Melatonin Synthesis: Pineal Gland, Secretion Timing, and Light Suppression
Melatonin secretion begins ~2 hours before sleep, peaks at 2–4am with a 10-fold rise from daytime baseline; 2 hours of 480nm blue light exposure delays this onset by 90 minutes or more.
| Measure | Value | Unit | Notes |
|---|---|---|---|
| Melatonin onset (DLMO) | ~2 | hours before sleep | Dim-light melatonin onset; gold standard circadian phase marker |
| Daytime melatonin level | <10 | pg/mL plasma | Suppressed during daytime by SCN-mediated sympathetic inhibition |
| Peak melatonin (nighttime) | 60–100 | pg/mL plasma | 10-fold rise; peaks 2–4am; falls before waking |
| Melatonin half-life | ~40 | minutes | Rapidly cleared by 6-hydroxymelatonin sulfation in liver |
| Blue light melatonin delay | 60–90 | minutes | 2h of 480nm LED light (≥200 lux) before bedtime; measured DLMO shift |
| Light threshold for suppression | 10–30 | lux | Sensitive to low-level light in some individuals; standard room light ~200–400 lux |
Biosynthesis Pathway
Melatonin (N-acetyl-5-methoxytryptamine) is synthesized in the pineal gland from tryptophan through a four-step pathway:
- Tryptophan → 5-hydroxytryptophan (5-HTP): via tryptophan hydroxylase (TPH1)
- 5-HTP → Serotonin (5-HT): via aromatic amino acid decarboxylase
- Serotonin → N-acetylserotonin: via arylalkylamine N-acetyltransferase (AANAT) — the rate-limiting step
- N-acetylserotonin → Melatonin: via acetylserotonin methyltransferase (ASMT)
AANAT activity is the key regulated step. During the day, norepinephrine release from the superior cervical ganglion (driven by the SCN) is inhibited, keeping AANAT activity low. At night, sympathetic norepinephrine activates β-adrenergic receptors on pinealocytes, triggering cAMP-dependent AANAT upregulation and melatonin synthesis.
Secretion Pattern
Melatonin secretion follows a predictable nightly profile:
- Onset (DLMO): rises from daytime baseline (<10 pg/mL) to detectable levels (~10 pg/mL) approximately 2 hours before habitual sleep time. This “dim-light melatonin onset” (DLMO) is the gold-standard clinical marker of circadian phase.
- Rise: levels increase 10-fold over 2–3 hours
- Peak: 60–100 pg/mL at 2–4am in typical morning-intermediate chronotypes
- Decline: falls before waking as morning light exposure and circadian withdrawal reduce AANAT activity
- Half-life: approximately 40 minutes; rapidly metabolized by hepatic 6-hydroxylation and sulfation to 6-sulfoxymelatonin (excreted in urine)
Light Suppression
The most clinically significant property of melatonin secretion is its suppression by light. Lewy et al. (1980) showed that bright light (≥2,500 lux) suppressed melatonin in humans — the first demonstration that light had measurable biological effects in adult humans beyond vision.
The light-suppression pathway:
- Retinal ipRGCs (melanopsin, peak ~480nm) detect blue light
- Signal travels via retinohypothalamic tract to SCN
- SCN activates paraventricular nucleus sympathetic output
- Superior cervical ganglion inhibits pineal norepinephrine release
- AANAT activity drops → melatonin synthesis halted
As little as 10–30 lux of dim light can measurably suppress melatonin in sensitive individuals. Standard indoor lighting (100–400 lux) causes partial suppression. LED screens and phones, even at lower intensities, are particularly potent because they are rich in 480nm blue wavelengths.
Cajochen et al. (2011) demonstrated that 2 hours of LED screen exposure (peaking at 460nm) before bedtime delayed DLMO by 90 minutes and shortened subsequent REM sleep, establishing a direct link between device use and sleep disruption.
Related Pages
Sources
- Lewy AJ et al. — Light suppresses melatonin secretion in humans. Science (1980)
- Brzezinski A — Melatonin in humans. N Engl J Med (1997)
- Cajochen C et al. — Evening exposure to blue light from LED screen suppresses melatonin. J Appl Physiol (2011)
- Arendt J — Melatonin and the mammalian pineal gland. Chapman & Hall (1995)
Frequently Asked Questions
What is melatonin's role in sleep?
Melatonin does not directly cause sleep but signals circadian timing — it marks the onset of the biological night. Its rise triggers physiological preparation for sleep including core body temperature reduction, decreased alertness, and reduced metabolic rate. The SCN uses melatonin to coordinate peripheral clocks throughout the body to the sleep-wake cycle.
Does taking melatonin supplements improve sleep?
Supplemental melatonin (0.3–0.5mg, physiological dose) is most effective for circadian phase shifting (jet lag, shift work, delayed sleep phase) rather than as a sedative. Most commercial doses (3–10mg) are pharmacological, not physiological, and provide little additional benefit over 0.5mg while causing potential next-day grogginess. Evidence for treating primary insomnia is weak.
At what dose should melatonin be taken?
Research suggests 0.3–0.5mg is the effective physiological dose for circadian phase shifting; this is substantially lower than the 3–10mg doses common in supplements. A landmark study by Lewy et al. showed 0.5mg was equally effective as 3mg for circadian shifting with fewer next-day side effects.