after they returned to Oslo from a conference in New York, 257 Norwegian physicians that were still suffering from jet lag from their flight to the U.S. were given either melatonin or a placebo pill. Of the physicians taking melatonin, one group took five milligrams at night, another took 0.5 milligrams at night, and another took 0.5 milligrams early in the evening, and then followed by taking the same dose one hour early each consecutive day. After the first day, all subjects of the trial showed gradual improvement; however, no significant in jet lag symptoms between the different groups was observed.

Reuters Health reported the latest investigation of the effects of melatonin as currently prescribed for jet lag in November 2000 (5). Dr. Scott A. Rivkees and Haiping Hao from Yale University's School of Medicine gave three baboons differing doses of Melatonin over a two-week period - after measuring their circadian rhythms. They monitored the animals' activities in a room kept constantly dim for the next ten to fourteen days. In the end, melatonin failed to shift the baboons' circadian rhythms. They did not fall asleep when given melatonin during the day either.

Some of the earlier research surrounding melatonin's effect on inducing sleep and modifying the biological clock points to the conclusion that it is indeed effective towards neutralizing jet lag. However, it seems that the procedures carried out in that set of research were more crude and less controlled than the later, mounting research that contradicts that conclusion. In this respect, the most credible experiment was the one carried out with baboons, followed by the one involving the Norwegian physicians. As mentioned, investigators of both trials concluded from their results that melatonin as currently prescribed is not effective against jet lag, contrary to much current anecdotal evidence - and as mentioned, previous research.

WWW Sources

2) "Melatonin" , basic definition of melatonin

3) "Jet Lag", a series of short summaries of various articles related to melatonin, jet lag, and both

4) "Melatonin No Cure For Jet Lag" , 1999 article containing the results from the largest trial to date

5) "Melatonin No Cure For Jet Lag, But May Fight Insomnia" , the latest clinical trial concerning synthetic melatonin and its effect on the circadian rhythm

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