Can melatonin help me sleep?

Melatonin (N-acetyl-5-methoxytryptamine) is a hormone produced by the pineal gland of the brain and secreted in response to darkness in the environment.¹ Its physiological function is to convey daily light cycle information and organize circadian rhythms with endogenous melatonin levels peaking at night.^2,3 Supplementing with exogenous melatonin may stimulate sleep similarly to the way the darkness of nightfall does, particularly in patients with circadian rhythm disorders.

Many adults take melatonin supplements when faced with difficulty falling or staying asleep. A 2022 analysis of data from the National Health and Nutrition Examination Survey (NHANES) (n=55,021) found that use of melatonin supplements increased from 0.4% in 2000 to 2.1% in 2018 in the United States (US).⁴

The American Academy of Sleep Medicine and the American College of Physicians (ACP) state that there is insufficient evidence to recommend melatonin as a sleep aid for those with insomnia.^5,6 ACP recommends cognitive-behavioral therapy (CBT) as a first-line treatment for insomnia in adults. They further recommend that if CBT is unsuccessful, physicians engage patients in discussions of the potential benefits and harms of short-term use of medications to decide whether pharmacological therapy is advisable.

Melatonin supplements have been shown in some small studies to improve sleep quality for adults with primary sleep disorders or other health conditions affecting sleep. Although they are generally safe when used at low doses for short periods of time, the long-term risks of melatonin use have not been well studied. Exogenous melatonin may interact with some medications, such as oral anticoagulants, antidepressants, and some types of antihypertensives.^7-11 Additionally, melatonin supplements are not FDA-regulated the same way pharmaceutical drugs are, and variations in supplement content and quality exist.¹² The FDA recommends speaking with your doctor before starting any new supplement to determine the potential benefits and any possible risks.

Efficacy

While melatonin is not recommended as a treatment for insomnia, a few small studies have found exogenous melatonin use to benefit sleep quality for specific health conditions. A 2017 meta-analysis of 12 randomized-controlled trials (n=1,383) tested the effect of exogenous melatonin versus placebo on sleep quality.¹³ Analyses revealed that melatonin was associated with reduced sleep onset latency (total mean difference 5.05 minutes, 95% Confidence Interval [CI] [1.59-8.51], p=0.004) and delayed sleep phase syndrome (22.05 minutes, CI [12.09-32.02], p<0.0001) compared with placebo. The authors concluded that melatonin supplementation is effective and can successfully treat primary sleep disorders (primary insomnia, delayed sleep phase syndrome, non-24-hour sleep wake syndrome in people who are blind, and rapid eye movement-behavior disorder) but suggested that further large-scale randomized-controlled trials are needed to assess exogenous melatonin use in other sleep disturbances beyond primary sleep disorders.

To examine the use of melatonin supplements among adults with chronic conditions affecting sleep not limited to primary sleep disorders, a 2021 meta-analysis pooled results from 23 randomized-controlled trials (n=1,965) to examine the effect of exogenous melatonin supplementation versus placebo on sleep quality.¹⁴ The authors found that melatonin supplementation had a beneficial effect on sleep quality as assessed by the Pittsburgh Sleep Quality Index (PSQI; scored 0-21 with scores >5 suggesting significant sleep difficulties) on patients with various chronic health conditions affecting sleep, including insomnia, asthma, cirrhosis, chronic obstructive pulmonary disease, and others. Those who took melatonin had a weighted mean difference of 1.24 points on their PSQI score (95% CI [0.71-1.77], p=0.000).

Adverse Effects

Melatonin supplements generally have a low risk of mild, transient side effects for healthy adults. According to a 2019 systematic review and meta-analysis, the most common adverse effects of short-term, exogenous melatonin use is daytime sleepiness (3.07% incidence among melatonin users vs 1.41% placebo, 1.66% difference).⁷ Other uncommon adverse effects include headache (2.71% melatonin vs 1.97% placebo, 0.74% difference), other sleep-related adverse events including red eyes, vivid dreams, or nightmares (1.30% melatonin vs 0.56% placebo, 0.74% difference), dizziness (0.86% melatonin vs 0.12% placebo, 0.74% difference) and hypothermia including feeling cold (0.87% melatonin vs 0.25% placebo, 0.62% difference). All adverse effects were classified as mild and of minor clinical significance, and all either resolved spontaneously after a few days of usage or immediately upon treatment discontinuation.

However, melatonin may interact with medications that are metabolized in a similar way, including antidepressants, the calcium channel blocker nifedipine, the oral anticoagulant warfarin, and other sedatives. This area remains understudied, so exact incidence and risk is unknown. There is one case report of severe sedation after a patient taking oxycodone, citalopram, and nortriptyline took supplemental melatonin; this adverse event was attributed to melatonin interacting with citalopram.⁸ A 2000 clinical trial found that a 5 mg of melatonin for four weeks mitigated the effects of nifedipine, resulting in a blood pressure increase of 6.5 mmHg systolic and 4.5 mmHg diastolic.⁹ There have been at least ten case studies of increased bleeding in patients taking melatonin and warfarin, although no life-threatening bleeding has been reported.¹⁰

A 2008 randomized control trial of middle to older aged adults (n=16) found that coadministration of melatonin with zolpidem, a sedative, further impaired psychomotor function.¹¹ At one hour after taking placebo, melatonin, zolpidem, or melatonin in conjunction with zolpidem, those on the combination had significantly slower reaction times (18 milliseconds placebo and melatonin, 60 milliseconds zolpidem, and 140 milliseconds combination) and had more collisions in a simulated driving exercise (0 placebo and melatonin, 1.3 zolpidem, 2.8 combination).

Caffeine may also interact with melatonin, increasing its bioavailability. A 2003 study of twelve adults under the age of 40 found that ingesting 200 mg of caffeine (equivalent to about 2-4 cups of coffee) one hour before taking 6 mg melatonin significantly increased serum concentrations of melatonin, with concentrations one hour after taking the melatonin of 8,000 ng/L with caffeine vs 3,000 ng/L without caffeine.¹⁵

Contents

As with all dietary supplements in the US, the FDA does not participate in the oversight or approval of melatonin supplements, their labeling, or their content.¹² A 2017 study analyzed 31 Canadian melatonin supplements and compared the actual electrochemical detection of melatonin to advertised melatonin content.¹⁶ Melatonin content in the supplements ranged from -83% to +478% of the labeled content, and lot-to-lot variability within a particular product varied by up to 465%, unrelated to manufacturer or product type. Regarding contamination, 26% of the supplements were found to contain serotonin, despite no manufacturer disclosure of this additional chemical content.

References:

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