Meliton
Also known as: N-acetyl-5-methoxytryptamine, Meliton, Pineal hormone, 5-methoxy-N-acetyltryptamine, Melatonin
Overview
Melatonin is a hormone naturally produced by the pineal gland in the brain, primarily responsible for regulating circadian rhythms and the sleep-wake cycle. As a supplement, it is widely used to improve sleep quality, treat sleep disorders such as insomnia and jet lag, and manage other conditions related to circadian rhythm disruptions. It acts as a chronobiotic, modulating biological timing, and possesses antioxidant properties. Research on melatonin is extensive, with numerous randomized controlled trials (RCTs), systematic reviews, and meta-analyses supporting its efficacy and safety, particularly for sleep-related outcomes in adults. It is available in various forms, including immediate and extended-release tablets, and is categorized as an endogenous hormone supplement and a dietary supplement for sleep regulation.
Benefits
Melatonin supplementation significantly improves sleep quality in adults, as evidenced by validated scales like the Pittsburgh Sleep Quality Index (PSQI). It effectively reduces sleep onset latency (the time it takes to fall asleep) and increases total sleep time, with optimal effects observed at doses around 4 mg/day. Beyond primary sleep benefits, melatonin may help regulate circadian rhythm disorders, offering improvements for shift workers and individuals experiencing jet lag. While less conclusively established, it also exhibits potential antioxidant and neuroprotective effects. Adults with sleep disturbances benefit most from melatonin; evidence in children and the elderly varies. Meta-analyses consistently show statistically significant improvements in sleep parameters with moderate effect sizes, and benefits typically manifest within days to weeks of consistent supplementation.
How it works
Melatonin primarily acts on melatonin receptors (MT1 and MT2) located in the suprachiasmatic nucleus (SCN) of the hypothalamus, which serves as the brain's central circadian pacemaker. By binding to these receptors, melatonin signals darkness to the brain, thereby modulating the sleep-wake cycle and promoting sleep initiation. Beyond its direct role in sleep regulation, melatonin also influences other physiological processes, including enhancing antioxidant defense mechanisms and modulating immune responses. When taken orally, melatonin is absorbed relatively quickly, though its bioavailability can vary significantly (10-56%) due to first-pass metabolism in the liver.
Side effects
Overall, melatonin has a favorable safety profile, even at higher doses (≥10 mg), with no significant increase in serious adverse events (SAEs) or withdrawals due to adverse events compared to placebo. Common side effects, reported in over 5% of users, include drowsiness, headache, and dizziness. Less common side effects (1-5%) may include nausea and vivid dreams. Rare side effects (less than 1%) can involve allergic reactions or mood changes. While generally safe, caution is advised when combining melatonin with sedatives or anticoagulants, as potential interactions, though not majorly reported, could occur. Melatonin is contraindicated during pregnancy and breastfeeding due to limited safety data in these populations. Special populations, such as the elderly and children, may require tailored dosing and careful monitoring due to potential differences in metabolism and sensitivity.
Dosage
For circadian rhythm adjustment, a minimum effective dose of approximately 0.3 mg to 1 mg is often sufficient. However, for improving sleep onset and duration, the optimal dosage range is typically 2-5 mg daily, with 4 mg/day showing peak efficacy. Studies have utilized doses up to 10 mg or more without significant safety concerns, but long-term safety data at these higher doses are limited. Melatonin is generally taken 30-60 minutes before bedtime to facilitate sleep improvement. Immediate-release formulations are preferred for promoting sleep onset, while extended-release forms may be beneficial for maintaining sleep throughout the night. Absorption can be influenced by food intake, and taking melatonin on an empty stomach may enhance its bioavailability.
FAQs
Is melatonin addictive?
No, there is no scientific evidence to suggest that melatonin is addictive or causes dependence, even with regular use.
Can melatonin cause next-day drowsiness?
Yes, next-day drowsiness is possible, especially with higher doses or extended-release formulations. It's important to assess individual tolerance.
How quickly does melatonin work?
Effects can be noticed within days of starting supplementation, but consistent use for 1-2 weeks may be required to observe full benefits.
Is melatonin safe for long-term use?
Melatonin is generally considered safe for long-term use at typical doses, but more extensive long-term studies are still needed to fully confirm this.
Does melatonin work for everyone?
Response to melatonin varies among individuals. It tends to be most effective for those with diagnosed circadian rhythm disruptions or primary insomnia.
Research Sources
- https://pubmed.ncbi.nlm.nih.gov/33417003/ – This systematic review and meta-analysis by Fatemeh et al. (2022) assessed melatonin's effect on adult sleep quality using the PSQI. It found significant improvement in sleep quality with melatonin supplementation across multiple RCTs, despite some heterogeneity in doses and populations. The study's quality was rated as high, supporting melatonin's efficacy for sleep.
- https://onlinelibrary.wiley.com/doi/10.1111/jpi.12782 – Menczel Schrire et al. (2022) conducted a systematic review and meta-analysis on the safety of high-dose melatonin (≥10 mg) in 79 RCTs. They concluded that high-dose melatonin did not increase serious adverse events or withdrawals, though it showed a modest increase in mild side effects like drowsiness and headache. The review highlighted a need for better safety reporting in future studies.
- https://onlinelibrary.wiley.com/doi/10.1111/jpi.12985 – Cruz-Sanabria et al. (2024) performed a dose-response meta-analysis to determine optimal melatonin dosages for sleep parameters. Their findings indicated that 4 mg/day is the optimal dose for reducing sleep onset latency and increasing total sleep time. The analysis included well-controlled RCTs, though acknowledged variability in study designs.
