Drug Guide


By Anthony McDaniel, M.D.

Melatonin also known chemically as N-acetyl-5-methoxytryptamine, is a naturally occurring compound found in animals, plants, and microbes. In animals, circulating levels of the hormone melatonin vary in a daily cycle, thereby allowing the entrainment of the circadian rhythms of several biological functions. Many biological effects of melatonin are produced through activation of melatonin receptors, while others are due to its role as a pervasive and powerful antioxidant, with a particular role in the protection of nuclear and mitochondrial DNA. In mammals, melatonin is secreted into the blood by the pineal gland in the brain. Known as the "hormone of darkness", it is secreted in darkness in both day-active (diurnal) and night-active (nocturnal) animals.

It may also be produced by a variety of peripheral cells such as bone marrow cells, lymphocytes and epithelial cells. Usually, the melatonin concentration in these cells is much higher than that found in the blood but it does not seem to be regulated by the photoperiod. Melatonin-rich plant feed, such as rice, ingested by chicks has been shown to reach and bind to melatonin receptors in their brains. No food has been found to elevate plasma melatonin levels in humans. Products containing melatonin have been available over-the-counter as a dietary supplement in the United States since before 1994. In many other countries, sale of the hormone remains illegal or requires a prescription, and the U.S. Postal Service lists melatonin among items prohibited by Germany. The hormone melatonin is used to treat circadian rhythm sleep disorders and some types of insomnia. Studies have found that the use of melatonin can help entrain the circadian clock to environmental cycles and have beneficial effects for the treatment of certain forms of insomnia. Prolonged release melatonin has shown good results in treating insomnia in older adults.

Other studies have found that for certain types of sleep disorders, melatonin is not effective. A 2006 review found that although it is safe for short term use (of three months or less), there is "no evidence that melatonin is effective in treating secondary sleep disorders or sleep disorders accompanying sleep restriction, such as jet lag and shiftwork disorder." However, a 2004 review found that melatonin significantly increased total sleep time in people suffering from sleep restriction. Melatonin appears to cause very few side effects in the short term, up to three months, when healthy people take it at low doses. A systematic review in 2006 looked specifically at efficacy and safety in two categories of melatonin usage: first, for sleep disturbances which are secondary to other diagnoses and, second, for sleep disorders such as jet lag and shift work which accompany sleep restriction.

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