MT

Melatonin

Hormones

What is Melatonin?

Melatonin (N-acetyl-5-methoxytryptamine) is a neurohormone produced primarily by the pineal gland in the brain, with smaller amounts synthesized in the retina, gut, bone marrow, and immune cells. Melatonin is the body's master chronobiotic—the hormone that synchronizes circadian rhythms and signals darkness to every cell. Its synthesis follows a strict light-dark cycle: production begins in the evening as light diminishes (dim light melatonin onset, or DLMO), peaks between 2–4 AM, and falls to nearly undetectable daytime levels. Light exposure—particularly blue light (460–480 nm)—potently suppresses melatonin production.

Melatonin is synthesized from serotonin through two enzymatic steps: serotonin is first acetylated by arylalkylamine N-acetyltransferase (AANAT), then methylated by hydroxyindole-O-methyltransferase (HIOMT). Beyond sleep regulation, melatonin has potent antioxidant properties, modulates immune function, influences reproductive seasonality in some species, and plays roles in thermoregulation and blood pressure regulation. Clinically, melatonin measurement is most useful for characterizing circadian rhythm disorders.

Why It Matters

Melatonin is the most reliable biomarker of circadian phase—the dim light melatonin onset (DLMO) is the gold standard for determining an individual's internal biological clock timing. This information is critical for diagnosing and treating circadian rhythm sleep-wake disorders (delayed sleep-wake phase disorder, advanced sleep-wake phase disorder, non-24-hour disorder in blind individuals, and shift work disorder). Proper circadian alignment affects not only sleep quality but also metabolic health, cardiovascular function, mood, and immune competence. Exogenous melatonin is widely used as a sleep aid and chronobiotic.

Normal Reference Ranges

GroupRangeUnit
Daytime<10pg/mL
Nighttime Peak (2–4 AM)60–200pg/mL

Reference ranges may vary by laboratory. Always compare results to the ranges provided by your testing facility.

What High MT Levels Mean

Common Causes

  • Normal nighttime physiology
  • Exogenous melatonin supplementation
  • Pineal gland tumors (pinealoma—extremely rare)
  • Delayed sleep-wake phase disorder (high melatonin at conventional bedtime due to delayed phase)
  • Beta-blocker medications (inhibit melatonin metabolism)
  • Reduced hepatic clearance (liver disease)

Possible Symptoms

  • Excessive daytime sleepiness (if melatonin elevated during waking hours)
  • Fatigue and lethargy
  • Difficulty waking in the morning
  • Hypothermia (melatonin lowers core body temperature)
  • Low mood (seasonal association)
  • Usually asymptomatic if nighttime elevation is physiological

What to do: Elevated daytime melatonin is uncommon and usually related to supplementation or a significantly delayed circadian phase. If melatonin supplements are being taken, reducing the dose or timing adjustment may be needed—many commercial melatonin supplements contain doses (3–10 mg) far exceeding physiological production (~0.3 mg). If delayed sleep-wake phase disorder is suspected, DLMO measurement and actigraphy can confirm the diagnosis, and treatment involves strategic bright light exposure in the morning combined with low-dose melatonin (0.5 mg) 5–7 hours before desired sleep onset. Pineal tumors are extremely rare and would present with other neurological symptoms.

What Low MT Levels Mean

Common Causes

  • Aging (melatonin production declines significantly with age)
  • Excessive nighttime light exposure (blue light from screens)
  • Shift work and irregular sleep schedules
  • Pineal calcification
  • Beta-adrenergic agonist medications
  • Advanced sleep-wake phase disorder
  • Neurodegenerative diseases (Alzheimer's, Parkinson's)
  • Surgical pinealectomy

Possible Symptoms

  • Insomnia or difficulty initiating sleep
  • Non-restorative sleep
  • Disrupted circadian rhythms
  • Jet lag susceptibility
  • Increased nighttime wakefulness in elderly

What to do: Low melatonin is most commonly a consequence of aging or excessive artificial light at night. Non-pharmacological interventions include reducing evening screen time or using blue-light blocking glasses, maintaining consistent sleep-wake schedules, ensuring morning bright light exposure, and sleeping in a dark environment. Low-dose melatonin supplementation (0.3–1 mg) taken 1–2 hours before desired bedtime can be effective for sleep onset insomnia in older adults. For circadian rhythm disorders, the timing of melatonin administration relative to the circadian phase is more important than the dose. Slow-release formulations may help with sleep maintenance.

When Is MT Testing Recommended?

  • When evaluating circadian rhythm sleep-wake disorders
  • When diagnosing delayed or advanced sleep phase syndrome
  • When assessing sleep disorders in blind individuals (non-24-hour disorder)
  • When evaluating shift workers with persistent sleep complaints

Frequently Asked Questions

DLMO is the time in the evening when melatonin levels begin to rise above daytime baseline, typically occurring 2–3 hours before habitual sleep onset under dim light conditions (<30 lux). It is considered the most reliable marker of circadian phase—the internal body clock's timing. DLMO is measured by collecting serial saliva or blood samples every 30–60 minutes in the evening under dim light conditions. In delayed sleep-wake phase disorder, DLMO occurs much later than normal (e.g., 1–3 AM instead of 8–9 PM), explaining why affected individuals cannot fall asleep at conventional times. Knowing the DLMO allows precise timing of chronotherapy: melatonin is most effective when administered 5–7 hours before DLMO, and bright light therapy is most effective when delivered after the core body temperature minimum.
Most commercial melatonin supplements contain supraphysiological doses (3–10 mg) that produce blood levels 10–100 times higher than normal nighttime levels. Research suggests that lower doses (0.3–1 mg) are often equally or more effective and produce plasma levels closer to the physiological nighttime range. Higher doses do not necessarily improve sleep and can cause next-day grogginess, vivid dreams, or headaches. The timing of melatonin is arguably more important than the dose: for difficulty falling asleep, take it 1–2 hours before desired bedtime. For circadian phase-shifting (jet lag, delayed sleep phase), take it 5–7 hours before DLMO. Start with the lowest dose (0.3–0.5 mg) and increase only if needed. Melatonin is generally well-tolerated for short-term use, though long-term safety data is limited.
Yes, this is well-documented. The photoreceptor cells in the retina that regulate circadian rhythms (intrinsically photosensitive retinal ganglion cells, or ipRGCs) are most sensitive to blue light with a peak wavelength around 460–480 nm—precisely the dominant emission wavelength of LEDs used in smartphones, tablets, computer monitors, and modern lighting. Studies show that 2 hours of evening exposure to blue-enriched light from screens can suppress melatonin by approximately 22% and delay melatonin onset by about 1.5 hours. Mitigation strategies include using night mode or blue-light filters on devices after sunset, wearing blue-light blocking glasses, dimming room lighting in the evening, and stopping screen use 1–2 hours before bed. Even dim room lighting from overhead LEDs can have modest melatonin-suppressive effects.

Related Biomarkers

5-HTSerotoninCortisolCortisol

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Medical Disclaimer: This information is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Reference ranges may vary between laboratories. Always consult your healthcare provider for interpretation of your specific test results.

Disclaimer: SymptomGPT is not a medical diagnosis tool and does not provide medical advice. Always consult a qualified healthcare professional. If you are experiencing a medical emergency, call 911 immediately.