Melatonin

background

Melatonin is a hormone produced in the brain by the pineal gland from the amino acid tryptophan. The production and release of melatonin are stimulated by darkness and decreased by light, suggesting that melatonin is involved in circadian rhythm (the internal body clock) and regulation of diverse body functions. Levels of melatonin in the blood are highest prior to bedtime.
The most common use of melatonin is to aid in sleep. The strongest evidence supporting the use of melatonin is for delayed sleep phase syndrome, insomnia in children and the elderly, jet lag, and sleep problems in people with behavioral, developmental, or mental disorders. The weakest evidence in support of melatonin is for work shift sleep disorder. Good evidence in support of melatonin for other uses is lacking.
New drugs that block the effects of melatonin are being developed. These include BMS-214778 and luzindole, and they may have uses in various disorders.

Related Terms

5-Methoxy-N-acetyltryptamine, 6-sulfatoxymelatonin, acetamide, agomelatine, aMT6s, beta-methyl-6-chloromelatonin, BMS-214778, CAS 73-31-4, hypnotic, indole, luzindol, luzindole, mel, MEL, melatonia, melatonine, Melaxen®, melaxene, MLT, MT, N-2-(5-methoxyindol-3-ethyl)-acetamide, N-acetil-5-metoxitriptamina (Spanish), N-acetyl-5-methoxytryptamine, neurohormone, ramelteon (CAS 196597-26-9, TAK-375), tryptophan.
Brand names: Accurate Release®; Appleheart Melatonin®; Circadin®; Inspired by Nature®; Mel®; Melatonin Controlled Release®; Melatonin Olympian Labs®; Melatonin Tablets®; Melatonin Time Release®; Melatonin-BioDynamax®; Melatonin-Metabolic Response Modifier®; Melatonin-New Hope Health Products®; Melatonin-Optimum Nutrition®; Melaxen®; Nature's Bounty®; Puritan's Pride®; Rozerem®; Twinlab® Melatonin; Valdoxan®.
Combination product examples: Melatonex® (vitamin B6); Melatonin Forte® (Piper methysticum, kavalactones, valerian); Melatonin PM Complex® (vitamin B6, vitamin B2, vitamin B3); Melatonin spray® (gamma-aminobutyric acid, pyridoxal-5-phosphate); Super Snooze with Melatonin® (valerian root, hop, skullcap, chamomile, passionflower).

evidence table

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.
 
Delayed sleep phase syndrome (DSPS) (Grade: B)
Delayed sleep phase syndrome is a condition that results in delayed sleep onset despite normal sleep patterns and duration. Studies report that melatonin may help improve the amount of time it takes to fall asleep. More research is needed before further conclusions can be made.
Insomnia (children) (Grade: B)
According to human research, melatonin may benefit children with insomnia. Melatonin has been studied for sleep-wake disorders in children and adolescents. More well-designed studies that focus on safety are needed in this population.
Insomnia (elderly) (Grade: B)
The production and elimination of melatonin from the body may be lower in older people with insomnia. Several human studies report that supplementing with melatonin may improve insomnia in the elderly. More research is needed before further conclusions can be made.
Jet lag (Grade: B)
Several human trials suggest that melatonin taken by mouth, started on the day of travel (close to the target bedtime at the destination) and continued for several days, reduces the number of days needed to begin a normal sleep pattern, shortens the time it takes to fall asleep, improves alertness, and reduces daytime fatigue. More trials are needed to confirm these findings, determine the most effective dosing, and study the use of melatonin together with prescription sleep aids.
Sleep disorders (people with behavioral, developmental, and mental disorders) (Grade: B)
Studies have looked at the use of melatonin in children with mental and nervous system disorders, including mental retardation, autism, vision loss, or epilepsy (seizure disorder). More research is needed before further conclusions can be made.
Sleep enhancement in healthy people (Grade: B)
People who have insomnia appear to have lower melatonin levels, and supplementing with melatonin may offer some benefit. Most human studies have been small and brief in duration. However, evidence does suggest that melatonin decreases the time it takes to fall asleep, as well as increases sleepiness and sleep duration. Melatonin may also help promote daytime sleep. More research is needed before firm conclusions can be made.
Age-related macular degeneration (vision loss with age) (Grade: C)
Melatonin may have antioxidant effects, which may contribute to its eye health benefits. Research suggests that melatonin may play a role in protecting the retina to delay macular degeneration. Well-designed clinical trials are needed before a conclusion can be made.
Aging (body temperature regulation) (Grade: C)
Melatonin may help regulate age-dependent changes in body temperature rhythm. More well-designed trials are needed before a conclusion can be made.
Alzheimer's disease/ cognitive decline (Grade: C)
Limited research has looked at the effects of melatonin on cognitive disorders. Some studies suggest a possible benefit. In elderly people with mild cognitive impairment, a combination treatment containing melatonin improved cognitive function scores and sense of smell, as well as speech fluency. More well-designed trials are needed before a conclusion can be made.
Anti-inflammatory (Grade: C)
According to limited human research, melatonin may be an effective anti-inflammatory; however, results are conflicting. Well-designed clinical trials are needed before a conclusion can be made.
Benzodiazepine withdrawal (Grade: C)
A small amount of research has looked at the use of melatonin to assist with withdrawal from benzodiazepines (antianxiety drugs) such as diazepam (Valium®) or lorazepam (Ativan®). Melatonin has been studied for this purpose in people with schizophrenia. Although early results are promising, further research is needed before a firm conclusion can be reached.
Cancer treatment (Grade: C)
Early human studies have looked at melatonin use in people with different types of late-stage cancer, including cancer of the brain, breast, colon, rectum, stomach, liver, lung, pancreas, testicles, immune system, skin, kidney, and soft tissues. Melatonin has been used together with many other agents and therapies. Some promising results have been found in non-small cell lung cancer and breast cancer. However, no clear conclusion can currently be made in this area. There is not enough evidence to support the use of melatonin for any type of cancer, for affecting other cancer therapies, or for reducing chemotherapy side effects.
Chronic fatigue syndrome (Grade: C)
Limited research has been conducted on the effects of melatonin in people with chronic fatigue syndrome. Early results suggest a lack of effect. Further research is needed in this area before a clear conclusion can be reached.
Chronic obstructive pulmonary disease (Grade: C)
Chronic obstructive pulmonary disease (COPD) is a chronic lung disease that makes it difficult to breathe. Early research showed that melatonin reduced oxidative stress and shortness of breath. Changes in lung function were lacking. Further research is needed.
Circadian rhythm sleep disorders (people with and without vision problems) (Grade: C)
In people with vision problems, light and dark signals are not received by the eye to trigger melatonin release and sleep. Some studies found inconclusive results for melatonin use in visually impaired children with sleep disorders. Others reported improvement in the time it takes to fall asleep and sleep duration in visually impaired people. Currently, research suggests that melatonin given in the evening may correct circadian rhythm (the internal body clock). Further research is needed before a conclusion can be made.
Delirium (Grade: C)
Melatonin has been studied for delirium (confusion and changes in brain function) in people with a hip fracture and was found to reduce delirium in elderly people. More research is needed in order for conclusions to be drawn.
Depression (Grade: C)
Melatonin has been suggested as a possible treatment for depression. However, human research remains inconclusive. More evidence is needed before a conclusion can be made.
Diabetes (additional therapy) (Grade: C)
Melatonin used with zinc may improve blood sugar control after meals in people with type 2 diabetes. However, results are inconsistent. More evidence is needed before a conclusion can be made.
Exercise performance (Grade: C)
Taking melatonin during the day may not affect jumping ability and strength. More research is needed before a conclusion can be made.
Fertility (Grade: C)
Melatonin may not affect fertilization and pregnancy in people undergoing
Fibromyalgia (Grade: C)
Early studies suggest that melatonin may improve symptoms of fibromyalgia (chronic body-wide pain). Further research is needed.
Glaucoma (Grade: C)
High doses of melatonin may increase eye pressure and the risk of glaucoma, age-related eye disease, nearsightedness, or retinal damage. However, early evidence suggests that melatonin may decrease eye pressure and may treat glaucoma. Further research is needed. People with glaucoma who are taking melatonin should be monitored by a healthcare professional.
Headache (Grade: C)
Studies have looked at the use of melatonin for migraine, cluster, tension-type headaches, and other headache syndromes (in people who suffer from regular headaches). Melatonin has also been studied for nighttime headaches and for primary headaches in children. Limited research suggests possible benefits, but high-quality studies are needed before a firm conclusion can be made.
Heart disease (Grade: C)
A combination treatment for heart disease that included melatonin was found to improve chest pain and have antioxidant, blood flow-improving, and blood pressure-lowering effects. Further high-quality research is needed.
High blood pressure (Grade: C)
Studies report that melatonin may lead to small reductions in blood pressure. Melatonin may also improve cholesterol and reduce oxidative stress in people with metabolic syndrome. A combination treatment for heart disease that included melatonin was found to have blood pressure-lowering effects. Melatonin has been studied with other agents for high blood pressure in elderly people. Further research is needed.
High cholesterol (Grade: C)
Early research found that melatonin used with zinc and the diabetes drug metformin may improve diabetes-related complications. Melatonin may improve blood pressure and cholesterol and reduce oxidative stress in people with metabolic syndrome. Melatonin has been studied with other agents for high blood pressure in elderly people. However, there is evidence that melatonin both increases and decreases cholesterol levels. More research is needed to clarify these mixed results.
HIV/AIDS (Grade: C)
There is a lack of evidence to support or recommend against the use of melatonin for AIDS. Melatonin should not be used in place of more proven therapies. People who have HIV/AIDS should be treated under the supervision of a medical doctor.
Liver inflammation (Grade: C)
Early research found that melatonin may improve liver function in people with nonalcoholic steatohepatitis (liver inflammation caused by fat buildup in the liver). Further research is needed.
Memory (Grade: C)
Early research suggests that melatonin may improve memory in certain stressful situations. Further research is required before a conclusion can be made.
Menopause (Grade: C)
Evidence is mixed with respect to the use of melatonin for menopause symptoms. Further research is needed before a conclusion can be made.
Pain (Grade: C)
In infants requiring intubation (a tube in the mouth or nose to improve breathing), melatonin may reduce pain. Further research is needed to determine the effects of melatonin in other populations with various types of pain.
Parkinson's disease (Grade: C)
There is limited research on the use of melatonin as a treatment for Parkinson's disease. Melatonin has been described as being well tolerated, but side effects may include skin flushing, diarrhea, stomach cramps, daytime sleepiness, vision changes, and headaches. Early research suggests that melatonin may improve sleep in people with Parkinson's disease. More research is needed before a firm conclusion can be made in this area.
Periodic limb movement disorder (Grade: C)
There is limited study for the use of melatonin as a treatment for periodic limb movement disorder (repetitive limb movements during sleep). Although early research suggests possible benefits, further studies are needed before conclusions can be made in this area.
REM sleep behavior disorder (Grade: C)
Melatonin has been suggested as a treatment for rapid eye movement (REM) sleep behavior disorder (acting out dreams during sleep), in which a person acts out vivid dreams through behaviors such as kicking, punching, and yelling. Early research describes benefits in people with this condition. However, better research is needed before a clear conclusion can be drawn.
Restless leg syndrome (Grade: C)
Early research suggests that melatonin may affect motor symptoms associated with restless leg syndrome. However, evidence remains inconclusive. Further research is required in this field.
Rett's syndrome (Grade: C)
Rett's syndrome is a genetic disorder that affects female children, causing slow head growth and development problems. There is limited research on the use of melatonin for improving sleep problems associated with Rett's syndrome. Further research is needed before conclusions can be made in this area.
Ringing in the ears (Grade: C)
Melatonin has been suggested as a treatment for ringing the ears; this use has been supported by some early research. However, further research is needed before a conclusion can be made.
Sarcoidosis (Grade: C)
Early research suggests that melatonin may be safe and effective for chronic sarcoidosis (chronic widespread inflammation) when other treatments fail or cause side effects. More research is needed before a conclusion can be made.
Schizophrenia (Grade: C)
Early research suggests that melatonin may improve sleep, daytime function, and mood in people who have schizophrenia. Further research is needed.
Seasonal affective disorder (SAD) (Grade: C)
Melatonin has been studied for symptoms of SAD. However, more high-quality research is needed before a clear conclusion can be reached.
Seizure disorder (Grade: C)
There is controversy on the role of melatonin in seizure disorder. Melatonin has been studied in children with intractable seizures (seizures that do not respond to treatment), nervous system damage, febrile seizures (seizures triggered by a fever), and epilepsy. It has been suggested that melatonin may protect against oxidative stress and damage, as well as improve sleep quality and seizure control. However, there are reports that melatonin may actually increase the risk of seizures. Better evidence is needed in this area before a conclusion on the safety or effectiveness of melatonin can be made.
Skin sun damage (Grade: C)
Several human studies have looked at the use of melatonin in protecting skin from sun damage. Although early results report reduced skin redness, further research is needed before a clear conclusion can be made.
Sleep disturbance (Grade: C)
Melatonin may improve sleep disturbances in many people, including those in intensive care or those with Alzheimer's disease, mental disorders, and end-stage kidney disease. Several studies report improved sleep patterns in young people with brain damage caused by tumors or surgery. Melatonin has been proposed as a therapy for disease caused by exposure to light during the nighttime, as well as for sleep disorder in elderly people with dementia. Early research suggests that melatonin may also be useful for people with asthma and depression; however, results are limited and/or inconclusive for those with Parkinson's disease, bipolar disorder, and schizophrenia, or those undergoing
Smoking (Grade: C)
Limited research has looked at the use of melatonin for symptoms of smoking withdrawal, including anxiety, restlessness, irritability, and cigarette craving. Although early results are promising, further research is necessary before a firm conclusion can be reached.
Stomach disorders (and intestine disorders) (Grade: C)
Early research suggests that melatonin may benefit people with indigestion and acid reflux disease. When used with traditional therapy, melatonin may reduce inflammation in people with Crohn's disease and ulcerative colitis (inflammatory bowel diseases that affect the intestines). Melatonin has also been studied for irritable bowel syndrome. More research is needed in this field.
Stroke (Grade: C)
Melatonin has been proposed as a treatment for nervous system damage after a stroke, based on its antioxidant effects. Melatonin levels may also be changed following a stroke, and it has been suggested that supplementing with melatonin may have benefits. However, human evidence is lacking at this time.
Surgery (Grade: C)
Limited studies have compared melatonin to standard drugs for anxiety before surgery. Melatonin has also been suggested as a treatment for delirium (confusion) following surgery. However, evidence is mixed, and further research is needed before a clear conclusion can be drawn.
Tardive dyskinesia (Grade: C)
Tardive dyskinesia (involuntary muscle movements) is a serious potential side effect of medications for mental disorders. Limited studies report mixed findings on melatonin use in people with TD. Further research is needed before a clear conclusion can be drawn.
Thrombocytopenia (low platelets) (Grade: C)
Thrombocytopenia is a condition in which platelets (parts of the blood that help promote clotting) are low. Higher platelet counts have been seen after melatonin use in people with low platelets due to cancer therapies. Stimulation of platelet production has been suggested but not proven. More research is needed in this area before a clear conclusion can be drawn.
Ulcers (Grade: C)
Early evidence suggests that melatonin may aid in the healing of ulcers. Further well-designed research is needed.
Urination (waking up at night to urinate) (Grade: C)
Melatonin may benefit elderly people who wake up during the night to urinate, but not teens and adolescents. Early research has produced conflicting results. More research is needed before a conclusion can be made.
Work shift sleep disorder (Grade: D)
Several studies have looked at melatonin use in people who work irregular shifts, such as emergency room personnel. Results are mixed. Further research is necessary before a clear conclusion can be drawn.