Melatonin (2023)

  • Zimmerman HJ. Unconventional drugs. Miscellaneous drugs and diagnostic chemicals. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 731-4.

    (Expert review of hepatotoxicity published in 1999; melatonin is not discussed).

  • Seeff L, Stickel F, Navarro VJ. Hepatotoxicity of herbals and dietary supplements. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 631-58.

    (Review of hepatotoxicity of herbal and dietary supplements [HDS] does not mention melatonin).

  • Guardiola-Lemaître B. Toxicology of melatonin. J Biol Rhythms. 1997;12:697–706. [PubMed: 9406047]

    (Discussion of potential side effects and toxicities of melatonin, most of which relate to alteration in circadian rhythms; ALT elevations and hepatotoxicity are not mentioned).

  • Arendt J. Safety of melatonin in long-term use. J Biol Rhythms. 1997;12:673–81. [PubMed: 9406044]

    (Potential long term adverse effects of melatonin include inhibition of reproductive function, delayed puberty and effects on circadian rhythm none of which have proven to be a problem).

  • Penev PD, Zee PC. Melatonin: a clinical perspective. Ann Neurol. 1997;42:545–53. [PubMed: 9382465]

    (Overview of the physiology of the pineal gland, melatonin and circadian rhythms and discussion of potential uses for melatonin).

  • Seabra ML, Bignotto M, Pinto LR Jr, Tufik S. Randomized, double-blind clinical trial, controlled with placebo, of the toxicology of chronic melatonin treatment. J Pineal Res. 2000;29:193–200. [PubMed: 11068941]

    (Controlled trial of melatonin [10 mg daily] vs placebo for 28 days in 40 volunteers found no changes or abnormalities of serum bilirubin, ALT, AST or Alk P during the 4 weeks of treatment).

  • Buscemi N, Vandermeer B, Hooton N, Pandya R, Tjosvold L, Hartling L, Vohra S, et al. Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis. BMJ. 2006;332:385–93. [PMC free article: PMC1370968] [PubMed: 16473858]

    (Systematic review of literature on efficacy and safety of melatonin for sleep disorders; in 9 randomized controlled trials there was no overall evidence of benefit; in 10 studies evaluating safety, there was no evidence of adverse effects occurring more often than with placebo with use limited to 3 months).

  • Erman M, Seiden D, Zammit G, Sainati S, Zhang J. An efficacy, safety, and dose-response study of Ramelteon in patients with chronic primary insomnia. Sleep Med. 2006;7:17–24. [PubMed: 16309958]

    (Controlled crossover trial of 4 doses of ramelteon vs placebo in 107 patients with chronic primary insomnia found no difference in rate of side effects compared to placebo, the most common being headache and somnolence; serum enzymes not tested).

  • Devi V, Shankar PK. Ramelteon: a melatonin receptor agonist for the treatment of insomnia. J Postgrad Med. 2008;54:45–8. [PubMed: 18296808]

    (Review of the mechanism of action, efficacy and safety of ramelteon, a melatonin receptor agonist, in treatment of insomnia).

  • Navarro VJ. Herbal and dietary supplement hepatotoxicity. Semin Liver Dis. 2009;29:373–82. [PubMed: 19826971]

    (Overview of the regulatory environment, clinical patterns, and future directions in research with HDS; melatonin is not listed or discussed).

  • Jacobsson I, Jönsson AK, Gerdén B, Hägg S. Spontaneously reported adverse reactions in association with complementary and alternative medicine substances in Sweden. Pharmacoepidemiol Drug Saf. 2009;18:1039–47. [PubMed: 19650152]

    (Review of 778 spontaneous reports of adverse reactions to complementary and alternative medications and herbals to the Swedish Registry; melatonin is not listed or discussed).

  • Mayer G, Wang-Weigand S, Roth-Schechter B, Lehmann R, Staner C, Partinen M. Efficacy and safety of 6-month nightly ramelteon administration in adults with chronic primary insomnia. Sleep. 2009;32:351–60. [PMC free article: PMC2647789] [PubMed: 19294955]

    (Controlled trial of 6 month course of ramelteon vs placebo in 451 adults with primary chronic insomnia; adverse effects were similar between the two groups; no mention of ALT levels).

  • Wade AG, Ford I, Crawford G, McConnachie A, Nir T, Laudon M, Zisapel N. Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: a randomized placebo controlled trial on age and endogenous melatonin as predictors of efficacy and safety. BMC Med. 2010;8:51. [PMC free article: PMC2933606] [PubMed: 20712869]

    (Controlled trial of 6 months of prolonged release melatonin vs placebo in 791 adults with primary insomnia; there were no "treatment-related trends" in changes in clinical laboratory tests).

  • Pearl PL, Drillings IM, Conry JA. Herbs in epilepsy: evidence for efficacy, toxicity, and interactions. Semin Pediatr Neurol. 2011;18:203–8. [PubMed: 22062945]

    (Review of herbal therapies for epilepsy including melatonin, adverse events are uncommon with melatonin and rarely require dose adjustment or discontinuation).

  • Garfinkel D, Zorin M, Wainstein J, Matas Z, Laudon M, Zisapel N. Efficacy and safety of prolonged-release melatonin in insomnia patients with diabetes: a randomized, double-blind, crossover study. Diabetes Metab Syndr Obes. 2011;4:307–13. [PMC free article: PMC3160855] [PubMed: 21887103]

    (Controlled 3 week cross over trial of a prolonged release melatonin in 36 diabetic patients with insomnia; no serious adverse events reported and no mention of ALT levels or liver injury).

  • De Leersnyder H, Zisapel N, Laudon M. Prolonged-release melatonin for children with neurodevelopmental disorders. Pediatr Neurol. 2011;45:23–6. [PubMed: 21723455]

    (Open label study of long term, prolonged release melatonin in 88 children with neurodevelopmental disorders reported no significant adverse events except for daytime somnolence).

  • Nickkholgh A, Schneider H, Sobirey M, Venetz WP, Hinz U. The use of high-dose melatonin in liver resection is safe: first clinical experience. J Pineal Res. 2011;50:381–8. Pelzl le H, Gotthardt DN, et al. [PubMed: 21480979]

    (Controlled trial of single high dose of melatonin [50 mg/kg] in 50 patients undergoing major liver resection found lower ALT and AST levels during the 4 immediate postoperative days, but the differences were not statistically significant).

  • Lemoine P, Wade AG, Katz A, Nir T, Zisapel N. Efficacy and safety of prolonged-release melatonin for insomnia in middle-aged and elderly patients with hypertension: a combined analysis of controlled clinical trials. Integr Blood Press Control. 2012;5:9–17. [PMC free article: PMC3278206] [PubMed: 22346363]

    (Review of 3 randomized controlled trials of prolonged release melatonin for insomnia in older patients with hypertension found rate of adverse events lower in treated than placebo subjects; "hepatobiliary disorders" were reported in 15 of 1834 [0.8%] patients on melatonin versus 4 of 1558 [0.2%] receiving placebo, but no details given).

  • Steindl PE, Finn B, Bendok B, Rothke S, Zee PC, Blei AT. Disruption of the diurnal rhythm of plasma melatonin in cirrhosis. Ann Intern Med. 1995;123:274–7. [PubMed: 7611593]

    (Analysis of plasma melatonin levels taken every 30 minutes for 24 hours in 6 patients with cirrhosis and 6 controls found elevated levels in cirrhotic patients during the day and delayed peaks during nighttime, but no correlation of these abnormalities with sleep disturbance).

  • Montagnese S, Middleton B, Mani AR, Skene DJ, Morgan MY. On the origin and the consequences of circadian abnormalities in patients with cirrhosis. Am J Gastroenterol. 2010;105:1773–81. [PubMed: 20332771]

    (Analysis of plasma melatonin levels taken hourly in 20 patients with cirrhosis and 9 controls found "central circadian disruption" and delayed peak levels during nighttime, but no correlation with sleep disturbance).

  • Morris CJ, Aeschbach D, Scheer FA. Circadian system, sleep and endocrinology. Mol Cell Endocrinol. 2012;349:91–104. [PMC free article: PMC3242827] [PubMed: 21939733]

    (Review of the biologic basis of circadian rhythm including the role of melatonin).

  • Ramelteon (Rozerem) for insomnia. Med Lett Drugs Ther. 2005;47(1221):89–91. [PubMed: 16267494]

    (Concise review of the mechanism of action, efficacy and safety of ramelteon published shortly after its approval for use in insomnia in the United States; adverse effects include somnolence, dizziness, nausea, fatigue, headache and insomnia, but no mention is made of ALT elevations or hepatotoxicity; mentions that melatonin itself is available in the US only as a "dietary supplement").

  • Lemoine P, Zisapel N. Prolonged-release formulation of melatonin (Circadin) for the treatment of insomnia. Expert Opin Pharmacother. 2012;13:895–905. [PubMed: 22429105]

    (Review of the physiology of melatonin, mechanism of action, and efficacy of safety of a prolonged release formulation [Circadin] for treatment of insomnia reported no significant differences of melatonin compared with placebo in type and frequency of adverse events).

  • Drugs for insomnia. Treat Guidel Med Lett. 2012;10(119):57–60. [PubMed: 22777275]

    (Guidelines for therapy of insomnia; mentions that melatonin has been "reported to be effective in some patients with insomnia" when taken 3-5 hours before desired time to sleep, but not when taken at bedtime; the hypnotic dose and purity of melatonin available as dietary supplements have not been established).

  • Andersen LP, Gögenur I, Rosenberg J, Reiter RJ. The Safety of Melatonin in Humans. Clin Drug Investig. 2016;36:169–75. [PubMed: 26692007]

    (Review of the safety of melatonin concludes that no studies of its use have reported serious adverse events and only mild events such as dizziness, headache, nausea and somnolence arose in short term trials; no mention of ALT elevations or hepatotoxicity despite “extensive biochemical testing” in some studies).

  • Drugs for chronic insomnia. Med Lett Drugs Ther. 2018;60(1562):201–5. [PubMed: 30625122]

    (Concise review of drugs used for insomnia mentions that melatonin has been reported to be effective “in some patients”; no mention of ALT elevations or hepatotoxicity).

  • Maras A, Schroder CM, Malow BA, Findling RL, Breddy J, Nir T, Shahmoon S, et al. Long-term efficacy and safety of pediatric prolonged-release melatonin for insomnia in children with autism spectrum disorder. J Child Adolesc Psychopharmacol. 2018;28:699–710. [PMC free article: PMC6306655] [PubMed: 30132686]

    (Among 95 children with autism treated with prolonged release melatonin [2, 5 or 10 mg] or placebo once daily for 13 weeks followed by an open label period, there were no treatment related serious adverse events and no mention of ALT elevations or hepatotoxicity).

  • Madsen MT, Zahid JA, Hansen CH, Grummedal O, Hansen JR, Isbrand A, Andersen UO, et al. The effect of melatonin on depressive symptoms and anxiety in patients after acute coronary syndrome: The MEDACIS randomized clinical trial. J Psychiatr Res. 2019;119:84–94. [PubMed: 31586772]

    (Among 252 adults with acute coronary syndrome treated with melatonin [25 mg] or placebo once daily for 12 weeks, there were no differences in rates of depression or in adverse events in the two treatment groups).

  • Foley HM, Steel AE. Adverse events associated with oral administration of melatonin: A critical systematic review of clinical evidence. Complement Ther Med. 2019;42:65–81. [PubMed: 30670284]

    (Systematic review of 50 randomized controlled trials found 26 articles reported no differences in rates of adverse events of melatonin compared to placebo and 24 with higher rates of minor and transient side effects with melatonin, usually drowsiness and fatigue; no mention of ALT elevations or hepatic adverse events).

  • FAQs

    Is it safe to take melatonin every night? ›

    If melatonin does seem to help, it's safe for most people to take nightly for one to two months. “After that, stop and see how your sleep is,” he suggests. “Be sure you're also relaxing before bed, keeping the lights low and sleeping in a cool, dark, comfortable bedroom for optimal results.”

    Why doesn't melatonin work for me ADHD? ›

    The ADHD brain, however, has a delay in melatonin onset. Research shows that the onset of melatonin for most adults is roughly 9:30 pm, but in adults with ADHD it happens more than an hour later. In children with ADHD, the melatonin onset is similarly late — around 10:15 pm.

    Is it safe to take 10 mg of melatonin every night? ›

    How many 10 mg melatonin should you take? In adults, 10 mg is the maximum recommended dosage. However, most people do not need doses of melatonin this high.

    Does melatonin lower your blood pressure? ›

    Single melatonin intake can lower BP, but only when melatonin is taken during the day, when general SCN neuronal activity is high and endogenous melatonin levels are low. This effect could be mediated via an immediate inhibition of SCN–neuronal activity inducing a state resembling nocturnal SCN output.

    What are the bad side effects of melatonin? ›

    Common side effects
    • Feeling sleepy or tired in the daytime. Do not drive, cycle or use tools or machinery if you're feeling this way. ...
    • Headache. Make sure you rest and drink plenty of fluids. ...
    • Stomach ache. ...
    • Feeling sick (nausea) ...
    • Feeling dizzy. ...
    • Feeling irritable or restless. ...
    • Dry mouth. ...
    • Dry or itchy skin.

    What are the negatives of taking melatonin nightly? ›

    You Might Increase Your Risk for Some Health Issues

    Even though melatonin is a hormone, not a supplement, it still has side effects and medical interactions, notes Dr. Weiss. "For example, some people might experience side effects after taking melatonin, including drowsiness, stomach aches or dizziness," says Dr.

    Does melatonin help with anxiety? ›

    A 2017 study indicated melatonin as an effective and safe option for treating people with anxiety following acute coronary syndrome (ACS). A 2018 study found that the administration of melatonin was more effective in improving anxiety and sleeping patterns than the drug oxazepam in people undergoing heart surgery.

    What happens if someone with ADHD takes melatonin? ›

    Better sleep method #3: Try melatonin. This natural hormone, which helps set the body's sleep-wake cycle, builds up late in the day and promotes shut-eye at night. And melatonin supplements, taken about an hour before bedtime, have been shown to help some adults with ADHD get to sleep.

    Why do I wake up in the middle of the night after taking melatonin? ›

    Light defeats melatonin.

    If you correctly take melatonin 2-3 hours before you want to fall asleep, but you continue to be exposed to bright light or “blue light” (such as every electronic screen you own, from your mobile phone to the TV), your body is getting mixed messages, and taking melatonin won't help.

    Can melatonin affect your heart? ›

    Melatonin supplements are commonly used for sleep problems. There's no evidence that melatonin is harmful to your heart, liver, or kidneys when taken as directed. But it can lower blood pressure and make bleeding more likely, especially if you take other blood pressure or blood-thinning medications.

    How long does 5mg melatonin last? ›

    How Long Does 5mg of Melatonin Last? Keep in mind that recommended doses tend to be between 1 and 5 milligrams, which means most melatonin supplements can stay in the body for up to 5 hours.

    How long does 5mg melatonin take to work? ›

    How Long Does It Take For 5mg Melatonin to Kick In? A typical melatonin dose is up to 5 mg and can take up to two hours to kick in. However, some people report melatonin working in as little as 20 minutes, which is why you'll want to get your bedtime routine started when you take your melatonin.

    How safe is melatonin for seniors? ›

    Melatonin is generally regarded as safe for seniors by physicians and pharmacists because its side effects are mild, it's not habit forming, and it does not cause withdrawal symptoms if you stop taking it suddenly. However, some of the side effects listed above may present additional challenges for older adults.

    Can you take 5mg of melatonin if you have high blood pressure? ›

    High blood pressure: Melatonin can raise blood pressure in people who are taking certain medications to control blood pressure. Avoid using it. Seizure disorders: Using melatonin might increase the risk of having a seizure.

    Why can't you take melatonin with blood pressure meds? ›

    Melatonin may increase blood pressure in individuals taking medication for hypertension and increase blood glucose levels in diabetics.

    How many times a week is it safe to take melatonin? ›

    For short-term sleep problems (insomnia) in adults

    Sometimes your doctor will recommend that you only take melatonin 2 or 3 times a week to see if that improves your sleep first.

    Can I take 5mg melatonin every night? ›

    A typical melatonin dose is around 0.1 to 10 milligrams, which is already substantially higher than what your body produces—between 10 to 80 micrograms a night. While it would be extremely rare to overdose on melatonin, taking too much can cause headaches, vomiting, and even changes in blood pressure.

    How can I increase melatonin naturally? ›

    6 ways to increase melatonin production for better sleep
    1. Get sunlight. Get at least 15 minutes of sunlight in the morning. ...
    2. Sleep in a completely dark room. ...
    3. Cut back on caffeine. ...
    4. Reduce screen time at night. ...
    5. Manage your stress. ...
    6. Eat magnesium-rich foods.
    Oct 21, 2022

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