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Melatonin

  • Vitamins & Supplements
  • Updated June 13, 2016

Melatonin is a hormone produced by the pineal gland that regulates sleep-wake cycles, also called circadian rhythms. As we age, our bodies make less melatonin, and melatonin production is particularly impaired in those with Alzheimer’s and other dementias. Melatonin supplements are generally safe and are used to treat insomnia. They may modestly improve sleep, which could theoretically lead to long-term protection against Alzheimer's. However, other insomnia treatments may be more effective and experts do not recommend melatonin for elderly people with dementia.

Evidence

No human clinical research has studied the direct benefits of melatonin for dementia prevention, though several trials have examined its short-term effects on cognitive function. Our search identified:

• 3 randomized clinical trials in healthy adults looking at effects on cognitive function
• 2 reviews/guidelines on sleep impairment effects from the US Department of Health & Human Services and the American Academy of Sleep Medicine
• 0 observational studies
• Numerous preclinical studies on possible mechanisms of action

Potential Benefit

Clinical trials in humans have reported mixed effects of melatonin on short-term cognitive functions. In one trial, melatonin improved verbal memory, with slight improvements in other cognitive tests [3]. Another trial showed that a single dose of melatonin enhanced memory functions while under stress, but not after stress [4]. However, in a third trial, melatonin cream did not result in significant effects on cognition [5]. Other clinical trials have found that melatonin treatment significantly lowered the risk of delirium, which is a risk factor for dementia [6][7]. But a trial of 452 patients found that treatment with melatonin after surgery did not reduce the incidence of delirium [8].

Preclinical studies suggest melatonin may inhibit neurodegenerative processes, but no clinical research has confirmed these effects.

APOE4 Carriers:

No clinical studies have tested whether melatonin effects are different in APOE4 carriers. One preclinical study tentatively reported that melatonin could protect from possible toxicity from APOE4 [9] but the findings have not yet been replicated. For more information on what the APOE4 gene allele means for your health, read our APOE4 information page.

For Dementia Patients

Clinical trials have not shown that melatonin can slow disease progression or improve cognitive function in patients with dementia or mild cognitive impairment. A recent meta-analysis of patients with Alzheimer's and other dementias concluded that there are no significant benefits of melatonin on cognitive scores or measures of sleep [10].In 2015, the American Academy of Sleep Medicine Clinical Practice Guideline recommended against the use of melatonin and sleep-promoting medications for elderly people with dementia due to increased risks of falls and other adverse events [2]

Safety

Clinical evidence suggests that melatonin supplementation is safe for short-term use by most healthy people [1][11][12]. The American Academy of Sleep Medicine, however, recommends against the use of melatonin and sleep-promoting medications for demented elderly patients due to increased risks of falls and other adverse events [2]. Although many healthy people have used it for periods longer than two years, the risks or benefits from long-term use have not been well studied.

Reports of serious adverse effects of melatonin supplementation are rare but include nausea, drowsiness, decreased blood-flow, and lower body temperature (hypothermia) [14]. Melatonin may also be unsafe in people with orthostatic hypotension, bleeding disorders, diabetes, depression, autoimmune diseases, seizure disorders, and transplant recipients [15]. In elderly patients with dementia, melatonin treatment has been shown to worsen caregiver ratings of patient mood [16]. It may also interfere with the action of other drugs.

NOTE: This is not a comprehensive safety evaluation or complete list of potentially harmful drug interactions. It is important to discuss safety issues with your physician before taking any new supplement or medication.

How to Use

Melatonin is available over-the-counter as a liquid, pill, and transdermal patch. As a sleep aid, melatonin is often taken orally in doses of 0.3 to 5 mg/day before bed. The most effective dose and length of treatment vary by individual. Treatment can range from a few days (for jet lag) to nine months (for trouble falling asleep) and should be overseen by a physician.

Melatonin was once derived from bovine pineal glands, which carried the risk of viral contamination [13]. But melatonin supplements are now made synthetically and do not carry this risk. As with most supplements, melatonin quality can be uncertain. Several organizations offer independent testing of supplement quality to earn "seals-of-approval."

Learn More

Download full scientific report

For information on finding a trusted brand of melatonin supplements, visit United States Pharmacopeial Convention (USP), ConsumerLab, or FDA Information on Dietary Supplements.

Quality testing and important facts about supplements are offered by the NIH Office of Dietary Supplements.

More dosage and safety information on melatonin from Mayo Clinic

Check for drug-drug and drug-supplement interactions on Drugs.com

References

  1. Schutte-Rodin S, Broch L, Buysse D et al. (2008) Clinical guideline for the evaluation and management of chronic insomnia in adults (PDF). Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine 4, 487-504.
  2. Auger RR, Burgess HJ, Emens JS et al. (2015) Clinical Practice Guideline for the Treatment of Intrinsic Circadian Rhythm Sleep-Wake Disorders: Advanced Sleep-Wake Phase Disorder (ASWPD), Delayed Sleep-Wake Phase Disorder (DSWPD), Non-24-Hour Sleep-Wake Rhythm Disorder (N24SWD), and Irregular Sleep-Wake Rhythm Disorder (ISWRD). An Update for 2015: An American Academy of Sleep Medicine Clinical Practice Guideline. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine 11, 1199-1236.
  3. Peck JS, LeGoff DB, Ahmed I et al. (2004) Cognitive effects of exogenous melatonin administration in elderly persons: a pilot study. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry 12, 432-436.
  4. Rimmele U, Spillmann M, Bartschi C et al. (2009) Melatonin improves memory acquisition under stress independent of stress hormone release. Psychopharmacology 202, 663-672.
  5. Scheuer C, Pommergaard HC, Rosenberg J et al. (2016) Effect of topical application of melatonin cream 12.5% on cognitive parameters: A randomized, placebo-controlled, double-blind crossover study in healthy volunteers. J Dermatolog Treat, 1-7.
  6. Al-Aama T, Brymer C, Gutmanis I et al. (2011) Melatonin decreases delirium in elderly patients: a randomized, placebo-controlled trial. International journal of geriatric psychiatry 26, 687-694.
  7. Hatta K, Kishi Y, Wada K et al. (2014) Preventive effects of ramelteon on delirium: a randomized placebo-controlled trial. JAMA psychiatry 71, 397-403.
  8. de Jonghe A, van Munster BC, Goslings JC et al. (2014) Effect of melatonin on incidence of delirium among patients with hip fracture: a multicentre, double-blind randomized controlled trial. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 186, E547-556.
  9. Poeggeler B, Miravalle L, Zagorski MG et al. (2001) Melatonin reverses the profibrillogenic activity of apolipoprotein E4 on the Alzheimer amyloid Abeta peptide. Biochemistry 40, 14995-15001.
  10. Trotti LM, Karroum EG (2016) Melatonin for Sleep Disorders in Patients with Neurodegenerative Diseases. Curr Neurol Neurosci Rep 16, 63.
  11. McCleery J, Cohen DA, Sharpley AL (2014) Pharmacotherapies for sleep disturbances in Alzheimer's disease. The Cochrane database of systematic reviews, Cd009178.
  12. Xu J, Wang LL, Dammer EB et al. (2015) Melatonin for sleep disorders and cognition in dementia: a meta-analysis of randomized controlled trials. American journal of Alzheimer's disease and other dementias 30, 439-447.
  13. Altun A, Ugur-Altun B (2007) Melatonin: therapeutic and clinical utilization. International journal of clinical practice 61, 835-845.
  14. Buscemi N, Vandermeer B, Hooton N et al. (2006) Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis. BMJ (Clinical research ed) 332, 385-393.
  15. Ray CA (2003) Melatonin attenuates the sympathetic nerve responses to orthostatic stress in humans. The Journal of physiology 551, 1043-1048.
  16. Riemersma-van der Lek RF, Swaab DF, Twisk J et al. (2008) Effect of bright light and melatonin on cognitive and noncognitive function in elderly residents of group care facilities: a randomized controlled trial. JAMA 299, 2642-2655.