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DIETARY SUPPLEMENT & NUTRACEUTICAL PROFILE CODE: [SUP-12] ID: TIP-MED-000636

Melatonin (Nutraceutical Circadian Rhythm Support)

Active Ingredient / Scientific Identity: Melatonin • Class: Clinical Nutrition & Nutraceutical Science • Indoleamine Pineal Hormone for Circadian Phase Alignment

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THE INDIAN PHARMACIST — Educational Reference Sheet
Profile: Melatonin (Nutraceutical Circadian Rhythm Support) ([SUP-12] | ID: TIP-MED-000636) • Last Reviewed: 2026-11-10
Source URL: https://theindianpharmacist.com/medicine/sup-12-melatonin/
Generic / Entity NameMelatonin (Nutraceutical Circadian Rhythm Support) ([SUP-12])
Verified Indian Brands / RefFSSAI Licensed Health Supplement / Nutraceutical Formulations (RDA Compliant)
Pharmacological ClassClinical Nutrition & Nutraceutical Science • Indoleamine Pineal Hormone for Circadian Phas
Available Dosage FormsFSSAI Nutraceutical Permitted Range: 0.5 mg to 3 mg (up to 5 mg in specialized sleep support) taken 30–60 minu
Regulatory ClassificationFSSAI Nutraceutical Regulation, 2022 (Circadian / Jet-Lag Sleep Support).
Key Warning & Review DateNext-morning drowsiness, vivid dreams/nightmares, headache, and mild transient hypothermia; avoid in autoimmune diseases, pre
Reviewed: 2026-11-10
Safety Matrix:⚖️ Regulatory Framework: FSSAI Nutraceutical Regulation, 2022 (Circadian / Je✔️ Standard Clinical Dispensing Precautions

1. Clinical & Scientific Overview

Melatonin (Nutraceutical Circadian Rhythm Support) (TIP-MED-000636, Reference Code [SUP-12]) is classified under Dietary Supplements & Nutraceuticals (FSSAI / ICMR-NIN) as a Clinical Nutrition & Nutraceutical Science • Indoleamine Pineal Hormone for Circadian Phase Alignment. Within the Indian regulatory and compendial framework, it is governed under FSSAI Nutraceutical Regulation, 2022 (Circadian / Jet-Lag Sleep Support)..

Verified Indian Market Examples / Compendial Status:
FSSAI Licensed Health Supplement / Nutraceutical Formulations (RDA Compliant)
Nutritional & Regulatory Reference: FSSAI Nutraceutical Permitted Range: 0.5 mg to 3 mg (up to 5 mg in specialized sleep support) taken 30–60 minutes before desired bedtime (for jet lag, take at target destination bedtime; lower doses 0.5–1 mg often phase-shift more physiologically than supraphysiological 10 mg doses, which cause receptor desensitisation and morning grogginess). (FSSAI Nutraceutical Regulation, 2022 (Circadian / Jet-Lag Sleep Support).).
Dosage Forms & Available Strengths:
FSSAI Nutraceutical Permitted Range: 0.5 mg to 3 mg (up to 5 mg in specialized sleep support) taken 30–60 minutes before desired bedtime (for jet lag, take at target destination bedtime; lower doses 0.5–1 mg often phase-shift more physiologically than supraphysiological 10 mg doses, which cause receptor desensitisation and morning grogginess).
Routes: Oral Nutritional Supplementation

Clinical Nutrition, ICMR-NIN RDA & FSSAI Nutraceutical Profile

Nutrient / Nutraceutical Identity:
Melatonin
Category:
Indoleamine Pineal Hormone for Circadian Phase Alignment
Natural Dietary Sources (Indian Context):
Endogenous pineal synthesis from L-tryptophan -> serotonin in response to darkness via the suprachiasmatic nucleus (SCN); trace amounts in tart cherries and pistachios

ICMR-NIN 2024 Recommended Dietary Allowance (RDA) & Tolerable Upper Intake Limit (UL): FSSAI Nutraceutical Permitted Range: 0.5 mg to 3 mg (up to 5 mg in specialized sleep support) taken 30–60 minutes before desired bedtime (for jet lag, take at target destination bedtime; lower doses 0.5–1 mg often phase-shift more physiologically than supraphysiological 10 mg doses, which cause receptor desensitisation and morning grogginess).

Deficiency Clinical Syndromes vs Chronic Excess / Hypervitaminosis Risks: Next-morning drowsiness, vivid dreams/nightmares, headache, and mild transient hypothermia; avoid in autoimmune diseases, pregnancy, lactation, and unmonitored paediatric use.

Drug–Nutrient Chelation & Timing Interactions: MAJOR CYP1A2 INTERACTION: Melatonin is >90% metabolised by hepatic CYP1A2 — Fluvoxamine increases plasma melatonin AUC by 17-FOLD and Cmax by 12-FOLD (strictly avoid combination!); ciprofloxacin, oral contraceptives, and caffeine also increase melatonin levels; additive sedation with CNS depressants.

FSSAI Health Supplement vs Therapeutic Drug Distinction: FSSAI Nutraceutical Regulation, 2022 (Circadian / Jet-Lag Sleep Support).

3. Mechanism of Action & Pharmacodynamics

Binds high-affinity G-protein-coupled MT1 receptors (suppressing SCN neuronal firing to promote sleep onset) and MT2 receptors (phase-shifting the circadian clock) in the hypothalamus without binding GABA-A receptors.

4. Therapeutic Indications & Evidence-Supported Uses

  • Physiological & Biochemical Role: Binds high-affinity G-protein-coupled MT1 receptors (suppressing SCN neuronal firing to promote sleep onset) and MT2 receptors (phase-shifting the circadian clock) in the hypothalamus without binding GABA-A receptors.
  • Dietary Sources: Endogenous pineal synthesis from L-tryptophan -> serotonin in response to darkness via the suprachiasmatic nucleus (SCN); trace amounts in tart cherries and pistachios
  • ICMR-NIN RDA & Upper Limits: FSSAI Nutraceutical Permitted Range: 0.5 mg to 3 mg (up to 5 mg in specialized sleep support) taken 30–60 minutes before desired bedtime (for jet lag, take at target destination bedtime; lower doses 0.5–1 mg often phase-shift more physiologically than supraphysiological 10 mg doses, which cause receptor desensitisation and morning grogginess).

🇮🇳 Jurisdiction & Indication Note: Indications and schedules reflect Indian compendial and regulatory records (CDSCO / Indian Pharmacopoeia & NFI / NLEM 2022). Where international reference labels (US FDA DailyMed / NCBI StatPearls) are cited for pharmacokinetic or mechanistic parameters, international approvals do not automatically imply CDSCO approval in India.

5. Educational Dosage Context, Formulations & Administration

Educational Dosing & Regimen Summary: FSSAI Nutraceutical Permitted Range: 0.5 mg to 3 mg (up to 5 mg in specialized sleep support) taken 30–60 minutes before desired bedtime (for jet lag, take at target destination bedtime; lower doses 0.5–1 mg often phase-shift more physiologically than supraphysiological 10 mg doses, which cause receptor desensitisation and morning grogginess).

Administration & Meal Timing: MAJOR CYP1A2 INTERACTION: Melatonin is >90% metabolised by hepatic CYP1A2 — Fluvoxamine increases plasma melatonin AUC by 17-FOLD and Cmax by 12-FOLD (strictly avoid combination!); ciprofloxacin, oral contraceptives, and caffeine also increase melatonin levels; additive sedation with CNS depressants.

6. Pharmacokinetics, Metabolism & Renal/Hepatic Adjustment

Absorption & Disposition:
Salt-form and meal-timing dependent gastrointestinal absorption; see bioavailability and drug-nutrient chelation notes (MAJOR CYP1A2 INTERACTION: Melatonin is >90% metabolised by hepatic CYP1A2 — Fluvoxamine increases plasma melatonin AUC by 17-FOLD and Cmax by 12-FOLD (strictly avoid combination!); ciprofloxacin, oral contraceptives, and caffeine also increase melatonin levels; additive sedation with CNS depressants.).
Metabolism & Biotransformation:
Incorporated into cellular coenzyme pools, metalloproteins, or membrane phospholipids.
Elimination & Renal Adjustment:
Caution with magnesium, potassium, calcium, vitamin D, and high-dose vitamin C/collagen (oxalate) in Chronic Kidney Disease.
Hepatic Impairment Considerations:
Caution with fat-soluble vitamins and concentrated lipophilic extracts in hepatobiliary disease.

7. Contraindications, Precautions & High-Risk Warnings

Contraindications & Red-Flag Precautions:
  • Supratherapeutic megadosing above the ICMR-NIN Tolerable Upper Intake Level (UL) without medical indication
  • Next-morning drowsiness, vivid dreams/nightmares, headache, and mild transient hypothermia; avoid in autoimmune diseases, pregnancy, lactation, and unmonitored paediatric use.

Key Clinical Precautions: Next-morning drowsiness, vivid dreams/nightmares, headache, and mild transient hypothermia; avoid in autoimmune diseases, pregnancy, lactation, and unmonitored paediatric use.

8. Adverse Effects Profile

Common & Mechanism-Related Adverse Effects:
  • Next-morning drowsiness, vivid dreams/nightmares, headache, and mild transient hypothermia; avoid in autoimmune diseases, pregnancy, lactation, and unmonitored paediatric use.
Serious / Dose-Limiting Adverse Effects:
  • Next-morning drowsiness, vivid dreams/nightmares, headache, and mild transient hypothermia; avoid in autoimmune diseases, pregnancy, lactation, and unmonitored paediatric use.

9. Major Drug–Drug, Drug–Food & Drug–Herb Interactions

  • MAJOR CYP1A2 INTERACTION: Melatonin is >90% metabolised by hepatic CYP1A2 — Fluvoxamine increases plasma melatonin AUC by 17-FOLD and Cmax by 12-FOLD (strictly avoid combination!); ciprofloxacin, oral contraceptives, and caffeine also increase melatonin levels; additive sedation with CNS depressants.

10. Clinical Monitoring, Patient Counselling & Storage

Clinical & Laboratory Monitoring: Verify whether the patient requires physiological nutritional maintenance (<=1 RDA under FSSAI) or high-dose therapeutic deficiency correction (Schedule H/medical supervision), and check for multi-supplement stacking.

Pharmacist Patient Counselling Points:

  • MAJOR CYP1A2 INTERACTION: Melatonin is >90% metabolised by hepatic CYP1A2 — Fluvoxamine increases plasma melatonin AUC by 17-FOLD and Cmax by 12-FOLD (strictly avoid combination!); ciprofloxacin, oral contraceptives, and caffeine also increase melatonin levels; additive sedation with CNS depressants.
  • Check all multivitamin and wellness labels to avoid accidentally doubling up on fat-soluble vitamins (A, D, E, K), iron, or zinc.
  • Health supplements support normal physiological nutrition and are NOT intended to diagnose, treat, cure, or prevent disease under Section 22 of the FSS Act, 2006.

Storage, Stability & Dispensing Safeguards: Store in a cool, dry place below 25°C away from moisture and direct sunlight; verify FSSAI License Number and Veg/Non-Veg symbol on packaging.

11. Visual Pharmacology & Mechanism Diagram (svg-v339-01-adme-12-step-journey)

THE 12-STEP ORAL DRUG JOURNEY THROUGH THE HUMAN BODY (LADME) Note: IV bolus enters Step 6 directly (F = 100%); Sublingual & Transdermal routes bypass Step 4–5 Portal First-Pass Metabolism 1. Oral Administration • Tablet / Capsule swallowed • Gastric emptying to duodenum pH 1.5–3.5 (Stomach) 2. Disintegration & Dissolution • Tablet breaks into granules • API dissolves in GI fluid Noyes-Whitney Dissolution Rate 3. GI Epithelial Absorption • Crosses intestinal villi • Passive / Active / P-gp efflux Small Intestine (Large Surface Area) 4. Portal Circulation • Mesenteric veins → Portal vein • Delivers blood to liver sinusoids Pre-systemic Venous Conduit 5. First-Pass Metabolism • Gut & hepatic CYP450 extraction • High: GTN, Propranolol, Morphine Determines Bioavailability (F = f_a × (1-E_H)) 6. Systemic Circulation • Hepatic vein → IVC → Heart • Unbound vs Albumin-bound drug Only FREE drug is active 7–8. Tissue Distribution (Vd) • Capillary permeation to organs • Blood-Brain & Placental barriers Vd = Dose / C_0 (L or L/kg) 9. Target Site of Action • Receptors (GPCR, Ion channel) • Enzymes & Carrier Transporters Pharmacodynamic Effect (E_max, EC50) 10. Hepatic Biotransformation • Phase I (CYP450 Oxidation/Hydrolysis) • Phase II (Glucuronidation/Sulfation) Converts lipophilic drug → hydrophilic metabolite 11. Renal & Biliary Elimination • Nephron: Filtration + Secretion − Reabsorption • Biliary excretion & Enterohepatic recycling Total Clearance CL_tot = CL_renal + CL_hepatic 12. Excretion from the Body • Urine (Primary polar metabolite route) • Bile/Faeces, Expired Air, Sweat, Milk Elimination Half-Life t1/2 = (0.693 × Vd) / CL
svg-v339-01-adme-12-step-journey — 8.1 Complete 12-Step Journey of an Orally Administered Drug (ADME): Figure 8.1: The 12-step physiological journey of a typical orally administered solid dosage form through Liberation, Absorption, Distribution, Metabolism, and Excretion (LADME). Note: Parenteral (IV), sublingual, and inhalational routes bypass gastrointestinal absorption and/or hepatic first-pass metabolism.

12. Authoritative References, Regulatory Sources & Editorial Disclaimer

Primary Compendial & Guideline Reference: ICMR-NIN (National Institute of Nutrition) Nutrient Requirements and Recommended Dietary Allowances (RDA) for Indians (2020/2024); FSSAI (Health Supplements, Nutraceuticals, Food for Special Dietary Use, Food for Special Medical Purpose, Functional Food and Novel Food) Regulations, 2022.

Official Verification Portals: ICMR-National Institute of Nutrition (NIN) — Dietary Guidelines & Nutrient Requirements for Indians • FSSAI — Food Safety and Standards (Health Supplements and Nutraceuticals) Regulations

Last Medically & Pharmaceutically Reviewed: 2026-11-10 • Verification Status: VERIFIED_EDUCATIONAL_CONTENT

Educational & Clinical Disclaimer: This reference profile is published solely for pharmacy education, academic study, and professional clinical reference. It does not substitute for patient-specific clinical judgement, qualified specialist oncology/medical supervision, or official CDSCO/IP prescribing information. Never self-medicate with prescription, Schedule H/H1/X, NDPS, or oncology medicines.

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Educational Reference Notice: This printout from THE INDIAN PHARMACIST (https://theindianpharmacist.com/medicine/sup-12-melatonin/, Last Reviewed: 2026-11-10) is an educational reference sheet for students and healthcare learners. It is NOT an official prescribing guideline or patient-specific treatment order.