Supplements

Melatonin

Evidence: strong_human

Mechanism of Action

Melatonin (N-acetyl-5-methoxytryptamine) is synthesized from serotonin in the pineal gland, regulated by the suprachiasmatic nucleus (SCN) via the retinohypothalamic tract. It binds MT1 and MT2 G-protein coupled receptors: MT1 activation suppresses neuronal firing in the SCN (sleep onset), while MT2 modulates circadian phase shifting. Beyond sleep, melatonin is a potent antioxidant that scavenges hydroxyl radicals, peroxynitrite, and singlet oxygen, and upregulates antioxidant enzymes (GPx, SOD, catalase) via Nrf2. It has anti-inflammatory properties (NF-kB suppression), immunomodulatory effects, oncostatic activity (anti-proliferative in several cancer types), and mitochondrial protective functions.

Dosing Protocol

Standard: 0.3-1mg for sleep onset (physiological); 3-5mg for jet lag; 10-20mg for oncological adjunct (under supervision)

Maintenance: 0.3-1mg for sleep (most people overdose; physiological replacement is 0.3mg)

Administration: oralsublingual

Timing: 30-60 minutes before desired sleep onset. For circadian phase advance: 4-6 hours before desired bedtime. Sublingual for faster onset. Dim lights 1-2 hours before taking.

Duration: Short-term for jet lag (3-5 days); ongoing at low dose for circadian support if needed; extended for oncological use under supervision

Notes

THE DOSE MYTH: Most people take 3-10mg, but physiological replacement dose is 0.3mg. MIT research showed 0.3mg is optimal for sleep onset without morning grogginess or receptor desensitization. Higher doses (3-5mg) are appropriate for jet lag and circadian resetting. The oncological dose (10-20mg+) is a different clinical application with separate evidence base. MTNR1B gene variants (rs10830963) affect glucose metabolism response to melatonin — clients with this variant may experience impaired glucose tolerance with evening melatonin. Always start with 0.3mg and titrate up. Address sleep hygiene before supplementation.

Stacking

  • Magnesium Glycinate
  • L-Theanine
  • Glycine
  • Tart Cherry Extract

Interactions

  • Benzodiazepines/sedatives [MEDIUM] — Additive sedation
  • Fluvoxamine (SSRI) [HIGH] — Fluvoxamine inhibits CYP1A2, massively increasing melatonin levels (up to 12-fold)
  • Immunosuppressants [MEDIUM] — Melatonin is immunostimulatory — may oppose immunosuppression
  • Anticoagulants [LOW] — Melatonin may have mild anticoagulant effects
  • Diabetes medications [LOW] — Melatonin may affect insulin sensitivity (MTNR1B receptor variant-dependent)

Contraindications

  • Autoimmune conditions (immunostimulatory)
  • Depression (may worsen in some individuals)
  • Seizure disorders (mixed data)
  • Pregnancy/lactation

Side Effects

  • Morning grogginess (dose too high)
  • Vivid dreams/nightmares
  • Headache
  • Nausea
  • Dizziness
  • Reduced libido (at high chronic doses)
  • Next-day drowsiness
  • Depression (rare)

Key Papers

  • 10.1371/journal.pone.0063773
  • 10.1016/j.sleep.2004.10.007
  • 10.1016/j.molcel.2018.11.020

Source Quality

Pharmaceutical-grade melatonin, USP verified. Low-dose formulations (0.3-1mg) are difficult to find — most products are 3-10mg (supraphysiological). Sublingual or liquid formulations allow precise low-dose titration. Extended-release for sleep maintenance (vs immediate-release for sleep onset). Brands: Life Extension (0.3mg available), NOW Melatonin (liquid for dose titration), Natrol.

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Disclaimer: This information is for educational purposes only and is not medical advice. BioAccelera Labs does not diagnose, treat, or prescribe. Consult a licensed healthcare provider before using any compound.

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