MELATONIN

What is melatonin?

Melatonin is a hormone secreted by the pineal gland in the brain.

Melatonin has a rapid, mild sleepiness-inducing effect. Because of this trait, properly timed melatonin supplements may help people adapt to changes in sleep-wake schedules, as may occur after jet travel across many time zones or in shift work. The effectiveness of melatonin for relieving insomnia is uncertain.

How does melatonin work?

The secretion of melatonin follows a daily rhythm governed by the body's master clock. This clock is located in the brain and is synchronized by regular exposure to the 24-hour cycle of darkness and light. Melatonin secretion may serve as a biological time cue.

Although its natural secretion in the body peaks at night, melatonin does not control sleep. If it did, night workers would not be able to sleep in the daytime when melatonin levels are low. Although most people sleep longer and more deeply at night than in the day, melatonin most likely is only one of many factors accounting for the superiority of nighttime sleep.

How much melatonin does the body produce?

Healthy young and middle-aged adults usually secrete about 5 to 25 micrograms of melatonin each night - at least 80 times less than is in the commonly sold 2 milligram (mg.) tablet or capsule. The amount of melatonin the body secretes tends to decline with age, a possible link with an age-related rise in difficulty sleeping.

What is the appropriate dose range for melatonin pills or capsules?

Major questions in the research community are whether and how much melatonin is effective for the various applications described below. Recent studies mainly have used doses from 1 mg to 5 mg. Debate still centers around the essential action of the hormone - shifting the biological clock, promoting sleep, or both. Some studies have found clock-shifting results at the very lowest doses (1/2 mg.). Studies emphasizing sleep-promoting action have tended to use somewhat higher doses (2 to 5 mg.), although it is not certain that these are necessary to achieve the desired effect. Although these questions are not yet resolved, a basic clinical principle is to use the lowest dose effective for the individual and to work upward. The popular impression that "more works better' has not been borne out in many studies of melatonin, and larger doses probably carry a higher risk of undesirable side effects.

Can melatonin reduce jet lag?

If flying eastward, you need to go to sleep earlier and get up earlier. If flying westward, you need to stay up later and sleep later. For the first few days after crossing multiple time zones, you are likely to be both sleepy during the day and restless at night. Taking melatonin at the right time may help jet travelers adapt faster. Timing is critical. If you take melatonin at the wrong time, your body clock may travel in the wrong direction. You might leave New York en route to London, for instance, but send your body clock to Honolulu.

While timing, dosages, and length of use are still being worked out, reducing jet lag is the best-tested application for melatonin, and it may be among the safest, as low dosages are taken for only a few days. The plan below has been used in several studies without causing serious side effects. It assumes that the goal is to sleep during normal nighttime hours at the travel destination.

When traveling east:

• On the day of departure, between 6 and 7 p.m. on home time, on the flight if necessary, a dose of melatonin is taken. Cautionary note: melatonin may lower alertness. If it is taken before departure, the traveler should not drive himself or herself to the airport.


• On the day of arrival, melatonin is taken at the new local bedtime and continued for four days.


• If the stay is less than four days, and travel is going to continue further in an eastward direction, melatonin is taken between 6 and 7 p.m. the day before departure, not at bedtime.


• On the day of arrival, melatonin is taken at the new local bedtime and continued for four days.

When traveling west:

• Melatonin offers little or no advantage on trips of fewer than five time zones westward. The body normally takes only a day or two to adapt to such changes.


• When crossing more than five time zones westward, starting on the day of arrival, a dose of melatonin is taken at local bedtime, and continued for four days.


• It the traveler awakens before 4 a.m., another tablet or capsule may be taken.

Can melatonin help people fall asleep faster and sleep more soundly?

Melatonin induces sleepiness and lowers body temperature slightly; perhaps a further aid to sleep since temperature normally falls around the time sleep begins.

Several small studies of individuals suggest that some people with trouble falling asleep and/or staying asleep may benefit from taking melatonin at bedtime.

People who have trouble falling asleep at a conventional bedtime - often staying awake until 3 a.m. or later - but then sleep well may have a disorder of sleep timing called the delayed sleep phase syndrome. Taking melatonin two hours before their current bedtime may help them fall asleep earlier. They would gradually move back the hour they take melatonin until they reach their desired bedtime.
Other people have the opposite problem. They cannot resist falling asleep earlier than a conventional bedtime: 9:00 p.m., for example. They then may awaken fully alert around 3 a.m. and be unable to fall back to sleep. Some people with this problem, called the advanced sleep phase syndrome, benefit from taking melatonin if they awaken between 2 and 5 a.m.

Persons who are totally blind (lack all light perception) may notice cyclic trouble staying alert during the day and sleeping at night. Because synchrony of daily rhythms ordinarily requires daylight exposure, their melatonin secretion pattern may not be anchored to the normal 11 p.m. to 7 a.m. rest period. In experimental studies, tests of blood, saliva and urine have been used successfully to track the melatonin rhythm, determining when it is in synchrony with the desired bedtime. With this information, blind persons may be advised to take melatonin at bedtime from then on to keep their body rhythms in line. One impressive study of a series of cases of totally blind children with irregular sleep patterns, including daytime sleep, found major improvement when they were given melatonin at bedtime.
People who live in at a northern latitude and/or spend most of their time indoors with little daylight exposure also may suffer from a disturbed sleep/wake rhythm. Elderly persons who live in nursing homes or other institutions may be most susceptible to this problem. Taking melatonin at an appropriate bedtime may help provide stability, but concerns about possible interactions with other medication, especially in the elderly, demand caution. As yet, there have been no studies testing the effect of melatonin in demented elderly persons.

Can melatonin help shift workers?

Possibly, but most researchers feel it is too early to say.

The timing would depend on whether you rotate forward or backward around the clock, the number of hours you shift, and the type of work you do. Melatonin may lower vigilance for several hours after it is taken both on the job and when driving.

Can melatonin extend life?

No studies of humans support this notion. In one group of animal studies, the pineal glands of young mice were transplanted into old mice, and vice versa. The old mice allegedly lived longer. The young mice allegedly died sooner. Some strains of mice used in these studies, however, have a genetic defect that keeps them from producing melatonin. The alleged benefits therefore could not have come from melatonin.

Can melatonin boost the immune system?

While some positive evidence comes from animal studies, more work must be done to confirm and extend these findings. It is a big leap from mice to humans.

Can melatonin cure cancer?

Some positive evidence comes from animal studies. More work must be done to confirm and extend these findings in both animals and humans.

Can melatonin prevent heart disease?

No evidence supports this notion.

Can melatonin counter infertility? Or is it contraceptive?

In animals, melatonin both stimulates and inhibits reproduction. In humans, most studies suggest but do not prove that it inhibits reproduction. In men, high doses reportedly lower both sperm motility and sex drive.

How safe is melatonin?

Current research suggests it probably is safe to use melatonin if you are:

• over 18 years old, and healthy


• not pregnant


• not breast-feeding


• not taking other medications except for minor analgesics and oral contraceptives

What are melatonin's side effects?

About eight out of 100 people taking 5 mg. melatonin or less per day to prevent jet lag feel sleepy in the daytime. Fewer than two out of 100 on this dose suffer a headache, feelings of fuzziness or giddiness, or nausea. In research studies using doses up to 300 mg. daily, the side effects occurring most frequently were diarrhea, abdominal pain and headaches. Recent studies indicate that sleeping even in a dimly lit bedroom after taking melatonin may result in unpleasant, fragmented sleep. Lights should be off, and shades drawn.