Melatonin

Uses

Principal Proposed Uses

Oral Uses

Topical Uses

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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. 65

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). 113

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. 1

Therapeutic Uses

Reasonably good evidence tells us that melatonin can help people with jet lag adjust to a new schedule. 46 Although it probably works in part by resetting the biological clock, it also appears to decrease or block wakefulness-promoting circuits in the nervous system 86 and may have other direct sedative effects. Based on this, melatonin has been tried for insomnia of various types, but results have been inconsistent 87 .

Three small double-blind studies suggest that use of melatonin might reduce symptoms of irritable bowel syndrome . 89-90,111 It has been suggested that melatonin might work through effects on the nervous system in the digestive tract.

Four double-blind studies performed by Saudi researchers reported that melatonin was useful for reducing anxiety prior to surgery, presumably due to its sedative effects. 2,3,95,102 However, other researchers have been unable to confirm these results. 99-100

Three, small, double-blind, placebo-controlled studies found evidence that melatonin may slightly reduce nighttime blood pressure . 67,88,101

Two preliminary double-blind trials hint that use of melatonin at a dose of 10 mg/day may reduce symptoms of tardive dyskinesia . 45,68

A preliminary double-blind study suggests that melatonin may improve quality of life in children with epilepsy, perhaps by improving sleep and reducing medication side effects. 69

One surprising double-blind study suggests that topical application of melatonin may increase hair growth in women with thinning hair, for reasons that are entirely unclear. 70

Oral melatonin has shown some potential for treating seasonal affective disorder , cluster headaches , 47-50,71 and irritable bowel syndrome .

Highly preliminary studies, including unblinded controlled trials, suggest that melatonin may enhance the effectiveness of standard therapy for breast cancer, prostate cancer, brain glioblastomas, non-small-cell lung cancer, and other forms of cancer. 4-6,51-53 (For information on why such studies are unreliable, see Why Does This Database Rely on Double-blind Studies? ) Melatonin has also shown some promise in animal studies for reducing side effects (specifically, cardiac toxicity) of the chemotherapy drug doxorubicin ; however, the only human trials supporting this use fall considerably beneath modern scientific standards. 103-110

Weak evidence supports a role for melatonin in reducing nicotine withdrawal symptoms. 91

On the basis of one uncontrolled trial, melatonin has been promoted as a treatment for fibromyalgia . 72

Based on theoretical reasoning and scant evidence, it has been suggested that melatonin can boost the immune system , prevent heart disease , and fight aging in general. 8-11

Evidence to date suggests that melatonin is not helpful for menopausal symptoms , 73chronic fatigue syndrome , 74 or migraines . 118

What Is the Scientific Evidence for Melatonin?

Sleep Disorders

Melatonin appears to produce sedation comparable to that of conventional pharmaceuticals used for inducing sleep 75 without impairing mental function. 76 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 ). 46,77

For example, one double-blind, placebo-controlled study enrolled 320 people and followed them for 4 days after a long plane trip. 12 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. 12 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. 44 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. 13

Shift Work

Studies of melatonin for the treatment of insomnia related to shift work have yielded mixed results. 15,19,20,42-44,92,117 Such as the results in a review of 15 randomized trials. Melatonin was associated with improved total sleep time, but not sleep quality when compared to placebo. The trials were low quality, making it difficult to draw specific conclusions about its effectiveness. 121

Sleep in the Elderly

Mixed results have been seen with the use of melatonin for treating insomnia in the elderly. 14-18,21,57,78,115 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. 79

Sleep Problems in Children

A 4-week, double-blind trial evaluated the benefits of melatonin for children with difficulty falling asleep. 22 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 80 and in a study of 20 developmentally disabled children with sleep problems. 23

Researchers have also focused on sleep problems in children and teens with autism spectrum disorders. In a systematic review of 5 randomized trials and 13 observational studies, melatonin was associated with faster sleep onset and longer sleep duration. 120

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. 24

Sleep in Hospitalized Patients

Benefits were seen in a small, double-blind trial of patients in a pulmonary intensive care unit. 25 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 , 26asthma (however, see Safety Issues), 81 head injury, 82schizophrenia , 27Alzheimer’s disease , 83 and Parkinson's disease . 94 Melatonin has also shown benefit for improving sleep in people with attention deficit disorder ; 93,112 it has failed, however, to show benefit for the symptoms of ADHD per se. 112

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. 28

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. 29

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. 30 Interestingly, another study failed to find melatonin helpful for reducing benzodiazepine use among people taking drugs in that family for anxiety . 58

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. 33 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. 34,35 Melatonin appears to work by increasing levels of the body's own tumor-fighting proteins, known as cytokines. 36

Headaches

Some evidence suggests that individuals with cluster headaches have lower than average levels of the hormone melatonin. 47-50 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. 59 Overall, use of melatonin produced better effects than placebo.

In a small randomized, crossover study, 48 men and women who suffered from migraines took melatonin (2 mg) every night for 8 weeks. The supplement did not decrease the number of migraine attacks. 118

Seasonal Affective Disorder

One study found that people with seasonal affective disorder (SAD) have higher levels of melatonin than those without the condition. 60 On this basis, it would seem that supplemental melatonin should worsen SAD symptoms. However, the evidence for such an effect is inconsistent. 61 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. 62 However, a study of melatonin used in the early morning or the late evening failed to find any benefit. 63

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. 84

Dementia

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 . 115 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. In a systematic review of 5 randomized trials including 323 people with dementia, researchers failed to find evidence that melatonin is helpful in enhancing memory and other cognitive abilities. 119 In 2 of the trials, however, melatonin was associated with short-term improvement in mood and behavior.

Safety Issues

A safety study found that melatonin at a dose of 10 mg daily produced no toxic effects when given to 40 healthy males for a period of 28 days. 37 However, this does not prove that melatonin is safe when taken on a regular basis over the long term. Keep in mind that melatonin is not truly a food supplement but a hormone. As we know from other hormones used in medicine, such as estrogen and cortisone, harmful effects can take years to appear. Hormones are powerful substances that have many subtle effects in the body, and we're far from understanding them fully. While in one small study, use of melatonin over an 8-day period by healthy men did not affect natural release of melatonin or levels of pituitary or sex hormones, 85 another study found effects on testosterone and estrogen metabolism in men and possible impairment of sperm function. 66 Also, a small study in women found possible effects on the important female hormone called LH (luteinizing hormone). 96

Melatonin appears to cause drowsiness and decreased mental attention for about 2 to 6 hours after using it and may also impair balance. 38,39,64 For this reason, you should not drive or operate machinery for several hours after taking melatonin. In a study of healthy middle-aged and older adults, however, an extended release version of melatonin, which is said to more closely mimic natural fluctuations of the hormone in the body, did not impair mental ability or driving skills 1 to 4 hours later compared to placebo. 116 In either case, melatonin does not appear to have any "hangover" effects the following day. 44

Based on theoretical ideas of how melatonin works, some authorities specifically recommend against using it in people with depression, schizophrenia, autoimmune diseases, and other serious illnesses. One study in postmenopausal women found evidence that melatonin might impair insulin action and glucose tolerance, suggesting that people with diabetes should not use it. 40 However, another study found melatonin safe and effective for people with diabetes. 41 Because of these contradictions, we suggest that individuals with diabetes seek physician supervision before using melatonin.

Two exceedingly preliminary studies reported by one research group has led to publicized concerns that use of the supplement melatonin might increase night-time asthma. 97 However, one double-blind study of melatonin in people with asthma found evidence of improved sleep without worsening of symptoms. 98 Again, at the current state of knowledge, caution must be advised for people with night-time asthma who wish to try melatonin.

There is some evidence that melatonin may interfere with the ability of blood to clot normally, at least in healthy volunteers, 114 though the clinical significance of this finding is at yet unknown.

Maximum safe dosages for young children, pregnant or nursing women, or those with serious liver or kidney disease have not been established.

Revisions

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