WHAT IS MELATONIN?

MELATONIN

Melatonin is widely sold in capsule or tablet form in health-food stores as a treatment for jet lag and other sleep disorders, as well as a cure-all that can prevent aging and such diseases as cancer. It could be called the pro­totype herbal drug. Melatonin is the molecule released by the pineal gland, so it is a normal part of the human body. It has been the object of scientific study, and some of the claims of substantial effects have been borne out in these studies. In fact, one of the most recently marketed sleep aids (ramelteon, Rozerem) is a melatonin mimic, and several more are in development. On the negative side, however, scientists have not estab­lished a clear-cut safe and effective dose, the safety of long-term use has never been established, and the content of preparations marketed as mel­atonin is unregulated and varies widely.

WHAT IS MELATONIN?

Melatonin is a neurotransmitter that is structurally related to serotonin. It is produced mainly by the pineal gland (a tiny gland that sits on top of the brain), by the retina, in the GI tract, and by some immune cells. Mela­tonin is released only at night. Visual signals travel from the eye to an area in the brain that sets the circadian rhythm, and then to the nerves that travel to the pineal gland and cause it to release melatonin into the bloodstream, where it has some of its actions. Melatonin is very fat soluble and easily enters the brain (whether from a pill or your own natural mela­tonin) and acts on receptors at certain places in the brain. Melatonin mainly acts on two receptors (MT1 and MT2) and also has actions medi­ated by nuclear hormone receptors and the direct interaction with cellu­lar constituents.

MELATONIN AND SLEEP

The very marked day-night rhythm in melatonin release is one reason why melatonin is associated with sleep. Normally, when darkness falls, the nerves that stimulate melatonin release become active, which then acts on its receptors to trigger sleep.

A growing number of research studies show that if melatonin is taken at a time earlier than normal bedtime (such as in the early evening or late afternoon), it can help people fall asleep faster. Scientists have studied melatonin for jet lag, night-shift workers, some insomniacs—even astro­nauts in the space shuttle! Melatonin can help with jet lag if people take it at the time that they would go to bed in their destination. Results are more mixed in other situations.

MELATONIN AND FERTILITY

Does melatonin actually create day-night rhythms in other aspects of body function? It may contribute to the fall in body temperature that occurs at night. In species other than humans, melatonin may be very important in allowing animals to breed at appropriate times of the year. The shorter days and longer nights of winter cause an increasing release of melatonin. For some species, like sheep, which breed during the short days of winter, this increasing release of melatonin improves fertility, while it decreases fertility in animals like hamsters, which breed in the summer, when days are long. Melatonin has a much less certain role in human reproduction. Humans are not "seasonal breeders": they main­tain fertility throughout the year. This fits nicely with the fact that the nightly rises in melatonin are not as great in humans as they are in other animals. Can human reproduction be affected by causing a larger night­time rise in melatonin? Some scientific studies suggest that melatonin can decrease fertility in humans, although there is little research in this area. Melatonin (in doses that exceed usual doses by tenfold) has even been tested as a contraceptive, but given the possible side effects on sleep, it has some real disadvantages in comparison to more completely

tested medications.

MELATONIN AND AGING

Melatonin has a measurable antioxidant action in model systems, although we are less certain that it has this action in humans who take supplemental melatonin. Much of aging-related tissue damage and dis­ease may result from by-products of oxygen metabolism (oxygen radicals) that damage tissue. Certain compounds, such as vitamin E, are known to ‘`scavenge" and eliminate these products before they interact with pro­teins and DNA and thus produce tissue damage. The melatonin molecule can act directly as a radical scavenger, and giving melatonin to experi­mental animals can prevent the DNA damage caused by compounds  known to produce such oxygen radicals. However, this research is in its early stages, and effectiveness in lower primates or humans has not been tested. Again, taking a psychoactive compound that might suppress fer­tility for years to delay aging seems like a strategy that offers more risks than rewards.

MELATONIN AND OTHER HEALTH BENEFITS

Melatonin is also claimed to improve immune function, lower blood pres­sure, prevent bone loss due to aging, influence GI motility, and even reverse the graying of hair! While there are isolated studies to support these claims, research in these areas is not abundant.

IS MELATONIN SAFE?

Melatonin may be effective in some situations, but is it safe? In animal studies designed to test toxicity, it proved to be pretty safe. However, we don't really know what an effective dose is for a person. Doses in scientific studies range from 0.1 to 5 milligrams, but in most health-food stores, melatonin is sold in amounts ranging from I to 5 milligrams. Further, users can purchase and consume unlimited quantities. Excessive doses might affect reproduction or other aspects of body function. Finally, we do not know conclusively the long-term effects of this drug. It isn't even known whether melatonin is effective if given for a long period of time. Most sleep medications lose their effectiveness with time, and it wouldn't be surprising if melatonin did as well. If so, a dangerous situation could develop if a person started increasing his dose to compensate for the loss of effect.