Melatonin
Melatonin is a hormone primarily known for regulating the body's sleep-wake cycle, or circadian rhythm. [36][25]
Produced by the pineal gland in response to darkness, its main application as a supplement is to facilitate sleep and help reset the body's internal clock, particularly for issues like jet lag or sleep phase disorders. [1][38]
Beyond sleep, emerging research highlights melatonin's role as a potent antioxidant and anti-inflammatory agent, suggesting a much broader impact on overall health and longevity. [24][5][6]
Melatonin's primary and most understood function is the regulation of circadian rhythms. [36] As light fades, the pineal gland releases melatonin, which binds to MT1 and MT2 receptors in the brain's suprachiasmatic nucleus (SCN)—the body's master clock—signaling that it is time to prepare for sleep. [51] However, its mechanisms extend far beyond sleep.
- Potent Antioxidant: Melatonin is a formidable antioxidant that protects cells from free radical damage. [39][8]It directly neutralizes reactive oxygen and nitrogen species and also stimulates the body's own production of antioxidant enzymes like superoxide dismutase (SOD). [39][37]It is particularly effective at protecting mitochondria, the cellular energy generators, from oxidative damage. [8][11]
- Anti-Inflammatory Agent: Melatonin exhibits significant anti-inflammatory properties by inhibiting key inflammatory pathways like NF-κB and reducing the production of pro-inflammatory cytokines. [35][48]Clinical trials have confirmed that supplementation can lower levels of inflammatory markers in the blood. [34][45]
- Immune and Mitochondrial Support: Melatonin acts as an "immune buffer," enhancing immune cell activity under normal conditions and acting as an anti-inflammatory during states of excessive inflammation. [43][41]It also plays a critical role in mitochondrial health, improving energy production efficiency and helping to clear out damaged mitochondria. [22][12]
Melatonin supplementation is most impactful for circadian rhythm disorders, such as Delayed Sleep-Wake Phase Disorder and jet lag. [30] Its efficacy for chronic insomnia in adults is considered modest, with the American Academy of Sleep Medicine recommending against its use for this purpose due to low-quality evidence. [13][17]
Evidence for its utility in shift work disorder is currently unclear, with conflicting results. [30][19]
A typical protocol for addressing general sleep difficulties is to start with a low dose of 0.5 to 1 milligram, taken 30 to 60 minutes before a desired bedtime. [40] The dose can be gradually increased if necessary, though most adults find a range of 1 to 5 milligrams to be sufficient. [40] A 2024 meta-analysis suggests an alternative strategy may be optimal: taking a 4 mg dose three hours before bedtime to better mimic the body's natural melatonin rise. [23][46][2]
The formulation matters:
- Immediate-Release (IR) is absorbed quickly and is best for individuals who have trouble falling asleep. [33][18]
- Extended-Release (ER) releases the hormone slowly and is designed for those who struggle with staying asleep. [18][50]
A common pitfall is the "more is better" mindset. Higher doses (above 5-10 mg) are not proven to be more effective and increase the risk of side effects like daytime drowsiness, headache, and nausea. [40][29]
Another pitfall is relying on melatonin as a cure for chronic insomnia, for which its benefits are limited and often outweighed by behavioral strategies. [10]
Pros
Cons
Drug Interactions and Contraindications: Melatonin can interact with numerous medications, including blood thinners, immunosuppressants, and drugs for diabetes and high blood pressure. [20] It is not recommended for individuals with certain conditions like autoimmune diseases, seizure disorders, or depression. [26][27]
Are melatonin supplements accurately labeled?
How does melatonin actually work for sleep?
Is it possible to become addicted to melatonin?
Is it true that a higher dose is more effective?
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