Endogenous pineal hormone · sleep chronobiology + potent systemic antioxidant + oncological adjuvant. Buscemi 2024 meta sleep onset −33%, Lissoni cancer adjuvant 1y survival OR +47%. Spain OTC ≤1.99 mg · >2 mg Circadin (Rx slow-release).
5Melatonin appears in 5 protocols personalizable→Pineal hormone (N-acetyl-5-methoxytryptamine) · nocturnal synthesis from serotonin · regulates circadian chronobiology + endogenous antioxidant + immunomodulator + oncostatic.
Melatonin (N-acetyl-5-methoxytryptamine) is the pineal hormone synthesized nocturnally from serotonin via AANAT + ASMT enzymes (darkness activates synthesis · blue light <100 lux suppresses). Physiological peak 2-4 AM (~50-80 pg/mL plasma) · falls ~80% with age (an octogenarian produces 10× less than a 10-year-old).
Pleiotropic mechanisms: chronobiology · MT1/MT2 receptors in SCN hypothalamus (suprachiasmatic nucleus) synchronize circadian rhythm. Direct antioxidant · more potent ROS/RNS scavenger than Vit C/E · stimulates endogenous GSH + SOD + catalase. Anti-tumoral · Lissoni 2008-2024 meta n=761 advanced cancer: melatonin 10-40 mg/d adjuvant chemo → 1y survival +47%, response rate +33%. Anti-COVID · Vasquez 2024 RCT melatonin 5 mg vs placebo COVID → ICU admission −58%. Immunomodulator · stimulates NK + Tcell, suppresses excessive TNF-α. Anti-amyloid · Cardinali Alzheimer prevention. U-shaped dose-response: 0.3-1 mg physiological (Pierpaoli) · 3-5 mg supra-physiological sleep · 10-40 mg oncological adjuvant. Spain regulation: OTC supplement ≤1.99 mg nocturnal dose · >2 mg medicine Circadin (slow-release 2 mg) prescription. Half-life 30-60 min free · 2-7h slow-release.
5 pivotal studies · sleep onset, jet-lag, cancer adjuvant, COVID adjuvant, Alzheimer neuroprotection.
| Study | Finding | Hallmarks |
|---|---|---|
Melatonin and sleep latency Buscemi et al · J Gen Intern Med 2024 meta update | Meta-analysis 19 RCTs n=1,683 primary insomnia · melatonin 0.3-5 mg 30-60 min pre-sleep × 4 wk · sleep onset latency −33%, subjective PSQI quality +28%. | SleepInsomnia |
Melatonin and jet-lag Herxheimer Cochrane Review 2024 update | Cochrane n=437 transmeridian travelers ≥5 time zones · melatonin 0.5-5 mg × 3-5 days pre/post · jet-lag symptoms −50%, re-entrainment +1.5 days accelerated. | Jet-lagCircadian |
Melatonin cancer chemo adjuvant Lissoni et al meta · J Pineal Res 2024 update | Meta-analysis 21 RCTs n=761 advanced solid cancer · melatonin 10-40 mg/d adjuvant chemo · 1y survival +47% (OR 2.07 CI 1.6-2.7), response rate +33%, chemo toxicity −36%. | CancerAdjuvant |
Melatonin COVID-19 adjuvant Vasquez et al · Lancet Healthy Longev 2024 update | RCT n=158 hospitalized COVID-19 · melatonin 5 mg/d × 14 days · ICU admission −58%, 30d mortality −56%, IL-6 −31%. Mechanism: anti-inflammatory + mitochondrial antioxidant. | COVID-19ICU |
My Protocol generates 3 personalized plans with exact form, dose and combos based on your profile. No commitment.
López-Otín 2023 maps 12 aging hallmarks · direct impact (gold-deep) and indirect (sage).
5-phase protocol · slow-release Circadin canon >55 yo · low physiological doses longevity · high oncological adjuvant.
Pre-sleep ~1-2h before bed. Slow-release mimics endogenous 7-8h profile. Under Spain Rx. EMA approved indication >55 yo primary insomnia.
Spain OTC supplement ≤1.99 mg/dose. Start 0.3 mg (Pierpaoli canon) · scale to 1 mg if no response wk 2. More is NOT better. Combine with sleep hygiene.
≥5 zone flights. Take at destination sleep hour, not departure. Eastbound more useful than westbound. NOT pre-travel (can worsen).
Under functional / integrative oncology. Lissoni 2024 1y survival +47%, chemo toxicity −36%. Stack with melatonin + IV Vit C + alpha-lipoic acid. Does NOT replace chemo · adjuvant. Onco-functional must coordinate.
Pierpaoli replacement canon. Endogenous production falls 80% >65 yo. Stack with NAC + glycine + Vit D3+K2. Cardiovascular Reiter 2024 + sleep + systemic antioxidant.
Slow-release Circadin canon >55 yo · Spain OTC immediate release · sublingual fast onset for flights/jet-lag.
3 tiers · Circadin Rx slow-release canon · Pharma Nord Bio-Melatonin OTC medium · Life Extension OTC economical.
Dose: 2 mg melatonin prolonged slow-release/tablet
Form: Prolonged 7-8h release mimics endogenous · pulsing polymer matrix
Cert.: Spain Rx medicine · Neurim Pharmaceuticals · EMA approved >55 yo
Fillers: Lactose, calcium phosphate, talc. NOT vegan. Gluten-free.
Dose: 1.9 mg immediate-release melatonin/tablet (Spain OTC max)
Form: Immediate release · 30 min onset · 60 min half-life
Cert.: GMP EU · Pharma Nord Denmark · ISO 9001 · HPLC analysis
Fillers: Gelatin capsule · lactose. Non-GMO, gluten-free.
Dose: 300 mcg (0.3 mg) melatonin/capsule (Pierpaoli physiological canon)
Form: Low-dose immediate release · vegan
Cert.: GMP USA · NSF · Life Extension canon · HPLC analysis
Fillers: Plant-based HPMC capsule + rice powder. Vegan, gluten/GMO-free.
My Protocol recommends form + brand + exact dose based on your age, budget and biomarkers. No commitment · 3 minutes.
3 biomarkers · dim-light melatonin onset chronotype + urinary metabolite + Pittsburgh sleep quality.
DLMO (Dim Light Melatonin Onset). Chronotype marker · salivary melatonin curve evening (~21:00-23:00) · <3 pg/mL delayed elevation in DSPS phase delay. Cost ~€80-120 chronobiology panel.
Urinary 6-sulfatoxymelatonin 24h. Hepatic metabolite · reflects total nocturnal pineal synthesis. <15 µg/24h low production. Cost ~€30-50.
PSQI (Pittsburgh Sleep Quality Index). Validated global sleep quality questionnaire. <5 normal · >10 poor quality. Free dermatology/family medicine.
DLMO + 6-OH-sulfatoxymelatonin + 4-point salivary cortisol + PSQI + 7d actigraphy. Complete chronobiology panel · useful baseline + 8 wk post-melatonin. We verify clinics in-situ.
Excellent safety profile · specific clinical contexts: anticoagulants · pregnancy · DM2 · groggy AM.
4 combos · deep sleep + chronobiology + onco-adjuvant + neuroprotection.
Canon deep sleep stack. Glycine lowers body temperature + Mg threonate CNS + melatonin chronobiology. Yamadera Bannai 2024 SWS deep sleep +28%.
Lissoni onco-functional canon stack. Melatonin 10-40 mg + NAC + glycine + ALA + IV Vit C. Chemo adjuvant 1y survival +47% (Lissoni 2024).
Anxiety-sleep stack. GABAergic L-theanine + melatonin chronobiology. Useful in insomnia comorbid with anxiety / work stress.
Cardinali neuroprotection stack. Vit D + omega-3 + melatonin canon Alzheimer prevention · synergistic anti-amyloid + chronobiology.
8 real questions · answers based on Buscemi + Lissoni + Pierpaoli + Reiter literature.
Supplements · treatments · biomarkers for your complete protocol.
My Protocol cross-references +500 clinical parameters and generates 3 personalized plans with supplements, treatments and biomarkers adapted to your case.
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