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Melatonin
What is it? Overview Usage Side Effects and Warnings
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Melatonin Overview

Melatonin is a natural hormone that regulates sleep. During daylight, the pineal gland in the brain produces an important neurotransmitter called serotonin. (A neurotransmitter is a chemical that relays messages between nerve cells.) But at night, the pineal gland stops producing serotonin and instead makes melatonin. This melatonin release helps trigger sleep.

The production of melatonin varies according to the amount of light you're exposed to; for example, your body produces more melatonin in a completely dark room than in a dimly lit one.

Melatonin supplements appear to be helpful for people whose natural sleep cycle has been disturbed, such as travelers suffering from jet lag. The hormone may also be helpful in various other sleep disorders.

Based on early reports that melatonin levels decline with age, the hormone was briefly marketed as a kind of fountain of youth. However, newer evidence suggests that melatonin levels do not decline with age after all. 1 There is a lot of evidence that melatonin can help prevent melanoma, and also help fight melanoma tumors and stop them from spreading. Read more about melanoma and melatonin Other potential benefits of melatonin remain largely speculative. Very weak evidence hints that melatonin might be helpful for functional dyspepsia (chronic indigestion of unknown cause). 2

Sources

Melatonin is not a nutrient. However, travelers and workers on rotating or late shifts can experience sleep disturbances that seem to be caused by changing melatonin levels.

You can boost your melatonin production naturally by getting thicker blinds for the bedroom windows or wearing a night mask. You can also take melatonin tablets.

Therapeutic Dosages

Melatonin is typically taken half an hour before bedtime for the first 4 days after traveling.

For ordinary insomnia, melatonin is usually taken about 30 minutes to 1 hour before bedtime. To fall asleep on Sunday night after staying up late Friday and Saturday, one study suggests using melatonin 5.5 hours before the desired bedtime.

The optimum dose of melatonin is not clear, but it is probably in the 1 to 5 mg range.

Melatonin is available in two forms: immediate-release (just plain melatonin, also called "quick-release") and slow-release (a special preparation, also called "controlled-release," designed to spread melatonin absorption over many hours). It seems reasonable to suppose that quick-release melatonin helps in falling asleep, while slow-release melatonin helps in staying asleep, but study results are inconsistent on this issue. 3

What Is the Scientific Evidence for Melatonin?

Sleep Disorders

Melatonin appears to produce sedation comparable to that of conventional pharmaceuticals used for inducing sleep 4 without impairing mental function. 5 Melatonin has shown promise as a treatment for a variety of sleep disorders, of which the best studied is jet lag.

Jet Lag

There is good evidence that melatonin can help you fall asleep when your bedtime rhythm has been disturbed by travel ( jet lag ). 6 For example, one double-blind, placebo-controlled study enrolled 320 people and followed them for 4 days after a long plane trip. 7 The participants were divided into four groups and given a daily dose of 5 mg of standard melatonin, 5 mg of slow-release melatonin, 0.5 mg of standard melatonin, or placebo. 8 The group that received 5 mg of standard melatonin slept better, took less time to fall asleep, and felt more energetic and awake during the day than the other three groups.

Another small double-blind trial found that airplane crews experienced improved rest when using melatonin (10 mg) as compared to placebo, and equivalent benefits as compared to the drug zopiclone. 9 Neither group experienced any impairment in mental function the following morning.

According to one review of the literature, melatonin treatment for jet lag is most effective for those who have crossed a significant number of time zones, perhaps eight. 10

Shift Work

Studies of melatonin for the treatment of insomnia related to shift work have yielded mixed results. 11 Researchers have been surprised by these findings, but suggest that perhaps working at night upsets the biological rhythm even more profoundly than traveling over many time zones, too profoundly for melatonin to help.

Sleep in the Elderly

Mixed results have been seen with the use of melatonin for treating insomnia in the elderly. 12 Not only have many studies failed to find melatonin helpful, those studies with positive results found widely varying benefits; for example, some studies found a decreased time to falling asleep, but no change in sleep throughout the night, while others found the reverse. These differences have not followed dose or type of melatonin in any obvious way, making them somewhat suspect.

General Insomnia

One small study failed to find benefit for general insomnia in healthy people. 13

Sleep Problems in Children

A 4-week, double-blind trial evaluated the benefits of melatonin for children with difficulty falling asleep. 14 A total of 40 children who had experienced this type of sleep problem for at least 1 year were given either placebo or melatonin at a dose of 5 mg. The results showed that use of melatonin significantly helped participants fall asleep more easily. Similar results were seen in a double-blind, placebo-controlled study of 62 children 15 and in a study of 20 developmentally disabled children with sleep problems. 16

Delayed Weekend Sleep Pattern (Monday Morning Fatigue)

Many individuals stay up late on Friday and Saturday nights, and then find it difficult to get to sleep at a reasonable hour on Sunday. A small double-blind, placebo-controlled study found evidence that taking melatonin 5.5 hours before the desired Sunday bedtime improved the ability of participants to fall asleep. 17

Sleep in Hospitalized Patients

Benefits were seen in a small, double-blind trial of patients in a pulmonary intensive care unit. 18 It is famously difficult to sleep in an ICU, and the resulting sleep deprivation is not helpful for those recovering from disease or surgery . In this study of 8 hospitalized individuals, 3 mg of controlled-release melatonin "dramatically improved" sleep quality and duration.

Other Sleep Problems and Sleep Problems Among People With Specific Medical Problems

Small double-blind trials have found benefits for improving sleep in people with diabetes , 19 asthma (however, see Safety Issues), 20 head injury, 21 schizophrenia , 22 Alzheimer’s disease , 23 and Parkinson's disease . 24 Melatonin has also shown benefit for improving sleep in people with attention deficit disorder ; 25 it has failed, however, to show benefit for the symptoms of ADHD per se. 26 Blind people often have trouble sleeping on any particular schedule, because there are no "light cues" available to help them get tired at night. A small double-blind, placebo-controlled, crossover trial found that the use of melatonin at a dose of 10 mg per day was able to resynchronize participants' sleep schedules. 27 Some individuals find it impossible to fall asleep until early morning, a condition called delayed sleep phase syndrome (DSPS). Melatonin may be beneficial for this syndrome. 28 Individuals trying to quit using sleeping pills in the benzodiazepine family may find melatonin helpful. A double-blind, placebo-controlled study of 34 individuals who regularly used such medications found that melatonin at a dose of 2 mg nightly (controlled-release formulation) could help them discontinue the use of the drugs. 29 Interestingly, another study failed to find melatonin helpful for reducing benzodiazepine use among people taking drugs in that family for anxiety . 30

Note: There can be risks in discontinuing benzodiazepine drugs. Consult your physician for advice.

Cancer Treatment

Melatonin has been used with conventional anticancer therapy in more than a dozen clinical studies. Results have been surprisingly good, although this research must be considered preliminary. For example, a double-blind study on 30 people with advanced brain tumors suggested that melatonin might prolong life and also improve the quality of life. 31 Participants received standard radiation treatment with or without 20 mg daily of melatonin. After 1 year, 6 of 14 individuals in the melatonin group were still alive, compared with just 1 of 16 from the control group. The melatonin group also had fewer side effects due to the radiation treatment—a notable improvement in their quality of life.

Improvements in symptoms and a possible reduction of mortality were also seen in other studies. 32 Melatonin appears to work by increasing levels of the body's own tumor-fighting proteins, known as cytokines. 33

Cluster Headaches

Some evidence suggests that individuals with cluster headaches have lower than average levels of the hormone melatonin. 34 35 36 In a double-blind, placebo-controlled study of 20 individuals with cluster headaches, use of melatonin (10 mg daily) for 14 days appeared to reduce headache severity and/or frequency in about half the participants. 37 Overall, use of melatonin produced better effects than placebo.

Seasonal Affective Disorder

One study found that people with seasonal affective disorder (SAD) have higher levels of melatonin than those without the condition. 38 On this basis, it would seem that supplemental melatonin should worsen SAD symptoms. However, the evidence for such an effect is inconsistent. 39 Some researchers have proposed that interaction between SAD and melatonin might be more complex than merely high or low levels, and that, when taken at certain times of day, melatonin might help the condition. A very small study found that when melatonin was given in the afternoon, it produced some benefit for people with SAD. 40 However, a study of melatonin used in the early morning or the late evening failed to find any benefit. 41 In a sizable Danish trial, researchers investigated the effects of melatonin on mood, sleep, and cognitive decline in elderly patients, most of whom suffered from dementia . 42 They found that melatonin 2.5 mg, given nightly for an average of 15 months, slightly improved sleep, but it worsened mood. The latter effect was reversed by adding light therapy during the day. Melatonin apparently had no significant effect on cognition.

Melatonin has shown equivocal effects for two conditions related to SAD: subsyndromal seasonal affective disorder (S-SAD) and weather associated syndrome (WAS). According to the one reported study, use of melatonin improved some symptoms but worsened others. 43

References

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  30. Cardinali DP, Gvozdenovich E, Kaplan MR, et al. A double blind-placebo controlled study on melatonin efficacy to reduce anxiolytic benzodiazepine use in the elderly. Neuroendocrinol Lett. 2002;23:55-60.
  31. Lissoni P, Meregalli S, Nosetto L, Barni S, Tancini G, Fossati V, Maestroni G. Increased survival time in brain glioblastomas by a radioneuroendocrine strategy with radiotherapy plus melatonin compared to radiotherapy alone. Oncology. 53(1):43-6.
  32. Lissoni P, Paolorossi F, Ardizzoia A, Barni S, Chilelli M, Mancuso M, Tancini G, Conti A, Maestroni GJ. A randomized study of chemotherapy with cisplatin plus etoposide versus chemoendocrine therapy with cisplatin, etoposide and the pineal hormone melatonin as a first-line treatment of advanced non-small cell lung cancer patients in a poor clinical state. J Pineal Res. 23(1):15-9.
  33. Neri B, de Leonardis V, Gemelli MT, di Loro F, Mottola A, Ponchietti R, Raugei A, Cini G. Melatonin as biological response modifier in cancer patients. Anticancer Res. 18(2B):1329-32.
  34. Chazot G, Claustrat B, Brun J, Jordan D, Sassolas G, Schott B. A chronobiological study of melatonin, cortisol growth hormone and prolactin secretion in cluster headache. Cephalalgia. 4(4):213-20.
  35. Leone M, Lucini V, D'Amico D, Grazzi L, Moschiano F, Fraschini F, Bussone G. Abnormal 24-hour urinary excretory pattern of 6-sulphatoxymelatonin in both phases of cluster headache. Cephalalgia. 18(10):664-7.
  36. Leone M, Lucini V, D'Amico D, Moschiano F, Maltempo C, Fraschini F, Bussone G. Twenty-four-hour melatonin and cortisol plasma levels in relation to timing of cluster headache. Cephalalgia. 15(3):224-9.
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  38. Káradóttir R, Axelsson J. Melatonin secretion in SAD patients and healthy subjects matched with respect to age and sex. Int J Circumpolar Health. 60(4):548-51.
  39. Rosenthal NE, Sack DA, Jacobsen FM, et al. Melatonin in seasonal affective disorder and phototherapy. J Neural Transm. 1986;21(Suppl):257-267.
  40. Lewy AJ, Bauer VK, Cutler NL, Sack RL. Melatonin treatment of winter depression: a pilot study. Psychiatry Res. 77(1):57-61.
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  43. Leppämäki S, Partonen T, Vakkuri O, Lönnqvist J, Partinen M, Laudon M. Effect of controlled-release melatonin on sleep quality, mood, and quality of life in subjects with seasonal or weather-associated changes in mood and behaviour. Eur Neuropsychopharmacol. 13(3):137-45.
 
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