What it does
Melatonin is a natural hormone that regulates the human biological clock. Double-blind research with young adults has shown that melatonin facilitates sleep.
1 Another study of healthy, young adults reported that melatonin significantly shortened the time needed to go to sleep, reduced the number of night awakenings, and improved sleep quality.
2 Other researchers reported the time needed to get to sleep was reduced with melatonin.
3 Melatonin is also helpful in relieving symptoms of jet lag. One double-blind trial, involving a sample of international flight crew members taking either melatonin or a placebo for three days before and five days after an international flight, found that melatonin significantly reduced symptoms of jet lag and resulted in a quicker recovery of preflight energy levels and alertness.
4 Less than 1 mg of melatonin has lowered pressure within the eyes of healthy people,
5 but studies have not yet been published on the effects of using melatonin with people who have glaucoma.
Melatonin might help some people suffering from depression. A small double-blind study suggested that supplementation with small amounts of melatonin (0.125 mg taken twice per day) may reduce winter depression.6 People with major depressive disorders sometimes have sleep disturbances. Melatonin has been shown to be effective at improving the quality of sleep of people with major depression.7 However, because of the possibility that melatonin could exacerbate depression, it should only be used for this purpose, under a doctor’s supervision. When some people take melatonin to treat sleep disorders, chronic tension headaches are relieved.8 Melatonin has also relieved cluster headaches in double-blind research.9 Some researchers have suggested that melatonin’s role in regulating core body temperature may be responsible for preventing cluster headaches,10 which have been reported to be triggered by increased body heat.11 Melatonin also regulates immunity. One group of doctors reported two successfully treated cases of sarcoidosis that it attributed to melatonin’s immune-modulating effect.12 Also, because of its effects on the immune system, melatonin has been given to people with cancer in many research trials. Low blood levels of melatonin are associated with an increased risk of uterine cancer.13 Melatonin has significantly reduced the level of prostate specific antigen (PSA, a marker for cancer) in prostate cancer patients.14 Melatonin inhibits breast cancer cells in test tubes15 and has put some women with breast cancer into remission in preliminary research.16 Melatonin supplementation has improved disease-free survival in people with melanoma17 and increased survival in people with brain cancer18 and lung cancer.19 Melatonin exerts anti-inflammatory activity that may be responsible for its anticancer properties.20 In a double-blind trial, people who had difficulty sleeping as a result of tinnitus were better able to sleep if given 3 mg melatonin per night for one month rather than a placebo.21 Although melatonin did not reduce overall symptom scores for tinnitus, people in this trial with higher symptom scores did appear to obtain some benefit. Melatonin supplementation may be helpful in treating epilepsy; 5–10 mg of melatonin taken at bedtime reduced the frequency of seizures and improved sleep in a group of children with epilepsy in a small, preliminary trial.22 However, in a group of children suffering from neurological disorders, 1–5 mg of melatonin per night led to an increase in the rate of seizures.23 Children with a seizure disorder called "myoclonus" were reported to have been cured by supplementing with 3–5 mg of melatonin per day in a preliminary trial.24 Until more is known, children with neurological conditions should take melatonin only under medical supervision. Melatonin may be useful in the treatment of fibromyalgia. In a small, uncontrolled preliminary study, 3 mg of melatonin at bedtime was found to reduce tender points associated with this disorder. Pain and fatigue improved only slightly.25 Children with Angelman’s syndrome (a rare, genetic disorder characterized by severe mental retardation, seizures, and sleep disturbances) may benefit from low amounts of melatonin. In an uncontrolled study, children with Angelman’s Syndrome who took 0.3 mg of melatonin one-half to one hour before bedtime had significant improvement in nighttime sleep patterns and a reduction in movement disturbances during sleep.26 Animal studies indicate that melatonin secretion may regulate cardiovascular activity,27 28 blood pressure,29 and blood flow to the brain.30 In healthy young men, oral administration of 1 mg of melatonin significantly reduced blood pressure and levels of stress hormones within 90 minutes.31 To date, no clinical trials in humans have tested the efficacy of melatonin for hypertension.
Where is it found?
Melatonin is produced by the pineal gland, located within the brain. Levels of melatonin in the body fluctuate with the cycles of night and day. The highest melatonin levels are found at night. Melatonin is present in foods only in trace amounts. Melatonin has been used in connection with the following conditions (refer to the individual health concern for complete information): Rating Health Concerns Angelman’s syndrome (sleep disturbances only) Cluster headaches Colon cancer Depression Insomnia Jet lag Schizophrenia (for sleep disturbances only) Tardive dyskinesia Tinnitus (insomnia-associated) Age-related cognitive decline Breast cancer Epilepsy Fibromyalgia Glaucoma Lung cancer Migraine headaches Myoclonus Prostate cancer Sarcoidosis Reliable and relatively consistent scientific data showing a substantial health benefit. Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit. An herb is primarily supported by traditional use, or the herb or supplement has little scientific support and/or minimal health benefit. Who is likely to be deficient? Although elderly people often have difficulty sleeping32 and melatonin supplements have been shown to improve sleep in the elderly,33 melatonin secretion does not appear to decline in healthy older adults to a significant degree, despite many preliminary reports to the contrary.34 Most of these preliminary studies failed to verify that older subjects were healthy and not using drugs that suppress melatonin secretion (e.g., aspirin, ibuprofen, beta-blockers). Routine replacement of melatonin in elderly persons is, therefore, not recommended. Adults with insomnia have been shown to have lower melatonin levels.35 Frequent travelers and shift workers are also likely to benefit from melatonin for the resynchronization of their sleep schedules,36 though a melatonin “deficiency” as such does not exist for these people. Patients with heart disease have been reported to have low melatonin levels, but whether this abnormality increases the risk of heart disease or whether heart disease leads to the low melatonin level is not yet known.37 People with schizophrenia were found to have low melatonin output and experienced significantly improved sleep following melatonin replacement supplementation.38
How much is usually taken?
Normally, the body secretes melatonin for several hours per night—an effect best duplicated with time-release supplements. Studies using timed-release melatonin for insomnia have reported good results.39 Many doctors suggest 1–3 mg of melatonin taken one to two hours before bedtime. Studies with people suffering from sarcoidosis or cancer have used very high amounts of melatonin—typically 20 mg per night. Such levels should never be taken without the supervision of a doctor. Melatonin should not be taken during the day.
Are there any side effects or interactions?
Melatonin is associated with few side effects. However, morning grogginess, undesired drowsiness, sleepwalking, and disorientation have been reported. Researchers have hypothesized that certain people should not use melatonin supplements, including pregnant or breast-feeding women, people with depression or schizophrenia, and those with autoimmune disease, including lupus, at least until more is known.40 41 In one study, administration of 3 mg per day of melatonin for three months resulted in a marked decline in sperm counts and a decline in sperm quality in two of eight healthy young men.42 In one of these two men, sperm count and quality became normal after melatonin was discontinued. Although this was a small study, it raises the possibility that long-term use of melatonin could lead to infertility. In a group of children suffering from neurological disorders, 1–5 mg of melatonin per night led to an increase in the rate of seizures despite the fact that sleep improved.43 Until more is known, children with neurological conditions should take melatonin only under medical supervision. Many other side effects have been attributed to melatonin supplementation, including inhibition of sex drive, severe headaches, abdominal cramps, and formation of rudimentary breasts in men.44 45 However, these associations have not been supported by solid evidence.46 47 48 49 Since none of these claims have been well documented or independently confirmed, these problems may not have been due to melatonin. Though most research reports that melatonin improves the quality of sleep, at least one trial has found that four of fifteen men given melatonin had their sleep patterns disturbed by supplemental melatonin.50 One case of painful gynecomastia (enlarged breasts) has been reported involving a 56-year-old man who had been suffering from amyotrophic lateral sclerosis (Lou Gehrig’s disease), and was taking 1–2 mg melatonin per day for one and a half years.51 As the signs and symptoms disappeared after melatonin was discontinued, the authors of the report suspected that melatonin caused this side effect. According to a preliminary report, blood levels of melatonin may be elevated in women with fibromyalgia.52 Data in this report did not indicate toxicity from melatonin, nor did the report suggest that melatonin causes or exacerbates the symptoms of fibromyalgia. It did suggest there is no current rationale for melatonin supplementation in people with fibromyalgia. One-time oral administration of 1 mg of melatonin to post-menopausal women reduced glucose tolerance and insulin sensitivity when tested 45 minutes after administration.53 This finding suggests that people with diabetes should use melatonin with caution and only under the supervision of a doctor.
Are there any drug interactions?
Certain medicines may interact with melatonin. Refer to drug interactions for a list of those medicines. Special United Kingdom considerations Melatonin is either not available or may require a prescription. People should check with their physicians.
1. Zhadanova IV, Wurtman RJ, Lynch HJ, et al. Sleep-inducing effects of low doses of melatonin ingested in the evening. Clin Pharmacol Ther 1995;57:552–8. 2. Waldhauser F, Saletu B, Trinchard-Lugan I. Sleep laboratory investigations on hypnotic properties of melatonin. Psychopharmacology 1990;100:222–6. 3. Hughes RJ, Sack RL, Lewy AJ. The role of melatonin and circadian phase in age-related sleep maintenance insomnia: assessment in a clinical trial of melatonin replacement. Sleep 1998;21:52–68. 4. Petrie K, Dawson AG, Thompson L, et al. A double-blind trial of melatonin as a treatment for jet lag in international cabin crew. Biol Psychiatry 1993;33:526–30. 5. Samples JR, Krause G, Lewy AJ. Effect of melatonin on intraocular pressure. Curr Eye Res 1988;7:649–53. 6. Lewy AJ, Bauer VK, Cutler NL, Sack RL. Melatonin treatment of winter depression: a pilot study. Psychiatr Res 1998;77:57–61. 7. Dolberg OT, Hirschmann S, Grunhaus L. Melatonin for the treatment of sleep disturbances in major depressive disorder. Am J Psychiatry 1998;155:1119–21. 8. Nagtegaal JE, Smits MG, Swart ACW, et al. Melatonin-responsive headache in delayed sleep phase syndrome: preliminary observations. Headache 1998;38:303–7. 9. Leone M, D’Amico D, Moschiano F, et al. Melatonin versus placebo in the prophylaxis of cluster headache: a double-blind pilot study with parallel groups. Cephalalgia 1996;16:494–6. 10. Peres MF, Seabra ML, Zukerman E, Tufik S. Cluster headache and melatonin. Lancet 2000;355:147 [letter]. 11. Blau JN, Engel HO. A new cluster headache precipitant: increased body heat. Lancet 1999;354:1001–2. 12. Cagnoni ML, Lomardi A, Cerinic MM, et al. Melatonin for treatment of chronic refractory sarcoidosis. Lancet 1995;346:1229–30 [letter]. 13. Grin W, Grüberger W. A significant correlation between melatonin deficiency and endometrial cancer. Gynecol Obstet Invest 1998;45:62–5. 14. Lissoni P, Cazzaniga M, Tancini GE, et al. Reversal of clinical resistance to LHRH analogue in metastatic prostate cancer by the pineal hormone melatonin: efficacy of LHRH analogue plus melatonin in patients progressing on LHRH analogue alone. Eur Urol 1997;31:178–81. 15. Blask DE, Wilson ST, Zalatan F. Physiological melatonin inhibition of human breast cancer cell growth in vitro: evidence for a glutathione-mediated pathway. Cancer Res 1997;57:1909–14. 16. Lissoni P, Barni S, Meregalli S, et al. Modulation of cancer endocrine therapy by melatonin: a phase II study of tamoxifen plus melatonin in metastatic breast cancer patients progressing under tamoxifen alone. Br J Cancer 1995;71:854–6. 17. Lissoni P, Brivio O, Brivio F, et al. Adjuvant therapy with the pineal hormone melatonin in patients with lymph node relapse due to malignant melanoma. J Pineal Res 1996;21:239–42. 18. Lissoni P, Barni S, Ardizzoia A, et al. A randomized study with the pineal hormone melatonin versus supportive care alone in patients with brain metastasis due to solid neoplasms. Cancer 1994;73:699–701. 19. Lissoni P, Barni S, Ardizzoia A, et al. Randomized study with the pineal hormone melatonin versus supportive care alone in advanced nonsmall cell lung cancer resistant to a first-line chemotherapy containing cisplatin. Oncology 1992;49:336–9. 20. Lissoni P, Rovelli F, Meregalli S, et al. Melatonin as a new possible anti-inflammatory agent. J Biol Regul Homeost Agents 1997;11:157–9. 21. Rosenberg SI, Silverstein H, Rowan PT, Olds MJ. Effect of melatonin on tinnitus. Laryngoscope 1998;108:305–10. 22. Fauteck J, Schmidt H, Lerchl A, et al. Melatonin in epilepsy: first results of replacement therapy and first clinical results. Biol Signals Recept 1999;8(1–2):105–10. 23. Sheldon SH. Pro-convulsant effects or oral melatonin in neurologically disabled children. Lancet 1998;351:1254. 24. Jan JE, Connolly MB, Hamilton D, et al. Melatonin treatment of non-epileptic myoclonus in children. Dev Med Child Neurol 1999;41:255–9 [review]. 25. Citera G, Arias MA, Maldonado-Cocco JA, et al. Clin Rheumatol 2000;19:9–13. 26. Zhdanova IV, Wurtman RJ, Wagstaff J. Effects of a low amount of melatonin on sleep in children with Angelman syndrome. J Pediatr Endocrinol Metab 1999;12:57–67. 27. Cagnacci A. Melatonin in relation to physiology in adult humans. J Pineal Res 1996;21:200–13 [review]. 28. Tan DX, Manchester LC, Reiter RJ, et al. Ischemia/reperfusion-induced arrhythmias in the isolated rat heart: prevention by melatonin. J Pineal Res 1998;25:184–91. 29. Chuang JI, Chen SS, Lin MT. Melatonin decreases brain serotonin release, arterial pressure and heart rate in rats. Pharmacology 1993;47:91–7. 30. Capsoni S, Stankov BM, Fraschini F. Reduction of regional cerebral blood flow by melatonin in young rats. Neuroreport 1995;6:1346–8. 31. Arangino S, Cagnacci A, Angiolucci M, et al. Effects of melatonin on vascular reactivity, catecholamine levels, and blood pressure in healthy men. Am J Cardiol 1999;83:1417–9. 32. Haimov I, Laudon M, Zisapel N, et al. Sleep disorders and melatonin rhythms in elderly people. BMJ 1994;309:167. 33. Singer C, McArthur A, Hughes R, et al. Melatonin and sleep in the elderly. J Am Geriatr Soc 1996;44:51 [abstr #A1]. 34. Zeitzer JM, Daniels JE, Duffy JF, et al. Do plasma melatonin concentrations decline with age? Am J Med 1999;107:432–6. 35. Attenburrow MEJ, Dowling BA, Sharpley AL, Cowen PJ. Case-control study of evening melatonin concentration in primary insomnia. BMJ 1996;312:1263–4. 36. Folkard S, Arendt J, Clark M. Can melatonin improve shift workers’ tolerance of the night shift? Some preliminary findings. Chronobiol Int 1993;10:315–20. 37. Sakotnik A, Liebmann PM, Stoschitzky K. Decreased melatonin synthesis in patients with coronary artery disease. Eur Heart J 1999;20:1314–7. 38. Shamir E, Laudon M, Barak Y, et al. Melatonin improves sleep quality of patients with chronic schizophrenia. J Clin Psychiatry 2000;61:373–7. 39. Garfinkel D, Laudon M, Nof D, Zisapel N. Improvement of sleep quality in elderly people by controlled-release melatonin. Lancet 1995;346:541–4. 40. Weaver DR. Reproductive safety of melatonin: a “wonder drug” to wonder about. J Biol Rhythms 1997;12:682–9. 41. Arendt J. Safety of melatonin in long-term use(?) J Biol Rhythms 1997;12:673–81. 42. Luboshitzky R, Shen-Orr Z, Nave R, Lavi S, Lavie P. Melatonin administration alters semen quality in healthy men. J Androl 2002;23:572–8. 43. Sheldon SH. Pro-convulsant effects or oral melatonin in neurologically disabled children. Lancet 1998;351:1254. 44. Shannon M. Alternative medicines toxicology: a review of selected agents. Clin Toxicol 1999;37:709–13. 45. Guardiola-Lemaître B. Toxicology of melatonin. J Biol Rhythms 1997;12:697–706. 46. Lamberg L. Melatonin potentially useful but safety, efficacy remain uncertain. JAMA 1996;276:1011–4. 47. Force RW, Hansen L, Badell M. Psychotic episode after melatonin. Ann Pharmacother 1997;31:1408 [letter]. 48. Porterfield LM. Can melatonin cause severe headaches? RN 1996;59:75. 49. Bornman MS, Schulenburg GW, Reif S, et al. Seminal plasma melatonin and semen parameters. S Afr Med J 1992;81:485–6. 50. Middleton B. Melatonin and fragmented sleep patterns. Lancet 1996;348:551–2 [letter]. 51. De Bleeker JL, Verstraete AG, Schelfhout VJ. Melatonin and painful gynecomastia. Neurology 1999;53:435–6 [letter]. 52. Korszun A, Sackett-Lundeen L, Papadopoulos E, et al. Melatonin levels in women with fibromyalgia and chronic fatigue syndrome. J Rheumatol 1999;26:2675–80. 53. Cagnacci A, Arangino S, Renzi A, et al. Influence of melatonin administration on glucose tolerance and insulin sensitivity of postmenopausal women. Clin Endocrinol 2001;54:339–46.
|
|||||||||||||||||||||
