MelatoninEdit
Melatonin is a neurohormone that plays a central role in coordinating sleep and wakefulness through the body’s circadian clock. In humans, it is produced mainly by the pineal gland, a small endocrine organ located near the center of the brain. Endogenous melatonin levels rise in the dark and fall with light exposure, helping to signal nighttime to the brain and to synchronize physiological processes with daily cycles. Beyond its natural function, melatonin is widely used as a supplement to address sleep problems and jet lag, and it remains the subject of ongoing medical and regulatory discussion around safety, dosing, and quality control.
Melatonin’s discovery and natural history go hand in hand with understanding the brain’s timekeeping system. The master clock that governs rhythms in many tissues is located in the suprachiasmatic nucleus of the hypothalamus, and light input detected by the retina informs this clock about day and night. Through this pathway, the brain signals the pineal gland to increase or decrease melatonin production. The synthesis of melatonin begins with the amino acid tryptophan, which is converted to serotonin and then to melatonin through enzymatic steps that involve N-acetyltransferase (AANAT) and hydroxyindole O-methyltransferase (HIOMT). The secreted hormone then acts on receptors in various tissues, most notably the MT1 and MT2 receptors in the brain, to influence sleep propensity and circadian phase. See pineal gland, circadian rhythm, serotonin, AANAT, HIOMT, and melatonin receptor MT1 and melatonin receptor MT2 for more detail.
Biochemistry and physiology
Production and regulation: Melatonin is produced in the pineal gland with a robust daily rhythm. Darkness stimulates production, while light inhibits it, helping to entrain sleep timing to the natural day-night cycle. The pattern is reinforced by signals from the SCN, the brain’s primary clock. See suprachiasmatic nucleus and circadian rhythm for context.
Synthesis pathway: The conversion from tryptophan to melatonin involves serotonin as an intermediate, with AANAT and HIOMT as key enzymes. This biochemical sequence underlies how shifts in light exposure can alter melatonin levels and, by extension, sleep timing. See tryptophan and serotonin for related pathways.
Receptors and actions: Melatonin exerts most of its effects through MT1 and MT2 receptors, which are distributed in the brain and elsewhere in the body. Activation of these receptors helps regulate sleep onset, maintenance, and circadian phase shifting. See melatonin receptor MT1 and melatonin receptor MT2.
Pharmacokinetics and broader roles: After secretion, melatonin circulates with a relatively short half-life, making timing critical for therapeutic use. Some research suggests roles beyond sleep—such as antioxidant effects and potential involvement in immune modulation—but evidence in humans is varied and continues to evolve. See antioxidants and immune system for broader context.
Medical uses and research
Insomnia and sleep onset: A substantial portion of research investigates melatonin as a treatment for insomnia, particularly in individuals with disrupted circadian rhythms or older adults with diminished endogenous melatonin. Results show modest improvements in sleep onset and total sleep time for some populations, with variability across studies. See insomnia for a general overview and jet lag for related circadian applications.
Jet lag and shift work: Melatonin is frequently studied as a strategy to ease jet lag and to help align sleep timing in shift workers. In many trials, melatonin reduces the time needed to fall asleep after time zone changes and improves subjective sleep quality, though effects depend on dosing, timing, and individual physiology. See jet lag and shift work sleep disorder.
Pediatric use and special populations: Melatonin has been used in certain pediatric sleep disorders and in some neurodevelopmental conditions, but long-term safety data are limited and dosing often differs from adults. Clinicians tend to adopt a cautious, individualized approach, weighing potential benefits against uncertainties about development, puberty timing, and interactions with other therapies. See pediatric sleep disorders and autism spectrum disorder when exploring related discussions, while noting that evidence is mixed across conditions.
Other indications and controversy: Beyond sleep, there are explorations of melatonin’s effects on mood disorders, aging-related changes, and immune function, but findings are not conclusive enough to support broad therapeutic claims. See seasonal affective disorder for a related, light-centered treatment domain and aging for context on age-related hormonal changes.
Safety, dosing, and regulation
Dosing practices: Over-the-counter melatonin products are sold in a range of doses, commonly from 0.5 mg to 5 mg, taken shortly before bedtime. Clinicians often tailor timing and dose to the individual’s sleep pattern, aiming for sufficient effect with minimal daytime grogginess. Higher doses do not necessarily produce better outcomes and can increase side effects. See dosage and sleep hygiene for practical considerations.
Safety and side effects: Short-term use is generally well tolerated, with common side effects including daytime sleepiness, dizziness, and headaches. Some people report vivid dreams or altered dream intensity. The long-term safety of regular, high-dose melatonin use remains less well characterized, particularly in children and adolescents. See adverse effects for a broader safety frame.
Interactions and contraindications: Melatonin can interact with certain medications, such as anticoagulants or antiplatelet agents, diabetes medications, and some immunosuppressants, potentially altering effectiveness or risk profiles. It can also enhance sedation when used with alcohol or other depressants. Individuals should discuss use with a clinician if they are pregnant, nursing, or taking prescription therapies. See drug interaction and pregnancy for related cautions.
Regulation and quality control: In many jurisdictions, melatonin is regulated as a dietary supplement rather than a drug. This means manufacturers are responsible for quality and labeling, but oversight can vary, and product potency and purity may differ across brands. Quality issues—such as mislabeled potency or contaminants—have been reported in some markets, prompting calls for stricter manufacturing standards and independent testing. See dietary supplement and Good Manufacturing Practice for regulatory context.
Practical considerations: Given variability in products and the nuances of timing, many healthcare providers emphasize sleep hygiene—consistent bedtimes, limited screen exposure before bed, and environmental factors—alongside any supplement use. See sleep hygiene.
Regulation and public policy (contextual note)
Regulatory frameworks around melatonin illustrate a broader debate about how to balance consumer access with safety standards. Proponents of market-based regulation argue that consumers benefit from a wide range of products and the ability to select based on price and perceived quality, provided labeling is accurate. Critics warn that over-the-counter access can yield inconsistent dosing and quality, potentially undermining safety and efficacy claims. In some regions, melatonin is available only by prescription, reflecting a stricter approach to ensure controlled prescribing and monitoring. See regulation and public policy for related discussions.