Melatonin
The main hormone your brain makes to control your sleep-wake cycle. It rises in response to darkness and helps you fall asleep. Also acts as a powerful antioxidant. Production drops with age, which can contribute to sleep problems in older adults. One of the most widely used supplements globally, available over-the-counter in the US.
Dosage
Oral: 0.5-5 mg 30-60 min before bed (lower doses often more effective)
Dosages shown are for research reference only. Always consult a qualified healthcare provider.
Administration
Oral (tablet, liquid, sublingual), injectable, or topical
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Effects
Sleep Regulation
Primary circadian rhythm hormone — signals nighttime to every cell.
Antioxidant
Potent scavenger — each molecule neutralizes up to 10 ROS in cascade reactions.
Immune Support
Enhances NK cell activity, T-cell function, and vaccine responsiveness.
Mechanism of Action
Melatonin (N-acetyl-5-methoxytryptamine) is synthesized in the pineal gland from serotonin through a two-step pathway: N-acetyltransferase (AANAT) converts serotonin to N-acetylserotonin, and hydroxyindole O-methyltransferase (HIOMT) converts it to melatonin. AANAT activity is under direct control of the suprachiasmatic nucleus (SCN) master circadian clock — it is strongly suppressed by light (via the retinohypothalamic tract) and activated in darkness, creating the characteristic nocturnal melatonin surge that signals nighttime to every cell in the body.
Melatonin acts through two high-affinity G protein-coupled receptors: MT1 (MTNR1A) and MT2 (MTNR1B), both of which are Gi/o-coupled, inhibiting adenylyl cyclase and reducing cAMP when activated. MT1 receptors in the SCN mediate the acute sleep-promoting effect — their activation inhibits the firing rate of SCN neurons, reducing the alerting signal from the master clock and promoting sleepiness. MT2 receptors in the SCN mediate circadian phase-shifting — their activation during the biological evening advances the clock phase (useful for jet lag and delayed sleep phase), while activation during the biological morning delays it. This dual receptor mechanism explains why melatonin both promotes acute sleepiness and shifts circadian timing.
Beyond sleep, melatonin is one of the most potent endogenous antioxidants. It directly scavenges hydroxyl radicals, superoxide anions, hydrogen peroxide, and peroxynitrite through electron donation. Uniquely, melatonin's antioxidant cascade is amplified — its metabolites (cyclic 3-hydroxymelatonin, AFMK, AMK) are themselves antioxidants, so each melatonin molecule can neutralize up to 10 reactive oxygen species in a cascade. Melatonin also upregulates antioxidant enzymes (superoxide dismutase, glutathione peroxidase, catalase) and downregulates pro-oxidant enzymes (nitric oxide synthase, lipoxygenase). In the immune system, MT1 receptors on T helper cells, natural killer cells, and eosinophils modulate immune function — melatonin generally enhances Th1 cellular immunity, increases NK cell activity, and augments antibody responses to vaccination, which has led to interest in melatonin as an immunomodulator in aging and cancer.
Regulatory Status
Available over the counter as dietary supplement in the US. Prescription-only in some European countries. Injectable forms through compounding pharmacies.
Risks & Safety
Common
daytime drowsiness, headache, vivid or unusual dreams, mild dizziness, next-morning grogginess at higher doses.
Serious
potential suppression of your body's own melatonin production with long-term use, drug interactions with blood thinners (warfarin) and immunosuppressants.
Rare
depressed mood, sleep-walking, allergic reactions.
Compare Melatonin With
Research Papers
32Published: February 9, 2026
AI Summary
Melatonin reduced liver damage from ischemia-reperfusion in aged rats by blocking NLRP3 inflammasome activation and pyroptosis. The hormone may help protect older patients during liver surgery or transplantation.
Published: January 20, 2026
AI Summary
People with autism often have suppressed melatonin signaling, and STAT3–NF-κB interactions strongly regulate this pathway. The review ties together how melatonin, mitochondria, inflammation, and other factors may contribute to autism and points to new treatment directions.
Published: March 25, 2026
AI Summary
Uterine response to oxytocin varied by time of day in mice, with melatonin-proficient and melatonin-deficient strains showing different baseline contractility. Circadian timing may matter for labor induction and birth outcomes.
Published: January 21, 2026
AI Summary
Combining melatonin and EGCG improved mouse oocyte maturation, reduced oxidative stress, and boosted embryo development better than either compound alone. The combination may help improve fertility treatment outcomes.
Published: December 24, 2025
AI Summary
Melatonin reduced kidney damage in obese rats by lowering fibrosis, inflammation, and injury markers, and partly by modulating circadian proteins. The hormone may be useful for obesity-related kidney disease.
Published: January 20, 2026
AI Summary
The pineal gland calcifies and loses cells with age, and people with Alzheimer's had more amyloid in the pineal and lower melatonin in spinal fluid. Pineal changes may contribute to dementia and could be a treatment target.
Published: January 19, 2026
AI Summary
Melatonin promoted nerve cell regeneration and improved learning in newborn rats with oxygen-deprivation brain injury, partly by acting through the JAK2/STAT3 pathway. The hormone may help treat neonatal brain damage.
Published: February 8, 2026
AI Summary
A walnut peptide and theanine combination improved sleep in stressed zebrafish, mice, and humans by calming the stress axis and restoring slow-wave sleep. The blend may offer a dietary approach to stress-related sleep problems.
Published: January 12, 2026
AI Summary
Abstract too short to summarize.
Published: February 6, 2026
AI Summary
Abstract too short to summarize.
Published: January 1, 2026
AI Summary
Abstract too short to summarize.
Published: January 30, 2026
AI Summary
Melatonin reversed autism-like behavior and restored Wnt signaling in mice exposed to valproic acid, and circadian disruption worsened these effects. The hormone may help treat sleep and behavioral issues in autism.
Published: April 29, 2026
AI Summary
Melatonin reduced lung inflammation and emphysema in COPD mice by blocking NLRP3-driven pyroptosis in alveolar macrophages. Targeting this cell death pathway may offer a new approach to treating COPD.
Published: January 6, 2026
AI Summary
Abstract too short to summarize.
Published: January 4, 2026
AI Summary
Hormones such as melanocortins, estrogens, and melatonin influence skin pigmentation and are relevant in conditions like melasma and vitiligo. Melatonin may lighten skin by reducing melanin, and the review covers both physiology and clinical use.
Published: February 10, 2026
AI Summary
Melatonin slowed triple-negative breast cancer growth by reducing glycolysis and DNA repair via YAP1-NAMPT signaling, and enhanced the effect of the PARP inhibitor Olaparib. The hormone may complement existing breast cancer treatments.
Published: December 30, 2025
AI Summary
Abstract too short to summarize.
Published: January 1, 2026
AI Summary
Abstract too short to summarize.
Published: January 28, 2026
AI Summary
Melatonin protected testosterone-producing Leydig cells from heat stress by activating the KEAP1-NRF2 pathway and reducing oxidative damage. The hormone may help preserve male fertility in hot environments.
Published: December 21, 2025
AI Summary
Agomelatine, a melatonin receptor agonist, rapidly improved depression-like behavior and restored synaptic plasticity in stressed mice via STAT3 signaling. The findings point to STAT3 as a target for faster-acting antidepressants.
Published: December 19, 2025
AI Summary
Genetic variants in diabetes-related genes, including the melatonin receptor gene MTNR1B, showed different associations across type 2 diabetes clusters. The results support using genetics to tailor diabetes treatment.
Published: February 11, 2026
AI Summary
Melatonin improved learning and memory in diabetic mice by blocking ferroptosis and ferritinophagy through direct binding to STING. The hormone may help treat diabetic cognitive decline by protecting brain cells from iron-dependent damage.
Published: December 16, 2025
AI Summary
Engineered cells that sense melatonin at night delivered GLP-1 therapy and normalized blood sugar in diabetic mice. The approach could reduce the need for injections by aligning drug delivery with circadian rhythms.
Published: February 16, 2026
AI Summary
Circadian clock genes influence immune function and may be therapeutic targets in autoimmune disease. The review covers melatonin, sleep, and time-restricted eating as non-drug ways to support circadian health.
Published: December 30, 2025
AI Summary
Night-restricted feeding in pigs increased liver fat by aligning insulin and melatonin rhythms and disrupting mitochondrial balance. The findings link late eating to fatty liver and suggest timing of meals matters for metabolic health.
Published: January 14, 2026
AI Summary
Abstract too short to summarize.
Published: December 9, 2025
AI Summary
Heart rate, breathing, sleep, and circadian rhythms all affect how the brain clears amyloid, with melatonin and blood flow playing key roles. Understanding these rhythms may lead to new Alzheimer's prevention and treatment strategies.
Published: December 9, 2025
AI Summary
Amyloid-induced memory loss in rats was linked to reduced hippocampal melatonin synthesis and impaired synaptic plasticity. Local melatonin production in the brain may be important for cognition and could be a treatment target.
Published: December 8, 2025
AI Summary
Abstract too short to summarize.
Published: March 5, 2026
AI Summary
Kidney ischemia-reperfusion injury involves mitochondrial dysfunction, and agents like melatonin, puerarin, and Schisandrin B may help by restoring mitochondrial health. The review outlines a mitochondrial-focused approach to acute kidney injury.
Published: April 14, 2026
AI Summary
Yeast beta-glucan and chicory inulin helped restore normal daily rhythms and reduced brain inflammation in mice with systemic inflammation. The effects were similar to melatonin and ibuprofen, suggesting prebiotics may support circadian and brain health.
Published: February 9, 2026
AI Summary
A casein phosphopeptide from infant formula improved sleep and memory in sleep-deprived zebrafish by modulating melatonin, GABA, and NMDA receptor signaling. A tripeptide called HPF was identified as a key active component.
Frequently Asked Questions
What is Melatonin?
The main hormone your brain makes to control your sleep-wake cycle. It rises in response to darkness and helps you fall asleep. Also acts as a powerful antioxidant. Production drops with age, which can contribute to sleep problems in older adults. One of the most widely used supplements globally, available over-the-counter in the US.
What is Melatonin used for?
The main hormone your brain makes to control your sleep-wake cycle. It rises in response to darkness and helps you fall asleep. Also acts as a powerful antioxidant. Production drops with age, which can contribute to sleep problems in older adults. One of the most widely used supplements globally, available over-the-counter in the US.
What is the dosage for Melatonin?
Oral (sleep): 0.5-5 mg once, 30-60 minutes before bed (lower doses of 0.5-1 mg are often more effective than higher doses). Extended-release forms available for sleep maintenance. Injectable: 10-20 mg for research protocols. High-dose IV: used in some anti-aging and oncology protocols.
What are the side effects of Melatonin?
Common: daytime drowsiness, headache, vivid or unusual dreams, mild dizziness, next-morning grogginess at higher doses. Serious: potential suppression of your body's own melatonin production with long-term use, drug interactions with blood thinners (warfarin) and immunosuppressants. Rare: depressed mood, sleep-walking, allergic reactions.
How does Melatonin work?
Melatonin (N-acetyl-5-methoxytryptamine) is synthesized in the pineal gland from serotonin through a two-step pathway: N-acetyltransferase (AANAT) converts serotonin to N-acetylserotonin, and hydroxyindole O-methyltransferase (HIOMT) converts it to melatonin. AANAT activity is under direct control of the suprachiasmatic nucleus (SCN) master circadian clock — it is strongly suppressed by light (via the retinohypothalamic tract) and activated in darkness, creating the characteristic nocturnal melatonin surge that signals nighttime to every cell in the body. Melatonin acts through two high-affinity G protein-coupled receptors: MT1 (MTNR1A) and MT2 (MTNR1B), both of which are Gi/o-coupled, inhibiting adenylyl cyclase and reducing cAMP when activated. MT1 receptors in the SCN mediate the acute sleep-promoting effect — their activation inhibits the firing rate of SCN neurons, reducing the alerting signal from the master clock and promoting sleepiness. MT2 receptors in the SCN mediate circadian phase-shifting — their activation during the biological evening advances the clock phase (useful for jet lag and delayed sleep phase), while activation during the biological morning delays it. This dual receptor mechanism explains why melatonin both promotes acute sleepiness and shifts circadian timing. Beyond sleep, melatonin is one of the most potent endogenous antioxidants. It directly scavenges hydroxyl radicals, superoxide anions, hydrogen peroxide, and peroxynitrite through electron donation. Uniquely, melatonin's antioxidant cascade is amplified — its metabolites (cyclic 3-hydroxymelatonin, AFMK, AMK) are themselves antioxidants, so each melatonin molecule can neutralize up to 10 reactive oxygen species in a cascade. Melatonin also upregulates antioxidant enzymes (superoxide dismutase, glutathione peroxidase, catalase) and downregulates pro-oxidant enzymes (nitric oxide synthase, lipoxygenase). In the immune system, MT1 receptors on T helper cells, natural killer cells, and eosinophils modulate immune function — melatonin generally enhances Th1 cellular immunity, increases NK cell activity, and augments antibody responses to vaccination, which has led to interest in melatonin as an immunomodulator in aging and cancer.
How is Melatonin administered?
Melatonin is administered via oral (tablet, liquid, sublingual), injectable, or topical.
What is the half-life of Melatonin?
The half-life of Melatonin is 40-60 minutes (oral); injectable forms have shorter half-life.
Is Melatonin legal?
Available over the counter as dietary supplement in the US. Prescription-only in some European countries. Injectable forms through compounding pharmacies.
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