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Melatonin

Melatonin

Description

Melatonin is a hormone produced naturally in the pineal gland at the base of the brain. It is important in regulating sleep, and may play a role in maintaining circadian rhythm, the body's natural time clock. The hypothalamus keeps track of the amount of sunlight that is taken in by the eye. The less sunlight, the more melatonin that is released by the pineal gland, thereby enhancing and regulating sleep. Melatonin can also be taken in an over-the-counter supplement mainly sold in health food stores and pharmacies.

General use

A variety of medical uses for melatonin have been reported but its current popularity stems from its promotion as a sleep aid and to reduce jet lag . However, medical experts caution that melatonin is not a harmless substance without risks. Natural melatonin production decreases with age and the decrease is associated with some sleep disorders , particularly in the elderly.

According to a Gallup Poll taken in 1995 for the National Sleep Foundation, about half of all American adults experience either occasional or chronic sleep problems. The use of melatonin supplements became popular in the mid-1990s as a way of treating insomnia . Numerous scientific studies have supported this claim, although there are a few studies that cast doubt on its effectiveness. People reporting the most benefit generally are those with mild and occasional insomnia and trouble falling asleep. Melatonin is not generally recommended for use on a regular basis since its long-term consequences are not known.

The second most popular use of melatonin is to ease the effects of jet lag, a physical condition caused by the disturbance of circadian rhythms, usually associate with air travel across several time zones. In one study of airline passengers, melatonin relieved jet lag when taken before, during, or after an eastward flight but was less effective on westbound flights. Another study indicated it was effective only if taken before a flight. A 1999 study by researchers at Columbia University of 257 travelers found melatonin was no more effective than a placebo as a jet lag antidote.

However in 2002, a review of nine trials revealed that taking 5 mg of melatonin between 10 pm and midnight at the destination helped travelers fall asleep faster and sleep better.

Melatonin has also been touted by some as an anti-aging agent following the results of an experiment in Italy. An Italian researcher reported that in a laboratory experiment, older mice appeared to grow younger and live longer after receiving melatonin. However, there have been no studies in humans to support this claim. Animal tests in Spain and China have appeared to show that melatonin can help prevent some cancers, heart disease , and brain degeneration. Further studies on the benefits, long-term effects, and proper dosage are being conducted through the National Institutes on Aging.

In laboratory and animal experiments, melatonin appears to protect cells and boost the immune system. Melatonin supplementation is sometimes part of a holistic treatment regimen for people with HIV or AIDS . There have been no human trials that support this claim.

In 2002, researchers in Turkey presented preliminary results of a trails that suggested melatonin could be useful in protecting peripheral blood cells from the damage caused by radiation therapy treatments given to cancer patients.

Preparations

Melatonin is available over the counter in varying doses of up to 3 mg per tablet. However, a fraction of this is required for insomnia, usually about 0.3 mg or less. Too much melatonin or taking it at the wrong time can interrupt normal circadian patterns. Melatonin is produced at its highest level in the pineal gland during darkness. Since melatonin occurs naturally in some foods, it can be sold as an over the counter dietary supplement. It is only one of two hormones (the other is DHEA ) not regulated by the U.S. Food and Drug Administration (FDA). Natural, animal, and bovine melatonin supplements contain actual extracts from pineal glands. Synthetic melatonin is made from non-animal ingredients and is suitable for vegetarians. It is similar in molecular structure to melatonin produced in the body.

The proper dosage is not known, but it appears to differ greatly depending on the individual and extent of the sleep disorder. Persons starting the hormone should begin with a very low dose, 100-300 mcg, which is 0.1-0.3 mg, or less, and gradually increase the dosage if needed. Melatonin is quick-acting and should be taken about 30 minutes prior to bedtime. For jet lag, the general recommendation is 300 mcg just before boarding the flight and 1.5 mg after arrival before going to bed. Melatonin should not be taken during the day.

A researcher reported in 2002 that cherries, especially tart varieties, are very rich in melatonin. He recommended choosing firm, plump, shiny cherries with green stems and avoiding those cherries that have become soft or developed brown spots. They can be frozen whole with stems after rinsing and draining well, then spread in a single layer on a baking sheet and frozen until firm. Cherries can be frozen in plastic freezer bags or containers. Cherry juice also retains the antioxidants and melatonin present in the fruit.

Precautions

Women who are on estrogen or estrogen replacement therapy should not take melatonin without consulting their doctor. Since the safety of melatonin use during pregnancy has not been adequately studied, women who are pregnant or breast feeding a child should not take melatonin. Also, women who are trying to get pregnant should avoid using it since some research suggests it may have a contraceptive effect. Studies in animals suggest melatonin can constrict blood vessels, which can raise blood pressure. Therefore, persons with hypertension or cardiovascular problems should consult with their doctor before taking the hormone. It is not recommended for people with lymphoma or leukemia , and should not be used by children.

Side effects

Few studies have been done on the long-term effects or correct dosing of melatonin. In one study of melatonin, about 10% of patients said they experienced minor side effects such as nightmares, headaches, morning hangover, depression , and impaired sex drive.

Interactions

Melatonin should not be taken by people using certain antidepressants, such as Prozac (a serotonin inhibitor) or Nardil (a monoamine oxidase inhibitor). Interaction between melatonin and these types of antidepressants can cause a stroke or heart attack . Preliminary symptoms include confusion, sweating, shaking, fever , lack of coordination, elevated blood pressure, diarrhea , and convulsions.

Resources

BOOKS

Cernaj, Ingborg. Boost Your Vitality With Melatonin: Programming Your Internal Clock for Health & Well Being. Sterling Publications, 1998.

Olcese, James, ed. Melatonin After Four Decades: An Assessment of Its Potential. Plenum Publishing Corp., 2000.

Rozencwaig, Roman and Walji Hasnain. The Melatonin and Aging Sourcebook. Hohm Press, 1997.

Sahelian, Ray. Melatonin: Nature's Sleeping Pill. Avery Publishing Group, 1997.

Watson, Ronald R., ed. Melatonin in the Promotion of Health. CRC Press, 1998.

PERIODICALS

"A Bowl of Cherries: Rick in Antioxidants, Melatonin." Environmental Nutrition (July 2002): 8.

Cupp, Melanie Johns. "Melatonin." American Family Physician (October 1, 1997): 14211426.

Goodwin, Jan. "Live Longer, Live Better." Vegetarian Times (October 1998): 7481.

Greer, Michael. "Exogenous Melatonin Protects Peripheral Blood Cells." Drug Week (July 26, 2002): 7.

McBride, Gail. "Melatonin Disrupts Sleep in Smith-Magenis Syndrome." The Lancet (November 6, 1999): 1618.

"Melatonin Might Not Be a Jet Lag Antidote." Environmental Nutrition (December 1999): 7.

Monson, Nancy. "What Really Works for Jet Lag." Shape (August 2002): 78.

"Nighttime Hormone Helps Starve Cancers." Science News (Octpber 2, 1999): 221.

Scheer, James F. "Dream-Weaver: Melatonin." Better Nutrition. (April 1998): 4648.

Silberman, Alex. "Forever Young?" Vegetarian Times (February 2000): 66.

Ternus, Maureen. "DHEA, Pregnenolone Hormone Hype Heats Up; But What Do We Really Know?" Environmental Nutrition (Sept. 1997): 12.

ORGANIZATIONS

National Sleep Foundation. 1522 K St. NW, Suite 510, Washington, DC 20005. (202) 7852300. Fax (202) 3473472. http://www.sleepfoundation.org.

Ken R. Wells

Teresa G. Odle

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melatonin

melatonin A hormone derived from serotonin and secreted by the pineal gland and retinas of vertebrates. Melatonin secretion by the pineal is linked to the dark–light cycle of the organism's environment, being greatest at night and lowest by day. The hormone is involved in regulating certain diurnal and seasonal changes in the body, such as the reproductive cycle in seasonally breeding animals. Melatonin also controls pigmentation changes; it triggers aggregation of the pigment melanin into melanophores in the skin, causing the skin to turn pale.

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melatonin

melatonin (mel-ă-toh-nin) n. a hormone produced by the pineal gland in darkness but not in bright light. Melatonin is a derivative of serotonin, with which it works to regulate the sleep cycle.

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melatonin

melatonin: see pineal gland.

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Melatonin

MELATONIN

OFFICIAL NAMES: Melatonin, 5-methoxy-N-acetyltrypt-amine

STREET NAMES: Melliquid, mellow tonin, somniset

DRUG CLASSIFICATIONS: Not scheduled

OVERVIEW

Melatonin is a natural hormone produced by many animals. In humans, it is produced in several parts of the body, including the pineal gland, which is a small organ located at the base of the brain. Historically, the pineal gland was thought to have some sort of metaphysical function. It was often called the "third eye" and was said to be "the seat of the soul" by Descartes. It is now known to be involved in the neuroendocrine system, which involves the interaction of the nervous and endocrine systems (organs that produce hormones). This interaction results in the regulation of essential body functions. The neuroendocrine system is responsible for the fight or flight response, as well as many other processes that keep people alive and healthy. Melatonin is thought to be important in maintaining certain essential physiological functions such as sleep.

There are many nerve fibers in the pineal gland. Some of these fibers release noradrenalin, a chemical messenger produced by the nervous system. Noradrenalin stimulates certain cells in the pineal gland, called pinealocytes, to produce and release melatonin.

Some parts of the brain, like the cerebral cortex, are much more highly evolved in humans than in other animals. The pineal gland, however, is a very basic organ that first evolved in primitive species. It is found in lampreys, fish, amphibians, and reptiles, as well as in mammals. The hormone melatonin has also been found in insects and plants.

Researchers first hypothesized the existence of melatonin almost 100 years ago. Back in 1917, scientists noticed that an unknown substance from the pineal gland affected melanophores, a kind of pigment cell found in frog skin. More than 40 years later, a dermatologist, Dr. Aaron Lerner, finally isolated this substance from the pineal gland and named it melatonin.

Over the next few decades, researchers learned that melatonin had many other effects in addition to influencing pigmentation in amphibians. Most current research has studied its influence on promoting sleep. Other studies have linked this hormone to other processes such as reducing jet lag, boosting the immune system, and fighting cancer.

Scientists have learned that the retina of the eye and parts of the gastrointestinal tract also produce melatonin. It is not known if the function of melatonin produced by these parts of the body differs from that made by the pineal gland.

The production of melatonin varies over the course of a day. Darkness stimulates the pineal gland to produce melatonin, while the presence of light inhibits the release of this hormone. Melatonin levels are so low during the daytime that they are almost immeasurable. The amount of melatonin starts to increase around 9 p.m. or 10 p.m. Levels continue to increase during the early part of the night and peak at about 2 a.m. to 4 a.m. and thereafter start to decrease through the rest of the morning.

While everyone follows this general pattern of diurnal melatonin secretion, each individual has his or her own unique pattern. Melatonin peaks and valleys can occur at different times in different people and may explain why some individuals are "morning" people, while others are "night owls."

This circadian rhythm of melatonin production is not limited to humans and animals. Certain types of alga show a daily variability in their synthesis of melatonin. Darkness stimulates melatonin production by these one-celled creatures.

The presence of light influences the pattern of melatonin release. In some people, melatonin is secreted for a shorter period during the shorter nights of summer. But in winter, melatonin release lasts longer during the prolonged darkness in these susceptible individuals. Some scientists hypothesize that this variation in melatonin production may be responsible for seasonal affective disorder (SAD). SAD is a form of depression that occurs during the winter. It is frequently successfully treated by exposure to artificial light.

Artificial light, like natural light, influences the synthesis of melatonin by the pineal gland. Exposure to light during the night will inhibit melatonin production. Research results show that women who work night shifts have an increased risk of getting breast cancer; scientists are investigating whether this alteration in melatonin production may be linked to the development of cancer.

Melatonin secretion also varies over the course of a lifetime. Newborn babies produce very little of this hormone, but after the first few months of life the pineal gland increases its production of melatonin. Very small babies produce a relatively constant amount of melatonin throughout the day and night. They do not have any diurnal variation in the production or release of melatonin. It is not until infants are between nine and 12 weeks old that the pineal gland starts to shift towards a nocturnal production of this hormone. Highest levels occur in children who are about four to seven years old. Older children and adults produce smaller amounts, as production gradually decreases during puberty. The typical adult male produces about 30 micrograms of melatonin during a typical day.

Because melatonin production goes down during puberty, some researchers suspect that the decreasing levels of this hormone are somehow linked to sexual maturation. Melatonin also influences the levels of certain reproductive hormones such as prolactin and luteinizing hormone. Due to these effects, many experts recommend that children, teenagers, pregnant women, and breastfeeding mothers do not take melatonin.

Researchers used to think that older adults produced very little melatonin. Since the elderly tend to have more problems with insomnia and other sleeping disorders, scientists hypothesized that these lower levels of melatonin were the cause of sleeping problems in this population.

However, a study published in the January 2001 issue of the American Journal of Physiology showed that melatonin levels are just as high in older adults as they are in younger individuals. Dr. J. B. Fourtillan measured melatonin levels in 34 healthy adults who were over 65 years of age and in 101 healthy adults who were under 30 years of age. The levels of this hormone did not differ between the two age groups.

Researchers still need to learn a lot about what melatonin does and how it can be safely used. Scientists have not completed enough studies to know exactly what functions melatonin carries out in the human body. Similarly, physicians do not understand at what time during the day or night melatonin should be taken or what dose is most effective. Nor do physicians know enough about the long-term effects of taking melatonin since it has only became popular in the 1990s.

In spite of this lack of information, several popular books came out during the 1990s advocating the supposed usefulness of melatonin as a treatment for everything from insomnia to jet lag to aging. Consumer interest in melatonin increased dramatically. It is estimated that millions of Americans take melatonin supplements as a "natural" remedy.

Although melatonin is a hormone and a drug, it is not regulated by the Food and Drug Administration (FDA). That is because melatonin is naturally found in certain foods. However, the amount of melatonin in over-the-counter medications is a great deal higher than what is found in food, or is produced by the human body. A typical supplement may contain anywhere from 500 micrograms to 5 mg. A supplement containing 500 micrograms will produce blood concentrations similar to those normally found in the human body. Doses of 1–5 mg will result in blood levels anywhere from 10 to 100 times higher than normal.

Melatonin can have different effects depending on when it is taken. If taken slightly before bedtime, it may be useful in adjusting a person's sleep schedule following a long flight. Taken during the day, however, it will not change the sleeping pattern; it will just make the person sleepy. Similarly, some cancer research suggests that melatonin may be helpful as a cancer therapy if given at the correct time of day. If it is given at the wrong time, it may end up having no effect or may actually increase the risk of developing cancer.

Because melatonin is not regulated by the FDA, commercially available preparations are not subject to the same scrutiny as medications under the direction of this federal agency. Melatonin supplements do not have to be extensively tested in animals and humans before being sold in over-the-counter preparations. Manufacturers do not have to maintain high production standards, nor do they have to be as concerned with instituting FDA-required safety checks. Manufacturers are, however, limited by law in one way: They cannot claim that their product will cure or treat anything. They can only make general statements. While they can say that melatonin helps people sleep, they cannot say that it treats insomnia.

CHEMICAL/ORGANIC COMPOSITION

Melatonin is made from tryptophan, a type of amino acid. Pinealocytes absorb tryptophan from the blood. Through a series of chemical reactions, the pinealocytes then convert the amino acid into melatonin.

Melatonin is a relatively simple type of chemical compound. It is rapidly absorbed and will reach its peak concentration within about an hour after it is swallowed. Melatonin is fat soluable, which means it is able to enter all the cells of the body, including brain cells. So melatonin can easily leave the bloodstream and enter brain cells. But melatonin does not remain in the bloodstream for very long as it is quickly broken down by the liver. It takes about 30 to 40 minutes for the liver to remove one half of the melatonin that is present in the blood.

Many over-the-counter drugs contain melatonin. Some of these products are made from animal sources. However, most commercially available melatonin is synthetic.

Since melatonin is naturally found in some foods, it is legal to sell it as a dietary supplement in the United States under the U.S. Dietary Supplement Health and Education Act (DSHEA) of 1994. Dietary supplements like multivitamins are not as carefully regulated by the federal government as are prescription medications. However, the amount of melatonin in food is very low. A person would have to eat 120 bananas or 30 large bowls of rice to get the same amount of melatonin that is contained in a 3-mg capsule. The amount of melatonin contained in dietary supplements is much, much higher than that produced by the pineal gland or obtained through food.

Since commercially available drugs containing melatonin are not regulated, they are not held to the same high standards of purity and efficacy as are other medications. Melatonin, being a hormone, is just as potentially dangerous as other naturally occurring substances such as estrogens and androgens.

Drugs that are not regulated by the FDA are more likely to be contaminated with impurities. They may also be inaccurately labeled and not contain the amount of melatonin listed on the label. According to the National Sleep Foundation, a batch of melatonin was examined and found to contain much more of the hormone than was listed on the label. According to another study, one third of the medications that supposedly contained melatonin did not contain any melatonin, while an additional 40% contained much less than was stated on the label.

While many commercially available preparations contain only melatonin, many others contain a combination of this hormone with other active ingredients. Some of these other ingredients may be vitamins such as pyridoxine, while others are natural remedies such as kava root and valerian. It is even available combined with acetaminophen, a common over-the-counter pain reliever. Frequently, the long-term effects and safety of these other ingredients are not known. Even less is known about any possible interactions between these substances and melatonin, because melatonin has been available and used commercially for only a short period of time. Many experts have suggested that it would be preferable to test melatonin in controlled studies to determine if it is effective and safe before it was released on the market and used by millions of people.

INGESTION METHODS

Melatonin is usually taken orally. It is available in pills, capsules, and liquids. It also can be absorbed from under the tongue. It is sometimes injected when it is used as a treatment for cancer.

Most commercial preparations contain much higher doses than the 30 micrograms typically produced by an average adult male. While researchers do not know what dose may be optimal for therapeutic use, several studies indicate that between 0.5 to 5.0 mg is sufficient for treating jet lag. Some studies suggest that time-release forms, however, may be ineffective.

The natural production of melatonin by the pineal gland varies during the course of a day. Melatonin levels are very low during the daylight hours and increase when it is dark. The time a person swallows an over-the-counter formulation of melatonin is just as important as the amount ingested. Taking melatonin during the middle of the day may not help people to sleep better at night and, instead, may make them tired and decrease their alertness.

Slow-release capsules are also available. However, the results of a review of 10 studies that investigated the effectiveness of melatonin for treating jet lag indicated that time-release capsules are not effective for treating jet lag.

THERAPEUTIC USE

Melatonin may be an effective treatment for several conditions. Studies suggest that it may be helpful in treating sleep disorders, jet lag, and even cancer. However, research on this topic is still very limited and experts have warned consumers that very little is known about the effectiveness or long-term safety of taking melatonin supplements.

Sleep disorders

While the popular press has publicized the usefulness of melatonin as a natural sleeping aid, the results of studies are often contradictory. Some studies suggest that melatonin is helpful in treating insomnia, while others have shown that it is absolutely useless.

Researchers still have not investigated melatonin's effectiveness in treating insomnia in most age groups. As of 2000, only three studies had investigated the usefulness of melatonin in treating insomnia in people younger than 65 years of age.

While the effectiveness of melatonin in treating sleep disorders in most people remains unclear, research shows that it can be helpful for certain individuals. For example, many blind people have sleep disorders, and melatonin has been shown to help promote sleep in this population. Studies have also shown that it is helpful in treating sleep disorders in disabled children.

Jet lag/shift work

People and animals follow a natural circadian rhythm. Humans and many animals tend to be diurnal. They get up in the morning, are active during the day, and sleep at night. Disruptions in this natural cycle can be difficult. With the advent of air travel, people could travel halfway around the world, passing through several time zones. Their circadian rhythm can be very disrupted by the time differences. Besides having difficulties sleeping at the appropriate time, people with jet lag may also experience constipation and other digestive difficulties.

Shift workers have a similar difficulty in trying to stay awake at a time when they would normally be asleep. Nurses working an evening shift may start to get sleepy while they are still at work, while those on the morning shift may have a great deal of difficulty getting up well before dawn.

Melatonin may be helpful for both shift workers and air travelers trying to adjust to the local time. According to a paper published in 2002, nine out of 10 studies that investigated the effectiveness of melatonin in treating jet lag demonstrated that melatonin did help ease this condition. Individuals who had traveled across five or more time zones and then took melatonin close to the time they wanted to fall asleep were more easily able to make the adjustment to local time. Doses between 0.5 mg and 5 mg were effective, although the larger dose helped a bit more in promoting sleep. Larger doses did not provide any additional benefits. Reviewers suggested that melatonin was more effective when crossing more time zones and for eastbound travelers. The study review also indicated that time-release preparations or


taking any form of melatonin earlier in the day was ineffective. Not only was it not helpful, but taking melatonin during the middle of day just made people sleepy and delayed their adjustment to the local time.

While more research is needed, a few studies indicate that melatonin can help people adjust to working the night shift. It can also help people readjust back to sleeping during the night and staying awake during the day when they discontinue working the night shift. In one study of 32 night workers published in 2002, those taking 0.5–3.0 mg of melatonin during the afternoon helped them sleep during the day before leaving for work.

In addition to questions concerning the effectiveness of melatonin for any condition, researchers still do not know enough about the long-term consequences of taking melatonin on a regular basis. Many experts caution that until melatonin has been proven to be safe and not cause serious side effects, using it as a therapeutic agent is too risky.

Cancer

In the 1970s, researchers noticed that the amount of melatonin found in the blood of certain cancer patients was lower than in healthy individuals. Soon afterwards, other studies showed that the nighttime increase in melatonin, which occurs naturally in most humans, was markedly decreased in some cancer patients.

Experts are not sure how melatonin influences the development of cancer. A recent study published in 1999 in Cancer Research suggests that melatonin may help to starve cancer cells. Tumors use a type of fat called linoleic acid as a food source. Melatonin prevented the tumor cells in rats from being able to metabolize linoleic, but only when it was given to rats during the late afternoon. When it was given to the rats earlier in the day it did not have any effect.

Most of the research investigating the effectiveness of melatonin in treating cancer have been conducted in rats and mice, or in test tube samples of human cells. However, there have been several clinical trials that show that melatonin may be helpful as a therapy for different types of cancer. Again, timing of the dose is very important. Several other studies have shown that melatonin is not effective, or even promotes tumor growth, depending on when during the day it is given.

Other conditions

While melatonin is not currently being used to treat these conditions, research is currently underway investigating its role in preventing Alzheimer's disease. A study published in Biochemistry in 2001 showed that melatonin can inhibit the development of amyloid beta, a toxic substance that has been linked to the development of Alzheimer's. Other studies suggest that melatonin may be helpful in reducing the side effects caused by medications that are used to treat schizophrenia.

USAGE TRENDS

No one knows the exact number of people who use melatonin. According to a CNN report, 20 million Americans have taken melatonin to treat jet lag or sleeping disorders. It is legal and therefore easy to buy this hormone in over-the-counter medication in the United States. Several other countries have had a different attitude towards such widespread use of a potentially dangerous hormone; several European countries and Canada restrict the sale of melatonin.

Scope and severity

While it is estimated that millions of Americans have taken melatonin, the scope and severity of its use in the United States is unknown. Regardless, the use of this hormone is probably much higher in the United States where it is legal than in Canada or Europe where it is not.

Age, ethnic, and gender trends

Since the elderly tend to have more problems with insomnia than do younger individuals, it is thought that this age group is more likely to use melatonin. However, there is no proof that this is true. Research studies investigating which groups use melatonin are needed before it is possible to definitively state who is more likely to use this hormone.

MENTAL EFFECTS

Very little is known about what types of long-term psychological effects can be caused by the use of melatonin.

It is clear, however, that melatonin has short-term mental effects. It definitely can cause drowsiness when taken during the day. Melatonin taken at night, however, will not cause daytime sleepiness. People who take melatonin are also less likely to respond correctly to visual and auditory signals. They are more likely to make mistakes and their reaction time decreases when they take this hormone. Several studies have shown that taking melatonin inhibits a person's ability to concentrate and can cause confusion. People should therefore not take it when they need to stay alert, such as when they will be driving a car. The effects begin within approximately an hour of taking melatonin and last for about two hours.

Some experts are concerned that melatonin may worsen depression and recommend that people who have a mental illness not take this hormone.

Paradoxically, when taken with other drugs, melatonin may have very different mental effects. It tends to stimulate some of the biochemical effects caused by methamphetamines; it can end up aggravating insomnia, instead of causing sleepiness, when taken with these drugs. Taking melatonin with benzodiazepines has been reported to cause anxiety.

PHYSIOLOGICAL EFFECTS

Melatonin causes general effects that are felt throughout the body and specific effects on certain organs. Melatonin reduces body temperature so people may feel slightly cooler after they take a supplement containing this substance in addition to becoming sleepy. Melatonin produced by the pineal gland also has this effect. However, there is a slight variation in the ability of melatonin to reduce body temperature. Melatonin is not as effective at lowering body temperature during the luteal phase of the menstrual cycle, which is just before ovulation. Physicians and many women have long known that a woman's body temperature increases slightly just before ovulation.

Melatonin also causes vasoconstriction, which is the narrowing of the blood vessels.

Sleep/circadian sleep rhythms

The most well-known effect of melatonin is that it regulates the sleep cycle. Production of melatonin by the pineal gland increases with darkness. Increased melatonin levels, in turn, promote sleep.

Melatonin is not essential for sleep to occur. Many people take naps during the daylight hours and can stay awake into the early hours of the morning, although melatonin levels are very low at this time. Still, most people find it very difficult to stay awake all night and sleep during the day. Melatonin does, somehow, make sleeping easier. The abnormal production of melatonin has been linked to sleeping difficulties. Many blind people who do not have any perception of light also have an abnormal pattern of melatonin production. They may not have higher levels during the night or their highest levels of melatonin can actually occur during the day. These individuals tend to have sleeping disorders. They may have difficulty sleeping at night and take naps during the daytime. Exactly how melatonin is related to the maintenance of a normal sleep cycle is not yet understood.

Reproductive effects

Melatonin influences the level of other hormones in the body. It has been shown to have a particularly strong effect on prolactin and luteinizing hormone, both of which are major reproductive hormones. Some authorities caution that it may reduce the sexual drive in men.

The natural production of melatonin by the pineal gland peaks at the age of only four or five years of age. Since a decrease in its production occurs during sexual maturation, researchers warn that taking it during adolescence may have a detrimental effect on puberty.

Immune effects

Melatonin has been shown to boost certain parts of the immune system. It boosts the activity of natural killer cells, a type of immune cell. It also prevents apoptosis, a type of destruction of T-lymphocytes, which are other important immune cells found in the bloodstream. Melatonin also limits the effect of corticosteroids on the immune system. Corticosteroids are very potent drugs that are sometimes used to inhibit the immune system. Some people have autoimmune diseases in which their immune system attacks the cells of their own bodies. Physicians frequently prescribe corticosteroids for these individuals.

Harmful side effects

As there has been very little research studying the safety of taking melatonin, most experts caution people against using it, or to limit their intake of it. However, it is known that melatonin may be particularly dangerous for certain people. People should not take melatonin if they:

  • Have not finished, or even started, puberty. The decreased production of melatonin by the pineal gland that occurs during late childhood and early adolescence may be linked to sexual maturation.
  • Are breast-feeding. Melatonin affects the level of prolactin, a hormone that controls the production of breast milk.
  • Are pregnant. Melatonin influences the levels of various sex hormones.
  • Have a history of stroke or other cerebrovascular disease. Melatonin causes vasoconstriction, which, under certain circumstances, can be a risk factor for cerebrovascular disease.
  • Have a history of liver disease. Melatonin is metabolized in the liver. Melatonin may remain within the body for a longer time and in larger amounts if the liver is not able to break down this hormone so that it can be excreted.
  • Have an autoimmune disease. Melatonin has been shown to boost some processes of the immune system. People who have an autoimmune disease already have an overactive immune system, which is attacking their own body. Taking a substance such as melatonin, which further stimulates immune activity, may make their symptoms much more severe.
  • Are depressed or have a neurological disorder. Although melatonin may be linked to the development of seasonal affective disorder (SAD), its exact role in emotional and neurological illnesses remains unclear.
  • Take certain medications such as benzodiazepines, methamphetamines, dehydroepiandrosterone, magnesium, zinc, corticosteroids, and succinylcholine.

Melatonin can cause some adverse effects. People should contact their health care provider if they have difficulty sleeping or feel too sleepy, develop a headache, chills, or itching, feel confused, or have a fast pulse after taking melatonin. Individuals who will be undergoing surgery should tell the anesthesiologist that they have been taking melatonin.

Long-term health effects

No one knows what kind of effects may result after taking melatonin for a long period time. It has not been studied and its widespread use only started during the 1990s. Many experts strongly warn people not to take melatonin, or to at least limit their use to a short period of time such as for a few days after taking a long trip as a short-term treatment for jet lag. But some experts caution that withdrawal may occur after taking very high doses of melatonin.

REACTIONS WITH OTHER DRUGS OR SUBSTANCES

Much remains unknown about melatonin's interaction with many other drugs and substances. However, it is known that melatonin does interact with, and may limit the effectiveness of, benzodiazepines, methamphetamines, dehydroepiandrosterone, magnesium, zinc, corticosteroids, and succinylcholine. People who are being treated with these drugs should not take melatonin.

Interactions between drugs or substances and endogenous melatonin

Selective serotonin reuptake inhibitors (SSRIs) are a type of antidepressant that stimulates the pineal gland's ability to produce melatonin. Antipsychotic drugs also have this effect. Other medicines have the opposite effect. Certain types of medicines used to treat cardiovascular disease called beta blockers reduce the production of melatonin by the pineal gland. Nonsteroidal anti-inflammatories, which are used to treat pain and/or fever, benzodiazepines, and caffeine also inhibit the production of melatonin.

Interactions between drugs or substances and exogenous melatonin

Individuals who take melatonin supplements and benzodiazepines may feel very anxious and unsettled. Instead of causing sleepiness, melatonin can aggravate insomnia when taken with metamphetamines.

TREATMENT AND REHABILITATION

Currently, there are no treatment or rehabilitation options for people who use melatonin. It is not known if long-term users may have difficulty with sleeping or other side effects when they quit taking melatonin supplements. Discontinuing the use of melatonin after short-term use, such as for adjusting to jet lag, has not proved to be difficult or to cause any side effects.

Some experts, however, are concerned that abruptly discontinuing the use of melatonin after taking very high doses may result in withdrawal. Whether or not this is truly the case, or how it is best to deal with any symptoms of withdrawal, is not known.

PERSONAL AND SOCIAL CONSEQUENCES

The long-term personal and social consequences of routinely using melatonin are not known. It is known, however, that millions of people take over-the-counter melatonin preparations containing very large doses of melatonin relative to the amount produced by the human body or contained in foods. Even less is known about its interaction with other drugs or "natural remedies." Many experts are concerned that such large-scale use of a hormone may not be safe. Serious health implications of using melatonin may not be discovered until many people have placed themselves at risk.

Melatonin can cause unpleasant side effects, even when taken for a short period of time. The use of melatonin has been linked to sleepiness, confused thinking, rapid heartbeat, chills, headache, inability to sleep, and itching. People who experience these symptoms when using melatonin should contact their health care provider.

LEGAL CONSEQUENCES

It is legal to possess and use melatonin in the United States. However, it is illegal to use melatonin without a prescription in other countries.

RESOURCES

Books

Shneerson, John. Handbook of Sleep Medicine. Oxford, UK: Blackwell Science Inc., 2000.

Smokensky, Michael, and Lynne Lamberg. The Body Clock Guide to Better Health. New York: Henry Holt & Company, Inc.,2000.

Periodicals

Pray, W. Steven. "Consult Your Pharmacist—The Sleep-Wake Cycle and Jet Lag." U.S. Pharmacist 24 no. 3 (1999): 10.

"What About Melatonin?" Nursing (May 2001).

Other

"Melatonin." May 2002 (July 8, 2002). <http://www.familydoctor.org/handouts/258.html>.

"Proper Dose of Melatonin Curbs Insomnia in Older Adults." 2002 (July 8, 2002). <http://www.endo-society.org/pubrelations/pressReleases/melatonin.cfm>.

Organizations

National Sleep Foundation, 1522 K Street, NW, Suite 500, Washington, DC, USA, 20005, (202) 347-3471, (202) 347-3472, [email protected], <http://www.sleepfoundation.org>.

Sue Wallace

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Melatonin

Melatonin


What Kind of Drug Is It?

Melatonin is a dietary supplement sold without a prescription at U.S. health stores or through Web sites. It is sold primarily as a sleep aid because it induces sleep. Researchers have studied melatonin's potential benefits for certain conditions, such as insomnia (difficulty sleeping); jet lag; and even cancer (the uncontrolled, abnormal growth of cells that can lead to serious illness and death).

However, taking melatonin supplements has not been proven by scientific studies to be effective for any condition. Much more research needs to be done to prove the positive claims of melatonin use. Also, because it is considered a dietary supplement, it is not regulated by the U.S. Food and Drug Administration (FDA). This means that the supplements are not produced under the strict guidelines of the FDA, so their side effects and long-term effects are not clearly known.

Melatonin is a hormone—a substance created by the body to control certain bodily functions. It is found naturally in humans and other animals. It is secreted by the pineal (PY-nee-uhl) gland, which is located in the middle of the brain. Melatonin helps to regulate when animals, including humans, fall asleep and when they wake up. This sleep/wake cycle is known as the circadian rhythm (sir-KAY-dee-in RIH-thum), the twenty-four-hour sleep/wake cycle in humans and other animals. Some people believe that taking melatonin supplements can help alleviate problems that can occur when this cycle is disrupted.

Official Drug Name: Melatonin, 5-methoxy-N-acetyltryptamine

Also Known As: Mel, Melliquid, mellow tonin, MLT, somniset

Drug Classifications: Not scheduled

Overview

Sleeping is a part of life. It allows the body to rest and repair itself after physical activity. Ruth Winter, writing in The Anti-Aging Hormones: That Can Help You Beat the Clock, stated that "most people need at least seven and a half hours [of sleep] to function adequately and be fully alert the next day, but some may need as little as five while others need nine to ten hours." Lack of sleep can cause a host of problems such as fatigue and poor mood. Thus, it is important to have a normal sleep/wake cycle for good health.


Melatonin plays an active role in maintaining a regular schedule for sleeping and waking. It induces sleep when it is secreted into the bloodstream by the pineal gland, a pea-sized gland that is part of the endocrine system. Darkness stimulates its secretion, while light, both natural and artificial, inhibits it.

The Dracula of Hormones

Melatonin has been called the "Dracula of hormones" because, like the vampire Dracula, it only comes out at night. Usually around 9 p.m., after daylight fades away and darkness arrives, the pineal gland begins releasing melatonin, causing sleepiness and initiating a decline in body temperature. The hormone is continually released throughout the night as the body sleeps until about 9 a.m. the next morning, when it is light again. Peak production occurs approximately between 2 a.m. and 4 a.m.

In the morning, when light hits the retina, messages are sent to the hypothalamus in the brain. In the hypothalamus, the messages find the suprachiasmatic (SOO-pruh-ky-uhz-MAH-tik) nucleus (SCN), prompting the SCN to send signals to the glands that control hormones, including the pineal gland. When the pineal gland receives a message from the SCN, it slows down the release of melatonin until darkness comes and it is time to sleep again. Daytime melatonin levels are so small they are usually undetectable. The decrease of melatonin in the morning signals the body temperature to rise, and the body feels awake and alert.

Discovering Melatonin

For centuries, the function of the pineal gland was unknown. This was partly due to the fact that melatonin is created in very small amounts, smaller than any other hormone, and is hard to detect. In the 1950s, Yale University dermatologist Dr. Aaron Lerner was conducting research on skin pigmentation, or color. Thinking the pineal gland may be involved in skin pigmentation, he began the process of trying to isolate a molecule from this gland that he believed may be responsible for lightening skin. In 1958, Lerner was finally successful in isolating a molecule from the pineal gland.

Because the molecule is chemically related to melanin (skin pigment) and serotonin, Lerner named his discovery melatonin. Though melatonin lightened the skin of frogs, it did not affect the color of the skin of humans. In the end, Lerner did not find a molecule that would help his research, but he did help answer the mystery of the pineal gland. He discovered a very powerful hormone that has helped researchers understand more about the human sleep/wake cycle.

After Lerner's discovery, other scientists began testing melatonin to see what benefits it may have. They found that injecting synthetic (human-made) melatonin into people could cause a tranquilizing effect and induce sleep. From there, more studies were done, and eventually melatonin was made into a dietary supplement that could be self-administered.

The Melatonin Craze


In the mid-1990s, when melatonin supplements became available without a prescription, a frenzy over the possible benefits of taking these supplements occurred. Some called it a "miracle" or "wonder" drug. Many praised it as an immune-booster, a youth serum, a cancer-fighter, and a cure for insomnia.

Various books were written about the wonders of melatonin. The craze eventually died down, and, as of the early twenty-first century, research has not been able to prove or disprove the benefits of melatonin. In 2000, University of Surrey's Josephine Arendt discussed the supplement. As quoted by Elizabeth Cohen in "Study Bolsters Melatonin Sleep Claims" on CNN.com, Arendt stated that "the hype and claims of the so-called miraculous powers of melatonin several years ago did a great disservice to a scientific field of real importance."

Melatonin as a Supplement

In 1994 melatonin became available over the counter as a dietary supplement. Manufacturers claimed melatonin could bring on sleep, ease jet lag, and more. Studies have been conducted and books written on the potential benefits of melatonin, but no one has been able to prove or disprove these claims. Most research suggests that melatonin can help regulate the sleep/wake cycle for conditions such as insomnia and jet lag, as well as problems from shift work (people working at night and sleeping during the day). It has also been regarded as an antioxidant and an immune-booster. Some people believe it also combats aging.

What Is It Made Of?

Melatonin is a hormone found naturally in the human body, in other animals, in certain plants, and even in some foods. It is made from tryptophan (TRIP-tuh-fan), an essential amino acid. When tryptophan is ingested, the body turns it into serotonin that is then made into melatonin. The pineal gland is the primary location for melatonin production but the retina and intestines make small amounts as well.

Melatonin supplements are either synthetic (human-made) or natural (contain animal products). They are chemically identical to the melatonin that is produced by the human body. Some people think that using the natural melatonin, typically made from the pineal glands of animals such as sheep, run a greater risk of being contaminated by a virus. Therefore, the synthetic version is the most recommended and most popular form of melatonin. However, since the FDA does not regulate it, one can never be sure of the effectiveness, purity, or safety of the supplement.

The Trouble with L-tryptophan


Tryptophan is an essential amino acid from which melatonin is made in the body. It was once available as a dietary supplement, known as L-tryptophan. Much like melatonin, it was marketed as a sleep aid. However, in 1989, a batch of L-tryptophan pills (all made in Japan) was contaminated and caused 1,500 people to contract the disease eosinophilia-myalgia syndrome (EMS; pronounced ee-oh-sin-oh-FIHlee-uh my-AL-jee-uh). EMS causes weakness, severe muscle and joint pain, headaches, fever, and shortness of breath. More than thirty people died from the disease in the United States. The FDA banned L-tryptophan, and from that point on Americans had to get tryptophan from food sources.

Some foods that contain tryptophan include the following:

  • Almonds
  • Bananas
  • Chicken
  • Cottage Cheese
  • Eggs
  • Ice Cream
  • Milk
  • Peanuts
  • Shrimp
  • Soy Nuts
  • Tofu
  • Tuna
  • Turkey
  • Yogurt

As a supplement, melatonin consists of much higher amounts of the hormone than are naturally secreted at any one time in the body. A single dose is usually 500 micrograms to 5 milligrams per dose, more than 10 times higher than what is normal in the human body.


Studies have not shown the high doses cause greater benefit or greater risk to the body. However, a doctor should be consulted before taking any supplement.

Age Factors

Before reaching puberty, children create the largest amounts of melatonin, with the highest levels between the ages of four and seven. At puberty, melatonin production begins to slow down and gradually decreases to an average of about 30 micrograms per day. Some researchers suggest that the decrease in the level of melatonin at puberty may be related to the fact that the child is maturing sexually.

Research findings have been inconsistent about whether or not melatonin continues to diminish with age. A number of scientists believe that melatonin production decreases as the body ages, which might explain why elderly people have greater sleep problems. However, a study by Dr. J. B. Fourtillan, published in the January 2001 issue of American Journal of Physiology, indicated that the levels of melatonin did not differ between a group of 34 healthy adults over age 65 and a group of 101 healthy adults under age 30.

How Is It Taken?

Melatonin is sold over the counter as a dietary supplement. It is available in pill form (tablets or capsules), as a cream or tea, or as a lozenge that can be dissolved under the tongue. Time-release capsules are also sold. Such capsules release the melatonin slowly over time after the dose is ingested. Manufacturers provide a range of doses. A person should consult a physician about the proper dose and how long to take the supplement as results can vary for each individual. Typical doses fall in the range of 0.1 milligram to 10 milligrams. However, a noticeable difference in effectiveness usually is not seen in doses over 5 milligrams. A person normally takes melatonin only a few days at a time.

The time of day that the supplement is taken also plays an important role in melatonin's effectiveness. Usually, melatonin is taken right before bedtime. Taking melatonin during the day has minimal effect other than drowsiness. In the treatment of jet lag, it is recommended that melatonin be taken on the day of travel and then for a few days after arrival at the destination.

Are There Any Medical Reasons for Taking This Substance?

Many studies suggest that taking melatonin may have positive effects on a number of human ailments, especially sleep-related conditions. However, such studies have not shown that taking melatonin supplements will result in healing or prevention of these ailments. More research needs to be completed in order to really know what melatonin supplements can do for the human body.

Helping the Blind

As reported by Elizabeth Cohen on CNN.com, a study on the blind was conducted by scientists at Oregon Health Sciences University. The blind tend to suffer sleep problems due to their inability to detect the daily light and dark cycles. The study revealed that the blind had more regular sleep cycles after taking melatonin. The scientists concluded that melatonin could help the sleep patterns of those who can see as well. However, one of the scientists, Dr. Al Lewy, pointed out the importance of knowing when, how, and why to take melatonin. "The concern I have," the doctor remarked, "is that people have been taking melatonin at the wrong time at the wrong dose for the wrong reasons."

Usage Trends

According to the Agency for Healthcare Research and Quality in "Melatonin for Treatment of Sleep Disorders," "Studies suggest that sleep disorders affect 50 to 70 million Americans, representing 20 percent of the population." Since naturally occurring melatonin induces sleep, many people take melatonin supplements to help combat these sleep disorders. Cohen claimed that in the year 2000 more than 20 million Americans took melatonin supplements to help regulate their sleep. In addition to taking melatonin for sleeprelated problems, people may also be taking melatonin for its supposed benefits for a number of other conditions.

Insomnia

Insomnia is a sleep disorder in which a person has difficulty falling or staying asleep. As reported in "Melatonin for Treatment of Sleep Disorders," insomnia affects 6 to 12 percent of adults. Medical treatment for insomnia can include taking sleep aids, like benzodiazepines, in order to help the patient fall asleep. (A separate entry on benzodiazepine is available in this encyclopedia.) Relaxation techniques are also used. Some researchers believe that melatonin supplements can be used in the treatment of insomnia as well. However, other researchers have not found melatonin to have much effect at all on those suffering from insomnia.

There is some promising news for those who suffer from a form of insomnia called delayed sleep phase syndrome (DSPS). People with this condition have a sleep/wake cycle that has them set to fall asleep much later in the night, like 4 a.m., and rise much later the following day, like noon. According to "Melatonin for Treatment of Sleep Disorders," when taking melatonin supplements, the time it takes to fall asleep "decreased greatly in people with delayed sleep phase syndrome." This finding was considered "clinically significant." However, the time it takes to fall asleep only "decreased marginally in patients with insomnia," which was considered "clinically insignificant."

Jet Lag

People need to adjust their watches to the local time when they travel through time zones. But humans also need their body clocks, or sleep/wake cycles, to adjust to the local time as well. Being out of


synch with the new time zone can result in feeling tired or awake or hungry at all the wrong times. An out-of-synch body clock, coupled with a lack of sleep during a flight that has crossed multiple time zones, can result in "jet lag." Symptoms of jet lag can include:

  • Constipation or diarrhea
  • Disorientation
  • Dry cough, eyes, and skin
  • Earache
  • Fatigue
  • Headache
  • Impaired concentration, coordination, or vision
  • Insomnia
  • Irritability
  • Loss of appetite
  • Low mood
  • Memory loss
  • Nausea
  • Sore throat
  • Swollen feet

Melatonin supplements are thought to help reduce jet lag by helping the body clock more rapidly adjust to the new time zone.

Shift Work

A large number of people work during the hours that most people sleep. Having to be awake and alert during the time when the body normally should be sleeping can cause problems in a person's sleep/wake cycle. Melanie Johns Cupp in American Family Physician pointed out that in a "trial involving 27 shift workers, melatonin was found capable of 'resetting' sleep patterns to match the change in schedule in approximately one half of the patients tested."

Seasonal Affective Disorder (SAD)

Seasonal affective disorder, or SAD, is a mood disorder that causes depression in the winter months when the days are shorter and less light is available. Symptoms include low mood, irritability, fatigue, weight gain, and cravings for carbohydrates—like pasta, potatoes, or bread. Some researchers suggest that SAD is caused by elevated melatonin levels at the wrong times (i.e., not at bedtime) and that taking melatonin supplements may help regulate its production. Other studies have found melatonin does not help curb the symptoms of SAD and may actually make the symptoms worse. Light therapy (going outside in natural light or looking at artificial light) is another form of treatment for SAD sufferers.

Melatonin and Jet Lag


To help combat jet lag, according to Health Services at Columbia: Go Ask Alice!, it is suggested that a person take melatonin at the start of and during a trip at specific times in order to achieve the best results. If traveling east, a person, on the day of travel, should take one dose of melatonin between 6 and 7 p.m. of his or her normal time zone. At the destination, the person should take one dose of melatonin during the first five days at bedtime (between 9 and 10 p.m.) of the local time.

When traveling west, a person should take one dose of melatonin at the local bedtime after arriving at the destination, and continue to do so for the next four days. Melatonin has not been proven to help when traveling less than five time zones to the west.

Cancer

Researchers have studied a number of ways that melatonin may be helpful in fighting cancer. Some evidence suggests that melatonin may help regulate other hormones. Therefore, it may be helpful with cancers that are triggered by hormones like estrogen, such as breast cancer, or testosterone, such as prostate


cancer. Melatonin has also been described as an immune-booster and antioxidant. Having a stronger immune system and a greater ability to fight off cancer-causing free radicals can aid in fighting cancer.

According to the University of Maryland Medical Center, other conditions thought to be improved by melatonin (although with limited or no research support), include: 1) osteoporosis—fragile bones; 2) menopause—a period in a woman's life in which menstruation ends; 3) eating disorders; 4) epilepsy—a disorder causing seizures; 5) heart disease; 6) inflammatory diseases; 7) attention-deficit/hyperactivity disorder (ADHD); and 8) sunburn. Others claim that melatonin can improve life span, aid a person trying to stop smoking, and help with benzodiazepine withdrawal.

Effects on the Body

Because research has not been able to prove or disprove the benefits of supplemental melatonin, it is difficult to pinpoint all of the effects it has on the body. If taken at the proper time, usually bedtime, melatonin has been shown to help regulate sleep. However, using too much melatonin or not using it according to directions could hinder instead of help the body's sleep/wake cycle.

Though found naturally in the human body, melatonin, if taken as a supplement, can have certain side effects. These include sleepiness, headache and dizziness, nausea, stomach cramps, irritability, and depression. Users claim it causes more intense dreams, even nightmares. Melatonin has also been found to prevent ovulation. Some women have even used it to avoid getting pregnant. Overall, no serious side effects have been reported, and no long-term effects, negative or positive, have been proven.

The Fountain of Youth?

Some researchers believe that melatonin holds the key to a longer life. Walter Pierpaoli, William Regelson, and Carol Colman reported in their book The Melatonin Miracle: Nature's Age-Reversing, Disease-Fighting, Sex-Enhancing Hormone, that "melatonin is a potent age-reversing compound." They added that "we are confident that melatonin's primary benefit is in its ability to prevent disease by preventing the downward spiral that leads to illness." Their beliefs stem from research with mice, including studies that revealed mice that had improved health and longer lives as a result of taking melatonin. They also cited studies that showed older mice live longer when given pineal glands from younger mice and that the younger mice with the older pineal glands die at an earlier age. However, no studies on humans have been done that conclude that melatonin helps diminish the aging process.

Reactions with Other Drugs or Substances

Melatonin is not recommended for users who are taking antidepressants, corticosteroids (steroids used to counteract inflammation), blood pressure medication, or drugs that suppress the immune system, as it may reduce the other medicine's effects. Taking melatonin along with other sleep aids should be avoided although melatonin may be helpful in getting through withdrawal from the highly addictive benzodiazepines. Withdrawal is the process of gradually cutting back on the amount of a drug being taken until it can be stopped entirely.


Melatonin has also been suggested as an aid in quitting smoking. In addition, certain drugs and substances have been found to lower the level of melatonin in the body. These include alcohol, caffeine, tobacco, some high blood pressure medications including beta-blockers, and anti-inflammatories such as ibuprofen. Amphetamines and cocaine may raise the level of melatonin in the body.

Treatment for Habitual Users

There is no treatment available for habitual users of melatonin. This supplement has not been proven to be an addictive substance, nor have any studies been conducted on whether or not a person can build up a tolerance to it or suffer any withdrawal symptoms when stopping its use. Tolerance is a condition in which higher and higher doses of a drug are needed to produce the original effect.

Consequences

Hormones are very powerful. They control the functions of many parts of the body naturally. Even though melatonin is considered a dietary supplement and is available without a prescription, it is important to consult with a physician before taking any hormones. A press release by Robert Sanders in UCBerkeleyNews notes that George E. Bentley, an assistant professor of integrative biology, has conducted research on melatonin and its effects in the brain. According to Bentley: "It really amazes me that melatonin is available in any pharmacy." He continued, "It is a powerful hormone, and yet people don't realize that it's as 'powerful' as any steroid. I'm sure that many people who take it wouldn't take steroids so glibly." Bentley noted that melatonin could have many unknown effects, but few data are available about how "it interacts with other hormone systems." (A separate entry on steroids is available in this encyclopedia.) Research has shown some benefits in taking melatonin as a supplement, primarily for sleep disorders, but its long-term effects are unknown. Therefore, people who take melatonin do not know what it may do to their bodies over time.

Melatonin is not recommended for some people. Healthy children produce large amounts of melatonin, so they should not take melatonin as a supplement. Nor is it recommended for women who are trying to become pregnant because melatonin can inhibit ovulation. Also, since the effects of melatonin on babies are not known, melatonin should not be used by pregnant or nursing mothers. People with certain immune-system conditions, like the disease leukemia, should not take melatonin either.

Because melatonin is a dietary supplement, it is not regulated by the FDA. Since the manufacturers do not have to follow strict guidelines, they can be more relaxed about ensuring a high quality product. This puts the user at risk of ingesting substances not listed on the bottle label or taking an amount of melatonin that is not reflected accurately on the label.

The Law

Melatonin is neither an illegal drug nor is it monitored by the U.S. government. It is illegal to use it without a prescription in other countries. Under the U.S. Dietary Supplement Health and Education Act (DSHEA) of 1994, it is legal to sell melatonin as a dietary supplement in the United States. According to this Act, a dietary supplement:

  • is a product (other than tobacco) that is intended to supplement the diet that bears or contains one or more of the following dietary ingredients: a vitamin, a mineral, an herb or other botanical, an amino acid, a dietary substance for use by people to supplement their diet by increasing the total daily intake, or a concentrate, metabolite, constituent, extract, or combinations of these ingredients.
  • is intended for ingestion in pill, capsule, tablet, or liquid form.
  • is not represented for use as a conventional food or as the sole item of a meal or diet.
  • is labeled as a "dietary supplement."
  • includes products such as an approved new drug, certified antibiotic, or licensed biologic that was marketed as a dietary supplement or food before approval, certification, or license (unless the Secretary of Health and Human Services waives this provision).

For More Information

Books

Bock, Steven J., and Michael Boyette. Stay Young the Melatonin Way. New York: Plume, 1995.

Pierpaoli, Walter, William Regelson, and Carol Colman. The Melatonin Miracle: Nature's Age-Reversing, Disease-Fighting, Sex-Enhancing Hormone. New York: Simon & Schuster, 1995.

Reiter, Russel J., and Jo Robinson. Melatonin: Your Body's Natural Wonder Drug. New York: Bantam Books, 1995.

Sahelian, Ray. Melatonin: Nature's Sleeping Pill. Marina Del Rey, CA: Be Happier Press, 1995.

Shneerson, John. Handbook of Sleep Medicine. Oxford, UK: Blackwell Science Inc., 2000.

Smokensky, Michael, and Lynne Lamberg. The Body Clock Guide to Better Health. New York: Henry Holt & Company, Inc., 2000.

Winter, Ruth. The Anti-Aging Hormones: That Can Help You Beat the Clock. New York: Three Rivers Press, 1997.

Periodicals

Cupp, Melanie Johns. "Melatonin." American Family Physician (October 1, 1997).

Fourtillan, J. B., and others. "Melatonin Secretion Occurs at a Constant Rate in Both Young and Older Men and Women." American Journal of Physiology: Endocrinology and Metabolism (January, 2001): pp. E11-22.

Pray, W. Steven. "Consult Your Pharmacist—The Sleep-Wake Cycle and Jet Lag." U.S. Pharmacist 24, no. 3 (1999): p. 10.

"What about Melatonin?" Nursing (May, 2001).

Web Sites

Buscemi, N., B. Vandermeer, R. Pandya, et al. "Melatonin for Treatment of Sleep Disorders" (November, 2004). Agency for Healthcare Research and Quality.http://www.ahrq.gov/clinic/epcsums/melatsum.htm (accessed July 26, 2005).

Cohen, Elizabeth. "Study Bolsters Melatonin Sleep Claims." CNN.com, October 12, 2000. http://archives.cnn.com/2000/HEALTH/alternative/10/12/melatonin.clock/ (accessed July 26, 2005).

"Dietary Supplement Health and Education Act of 1994" (December 1, 1995). U.S. Food and Drug Administration: Center for Food Safety and Applied Nutrition.http://www.cfsan.fda.gov/~dms/dietsupp.html (accessed July 26, 2005).

"Melatonin." Drug Digest.http://www.drugdigest.org/DD/DVH/HerbsWho/0,3923,4060|Melatonin,00.html (accessed July 26, 2005).

"Melatonin." familydoctor.org.http://familydoctor.org/258.xml?printxml (accessed July 26, 2005).

"Melatonin." University of Maryland Medical Center.http://www.umm.edu/altmed/ConsSupplements/Melatonincs.html (accessed July 26, 2005).

"Melatonin: The Basic Facts." National Sleep Foundation. http://www.sleepfoundation.org/sleeplibrary/index.php?secid=&id=60 (accessed July 26, 2005).

"Melatonin—Jet Lag?" (September 27, 1996). Health Services at Columbia: Go Ask Alice!http://www.goaskalice.columbia.edu/0970.html (accessed July 26, 2005).

Sanders, Robert. "Popular Supplement Melatonin Found to Have Broader Effects in Brain Than Once Thought." UCBerkeleyNews, February 7, 2005. http://www.berkeley.edu/news/media/releases/2005/02/07_melatoninfin.shtml (accessed July 26, 2005).

See also: Benzodiazepine; Herbal Drugs

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