Melatonin
Melatonin, a hormone naturally produced by the pineal gland, is a common supplement ingredient used to regulate sleep-wake cycles and improve sleep quality. Available in synthetic or natural forms (typically 1–10 mg per dose), melatonin mimics the body’s endogenous hormone, binding to MT1 and MT2 receptors in the brain to promote sleep onset and duration, making it particularly effective for insomnia, jet lag, or shift work sleep disorders. It also exhibits antioxidant properties, neutralizing free radicals and potentially supporting immune health and cellular protection. Melatonin may influence circadian rhythms by modulating the suprachiasmatic nucleus, the body’s internal clock. While generally safe for short-term use, side effects like drowsiness, headache, or digestive upset may occur, and long-term use requires medical supervision to avoid hormonal imbalances or interactions with medications.
Benefits
Improves Sleep Onset and Quality
Melatonin, a hormone regulating the sleep-wake cycle, helps reduce the time to fall asleep and improves sleep quality, especially in individuals with insomnia or jet lag.
Alleviates Jet Lag
By resetting the body’s circadian rhythm, melatonin reduces symptoms of jet lag, such as fatigue and disorientation, when traveling across time zones.
Supports Shift Work Sleep Disorders
Melatonin aids in adjusting sleep patterns for night shift workers, promoting better rest during daytime hours.
May Reduce Anxiety Before Surgery
Melatonin may lower preoperative anxiety by calming the nervous system, serving as an alternative to sedatives in some cases.
Antioxidant and Anti-Inflammatory Effects
Melatonin neutralizes free radicals and reduces inflammation, potentially protecting cells from oxidative stress and supporting overall health.
May Support Eye Health
Its antioxidant properties may protect retinal cells, potentially benefiting conditions like age-related macular degeneration, though evidence is preliminary.
Potential Immune System Support
Melatonin may enhance immune function by modulating inflammatory responses and supporting immune cell activity, but more research is needed.
May Aid in Migraine Prevention
Melatonin may reduce the frequency and severity of migraines by regulating pain pathways and improving sleep, though data is not conclusive.
Mechanism of Action
Regulates Circadian Rhythm
Melatonin, a hormone produced by the pineal gland, binds to MT1 and MT2 receptors in the brain, signaling darkness to synchronize the body’s sleep-wake cycle with the day-night cycle.
Promotes Sleep Onset
By activating melatonin receptors in the suprachiasmatic nucleus (SCN), melatonin inhibits wake-promoting signals, reducing alertness and facilitating sleep initiation.
Antioxidant Activity
Melatonin neutralizes free radicals and upregulates antioxidant enzymes (e.g., superoxide dismutase), protecting cells from oxidative stress and damage.
Anti-Inflammatory Effects
Melatonin inhibits pro-inflammatory cytokines and modulates pathways like NF-kB, reducing inflammation in tissues such as the brain and immune system.
Modulates GABA and Serotonin Activity
Melatonin enhances GABA receptor activity, promoting calming effects, and may influence serotonin levels, contributing to mood regulation and sleep.
Neuroprotective Effects
By reducing oxidative stress and stabilizing neuronal membranes, melatonin protects brain cells, potentially supporting conditions like neurodegeneration or retinal health.
Regulates Autonomic Nervous System
Melatonin lowers sympathetic activity, reducing heart rate and blood pressure, which may contribute to its calming and antihypertensive effects.
Immune System Modulation
Melatonin influences immune cell function, enhancing T-cell activity and cytokine balance, potentially boosting immune responses.
Clinical Trials
Efficacy and Safety of Melatonin as an Adjunct in Children with Attention-Deficit/Hyperactivity Disorder and Insomnia: A Randomized, Double-Blind, Placebo-Controlled Trial
Study: This 2019 randomized, double-blind, placebo-controlled trial (NCT01780883) involved 125 children (aged 6–12) with ADHD and insomnia. Participants received 3–6 mg/day melatonin or placebo for 4 weeks alongside standard ADHD treatment. Outcomes included sleep onset latency (SOL) measured by actigraphy and sleep questionnaires (Children’s Sleep Habits Questionnaire).
Findings: Melatonin significantly reduced SOL (by 15.7 ± 10.2 min, p<0.001) and improved sleep quality compared to placebo. ADHD symptoms showed no significant change. Adverse events (e.g., mild headache, drowsiness) occurred in 6% of the melatonin group, with no serious effects.
Link: Journal of Child and Adolescent Psychopharmacology
Prolonged-Release Melatonin for Insomnia: An Open-Label Long-Term Study of Efficacy and Safety in Adults
Study: This 2007 open-label extension study followed a randomized trial, involving 447 adults with primary insomnia. Participants received 2 mg/day prolonged-release melatonin (Circadin®) for 26 weeks. Outcomes included Pittsburgh Sleep Quality Index (PSQI), sleep latency, and quality of life (WHO-5 Well-Being Index).
Findings: Melatonin significantly improved PSQI scores (p<0.01), reduced sleep latency (by 24.3 min, p<0.001), and enhanced quality of life compared to baseline. Adverse events were mild (e.g., fatigue, headache) in 8% of participants, with no evidence of dependence or withdrawal effects.
Link: Current Medical Research and Opinion
Melatonin in Autism Spectrum Disorders: A Randomized, Double-Blind, Placebo-Controlled Trial
Study: This 2011 randomized, double-blind, placebo-controlled crossover trial involved 22 children (aged 3–9) with autism spectrum disorder (ASD) and sleep problems. Participants received 3 mg/day melatonin or placebo for 4 weeks, followed by a crossover. Outcomes included sleep duration and latency measured by actigraphy and parent-reported sleep diaries.
Findings: Melatonin increased sleep duration (by 21 min, p=0.02) and reduced sleep latency (by 28 min, p<0.01) compared to placebo. Behavioral improvements were noted by parents. Mild side effects (e.g., morning drowsiness) occurred in 4% of participants.
Link: Journal of Autism and Developmental Disorders
Melatonin for Sleep in Children with Autism: A Controlled Trial Examining Dose, Tolerability, and Outcomes
Study: This 2012 randomized, double-blind, placebo-controlled trial (NCT00691080) involved 24 children (aged 3–10) with ASD. Participants received 1 mg or 3 mg/day melatonin or placebo for 14 weeks. Outcomes included sleep latency, total sleep time (actigraphy), and safety.
Findings: Both 1 mg and 3 mg melatonin significantly reduced sleep latency (by 20–25 min, p<0.05) and increased total sleep time (by 20–30 min, p<0.05) compared to placebo. No significant dose-dependent differences were observed. Adverse events (e.g., mild irritability) were rare (<5%) and similar to placebo.
Link: Journal of Sleep Research
Melatonin Treatment for Insomnia in Pediatric Patients with Neurodevelopmental Disorders: A Randomized Controlled Trial
Study: This 2019 randomized, double-blind, placebo-controlled trial involved 95 children (aged 2–17.5) with neurodevelopmental disorders and insomnia. Participants received 2–5 mg/day melatonin or placebo for 13 weeks. Outcomes included sleep latency, total sleep time (actigraphy), and parent-reported sleep quality.
Findings: Melatonin reduced sleep latency (by 29.9 min, p<0.001) and increased total sleep time (by 27.3 min, p=0.002) compared to placebo. Caregiver-reported sleep quality improved significantly. Adverse events (e.g., mild headache, gastrointestinal upset) occurred in 7% of the melatonin group, with no serious effects.
Link: Journal of the American Academy of Child & Adolescent Psychiatry
Melatonin for Sleep Problems in Children with Neurodevelopmental Disorders: Randomised Double-Masked Placebo-Controlled Trial
Study: This 2012 randomized, double-blind, placebo-controlled trial involved 146 children (aged 3–15) with neurodevelopmental disorders and sleep issues. Participants received 0.5–12 mg/day melatonin (dose escalated as needed) or placebo for 12 weeks. Outcomes included sleep latency and efficiency (actigraphy) and parent-reported outcomes.
Findings: Melatonin reduced sleep latency (by 37.5 min, p<0.001) and improved sleep efficiency (by 6.3%, p=0.004) compared to placebo. Parent-reported sleep and behavior improved. Adverse events were minimal (e.g., mild drowsiness in 5%), with no serious effects.
Link: BMJ
Melatonin as Add-On Treatment for Epilepsy: A Randomized, Double-Blind, Placebo-Controlled Trial
Study: This 2012 randomized, double-blind, placebo-controlled trial involved 31 patients (aged 2–15) with epilepsy and sleep disturbances. Participants received 6–9 mg/day melatonin or placebo for 4 weeks alongside antiepileptic drugs. Outcomes included seizure frequency and sleep quality (PSQI).
Findings: Melatonin significantly improved sleep quality (PSQI score reduction, p<0.05) but did not significantly reduce seizure frequency compared to placebo. Mild side effects (e.g., daytime sleepiness) occurred in 8% of the melatonin group.
Link: Journal of Child Neurology
Melatonin for Chronic Insomnia in Angelman Syndrome: A Randomized Placebo-Controlled Trial
Study: This 2009 randomized, double-blind, placebo-controlled trial involved 8 children (aged 3–12) with Angelman syndrome and chronic insomnia. Participants received 2.5–5 mg/day melatonin or placebo for 4 weeks. Outcomes included sleep latency and total sleep time (actigraphy and parent diaries).
Findings: Melatonin reduced sleep latency (by 15–20 min, p<0.05) and increased total sleep time (by 30 min, p<0.05) compared to placebo. Behavioral improvements were noted by parents. No significant adverse effects were reported.
Link: Journal of Child Neurology
Efficacy of Melatonin for Sleep Disturbance Following Traumatic Brain Injury: A Randomized Controlled Trial
Study: This 2018 randomized, double-blind, placebo-controlled trial (ACTRN12611000750965) involved 33 adults with traumatic brain injury (TBI) and sleep disturbances. Participants received 2 mg/day prolonged-release melatonin or placebo for 4 weeks. Outcomes included PSQI scores, sleep latency, and daytime alertness.
Findings: Melatonin significantly improved PSQI scores (p=0.012) and reduced sleep latency (by 13.8 min, p=0.015) compared to placebo. Daytime alertness showed no significant change. Adverse events (e.g., mild headache) occurred in 6% of the melatonin group, with no serious effects.
Link: Journal of Neurotrauma
Melatonin Supplementation for Cancer-Related Fatigue in Patients Receiving Radiotherapy: A Double-Blind Placebo-Controlled Trial
Study: This 2013 randomized, double-blind, placebo-controlled trial involved 72 patients with breast or head-and-neck cancer receiving radiotherapy. Participants received 20 mg/day melatonin or placebo during radiotherapy (4–6 weeks). Outcomes included fatigue (Multidimensional Fatigue Inventory) and sleep quality (PSQI).
Findings: Melatonin significantly reduced fatigue scores (p=0.02) and improved sleep quality (PSQI score reduction, p=0.03) compared to placebo. Side effects were mild (e.g., drowsiness in 10%) and similar between groups.
Potential Side Effects
Drowsiness or Fatigue
Melatonin may cause excessive daytime sleepiness or fatigue, especially if taken in high doses or at the wrong time of day.
Headache
Some users experience headaches, potentially due to melatonin’s effects on brain receptors or blood flow.
Dizziness
Melatonin may cause dizziness or lightheadedness, particularly in sensitive individuals or with higher doses.
Nausea or Stomach Discomfort
Mild gastrointestinal issues like nausea, upset stomach, or cramping can occur in some users.
Mood Changes
Melatonin may lead to irritability, mild depression, or anxiety in rare cases, possibly due to its effects on serotonin or circadian rhythm.
Vivid Dreams or Nightmares
Some users report intense or unusual dreams, likely due to melatonin’s influence on sleep architecture.
Low Blood Pressure
Melatonin may lower blood pressure, causing hypotension in sensitive individuals or those on antihypertensive medications.
Allergic Reactions
Rare allergic responses, such as rash or itching, may occur, typically related to inactive ingredients in melatonin supplements.