Alternative names for melatonin

N-acetyl-5-methoxytryptamine

Melatonin is produced by various tissues in the body, although the major source is the pineal gland in the brain. Melatonin (blue) is produced naturally from the amino acid tryptophan, by the pineal gland (purple) at night-time. Night-time is detected by reduced light entering the eyes (left), and the arrow shows the melatonin secretion signal sent by the optic nerve to the pineal gland once darkness has fallen.

What is melatonin?

The production and release of melatonin from the pineal gland occurs with a clear daily (circadian) rhythm, with peak levels occurring at night. Once produced, it is secreted into the blood stream and cerebrospinal fluid (the fluid around the brain & spinal cord) and conveys signals to distant organs. Melatonin is carried by the circulatory system from the brain to all areas of the body. Tissues expressing proteins called receptors specific for melatonin are able to detect the peak in circulating melatonin at night and this signals to the body that it is night-time. Night-time levels of melatonin are at least 10-fold higher than daytime concentrations.

In addition to its circadian rhythm, melatonin levels also have a seasonal (or circannual) rhythm, with higher levels in the autumn and winter when nights are longer, and lower levels in the spring and summer.

In many animals (including a wide range of mammals and birds), melatonin from the pineal gland is essential for the regulation of the body’s seasonal biology (e.g. reproduction, behaviour and coat growth) in response to changing day length. The importance of pineal melatonin in human biology is not clear, although it may help to synchronise circadian rhythms in different parts of the body.

In humans, nocturnal levels of melatonin decrease across puberty. The level of circulating melatonin can be detected in samples of blood and saliva, and this is used in clinical research to identify internal circadian rhythms.

Most of the research into the function of the pineal gland involves the human brain's responses to melatonin rhythms. The evidence supports two roles for melatonin in humans: the involvement of nocturnal melatonin secretion in initiating and maintaining sleep, and control by the day/night melatonin rhythm of the timing of other 24-hour rhythms. Melatonin has, therefore, often been referred to as a ‘sleep hormone’; although it is not essential for human sleep, we sleep better during the time that melatonin is secreted. Recent studies have shown that melatonin may also have a role in glucose metabolism, however, more research is needed in this area.

Association between tumours of the pineal gland and the timing of puberty suggests that melatonin may also have a minor role in reproductive development, although the mechanism of this action is uncertain. Melatonin secretion by the human pineal gland varies markedly with age. Melatonin secretion starts during the third or fourth months of life and coincides with the consolidation of night-time sleep. Following a rapid increase in secretion, nocturnal melatonin levels peak at ages one to three years, then decline slightly to a plateau that persists throughout early adulthood. After a steady decline in most people, night-time levels of melatonin in a 70-year old are only a quarter or less of those seen in young adults.

Night-time melatonin secretion is suppressed by a relatively dim light when pupils are dilated. This has been suggested as the main way through which prolonged use of devices such as laptops and smartphones before bedtime can have a negative impact on melatonin secretion, circadian rhythms and sleep.

In addition to its production in the body, melatonin can also be taken in capsule form. The clinical uses of melatonin include treatment of age-associated insomnia, jet lag, and shift work. When administered at an appropriate time of day, it can reset the body’s circadian rhythm (see the articles on jet lag and circadian rhythm sleep disorders). This resetting effect of melatonin has been reported for many dose strengths, including those that are equivalent to the concentration of melatonin naturally produced by the pineal gland. Higher doses of melatonin can reset circadian rhythms, bring on sleepiness and lower core body temperature.

How is melatonin controlled?  

In humans and other mammals, the daily rhythm of pineal melatonin production is driven by the 'master' circadian clock. This 'clock' is in a region of the brain called the suprachiasmatic nuclei, which expresses a series of genes termed clock genes that continuously oscillate throughout the day. This is synchronised to the solar day via light input from the eyes. The suprachiasmatic nuclei link to the pineal gland through a complex pathway in the nervous system, passing through different brain areas, into the spinal cord and then finally reaching the pineal gland. During the day, the suprachiasmatic nuclei stops melatonin production by sending inhibitory messages to the pineal gland. At night however, the suprachiasmatic nuclei are less active, and the inhibition exerted during the day is reduced resulting in melatonin production by the pineal gland.

Light is an important regulator of melatonin production from the pineal gland. Firstly, it can reset a specific area of the brain (the suprachiasmatic nuclei clock) and, as a result, the timing of the melatonin production. Secondly, exposure to light during the body's biological night reduces melatonin production and release.

What happens if I have too much melatonin?

There are large variations in the amount of melatonin produced by individuals and these are not associated with any health problems. The main consequences of swallowing large amounts of melatonin are drowsiness and reduced core body temperature. Very large doses have effects on the performance of the human reproductive system. There is also evidence that very high concentrations of melatonin have an antioxidant effect, although the purpose of this has not yet been established.

What happens if I have too little melatonin?

Deficiencies of this hormone can lead to sleep disruptions and insomnia. Melatonin supplementation can effectively treat this problem after medical diagnosis. Decreased levels of melatonin, which exceed those seen during normal ageing, have been reported in neurodegenerative disorders, especially in Alzheimer's disease and other types of senile dementia.