Circulating melatonin exposure, route and timing specified

What acts on it

1. Concurrent caffeine raised melatonin peak concentration by 142% and AUC by 120% on average.

   Caffeine → Circulating melatonin exposure, route and timing specified source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/melatonin-research/14616429.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6a8b06b9e1bcb570dca49735b73c2c7360a77381ae6fa25744bcccee7ceb52d8", "start_char": 0, "end_char": 1070, "text_sha256": "6a8b06b9e1bcb570dca49735b73c2c7360a77381ae6fa25744bcccee7ceb52d8"}

   experimental_model

   Concurrent caffeine interaction study

   exposure

   6 mg melatonin alone or with three 200 mg caffeine doses

   limitations

   Caffeine schedule and amount were study-specific. CYP1A2 inhibition was the proposed mechanism; higher melatonin exposure does not imply better sleep while using caffeine.

   nutrient_topic

   Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin

   organism

   Twelve humans, six smokers and six nonsmokers

   plain_language

   One substance can promote wakefulness while increasing blood exposure to another substance.

   primary_references

   [melatonin-p14616429] Effects of caffeine intake on the pharmacokinetics of melatonin, a probe drug for CYP1A2 activity. (2003). https://pubmed.ncbi.nlm.nih.gov/14616429/ DOI: 10.1046/j.1365-2125.2003.01933.x

   tissue_or_cell_type

   Oral melatonin pharmacokinetics

   Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 708–719

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Concurrent caffeine interaction study · source_derived_draft · unverified_draft

   ### melatonin-caffeine-exposure Concurrent caffeine raised melatonin peak concentration by 142% and AUC by 120% on average. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: One substance can promote wakefulness while increasing blood exposure to another substance. organism: Twelve humans, six smokers and six nonsmokers tissue_or_cell_type: Oral melatonin pharmacokinetics experimental_model: Concurrent caffeine interaction study limitations: Caffeine schedule and amount were study-specific. CYP1A2 inhibition was the proposed mechanism; higher melatonin exposure does not imply better sleep while using caffeine. exposure: 6 mg melatonin alone or with three 200 mg caffeine doses evidence_span: {"source_cache": "artifacts/melatonin-research/14616429.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6a8b06b9e1bcb570dca49735b73c2c7360a77381ae6fa25744bcccee7ceb52d8", "start_char": 0, "end_char": 1070, "text_sha256": "6a8b06b9e1bcb570dca49735b73c2c7360a77381ae6fa25744bcccee7ceb52d8"} [melatonin-p14616429] Effects of caffeine intake on the pharmacokinetics of melatonin, a probe drug for CYP1A2 activity. (2003). https://pubmed.ncbi.nlm.nih.gov/14616429/ DOI: 10.1046/j.1365-2125.2003.01933.x

   Complete structured claim and evidence

2. Melatonin AUC and peak concentrations were about four- to fivefold higher in oral-contraceptive users than nonusers.

   Study-specific oral contraceptive formulations → Circulating melatonin exposure, route and timing specified source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/melatonin-research/18490497.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ab9a91b566e88a73ccbd20d9152934f6a048348bc18ec0c2535ec5a9142dc0e4", "start_char": 0, "end_char": 927, "text_sha256": "ab9a91b566e88a73ccbd20d9152934f6a048348bc18ec0c2535ec5a9142dc0e4"}

   experimental_model

   Pharmacokinetic comparison by contraceptive use and genotype

   exposure

   6 mg melatonin; oral contraceptive users versus nonusers

   limitations

   Formulations were not universal across all contraceptives. Exposure comparison is not proof all hormone treatments behave identically; genotype effects were nonsignificant.

   nutrient_topic

   Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin

   organism

   29 human participants

   plain_language

   Medication context changes how a dose appears in the bloodstream.

   primary_references

   [melatonin-p18490497] The effect of oral contraceptives on the pharmacokinetics of melatonin in healthy subjects with CYP1A2 g.-163C>A polymorphism. (2008). https://pubmed.ncbi.nlm.nih.gov/18490497/ DOI: 10.1177/0091270008318669

   tissue_or_cell_type

   Melatonin clearance

   Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 721–732

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pharmacokinetic comparison by contraceptive use and genotype · source_derived_draft · unverified_draft

   ### melatonin-contraceptive-exposure Melatonin AUC and peak concentrations were about four- to fivefold higher in oral-contraceptive users than nonusers. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Medication context changes how a dose appears in the bloodstream. organism: 29 human participants tissue_or_cell_type: Melatonin clearance experimental_model: Pharmacokinetic comparison by contraceptive use and genotype limitations: Formulations were not universal across all contraceptives. Exposure comparison is not proof all hormone treatments behave identically; genotype effects were nonsignificant. exposure: 6 mg melatonin; oral contraceptive users versus nonusers evidence_span: {"source_cache": "artifacts/melatonin-research/18490497.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ab9a91b566e88a73ccbd20d9152934f6a048348bc18ec0c2535ec5a9142dc0e4", "start_char": 0, "end_char": 927, "text_sha256": "ab9a91b566e88a73ccbd20d9152934f6a048348bc18ec0c2535ec5a9142dc0e4"} [melatonin-p18490497] The effect of oral contraceptives on the pharmacokinetics of melatonin in healthy subjects with CYP1A2 g.-163C>A polymorphism. (2008). https://pubmed.ncbi.nlm.nih.gov/18490497/ DOI: 10.1177/0091270008318669

   Complete structured claim and evidence

3. Fluvoxamine increased melatonin AUC about 17-fold and peak concentration about 12-fold on average.

   Fluvoxamine → Circulating melatonin exposure, route and timing specified source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/melatonin-research/10668847.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f3c51771fcf28fd453299490bdedee5088501fb2447e3683edd68b93590d544", "start_char": 0, "end_char": 1563, "text_sha256": "0f3c51771fcf28fd453299490bdedee5088501fb2447e3683edd68b93590d544"}

   experimental_model

   Single-dose drug interaction study

   exposure

   5 mg melatonin with or without 50 mg fluvoxamine

   limitations

   Very small study; one CYP2D6 poor metabolizer affected fluvoxamine exposure. Increased melatonin exposure is consistent with inhibited elimination, not proof of increased pineal synthesis.

   nutrient_topic

   Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin

   organism

   Five healthy male volunteers

   plain_language

   Slowing clearance can sharply raise exposure to an unchanged swallowed dose.

   primary_references

   [melatonin-p10668847] Increased bioavailability of oral melatonin after fluvoxamine coadministration. (2000). https://pubmed.ncbi.nlm.nih.gov/10668847/ DOI: 10.1067/mcp.2000.104071

   tissue_or_cell_type

   Oral melatonin pharmacokinetics

   Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 695–706

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-dose drug interaction study · source_derived_draft · unverified_draft

   ### melatonin-fluvoxamine-exposure Fluvoxamine increased melatonin AUC about 17-fold and peak concentration about 12-fold on average. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Slowing clearance can sharply raise exposure to an unchanged swallowed dose. organism: Five healthy male volunteers tissue_or_cell_type: Oral melatonin pharmacokinetics experimental_model: Single-dose drug interaction study limitations: Very small study; one CYP2D6 poor metabolizer affected fluvoxamine exposure. Increased melatonin exposure is consistent with inhibited elimination, not proof of increased pineal synthesis. exposure: 5 mg melatonin with or without 50 mg fluvoxamine evidence_span: {"source_cache": "artifacts/melatonin-research/10668847.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f3c51771fcf28fd453299490bdedee5088501fb2447e3683edd68b93590d544", "start_char": 0, "end_char": 1563, "text_sha256": "0f3c51771fcf28fd453299490bdedee5088501fb2447e3683edd68b93590d544"} [melatonin-p10668847] Increased bioavailability of oral melatonin after fluvoxamine coadministration. (2000). https://pubmed.ncbi.nlm.nih.gov/10668847/ DOI: 10.1067/mcp.2000.104071

   Complete structured claim and evidence

4. Endogenous melatonin was about 3.5-fold higher in the late condition.

   Late-evening glucose challenge relative to habitual bedtime → Circulating melatonin exposure, route and timing specified source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/melatonin-research/35015083.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "14878cd566ac009dde6fd0a6cc78adf1a4b48cfb2bc09e262568c909f84f236e", "start_char": 0, "end_char": 1688, "text_sha256": "14878cd566ac009dde6fd0a6cc78adf1a4b48cfb2bc09e262568c909f84f236e"}

   experimental_model

   Randomized crossover early versus late glucose-challenge study

   exposure

   75 g OGTT four versus one hour before habitual bedtime after eight-hour fast

   limitations

   Glucose drinks simulated meal timing. Timing, endogenous melatonin and other circadian factors co-varied; the intervention did not selectively manipulate melatonin alone.

   nutrient_topic

   Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin

   organism

   845 Spanish adults

   plain_language

   Late carbohydrate exposure coincided with a stronger night signal.

   primary_references

   [melatonin-p35015083] Interplay of Dinner Timing and MTNR1B Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial. (2022). https://pubmed.ncbi.nlm.nih.gov/35015083/ DOI: 10.2337/dc21-1314

   tissue_or_cell_type

   Endogenous melatonin and evening glucose handling

   Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 1150–1161

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized crossover early versus late glucose-challenge study · source_derived_draft · unverified_draft

   ### melatonin-late-challenge-hormone Endogenous melatonin was about 3.5-fold higher in the late condition. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Late carbohydrate exposure coincided with a stronger night signal. organism: 845 Spanish adults tissue_or_cell_type: Endogenous melatonin and evening glucose handling experimental_model: Randomized crossover early versus late glucose-challenge study limitations: Glucose drinks simulated meal timing. Timing, endogenous melatonin and other circadian factors co-varied; the intervention did not selectively manipulate melatonin alone. exposure: 75 g OGTT four versus one hour before habitual bedtime after eight-hour fast evidence_span: {"source_cache": "artifacts/melatonin-research/35015083.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "14878cd566ac009dde6fd0a6cc78adf1a4b48cfb2bc09e262568c909f84f236e", "start_char": 0, "end_char": 1688, "text_sha256": "14878cd566ac009dde6fd0a6cc78adf1a4b48cfb2bc09e262568c909f84f236e"} [melatonin-p35015083] Interplay of Dinner Timing and MTNR1B Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial. (2022). https://pubmed.ncbi.nlm.nih.gov/35015083/ DOI: 10.2337/dc21-1314

   Complete structured claim and evidence

5. Mean time to peak concentration was about 41 minutes after the tested oral dose.

   Melatonin → Circulating melatonin exposure, route and timing specified source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/melatonin-research/26893170.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "adf51f044cbe9fe89a19af5452dbf050dc60d611a590bc2544aed1c39ff4571c", "start_char": 0, "end_char": 1763, "text_sha256": "adf51f044cbe9fe89a19af5452dbf050dc60d611a590bc2544aed1c39ff4571c"}

   experimental_model

   Oral versus intravenous crossover pharmacokinetics

   exposure

   10 mg oral and 10 mg intravenous on separate days

   limitations

   Specific immediate-release preparation and study population. Bioavailability varies by formulation and individual; not a dosing recommendation.

   nutrient_topic

   Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin

   organism

   Twelve healthy men

   plain_language

   Immediate-release blood exposure rises relatively quickly in this experiment.

   primary_references

   [melatonin-p26893170] Pharmacokinetics of oral and intravenous melatonin in healthy volunteers. (2016). https://pubmed.ncbi.nlm.nih.gov/26893170/ DOI: 10.1186/s40360-016-0052-2

   tissue_or_cell_type

   Plasma exposure

   Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 669–680

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oral versus intravenous crossover pharmacokinetics · source_derived_draft · unverified_draft

   ### melatonin-oral-peak Mean time to peak concentration was about 41 minutes after the tested oral dose. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Immediate-release blood exposure rises relatively quickly in this experiment. organism: Twelve healthy men tissue_or_cell_type: Plasma exposure experimental_model: Oral versus intravenous crossover pharmacokinetics limitations: Specific immediate-release preparation and study population. Bioavailability varies by formulation and individual; not a dosing recommendation. exposure: 10 mg oral and 10 mg intravenous on separate days evidence_span: {"source_cache": "artifacts/melatonin-research/26893170.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "adf51f044cbe9fe89a19af5452dbf050dc60d611a590bc2544aed1c39ff4571c", "start_char": 0, "end_char": 1763, "text_sha256": "adf51f044cbe9fe89a19af5452dbf050dc60d611a590bc2544aed1c39ff4571c"} [melatonin-p26893170] Pharmacokinetics of oral and intravenous melatonin in healthy volunteers. (2016). https://pubmed.ncbi.nlm.nih.gov/26893170/ DOI: 10.1186/s40360-016-0052-2

   Complete structured claim and evidence

6. Oral melatonin AUC was higher after seven days of smoking abstinence than during smoking.

   Abstinence from cigarette smoking → Circulating melatonin exposure, route and timing specified source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/melatonin-research/15824912.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c9b44dc6db12d52916bdcf69db0dd31eec1107fa54539057ea07346f1e69894c", "start_char": 0, "end_char": 1764, "text_sha256": "c9b44dc6db12d52916bdcf69db0dd31eec1107fa54539057ea07346f1e69894c"}

   experimental_model

   Within-person smoking versus seven-day abstinence study

   exposure

   25 mg oral melatonin after nighttime sampling

   limitations

   High pharmacological dose and small cohort. Smoking affected exogenous exposure without a significant endogenous nighttime AUC change; do not conflate the two.

   nutrient_topic

   Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin

   organism

   Eight habitual smokers

   plain_language

   Stopping an enzyme-inducing exposure can change supplemental melatonin pharmacokinetics.

   primary_references

   [melatonin-p15824912] Influence of cigarette smoking on melatonin levels in man. (2005). https://pubmed.ncbi.nlm.nih.gov/15824912/ DOI: 10.1007/s00228-005-0908-7

   tissue_or_cell_type

   Endogenous night secretion versus exogenous exposure

   Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 734–745

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Within-person smoking versus seven-day abstinence study · source_derived_draft · unverified_draft

   ### melatonin-smoking-abstinence-exposure Oral melatonin AUC was higher after seven days of smoking abstinence than during smoking. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Stopping an enzyme-inducing exposure can change supplemental melatonin pharmacokinetics. organism: Eight habitual smokers tissue_or_cell_type: Endogenous night secretion versus exogenous exposure experimental_model: Within-person smoking versus seven-day abstinence study limitations: High pharmacological dose and small cohort. Smoking affected exogenous exposure without a significant endogenous nighttime AUC change; do not conflate the two. exposure: 25 mg oral melatonin after nighttime sampling evidence_span: {"source_cache": "artifacts/melatonin-research/15824912.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c9b44dc6db12d52916bdcf69db0dd31eec1107fa54539057ea07346f1e69894c", "start_char": 0, "end_char": 1764, "text_sha256": "c9b44dc6db12d52916bdcf69db0dd31eec1107fa54539057ea07346f1e69894c"} [melatonin-p15824912] Influence of cigarette smoking on melatonin levels in man. (2005). https://pubmed.ncbi.nlm.nih.gov/15824912/ DOI: 10.1007/s00228-005-0908-7

   Complete structured claim and evidence