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 disease and other dementias. Melatonin is mainly used to treat sleep problems such as insomnia. Although numerous clinical trials have tested the effects of melatonin on cognitive function, the results have been mixed and inconsistent. Melatonin is generally safe in healthy adults, but experts do not recommend melatonin for elderly people with dementia due to risks of falls and other adverse events.
Numerous meta-analyses have examined the short-term effects of melatonin on cognitive function, but results have been mixed and inconsistent. Our search identified:
• 8 meta-analyses or systematic reviews of clinical trials testing melatonin treatment • 2 reviews/guidelines on sleep impairment from the US Department of Health & Human Services and the American Academy of Sleep Medicine • 1 meta-analysis of studies in animals • Numerous preclinical studies on possible mechanisms of action
Clinical trials in humans have reported mixed findings with regards to the effects of melatonin on short-term cognitive functions. In one trial, melatonin improved verbal memory, with slight improvements in other cognitive tests [1]. Another trial showed that a single dose of melatonin enhanced memory functions while under stress, but not after stress [2]. However, in a third trial, melatonin cream did not result in significant effects on cognition [3]. The effects of melatonin on cognitive function may also depend on what time of the day it is administered. In a meta-analysis of 11 randomized controlled trials in healthy people, melatonin treatment during the daytime worsened performance on attention tasks [4]. In general, melatonin treatment is recommended at night, before bedtime. Thus, it is not unusual for melatonin treatment during the day to cause fatigue and sleepiness, contributing to reduced cognitive performance.
In models of Alzheimer’s disease, melatonin has been shown to ameliorate cognitive dysfunction and decrease biological markers of the disease [5], but no clinical research has confirmed these effects.
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 [6] 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.
Results have been mixed and inconsistent with regards to the effects of melatonin in dementia patients. A 2021 meta-analysis of randomized controlled trials in people with Alzheimer’s disease reported that melatonin treatment improved cognitive function in some people but not others and suggested that benefits may depend on the stage of disease and duration of treatment [4]. A high quality meta-analysis from 2020 reported that melatonin treatment may have little or no effect on sleep outcomes or cognition in people with Alzheimer’s disease and sleep disturbances [7]. A randomized controlled study suggested that the combined use of light therapy in the morning and melatonin in the evening may be a possible approach in addressing circadian dysregulation in Alzheimer’s patients [8; 9]. In the 2015 American Academy of Sleep Medicine Clinical Practice Guideline, recommendations were made against the use of melatonin and sleep-promoting medications for elderly people with dementia due to increased risks of falls and other adverse events [10]. Thus, the benefit to risk ratio of melatonin use needs to be carefully evaluated with healthcare providers, particularly in dementia patients.
Clinical evidence suggests that melatonin supplementation is generally safe for short-term use by most healthy people [11; 12; 13]. 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 [10]. 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]. Melatonin 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.
Melatonin is available over-the-counter in the US as a liquid, pill, and transdermal patch. In the EU, UK, Australia, and Canada, melatonin is available with prescription [17]. As a sleep aid, melatonin is often taken orally in doses of 0.3 to 5.0 mg/day before bedtime. 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 [18]. 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” [19].
Full scientific report (PDF) on Cognitive Vitality Reports
Check for drug-drug and drug-supplement interactions on Drugs.com