Melatonin is a timing signal. Strongest uses are jet lag after eastward flights, delayed sleep onset; insomnia gains are small. Forms made to last the night can lower nighttime blood pressure. Next-day sleepiness, headache, dizziness, and vivid dreams are common. Over-the-counter products often fail to match the labeled dose. Not a general longevity drug; long-term heart effects remain unresolved. (Full Review)

Protocol

Timing

Evening only, typically 30–180 minutes before desired sleep

Dose-response work favors about 3 hours before the sleep episode for onset

Immediate-release amount

0.5–5 mg

Physiologic-range 0.3 mg can phase-shift; higher milligrams are not consistently better for sleep

Prolonged-release

2 mg, 1–2 hours before bed after food

Studied up to 13 weeks in adults 55 years and older with primary insomnia

Time to effect

Jet lag

2–4 nights

Jet-lag benefit over 2–4 destination nights

Sleep onset

First night

Sleep-onset change can appear the first night

Migraine prevention

About 12 weeks

Migraine prevention over about 12 weeks

Benefits

High: Jet lag after eastward travel; sleep onset; subjective sleep quality; nocturnal blood pressure with controlled-release forms

Medium: Migraine day reduction

Low: Heartburn in gastroesophageal reflux; solid-tumor one-year survival

Speculative: Human lifespan or healthspan extension; mitochondrial antioxidant replacement

Contraindications

Pregnancy and lactation

Uncontrolled epilepsy

Child-Pugh class C cirrhosis

Unstable warfarin anticoagulation without INR monitoring

Autoimmune disease under active immunosuppression, pending specialist review

Children and adolescents outside specialist sleep care

Anyone who must drive or operate machinery the same night until next-day alertness is known

Key Interactions

CYP1A2 inhibitors (fluvoxamine, oral contraceptives, ciprofloxacin, grapefruit juice)

CYP1A2 inducers (smoking, carbamazepine, rifampin)

Sedating prescription drugs (benzodiazepines, zolpidem, trazodone, opioids)

Over-the-counter sedatives (diphenhydramine, doxylamine, alcohol)

Anticoagulants (warfarin)

Antihypertensives (amlodipine, lisinopril) and nifedipine

Glucose-lowering drugs and evening carbohydrate loads

Immunosuppressants (tacrolimus, cyclosporine) and immunostimulants

Additive sleep supplements (magnesium glycinate, L-Theanine, glycine, valerian)

Caffeine

Risk & Side Effects

High: Next-day somnolence, headache, dizziness, and vivid dreams

Low: Delivered dose that does not match the label; incident heart failure in insomnia records; reproductive-hormone suppression; fracture after repeated prescriptions

Speculative: Lasting pineal shutdown after stopping

Monitoring

Marker	Target	Why
Sleep onset latency	<20 minutes	Tracks the sleep-timing effect
Pittsburgh Sleep Quality Index (PSQI)	<5	Composite sleep quality
Morning residual sleepiness (0–10)	No established target; track return to personal baseline	Captures next-day somnolence
Nocturnal systolic dip	10–20% below daytime	Controlled-release melatonin can deepen the dip
Fasting glucose	70–90 mg/dL (3.9–5.0 mmol/L)	Evening melatonin can raise fasting glucose in MTNR1B carriers

Cadence: One- to two-week baseline sleep diary; then one week, four weeks, and every three to six months

Qualitative Assessment

First-night versus week-four ease of falling asleep at the intended hour
Morning grogginess, vivid dreams, and next-day driving comfort
Headache or dusk-onset temperature drop that feels excessive
Stable mood; new low mood is a reported, uncommon adverse effect

Melatonin for Health & Longevity

Protocol

Benefits

Risk & Side Effects

Monitoring

Qualitative Assessment