Melatonin is the body's own nighttime hormone. As a supplement it offers a modest, well-tolerated way to fall asleep faster and reset a disrupted body clock — its most reliable effects. It may gently lower nighttime blood pressure and improve heart, metabolic, and cellular-defense markers, though these longevity benefits remain promising rather than proven. (Full Review)

Protocol

Dose

0.3–0.5 mg

Low, near-physiologic; 1–3 mg common over-the-counter, sleep benefit peaks near 4 mg

Timing

30–60 min before bed

2–3 hours before target bedtime to advance a delayed clock

Form

Immediate-release

Prolonged-release 2 mg for sleep maintenance; choose third-party-tested product

Time to effect

Sleep & jet lag

Same night

Sleep-onset and jet-lag effects are immediate

Blood pressure

Weeks

Builds over weeks of consistent use

Metabolic & antioxidant

Weeks

Marker changes seen over similar timeframes in trials

Benefits

High: Faster sleep onset and improved sleep quality; circadian rhythm realignment for jet lag and delayed sleep phase

Medium: Reduced nocturnal blood pressure; improved cardiometabolic markers; enhanced antioxidant capacity and reduced oxidative stress; prevention of delirium in hospitalized older adults

Low: Adjuvant support in cancer care; migraine and headache prevention

Speculative: Neuroprotection and cognitive preservation; direct lifespan extension and healthspan

Contraindications

Pregnancy and breastfeeding

Transplant recipients on essential immunosuppression

Children and adolescents (except under clinician direction)

Active autoimmune disease flares

Anyone who must remain fully alert

Key Interactions

CYP1A2-inhibiting drugs (fluvoxamine, ciprofloxacin)

Estrogens and oral contraceptives

CYP1A2-inducing agents (tobacco smoke, carbamazepine, omeprazole)

Sedatives and central-nervous-system depressants (benzodiazepines, Z-drugs, opioids, gabapentinoids)

Anticoagulants and antiplatelet drugs (warfarin, aspirin, clopidogrel)

Antihypertensive drugs (esp. nifedipine)

Antidiabetic drugs

Immunosuppressant drugs (corticosteroids, ciclosporin)

Sedating antihistamines (diphenhydramine, doxylamine) and alcohol

Sedating or blood-pressure-lowering supplements; St. John's Wort

Risk & Side Effects

High: Daytime drowsiness and next-day grogginess; headache and dizziness

Medium: Impaired glucose tolerance with evening or mealtime dosing; nausea and gastrointestinal upset

Low: Vivid dreams and nightmares; morning hormonal and circadian disruption from mistimed or high doses

Speculative: Reproductive and pubertal hormone effects; autoimmune disease aggravation

Monitoring

Marker	Target	Why
Fasting blood glucose	70–85 mg/dL	Melatonin near meals can raise blood sugar
Hemoglobin A1c	Below 5.4%	Detects sustained glucose impact over ~3 months
Nighttime blood pressure	Below 120/70 mmHg (asleep)	Tracks melatonin's main cardiovascular effect
Urinary 6-sulfatoxymelatonin	Higher overnight, age-appropriate	Reflects the body's own melatonin output

Cadence: Baseline, then recheck at 4 and 12 weeks after starting, then every 6–12 months if used long-term

Qualitative Assessment

Sleep-onset time: falling asleep faster and more consistently
Morning grogginess: absence of next-day sedation
Daytime energy: improved daytime alertness and stable energy
Mood: steady or improved mood
Dream experience: dreams remain normal rather than disturbingly vivid
Overall sleep quality: feeling more rested on waking

Melatonin for Health & Longevity

Protocol

Benefits

Risk & Side Effects

Monitoring

Qualitative Assessment