Melatonin (N-acetyl-5-methoxytryptamine)

3 imperatives to transform health care in America. You're invited to watch it live

Free

E-newsletter

Subscribe to Housecall

Our weekly general interest
e-newsletter keeps you up to date on a wide variety of health topics.

Sign up now

Evidence

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.

Jet lag
Several human trials have suggested 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 required to establish a normal sleep pattern, diminishes sleep latency (the time it takes to fall asleep), improves alertness, and reduces daytime fatigue. Although these results are compelling, the majority of studies have had problems with their designs and reporting, and some trials have not found benefits. Overall, the scientific evidence does suggest benefits of melatonin in up to half of people who take it for jet lag. More trials are needed to confirm these findings, to determine optimal dosing, and to evaluate use in combination with prescription sleep aids. 		A
Delayed sleep phase syndrome (DSPS)
Delayed sleep phase syndrome is a condition that results in delayed sleep onset despite normal sleep architecture and sleep duration. Although these results are promising, additional research with larger studies is needed before a stronger recommendation can be made. 		B
Insomnia (in the elderly)
Several human studies have reported that melatonin taken by mouth before bedtime decreases sleep latency (the time it takes to fall asleep) in elderly individuals with insomnia. Improved sleep quality and morning alertness has also been reported. However, most studies have not been of high quality in their designs, and some research has found limited or no benefits. The majority of trials have been brief in duration (several days long), and long-term effects are not known. 		B
Sleep disorders (children with behavioral, developmental, and intellectual disorders)
There have been multiple trials investigating melatonin use in children with various neuropsychiatric disorders, including mental retardation, autism, psychiatric disorders, visual impairment, or epilepsy. Studies have demonstrated reduced sleep latency (the time it takes to fall asleep) and increased sleep duration. Well-designed controlled trials in select patient populations are needed before a stronger or more specific recommendation can be made. 		B
Sleep enhancement in healthy people
Multiple human studies have measured the effects of melatonin supplements on sleep in healthy individuals. A wide range of doses has been used, often taken by mouth 30-60 minutes prior to sleep time. Most trials have been small and brief in duration, and have not been rigorously designed or reported. However, the weight of scientific evidence does suggest that melatonin decreases sleep latency (the time it takes to fall asleep), increases the feeling of sleepiness, and may increase the duration of sleep. Better research is needed in this area. 		B
Age-related macular degeneration
Melatonin may exert antioxidant effects, which may contribute to its beneficial effects on the eyes. According to clinical research, 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. 		C
Aging (thermoregulation)
Melatonin may be helpful in regulating age-dependent changes in body temperature rhythm. More well-designed trials are needed before a conclusion can be made. 		C
Anti-inflammatory
Based on 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. 		C
Anxiety (preoperative)
Results are mixed. Melatonin may be as effective as benzodiazepines such as midazolam (Versed®). Additional research is needed to confirm these findings. 		C
Benzodiazepine tapering
A small amount of research has examined the use of melatonin to assist with tapering or cessation of benzodiazepines such as diazepam (Valium®) or lorazepam (Ativan®). Although preliminary results are promising, further study is necessary before a firm conclusion can be reached. 		C
Cancer treatment
There are several early-phase and controlled human trials of melatonin in patients with various advanced-stage malignancies, including brain, breast, colorectal, gastric, liver, lung, pancreatic, and testicular cancers, as well as lymphoma, melanoma, renal cell carcinoma, and soft-tissue sarcoma. Currently, no clear conclusion can be drawn in this area. There is not enough definitive scientific evidence to discern if melatonin is beneficial against any type of cancer, whether it increases (or decreases) the effectiveness of other cancer therapies, or if it safely reduces chemotherapy side effects. 		C
Chronic fatigue syndrome
There is limited research into melatonin given to patients with chronic fatigue syndrome. Benefits have been reported. Further research is needed in this area before a clear conclusion can be reached. 		C
Circadian rhythm entraining (in blind persons)
Limited human research is available in this area. Present studies and individual cases suggest that melatonin, administered in the evening, may correct circadian rhythm. Large, well-designed controlled trials are needed before a stronger recommendation can be made. 		C
Cognitive disorders
There is not enough evidence to support the use of melatonin in managing the cognitive and noncognitive conditions of dementia. 		C
Depression
Melatonin has been suggested as serving as a possible treatment for depression. There is some support in animal research. However, human research remains inconclusive. More evidence is needed before a conclusion can be made. 		C
Diabetes (adjunct therapy)
Melatonin when used with zinc may improve glycemic control in patients with poor response to metformin. More evidence is needed before a conclusion can be made. 		C
Exercise performance
Based on human research, daytime administration of melatonin had no effects on maximal jumping ability or on maximal strength. More well-designed trials are needed before a conclusion can be made. 		C
Gastrointestinal disorders
Several studies show that treatment with melatonin may be useful in patients with functional dyspepsia. Other research has shown that melatonin has some beneficial effects in patients with irritable bowel syndrome (IBS) and possibly inflammatory bowel disease (IBD), although findings have been mixed. Well-designed clinical trials are required before a strong recommendation can be made. 		C
Glaucoma
It has been theorized that high doses of melatonin may increase intraocular pressure and the risk of glaucoma, age-related maculopathy and myopia, or retinal damage. However, there is preliminary evidence that melatonin may actually decrease intraocular pressure in the eye and delay macular degeneration, and it has been suggested as a possible therapy for glaucoma. Additional study is necessary in this area. Patients with glaucoma taking melatonin should be monitored by a healthcare professional. 		C
Headache (prevention)
Several small studies have examined the possible role of melatonin in preventing various forms of headache, including migraine, cluster, and tension-type headaches, and other headache syndromes (in people who suffer from regular headaches). Limited initial research suggests possible benefits in all three types of headache, although well-designed controlled studies are needed before a firm conclusion can be drawn. 		C
High blood pressure (hypertension)
Several controlled studies in patients with high blood pressure report small reductions blood pressure when taking melatonin orally (by mouth) or intranasally (inhaled through the nose). Specifically, nocturnal high blood pressure may improve with melatonin use. Better-designed research is necessary before a firm conclusion can be reached. 		C
High cholesterol (diabetes-related complication, adjunct therapy)
One clinical trial found that melatonin when used with zinc and the diabetes drug metformin may improve diabetes-related complications such as impaired lipid profile. However, there is also evidence that melatonin increases cholesterol levels. More research is needed to clarify these mixed results. 		C
HIV/AIDS
There is a lack of well-designed scientific evidence to recommend for or against the use of melatonin as a treatment for AIDS. Melatonin should not be used in place of more proven therapies, and patients with HIV/AIDS should be treated under the supervision of a medical doctor. 		C
Insomnia (children)
Based on human research, melatonin may be beneficial in children with insomnia. More well-designed studies are needed before a conclusion can be made. 		C
Memory
Preliminary research has suggested that melatonin may improve memory in certain stressful situations. Further research is required before a conclusion can be made. 		C
Menopause
Melatonin has shown some beneficial effects for symptoms associated with menopause. Further research using a larger number of patients is needed before a conclusion can be made. 		C
Parkinson's disease
There is very limited research to date for the use of melatonin as a treatment for Parkinson's disease. Melatonin was indicated as being well tolerated, but side effects may have included skin flushing, diarrhea, abdominal cramps, somnolence during the day, scotoma lucidum, and headaches. Melatonin had no effect on signs of parkinsonism or levodopa effects. Further research of higher methodological strength is needed before a recommendation can be made in this area. 		C
Periodic limb movement disorder
There is very limited study to date for the use of melatonin as a treatment for periodic limb movement disorder. Better-designed research is needed before a recommendation can be made in this area. 		C
REM sleep behavior disorder
Limited case reports describe benefits in patients with REM sleep behavior disorder who received melatonin. However, better research is needed before a clear conclusion can be drawn. 		C
Restless leg syndrome
Preliminary research has suggested that melatonin may have a detrimental effect on motor symptoms associated with restless leg syndrome; however, evidence remains inconclusive. Further study is required in this field. 		C
Rett's syndrome
Rett syndrome is a presumed genetic disorder that affects female children, characterized by decelerated head growth and global developmental regression. There is limited research of the possible role of melatonin in improving sleep disturbance associated with Rett syndrome. Further research is needed before a firm recommendation can be made in this area. 		C
Sarcoidosis
Beneficial effects have been reported in people with chronic sarcoidosis who took melatonin. Additional research is needed before a recommendation can be made. 		C
Seasonal affective disorder (SAD)
There are several small, brief studies of melatonin in patients with SAD. This research is not well designed or reported, and further study is necessary before a clear conclusion can be reached. 		C
Seizure disorder (children)
The role of melatonin in seizure disorders is controversial. Better evidence is needed in this area before a clear conclusion can be drawn regarding the safety or effectiveness of melatonin. 		C
Sleep disturbance
Melatonin may improve sleep disturbances in a wide range of patients, including those in the intensive care unit (ICU) and patients with Alzheimer's disease. Several published cases report improvements in sleep patterns in young people with damage to the pineal gland area of the brain due to tumors or surgery. Based on preliminary research, melatonin may improve sleep in patients with asthma or depression. Further research is needed in these areas before a firm conclusion can be reached. 		C
Sleep quality
A small amount of research has examined the use of melatonin to improve sleep quality. Further research is necessary before firm conclusions can be reached. 		C
Smoking cessation
Although preliminary results are promising, due to weaknesses in the design and reporting of this research, further research is necessary before a firm conclusion can be reached. 		C
Stroke
At this time, the effects of melatonin supplements immediately after stroke are not clear. 		C
Tardive dyskinesia
Tardive dyskinesia (TD) is a serious potential side effect of antipsychotic medications, characterized by involuntary muscle movements. Limited small studies of melatonin use in patients with TD report mixed findings. Additional research is necessary before a clear conclusion can be drawn. 		C
Thrombocytopenia (low platelets)
Increased platelet counts after melatonin use have been observed in patients with decreased platelets due to cancer therapies (several studies reported by the same author). Stimulation of platelet production (thrombopoiesis) has been suggested but not clearly demonstrated. Additional research is necessary in this area before a clear conclusion can be drawn. 		C
Tinnitus
Melatonin use has been associated with improvement of tinnitus and sleep. However, additional research is needed before a conclusion can be made. 		C
Urination (nocturia)
Melatonin may have beneficial effects for nocturia in the elderly. Further research is needed to before a recommendation can be made. 		C
UV-induced erythema prevention/sunburn
It has been proposed that the antioxidant properties of melatonin may be protective. Results have been mixed. Further study is necessary before a clear conclusion can be drawn about its clinical effectiveness in humans. 		C
Work shift sleep disorder
There are several studies of melatonin use in people who work irregular shifts, such as emergency room personnel. Modest improvements have been reported when melatonin was used with bright light. Results are mixed. Additional research is necessary before a clear conclusion can be drawn. 		D

Key to grades
A Strong scientific evidence for this use
B Good scientific evidence for this use
C Unclear scientific evidence for this use
D Fair scientific evidence against this use (it may not work)
F Strong scientific evidence against this use (it likely does not work)

Grading rationale

Uses based on tradition or theory

The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Acetaminophen toxicity, acute respiratory distress syndrome (ARDS), adaptogen, addiction, ADHD, adrenal insufficiency, aflatoxin toxicity, aging, alcoholic liver disease, alopecia (baldness), aluminum toxicity, Alzeimer's disease, amenorrhea, amyotrophic lateral sclerosis (ALS), analgesic, antioxidant, antiparasitic, anxiety (travel anxiety in animals), ataxia (Machado-Joseph disease), atopic dermatitis, autoimmune diseases (demyelination), beta-blocker sleep disturbance, bipolar disorder, bladder disorders, bone diseases (fibrous dysplasia), bone healing, brain injuries, cachexia, cardiac syndrome X, cardiovascular conditions, cataracts, central nervous system diseases (Venezuelan equine encephalomyelitis virus), chemotherapy toxicity, cholestatic liver injury, colic, colitis, contraception, coronary artery disease, delirium, dental conditions, Duchenne muscular dystrophy, duodenal ulcer, eating disorders (low-level, enhanced circadian rhythm), eczema, edema (swelling), endometriosis, erectile dysfunction, esophagitis (inflammation of the esophagus), exercise recovery, fetal development, fibromyalgia, food preservation, fragile X syndrome, gastric ulcers, gastritis (inflammation of the stomach lining), gastroesophageal reflux disease (GERD), gentamicin toxicity, growth (growing pains), heart attack prevention, heart disease, helminthic infections, hepatic encephalopathy, hormonal/endocrine disorders (McCune-Albright syndrome), hyperpigmentation, immune system diseases (Langerhans cell histiocytosis), immunostimulant, infant development / neonatal care, interstitial cystitis, intestinal motility disorders, ischemia-reperfusion injury protection, ischemic stroke (impaired nocturnal excretion), itching, jaundice, jellyfish stings, kidney protection (amikacin-induced, cyclosporin-induced), lead toxicity, liver damage, lung inflammation, major depressive disorder (low nocturnal melatonin), malaria, mania, melatonin deficiency, metabolic disorders, migraine (impaired pineal function), movement disorders, multiple sclerosis, myocardial injury, nerve regeneration, neurodegenerative disorders, neurofibromatous scoliosis, neurological disorders, neuropathy (neuronal damage from bacterial meningitis), neuroprotective, nitrate tolerance, noise-induced hearing loss, non-Hodgkin's lymphoma, obesity, obstructive sleep apnea, organophosphate poisoning, osteoarthritis, ovarian disorders, pain, pancreatitis, phenylketonuria (PKU), photoprotection, polycystic ovarian syndrome (PCOS), postmenopausal osteoporosis, post-operative adjunct, post-operative delirium, pregnancy nutritional supplement, premenstrual dysphoric disorder (PMDD), protection against alcohol toxicity, psychiatric disorders, pulmonary fibrosis, radiation protection, retinal protection, rheumatic diseases, scalds, schizophrenia, sepsis, sexual activity enhancement, shock, spinal cord injury, spine problems (idiopathic scoliosis), stomach ulcers, stomatitis, stroke, sudden infant death syndrome (SIDS) prevention, surgical recovery, tachycardia, testicular damage, toluene neurotoxicity, toxic liver damage, toxicity, transplants (ovary), tuberculosis, ulcer, ulcerative colitis, uterine disorders, Wilson's disease, wound healing.

Dosing Related terms
NS_patient-melatonin Portions of this document last updated: Sept. 1, 2012

THIS EVIDENCE-BASED MONOGRAPH WAS PREPARED BY
THE NATURAL STANDARD RESEARCH COLLABORATION
(www.naturalstandard.com)

Advertisement


Text Size: smaller largerlarger