Nutrient chapter

Melatonin

Melatonin. Species, exposure and limitations are retained in each linked claim.

96 recorded mechanisms · 4 availability situations · 6 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

What the sources say this nutrient does, one relationship at a time. Plain wording comes first; the technical statement follows.

Purified human pineal TPH catalyzed tryptophan hydroxylation to 5-hydroxytryptophan.
Human tryptophan hydroxylase 1 / TPH1 → 5-Hydroxy-L-tryptophan source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/10525150.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "032acfb7b1818f5282f5457e093a7e371895bbdc95f058c8958766fc57f9118f", "start_char": 0, "end_char": 1489, "text_sha256": "032acfb7b1818f5282f5457e093a7e371895bbdc95f058c8958766fc57f9118f"}
experimental_model
Recombinant enzyme purification and catalysis
exposure
L-tryptophan with tetrahydrobiopterin; purified tetrameric enzyme
limitations
TPH1 and neuronal TPH2 are distinct. A cofactor-dependent reaction does not prove supplemental cofactor increases melatonin in a replete person.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human pineal TPH1 expressed in E. coli
plain_language
The amino acid tryptophan must pass through an enzyme-controlled first step.
primary_references
[melatonin-p10525150] Cloning and expression of recombinant human pineal tryptophan hydroxylase in Escherichia coli: purification and characterization of the cloned enzyme. (1999). https://pubmed.ncbi.nlm.nih.gov/10525150/ DOI: 10.1016/s0167-4838(99)00184-3
tissue_or_cell_type
Tryptophan hydroxylation
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 136–147
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant enzyme purification and catalysis · source_derived_draft · unverified_draft
### melatonin-tph1-hydroxylation Purified human pineal TPH catalyzed tryptophan hydroxylation to 5-hydroxytryptophan. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The amino acid tryptophan must pass through an enzyme-controlled first step. organism: Human pineal TPH1 expressed in E. coli tissue_or_cell_type: Tryptophan hydroxylation experimental_model: Recombinant enzyme purification and catalysis limitations: TPH1 and neuronal TPH2 are distinct. A cofactor-dependent reaction does not prove supplemental cofactor increases melatonin in a replete person. exposure: L-tryptophan with tetrahydrobiopterin; purified tetrameric enzyme evidence_span: {"source_cache": "artifacts/melatonin-research/10525150.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "032acfb7b1818f5282f5457e093a7e371895bbdc95f058c8958766fc57f9118f", "start_char": 0, "end_char": 1489, "text_sha256": "032acfb7b1818f5282f5457e093a7e371895bbdc95f058c8958766fc57f9118f"} [melatonin-p10525150] Cloning and expression of recombinant human pineal tryptophan hydroxylase in Escherichia coli: purification and characterization of the cloned enzyme. (1999). https://pubmed.ncbi.nlm.nih.gov/10525150/ DOI: 10.1016/s0167-4838(99)00184-3
Complete structured claim and evidence
Human AANAT transferred an acetyl group from acetyl-CoA to serotonin, producing N-acetylserotonin.
Human arylalkylamine N-acetyltransferase / AANAT → N-Acetylserotonin source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/10722724.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7fb8418b17e92c5b3fed5d9c08afdb32f28c922dfe94274d3bb02b7e12b2b8c8", "start_char": 0, "end_char": 1857, "text_sha256": "7fb8418b17e92c5b3fed5d9c08afdb32f28c922dfe94274d3bb02b7e12b2b8c8"}
experimental_model
Purified recombinant enzyme substrate-specificity study
exposure
Serotonin and radiolabeled acetyl-CoA; product HPLC
limitations
Biochemical mechanism, not evidence that dietary B5 or acetyl-CoA availability limits melatonin production in all humans.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human AANAT expressed in bacteria
plain_language
Serotonin is modified before it becomes melatonin.
primary_references
[melatonin-p10722724] Substrate specificity and inhibition studies of human serotonin N-acetyltransferase. (2000). https://pubmed.ncbi.nlm.nih.gov/10722724/ DOI: 10.1074/jbc.275.12.8794
tissue_or_cell_type
Serotonin acetylation
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 175–186
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant enzyme substrate-specificity study · source_derived_draft · unverified_draft
### melatonin-aanat-serotonin Human AANAT transferred an acetyl group from acetyl-CoA to serotonin, producing N-acetylserotonin. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Serotonin is modified before it becomes melatonin. organism: Human AANAT expressed in bacteria tissue_or_cell_type: Serotonin acetylation experimental_model: Purified recombinant enzyme substrate-specificity study limitations: Biochemical mechanism, not evidence that dietary B5 or acetyl-CoA availability limits melatonin production in all humans. exposure: Serotonin and radiolabeled acetyl-CoA; product HPLC evidence_span: {"source_cache": "artifacts/melatonin-research/10722724.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7fb8418b17e92c5b3fed5d9c08afdb32f28c922dfe94274d3bb02b7e12b2b8c8", "start_char": 0, "end_char": 1857, "text_sha256": "7fb8418b17e92c5b3fed5d9c08afdb32f28c922dfe94274d3bb02b7e12b2b8c8"} [melatonin-p10722724] Substrate specificity and inhibition studies of human serotonin N-acetyltransferase. (2000). https://pubmed.ncbi.nlm.nih.gov/10722724/ DOI: 10.1074/jbc.275.12.8794
Complete structured claim and evidence
Human ASMT catalyzes the terminal methylation step converting N-acetylserotonin to melatonin using SAM.
Human acetylserotonin O-methyltransferase / ASMT → Melatonin source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/22775292.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6896e0a7e08f764e1ff8c370601b0477c594e4e1c945df52d0f564e9049a9349", "start_char": 0, "end_char": 1205, "text_sha256": "6896e0a7e08f764e1ff8c370601b0477c594e4e1c945df52d0f564e9049a9349"}
experimental_model
X-ray structure and radioenzymatic variant characterization
exposure
SAM-dependent methyltransferase structure and enzyme activity assays
limitations
Reduced recombinant enzyme activity does not quantify pineal secretion or diagnose a sleep problem in an individual. Variant effects differ; no single universal melatonin-deficiency syndrome.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human ASMT and 20 nonsynonymous variants
plain_language
A methyl group completes the molecule.
primary_references
[melatonin-p22775292] Crystal structure and functional mapping of human ASMT, the last enzyme of the melatonin synthesis pathway. (2013). https://pubmed.ncbi.nlm.nih.gov/22775292/ DOI: 10.1111/j.1600-079x.2012.01020.x
tissue_or_cell_type
Final melatonin synthesis step
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 201–212
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray structure and radioenzymatic variant characterization · source_derived_draft · unverified_draft
### melatonin-asmt-methylation Human ASMT catalyzes the terminal methylation step converting N-acetylserotonin to melatonin using SAM. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A methyl group completes the molecule. organism: Human ASMT and 20 nonsynonymous variants tissue_or_cell_type: Final melatonin synthesis step experimental_model: X-ray structure and radioenzymatic variant characterization limitations: Reduced recombinant enzyme activity does not quantify pineal secretion or diagnose a sleep problem in an individual. Variant effects differ; no single universal melatonin-deficiency syndrome. exposure: SAM-dependent methyltransferase structure and enzyme activity assays evidence_span: {"source_cache": "artifacts/melatonin-research/22775292.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6896e0a7e08f764e1ff8c370601b0477c594e4e1c945df52d0f564e9049a9349", "start_char": 0, "end_char": 1205, "text_sha256": "6896e0a7e08f764e1ff8c370601b0477c594e4e1c945df52d0f564e9049a9349"} [melatonin-p22775292] Crystal structure and functional mapping of human ASMT, the last enzyme of the melatonin synthesis pathway. (2013). https://pubmed.ncbi.nlm.nih.gov/22775292/ DOI: 10.1111/j.1600-079x.2012.01020.x
Complete structured claim and evidence
The phase-advance response peaked about five hours before dim-light melatonin onset in the three-pulse experiment.
Melatonin → Phase of the endogenous melatonin circadian rhythm source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/18006583.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9eb1409f6e4c58eadfaf1554930378e03860dc9dc1201de6d104b6de784758ea", "start_char": 0, "end_char": 1518, "text_sha256": "9eb1409f6e4c58eadfaf1554930378e03860dc9dc1201de6d104b6de784758ea"}
experimental_model
Double-blind counterbalanced phase-response experiment
exposure
3 mg once daily for three days at different circadian times; dim-light onset measured
limitations
Timing is relative to individual biological phase, not a universal clock hour. This experimental schedule is not a dosing instruction.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
27 healthy young adults
plain_language
The same hormone can move the body clock earlier when given at the appropriate biological time.
primary_references
[melatonin-p18006583] A three pulse phase response curve to three milligrams of melatonin in humans. (2008). https://pubmed.ncbi.nlm.nih.gov/18006583/ DOI: 10.1113/jphysiol.2007.143180
tissue_or_cell_type
Circadian melatonin timing
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 838–849
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind counterbalanced phase-response experiment · source_derived_draft · unverified_draft
### melatonin-phase-advance The phase-advance response peaked about five hours before dim-light melatonin onset in the three-pulse experiment. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same hormone can move the body clock earlier when given at the appropriate biological time. organism: 27 healthy young adults tissue_or_cell_type: Circadian melatonin timing experimental_model: Double-blind counterbalanced phase-response experiment limitations: Timing is relative to individual biological phase, not a universal clock hour. This experimental schedule is not a dosing instruction. exposure: 3 mg once daily for three days at different circadian times; dim-light onset measured evidence_span: {"source_cache": "artifacts/melatonin-research/18006583.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9eb1409f6e4c58eadfaf1554930378e03860dc9dc1201de6d104b6de784758ea", "start_char": 0, "end_char": 1518, "text_sha256": "9eb1409f6e4c58eadfaf1554930378e03860dc9dc1201de6d104b6de784758ea"} [melatonin-p18006583] A three pulse phase response curve to three milligrams of melatonin in humans. (2008). https://pubmed.ncbi.nlm.nih.gov/18006583/ DOI: 10.1113/jphysiol.2007.143180
Complete structured claim and evidence
The phase-delay response peaked about eleven hours after dim-light melatonin onset.
Melatonin → Phase of the endogenous melatonin circadian rhythm source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/18006583.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9eb1409f6e4c58eadfaf1554930378e03860dc9dc1201de6d104b6de784758ea", "start_char": 0, "end_char": 1518, "text_sha256": "9eb1409f6e4c58eadfaf1554930378e03860dc9dc1201de6d104b6de784758ea"}
experimental_model
Double-blind counterbalanced phase-response experiment
exposure
3 mg once daily for three days at different circadian times; dim-light onset measured
limitations
Timing is relative to individual biological phase, not a universal clock hour. This experimental schedule is not a dosing instruction.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
27 healthy young adults
plain_language
A different timing can move the clock in the opposite direction.
primary_references
[melatonin-p18006583] A three pulse phase response curve to three milligrams of melatonin in humans. (2008). https://pubmed.ncbi.nlm.nih.gov/18006583/ DOI: 10.1113/jphysiol.2007.143180
tissue_or_cell_type
Circadian melatonin timing
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 851–862
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind counterbalanced phase-response experiment · source_derived_draft · unverified_draft
### melatonin-phase-delay The phase-delay response peaked about eleven hours after dim-light melatonin onset. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A different timing can move the clock in the opposite direction. organism: 27 healthy young adults tissue_or_cell_type: Circadian melatonin timing experimental_model: Double-blind counterbalanced phase-response experiment limitations: Timing is relative to individual biological phase, not a universal clock hour. This experimental schedule is not a dosing instruction. exposure: 3 mg once daily for three days at different circadian times; dim-light onset measured evidence_span: {"source_cache": "artifacts/melatonin-research/18006583.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9eb1409f6e4c58eadfaf1554930378e03860dc9dc1201de6d104b6de784758ea", "start_char": 0, "end_char": 1518, "text_sha256": "9eb1409f6e4c58eadfaf1554930378e03860dc9dc1201de6d104b6de784758ea"} [melatonin-p18006583] A three pulse phase response curve to three milligrams of melatonin in humans. (2008). https://pubmed.ncbi.nlm.nih.gov/18006583/ DOI: 10.1113/jphysiol.2007.143180
Complete structured claim and evidence
Room light delayed measured melatonin onset in 99% of participants relative to dim light.
Evening room-light exposure compared with dim light → Circadian onset of endogenous melatonin secretion source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/melatonin-research/21193540.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "899cae7b15ef3be8a3d4660202e8f675722295da9cb69a0eef3bdcf2470aeb23", "start_char": 0, "end_char": 1666, "text_sha256": "899cae7b15ef3be8a3d4660202e8f675722295da9cb69a0eef3bdcf2470aeb23"}
experimental_model
Controlled-light profiles analyzed retrospectively
exposure
Room light below 200 lux versus dim light below 3 lux before bed; light during usual sleep hours
limitations
Study light conditions are not universal thresholds for all eyes, spectra or exposure durations. Suppression is not dietary deficiency.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
116 healthy adults aged 18-30
plain_language
The conditions during measurement can change when the night signal appears.
primary_references
[melatonin-p21193540] Exposure to room light before bedtime suppresses melatonin onset and shortens melatonin duration in humans. (2011). https://pubmed.ncbi.nlm.nih.gov/21193540/ DOI: 10.1210/jc.2010-2098
tissue_or_cell_type
Circulating melatonin under different light conditions
trigger_kind
biomarker_context Imported condition classification; unverified.
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 877–888
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled-light profiles analyzed retrospectively · source_derived_draft · unverified_draft
### melatonin-light-onset Room light delayed measured melatonin onset in 99% of participants relative to dim light. Condition category: biomarker_context nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The conditions during measurement can change when the night signal appears. organism: 116 healthy adults aged 18-30 tissue_or_cell_type: Circulating melatonin under different light conditions experimental_model: Controlled-light profiles analyzed retrospectively limitations: Study light conditions are not universal thresholds for all eyes, spectra or exposure durations. Suppression is not dietary deficiency. exposure: Room light below 200 lux versus dim light below 3 lux before bed; light during usual sleep hours evidence_span: {"source_cache": "artifacts/melatonin-research/21193540.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "899cae7b15ef3be8a3d4660202e8f675722295da9cb69a0eef3bdcf2470aeb23", "start_char": 0, "end_char": 1666, "text_sha256": "899cae7b15ef3be8a3d4660202e8f675722295da9cb69a0eef3bdcf2470aeb23"} [melatonin-p21193540] Exposure to room light before bedtime suppresses melatonin onset and shortens melatonin duration in humans. (2011). https://pubmed.ncbi.nlm.nih.gov/21193540/ DOI: 10.1210/jc.2010-2098
Complete structured claim and evidence
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
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
Mean plasma melatonin was about 50 versus 75 pg/mL in magnesium-deficient versus adequate-diet rats.
Magnesium → Rat plasma melatonin concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/melatonin-research/17172005.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "32a85d5fa095aeb2258c9ee44e480deb8c3292aafc9bd13edb4172d1743caf50", "start_char": 0, "end_char": 969, "text_sha256": "32a85d5fa095aeb2258c9ee44e480deb8c3292aafc9bd13edb4172d1743caf50"}
experimental_model
Controlled dietary magnesium-deficiency pilot
exposure
150 versus 1000 ppm magnesium diet for four weeks
limitations
Animal dietary exposure; enzyme mechanism was not established by this experiment. No human intake threshold or universal repletion-failure rule can be derived.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Male Sprague-Dawley rats
plain_language
A nutrient shortage altered the measured hormone level in an animal experiment.
primary_references
[melatonin-p17172005] Dietary magnesium deficiency decreases plasma melatonin in rats. (2006). https://pubmed.ncbi.nlm.nih.gov/17172005/
tissue_or_cell_type
Dark-phase plasma melatonin
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 760–771
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled dietary magnesium-deficiency pilot · source_derived_draft · unverified_draft
### melatonin-magnesium-low-melatonin Mean plasma melatonin was about 50 versus 75 pg/mL in magnesium-deficient versus adequate-diet rats. Condition category: nutrient_deficiency nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A nutrient shortage altered the measured hormone level in an animal experiment. organism: Male Sprague-Dawley rats tissue_or_cell_type: Dark-phase plasma melatonin experimental_model: Controlled dietary magnesium-deficiency pilot limitations: Animal dietary exposure; enzyme mechanism was not established by this experiment. No human intake threshold or universal repletion-failure rule can be derived. exposure: 150 versus 1000 ppm magnesium diet for four weeks evidence_span: {"source_cache": "artifacts/melatonin-research/17172005.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "32a85d5fa095aeb2258c9ee44e480deb8c3292aafc9bd13edb4172d1743caf50", "start_char": 0, "end_char": 969, "text_sha256": "32a85d5fa095aeb2258c9ee44e480deb8c3292aafc9bd13edb4172d1743caf50"} [melatonin-p17172005] Dietary magnesium deficiency decreases plasma melatonin in rats. (2006). https://pubmed.ncbi.nlm.nih.gov/17172005/
Complete structured claim and evidence
Evening pyridoxine did not significantly change melatonin onset, peak, mean or AUC relative to placebo.
Pyridoxine → Nocturnal circulating melatonin concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/12080281.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "04727c17cd3152a4749ec25ff15b36b827efb885501ce058d436fbbea1e9e7a9", "start_char": 0, "end_char": 1222, "text_sha256": "04727c17cd3152a4749ec25ff15b36b827efb885501ce058d436fbbea1e9e7a9"}
experimental_model
Placebo-controlled evening pyridoxine experiment
exposure
100 mg pyridoxine at 17:00; evening/night sampling
limitations
Acute exposure in healthy men. Null supplementation response does not negate the enzymatic requirement for PLP or settle effects in B6 deficiency.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Twelve healthy men
plain_language
An enzyme needs B6, but giving extra B6 did not increase the hormone in this experiment.
primary_references
[melatonin-p12080281] The effect of pyridoxine administration on melatonin secretion in normal men. (2002). https://pubmed.ncbi.nlm.nih.gov/12080281/
tissue_or_cell_type
Melatonin secretion, temperature and polysomnography
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 773–784
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Placebo-controlled evening pyridoxine experiment · source_derived_draft · unverified_draft
### melatonin-b6-secretion-null Evening pyridoxine did not significantly change melatonin onset, peak, mean or AUC relative to placebo. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: An enzyme needs B6, but giving extra B6 did not increase the hormone in this experiment. organism: Twelve healthy men tissue_or_cell_type: Melatonin secretion, temperature and polysomnography experimental_model: Placebo-controlled evening pyridoxine experiment limitations: Acute exposure in healthy men. Null supplementation response does not negate the enzymatic requirement for PLP or settle effects in B6 deficiency. exposure: 100 mg pyridoxine at 17:00; evening/night sampling evidence_span: {"source_cache": "artifacts/melatonin-research/12080281.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "04727c17cd3152a4749ec25ff15b36b827efb885501ce058d436fbbea1e9e7a9", "start_char": 0, "end_char": 1222, "text_sha256": "04727c17cd3152a4749ec25ff15b36b827efb885501ce058d436fbbea1e9e7a9"} [melatonin-p12080281] The effect of pyridoxine administration on melatonin secretion in normal men. (2002). https://pubmed.ncbi.nlm.nih.gov/12080281/
Complete structured claim and evidence
First-phase beta-cell glucose responsiveness was suppressed by about 40% in risk carriers.
Melatonin → First-phase beta-cell responsiveness to glucose source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/42346809.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8e4b84650338084b0a878a3b06138c9ef65502d7f9b119877434421b5131bc6", "start_char": 0, "end_char": 1941, "text_sha256": "a8e4b84650338084b0a878a3b06138c9ef65502d7f9b119877434421b5131bc6"}
experimental_model
Randomized double-blind placebo-controlled crossover physiology trial
exposure
5 mg oral melatonin; five-day laboratory protocol
limitations
Small genotype-stratified acute study published in 2026. Stronger carrier findings are not a population-wide diabetes risk estimate or evidence about all chronic formulations.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
21 healthy European-ancestry participants: 10 risk carriers, 11 noncarriers
plain_language
The early insulin-secretion response was specifically impaired.
primary_references
[melatonin-p42346809] Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With MTNR1B Diabetes Risk Variant. (2026). https://pubmed.ncbi.nlm.nih.gov/42346809/ DOI: 10.2337/dc26-0164
tissue_or_cell_type
Insulin-modified IV glucose test and beta-cell modeling
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 1202–1213
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled crossover physiology trial · source_derived_draft · unverified_draft
### melatonin-2026-first-phase First-phase beta-cell glucose responsiveness was suppressed by about 40% in risk carriers. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The early insulin-secretion response was specifically impaired. organism: 21 healthy European-ancestry participants: 10 risk carriers, 11 noncarriers tissue_or_cell_type: Insulin-modified IV glucose test and beta-cell modeling experimental_model: Randomized double-blind placebo-controlled crossover physiology trial limitations: Small genotype-stratified acute study published in 2026. Stronger carrier findings are not a population-wide diabetes risk estimate or evidence about all chronic formulations. exposure: 5 mg oral melatonin; five-day laboratory protocol evidence_span: {"source_cache": "artifacts/melatonin-research/42346809.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8e4b84650338084b0a878a3b06138c9ef65502d7f9b119877434421b5131bc6", "start_char": 0, "end_char": 1941, "text_sha256": "a8e4b84650338084b0a878a3b06138c9ef65502d7f9b119877434421b5131bc6"} [melatonin-p42346809] Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With MTNR1B Diabetes Risk Variant. (2026). https://pubmed.ncbi.nlm.nih.gov/42346809/ DOI: 10.2337/dc26-0164
Complete structured claim and evidence
GPR50 abolished MT1 G-protein coupling within the heterodimer.
Human melatonin-related orphan receptor / GPR50 → MT1 coupling to inhibitory G proteins source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/melatonin-research/16778767.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19c9ae903fb7926bb21cc3bda0a610612b16a899f850b8e787581b72ac434135", "start_char": 0, "end_char": 1204, "text_sha256": "19c9ae903fb7926bb21cc3bda0a610612b16a899f850b8e787581b72ac434135"}
experimental_model
Biochemical and biophysical receptor heteromer experiments
exposure
Full-length versus C-terminally truncated GPR50
limitations
Cell-system regulation; does not establish that a person with poor sleep has excess GPR50 or that more melatonin overcomes it.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human receptors in cultured cells
plain_language
Available hormone and functional receptor machinery are different requirements.
primary_references
[melatonin-p16778767] The orphan GPR50 receptor specifically inhibits MT1 melatonin receptor function through heterodimerization. (2006). https://pubmed.ncbi.nlm.nih.gov/16778767/ DOI: 10.1038/sj.emboj.7601193
tissue_or_cell_type
GPR50-MT1/MT2 interactions
trigger_kind
machinery_impairment Imported condition classification; unverified.
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 461–472
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemical and biophysical receptor heteromer experiments · source_derived_draft · unverified_draft
### melatonin-gpr50-mt1-coupling GPR50 abolished MT1 G-protein coupling within the heterodimer. Condition category: machinery_impairment nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Available hormone and functional receptor machinery are different requirements. organism: Human receptors in cultured cells tissue_or_cell_type: GPR50-MT1/MT2 interactions experimental_model: Biochemical and biophysical receptor heteromer experiments limitations: Cell-system regulation; does not establish that a person with poor sleep has excess GPR50 or that more melatonin overcomes it. exposure: Full-length versus C-terminally truncated GPR50 evidence_span: {"source_cache": "artifacts/melatonin-research/16778767.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19c9ae903fb7926bb21cc3bda0a610612b16a899f850b8e787581b72ac434135", "start_char": 0, "end_char": 1204, "text_sha256": "19c9ae903fb7926bb21cc3bda0a610612b16a899f850b8e787581b72ac434135"} [melatonin-p16778767] The orphan GPR50 receptor specifically inhibits MT1 melatonin receptor function through heterodimerization. (2006). https://pubmed.ncbi.nlm.nih.gov/16778767/ DOI: 10.1038/sj.emboj.7601193
Complete structured claim and evidence
Human pineal TPH activity was measured with BH4, and a transient 4alpha-hydroxytetrahydrobiopterin intermediate was detected.
Tetrahydrobiopterin / BH4 → Human tryptophan hydroxylase 1 / TPH1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/10525150.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "032acfb7b1818f5282f5457e093a7e371895bbdc95f058c8958766fc57f9118f", "start_char": 0, "end_char": 1489, "text_sha256": "032acfb7b1818f5282f5457e093a7e371895bbdc95f058c8958766fc57f9118f"}
experimental_model
Recombinant enzyme purification and catalysis
exposure
L-tryptophan with tetrahydrobiopterin; purified tetrameric enzyme
limitations
TPH1 and neuronal TPH2 are distinct. A cofactor-dependent reaction does not prove supplemental cofactor increases melatonin in a replete person.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human pineal TPH1 expressed in E. coli
plain_language
The pterin cofactor participates chemically; it is not interchangeable with folate.
primary_references
[melatonin-p10525150] Cloning and expression of recombinant human pineal tryptophan hydroxylase in Escherichia coli: purification and characterization of the cloned enzyme. (1999). https://pubmed.ncbi.nlm.nih.gov/10525150/ DOI: 10.1016/s0167-4838(99)00184-3
tissue_or_cell_type
Tryptophan hydroxylation
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 149–160
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant enzyme purification and catalysis · source_derived_draft · unverified_draft
### melatonin-tph1-bh4 Human pineal TPH activity was measured with BH4, and a transient 4alpha-hydroxytetrahydrobiopterin intermediate was detected. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The pterin cofactor participates chemically; it is not interchangeable with folate. organism: Human pineal TPH1 expressed in E. coli tissue_or_cell_type: Tryptophan hydroxylation experimental_model: Recombinant enzyme purification and catalysis limitations: TPH1 and neuronal TPH2 are distinct. A cofactor-dependent reaction does not prove supplemental cofactor increases melatonin in a replete person. exposure: L-tryptophan with tetrahydrobiopterin; purified tetrameric enzyme evidence_span: {"source_cache": "artifacts/melatonin-research/10525150.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "032acfb7b1818f5282f5457e093a7e371895bbdc95f058c8958766fc57f9118f", "start_char": 0, "end_char": 1489, "text_sha256": "032acfb7b1818f5282f5457e093a7e371895bbdc95f058c8958766fc57f9118f"} [melatonin-p10525150] Cloning and expression of recombinant human pineal tryptophan hydroxylase in Escherichia coli: purification and characterization of the cloned enzyme. (1999). https://pubmed.ncbi.nlm.nih.gov/10525150/ DOI: 10.1016/s0167-4838(99)00184-3
Complete structured claim and evidence
The human TPH catalytic domain positioned tryptophan and a pterin analogue near its catalytic non-heme iron.
Human tryptophan hydroxylase 1 / TPH1 → Ferrous iron source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/11747434.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c98a1e028f9c3d7f749d37794a8e976c8c808e0ca9c5f08c394d9d29ae639e06", "start_char": 0, "end_char": 2063, "text_sha256": "c98a1e028f9c3d7f749d37794a8e976c8c808e0ca9c5f08c394d9d29ae639e06"}
experimental_model
NMR substrate/cofactor geometry and enzyme modeling
exposure
L-tryptophan and bound BH2 cofactor analogue
limitations
BH2 was a structural analogue in this experiment, not a demonstration that BH2 replaces physiological BH4. No clinical iron-deficiency threshold measured.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Recombinant human TPH1 catalytic domain
plain_language
The upstream hydroxylation machinery contains iron; giving more iron is not automatically a way to make more melatonin.
primary_references
[melatonin-p11747434] Conformation of the substrate and pterin cofactor bound to human tryptophan hydroxylase. Important role of Phe313 in substrate specificity. (2001). https://pubmed.ncbi.nlm.nih.gov/11747434/ DOI: 10.1021/bi015722x
tissue_or_cell_type
Non-heme iron active site
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 162–173
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · NMR substrate/cofactor geometry and enzyme modeling · source_derived_draft · unverified_draft
### melatonin-tph1-iron The human TPH catalytic domain positioned tryptophan and a pterin analogue near its catalytic non-heme iron. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The upstream hydroxylation machinery contains iron; giving more iron is not automatically a way to make more melatonin. organism: Recombinant human TPH1 catalytic domain tissue_or_cell_type: Non-heme iron active site experimental_model: NMR substrate/cofactor geometry and enzyme modeling limitations: BH2 was a structural analogue in this experiment, not a demonstration that BH2 replaces physiological BH4. No clinical iron-deficiency threshold measured. exposure: L-tryptophan and bound BH2 cofactor analogue evidence_span: {"source_cache": "artifacts/melatonin-research/11747434.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c98a1e028f9c3d7f749d37794a8e976c8c808e0ca9c5f08c394d9d29ae639e06", "start_char": 0, "end_char": 2063, "text_sha256": "c98a1e028f9c3d7f749d37794a8e976c8c808e0ca9c5f08c394d9d29ae639e06"} [melatonin-p11747434] Conformation of the substrate and pterin cofactor bound to human tryptophan hydroxylase. Important role of Phe313 in substrate specificity. (2001). https://pubmed.ncbi.nlm.nih.gov/11747434/ DOI: 10.1021/bi015722x
Complete structured claim and evidence
The human AANAT assay used acetyl-CoA as the acetyl donor in N-acetylserotonin formation.
Acetyl-CoA → Human arylalkylamine N-acetyltransferase / AANAT source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/10722724.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7fb8418b17e92c5b3fed5d9c08afdb32f28c922dfe94274d3bb02b7e12b2b8c8", "start_char": 0, "end_char": 1857, "text_sha256": "7fb8418b17e92c5b3fed5d9c08afdb32f28c922dfe94274d3bb02b7e12b2b8c8"}
experimental_model
Purified recombinant enzyme substrate-specificity study
exposure
Serotonin and radiolabeled acetyl-CoA; product HPLC
limitations
Biochemical mechanism, not evidence that dietary B5 or acetyl-CoA availability limits melatonin production in all humans.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human AANAT expressed in bacteria
plain_language
This connects melatonin synthesis to the B5-derived coenzyme-A system.
primary_references
[melatonin-p10722724] Substrate specificity and inhibition studies of human serotonin N-acetyltransferase. (2000). https://pubmed.ncbi.nlm.nih.gov/10722724/ DOI: 10.1074/jbc.275.12.8794
tissue_or_cell_type
Serotonin acetylation
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 188–199
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant enzyme substrate-specificity study · source_derived_draft · unverified_draft
### melatonin-aanat-acetyl-coa The human AANAT assay used acetyl-CoA as the acetyl donor in N-acetylserotonin formation. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This connects melatonin synthesis to the B5-derived coenzyme-A system. organism: Human AANAT expressed in bacteria tissue_or_cell_type: Serotonin acetylation experimental_model: Purified recombinant enzyme substrate-specificity study limitations: Biochemical mechanism, not evidence that dietary B5 or acetyl-CoA availability limits melatonin production in all humans. exposure: Serotonin and radiolabeled acetyl-CoA; product HPLC evidence_span: {"source_cache": "artifacts/melatonin-research/10722724.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7fb8418b17e92c5b3fed5d9c08afdb32f28c922dfe94274d3bb02b7e12b2b8c8", "start_char": 0, "end_char": 1857, "text_sha256": "7fb8418b17e92c5b3fed5d9c08afdb32f28c922dfe94274d3bb02b7e12b2b8c8"} [melatonin-p10722724] Substrate specificity and inhibition studies of human serotonin N-acetyltransferase. (2000). https://pubmed.ncbi.nlm.nih.gov/10722724/ DOI: 10.1074/jbc.275.12.8794
Complete structured claim and evidence
Human ASMT has a SAM-dependent O-methyltransferase catalytic domain.
S-Adenosyl-L-methionine → Human acetylserotonin O-methyltransferase / ASMT source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/22775292.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6896e0a7e08f764e1ff8c370601b0477c594e4e1c945df52d0f564e9049a9349", "start_char": 0, "end_char": 1205, "text_sha256": "6896e0a7e08f764e1ff8c370601b0477c594e4e1c945df52d0f564e9049a9349"}
experimental_model
X-ray structure and radioenzymatic variant characterization
exposure
SAM-dependent methyltransferase structure and enzyme activity assays
limitations
Reduced recombinant enzyme activity does not quantify pineal secretion or diagnose a sleep problem in an individual. Variant effects differ; no single universal melatonin-deficiency syndrome.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human ASMT and 20 nonsynonymous variants
plain_language
The methyl-donor pool connects this step to methionine and one-carbon metabolism.
primary_references
[melatonin-p22775292] Crystal structure and functional mapping of human ASMT, the last enzyme of the melatonin synthesis pathway. (2013). https://pubmed.ncbi.nlm.nih.gov/22775292/ DOI: 10.1111/j.1600-079x.2012.01020.x
tissue_or_cell_type
Final melatonin synthesis step
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 214–225
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray structure and radioenzymatic variant characterization · source_derived_draft · unverified_draft
### melatonin-asmt-sam Human ASMT has a SAM-dependent O-methyltransferase catalytic domain. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The methyl-donor pool connects this step to methionine and one-carbon metabolism. organism: Human ASMT and 20 nonsynonymous variants tissue_or_cell_type: Final melatonin synthesis step experimental_model: X-ray structure and radioenzymatic variant characterization limitations: Reduced recombinant enzyme activity does not quantify pineal secretion or diagnose a sleep problem in an individual. Variant effects differ; no single universal melatonin-deficiency syndrome. exposure: SAM-dependent methyltransferase structure and enzyme activity assays evidence_span: {"source_cache": "artifacts/melatonin-research/22775292.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6896e0a7e08f764e1ff8c370601b0477c594e4e1c945df52d0f564e9049a9349", "start_char": 0, "end_char": 1205, "text_sha256": "6896e0a7e08f764e1ff8c370601b0477c594e4e1c945df52d0f564e9049a9349"} [melatonin-p22775292] Crystal structure and functional mapping of human ASMT, the last enzyme of the melatonin synthesis pathway. (2013). https://pubmed.ncbi.nlm.nih.gov/22775292/ DOI: 10.1111/j.1600-079x.2012.01020.x
Complete structured claim and evidence
The N17K ASMT variant was among variants with reduced or abolished activity in the radioenzymatic screen.
Human ASMT p.Asn17Lys / N17K variant → Human ASMT catalytic activity source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/melatonin-research/22775292.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6896e0a7e08f764e1ff8c370601b0477c594e4e1c945df52d0f564e9049a9349", "start_char": 0, "end_char": 1205, "text_sha256": "6896e0a7e08f764e1ff8c370601b0477c594e4e1c945df52d0f564e9049a9349"}
experimental_model
X-ray structure and radioenzymatic variant characterization
exposure
SAM-dependent methyltransferase structure and enzyme activity assays
limitations
Reduced recombinant enzyme activity does not quantify pineal secretion or diagnose a sleep problem in an individual. Variant effects differ; no single universal melatonin-deficiency syndrome.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human ASMT and 20 nonsynonymous variants
plain_language
More precursor does not automatically repair an altered enzyme.
primary_references
[melatonin-p22775292] Crystal structure and functional mapping of human ASMT, the last enzyme of the melatonin synthesis pathway. (2013). https://pubmed.ncbi.nlm.nih.gov/22775292/ DOI: 10.1111/j.1600-079x.2012.01020.x
tissue_or_cell_type
Final melatonin synthesis step
trigger_kind
machinery_impairment Imported condition classification; unverified.
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 227–238
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray structure and radioenzymatic variant characterization · source_derived_draft · unverified_draft
### melatonin-asmt-n17k The N17K ASMT variant was among variants with reduced or abolished activity in the radioenzymatic screen. Condition category: machinery_impairment nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: More precursor does not automatically repair an altered enzyme. organism: Human ASMT and 20 nonsynonymous variants tissue_or_cell_type: Final melatonin synthesis step experimental_model: X-ray structure and radioenzymatic variant characterization limitations: Reduced recombinant enzyme activity does not quantify pineal secretion or diagnose a sleep problem in an individual. Variant effects differ; no single universal melatonin-deficiency syndrome. exposure: SAM-dependent methyltransferase structure and enzyme activity assays evidence_span: {"source_cache": "artifacts/melatonin-research/22775292.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6896e0a7e08f764e1ff8c370601b0477c594e4e1c945df52d0f564e9049a9349", "start_char": 0, "end_char": 1205, "text_sha256": "6896e0a7e08f764e1ff8c370601b0477c594e4e1c945df52d0f564e9049a9349"} [melatonin-p22775292] Crystal structure and functional mapping of human ASMT, the last enzyme of the melatonin synthesis pathway. (2013). https://pubmed.ncbi.nlm.nih.gov/22775292/ DOI: 10.1111/j.1600-079x.2012.01020.x
Complete structured claim and evidence
Binding involving both phosphorylated Thr31 and Ser205 lowered ovine AANAT substrate Km to about 30 micromolar.
14-3-3 proteins in AANAT biochemical experiments → AANAT arylalkylamine substrate affinity source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/15644438.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d8be6407faaad634dbbe950dcc278cfcbe12aa24c08caafcc0ff740e8945b552", "start_char": 0, "end_char": 1693, "text_sha256": "d8be6407faaad634dbbe950dcc278cfcbe12aa24c08caafcc0ff740e8945b552"}
experimental_model
Phosphorylation, binding and enzyme-kinetic experiments
exposure
Thr31 and Ser205 phosphorylation; night versus light exposure
limitations
Residue numbering and kinetic states refer to ovine enzyme. Two-site and one-site binding have different effects; not a universal activation rule for all phosphorylation.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Sheep AANAT and 14-3-3 biochemical systems
plain_language
A regulatory partner can make the enzyme bind its substrate more effectively.
primary_references
[melatonin-p15644438] Melatonin synthesis: 14-3-3-dependent activation and inhibition of arylalkylamine N-acetyltransferase mediated by phosphoserine-205. (2005). https://pubmed.ncbi.nlm.nih.gov/15644438/ DOI: 10.1073/pnas.0406871102
tissue_or_cell_type
Pineal enzyme regulation
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 240–251
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Phosphorylation, binding and enzyme-kinetic experiments · source_derived_draft · unverified_draft
### melatonin-aanat-dual-binding Binding involving both phosphorylated Thr31 and Ser205 lowered ovine AANAT substrate Km to about 30 micromolar. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A regulatory partner can make the enzyme bind its substrate more effectively. organism: Sheep AANAT and 14-3-3 biochemical systems tissue_or_cell_type: Pineal enzyme regulation experimental_model: Phosphorylation, binding and enzyme-kinetic experiments limitations: Residue numbering and kinetic states refer to ovine enzyme. Two-site and one-site binding have different effects; not a universal activation rule for all phosphorylation. exposure: Thr31 and Ser205 phosphorylation; night versus light exposure evidence_span: {"source_cache": "artifacts/melatonin-research/15644438.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d8be6407faaad634dbbe950dcc278cfcbe12aa24c08caafcc0ff740e8945b552", "start_char": 0, "end_char": 1693, "text_sha256": "d8be6407faaad634dbbe950dcc278cfcbe12aa24c08caafcc0ff740e8945b552"} [melatonin-p15644438] Melatonin synthesis: 14-3-3-dependent activation and inhibition of arylalkylamine N-acetyltransferase mediated by phosphoserine-205. (2005). https://pubmed.ncbi.nlm.nih.gov/15644438/ DOI: 10.1073/pnas.0406871102
Complete structured claim and evidence
Binding through Ser205 alone raised substrate Km to about 1200 micromolar in the ovine AANAT system.
14-3-3 proteins in AANAT biochemical experiments → AANAT arylalkylamine substrate affinity source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/15644438.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d8be6407faaad634dbbe950dcc278cfcbe12aa24c08caafcc0ff740e8945b552", "start_char": 0, "end_char": 1693, "text_sha256": "d8be6407faaad634dbbe950dcc278cfcbe12aa24c08caafcc0ff740e8945b552"}
experimental_model
Phosphorylation, binding and enzyme-kinetic experiments
exposure
Thr31 and Ser205 phosphorylation; night versus light exposure
limitations
Residue numbering and kinetic states refer to ovine enzyme. Two-site and one-site binding have different effects; not a universal activation rule for all phosphorylation.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Sheep AANAT and 14-3-3 biochemical systems
plain_language
The same partner can have a different effect when the binding arrangement changes.
primary_references
[melatonin-p15644438] Melatonin synthesis: 14-3-3-dependent activation and inhibition of arylalkylamine N-acetyltransferase mediated by phosphoserine-205. (2005). https://pubmed.ncbi.nlm.nih.gov/15644438/ DOI: 10.1073/pnas.0406871102
tissue_or_cell_type
Pineal enzyme regulation
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 253–264
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Phosphorylation, binding and enzyme-kinetic experiments · source_derived_draft · unverified_draft
### melatonin-aanat-single-binding Binding through Ser205 alone raised substrate Km to about 1200 micromolar in the ovine AANAT system. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same partner can have a different effect when the binding arrangement changes. organism: Sheep AANAT and 14-3-3 biochemical systems tissue_or_cell_type: Pineal enzyme regulation experimental_model: Phosphorylation, binding and enzyme-kinetic experiments limitations: Residue numbering and kinetic states refer to ovine enzyme. Two-site and one-site binding have different effects; not a universal activation rule for all phosphorylation. exposure: Thr31 and Ser205 phosphorylation; night versus light exposure evidence_span: {"source_cache": "artifacts/melatonin-research/15644438.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d8be6407faaad634dbbe950dcc278cfcbe12aa24c08caafcc0ff740e8945b552", "start_char": 0, "end_char": 1693, "text_sha256": "d8be6407faaad634dbbe950dcc278cfcbe12aa24c08caafcc0ff740e8945b552"} [melatonin-p15644438] Melatonin synthesis: 14-3-3-dependent activation and inhibition of arylalkylamine N-acetyltransferase mediated by phosphoserine-205. (2005). https://pubmed.ncbi.nlm.nih.gov/15644438/ DOI: 10.1073/pnas.0406871102
Complete structured claim and evidence
Nighttime light exposure decreased ovine AANAT Thr31 phosphorylation.
Light exposure during biological night → Sheep AANAT Thr31 phosphorylation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/15644438.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d8be6407faaad634dbbe950dcc278cfcbe12aa24c08caafcc0ff740e8945b552", "start_char": 0, "end_char": 1693, "text_sha256": "d8be6407faaad634dbbe950dcc278cfcbe12aa24c08caafcc0ff740e8945b552"}
experimental_model
Phosphorylation, binding and enzyme-kinetic experiments
exposure
Thr31 and Ser205 phosphorylation; night versus light exposure
limitations
Residue numbering and kinetic states refer to ovine enzyme. Two-site and one-site binding have different effects; not a universal activation rule for all phosphorylation.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Sheep AANAT and 14-3-3 biochemical systems
plain_language
Light can alter the enzyme-regulation state, not merely the amount of starting amino acid.
primary_references
[melatonin-p15644438] Melatonin synthesis: 14-3-3-dependent activation and inhibition of arylalkylamine N-acetyltransferase mediated by phosphoserine-205. (2005). https://pubmed.ncbi.nlm.nih.gov/15644438/ DOI: 10.1073/pnas.0406871102
tissue_or_cell_type
Pineal enzyme regulation
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 266–277
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Phosphorylation, binding and enzyme-kinetic experiments · source_derived_draft · unverified_draft
### melatonin-night-light-t31 Nighttime light exposure decreased ovine AANAT Thr31 phosphorylation. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Light can alter the enzyme-regulation state, not merely the amount of starting amino acid. organism: Sheep AANAT and 14-3-3 biochemical systems tissue_or_cell_type: Pineal enzyme regulation experimental_model: Phosphorylation, binding and enzyme-kinetic experiments limitations: Residue numbering and kinetic states refer to ovine enzyme. Two-site and one-site binding have different effects; not a universal activation rule for all phosphorylation. exposure: Thr31 and Ser205 phosphorylation; night versus light exposure evidence_span: {"source_cache": "artifacts/melatonin-research/15644438.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d8be6407faaad634dbbe950dcc278cfcbe12aa24c08caafcc0ff740e8945b552", "start_char": 0, "end_char": 1693, "text_sha256": "d8be6407faaad634dbbe950dcc278cfcbe12aa24c08caafcc0ff740e8945b552"} [melatonin-p15644438] Melatonin synthesis: 14-3-3-dependent activation and inhibition of arylalkylamine N-acetyltransferase mediated by phosphoserine-205. (2005). https://pubmed.ncbi.nlm.nih.gov/15644438/ DOI: 10.1073/pnas.0406871102
Complete structured claim and evidence
Nighttime light exposure decreased ovine AANAT Ser205 phosphorylation.
Light exposure during biological night → Sheep AANAT Ser205 phosphorylation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/15644438.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d8be6407faaad634dbbe950dcc278cfcbe12aa24c08caafcc0ff740e8945b552", "start_char": 0, "end_char": 1693, "text_sha256": "d8be6407faaad634dbbe950dcc278cfcbe12aa24c08caafcc0ff740e8945b552"}
experimental_model
Phosphorylation, binding and enzyme-kinetic experiments
exposure
Thr31 and Ser205 phosphorylation; night versus light exposure
limitations
Residue numbering and kinetic states refer to ovine enzyme. Two-site and one-site binding have different effects; not a universal activation rule for all phosphorylation.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Sheep AANAT and 14-3-3 biochemical systems
plain_language
Light can alter the enzyme-regulation state, not merely the amount of starting amino acid.
primary_references
[melatonin-p15644438] Melatonin synthesis: 14-3-3-dependent activation and inhibition of arylalkylamine N-acetyltransferase mediated by phosphoserine-205. (2005). https://pubmed.ncbi.nlm.nih.gov/15644438/ DOI: 10.1073/pnas.0406871102
tissue_or_cell_type
Pineal enzyme regulation
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 279–290
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Phosphorylation, binding and enzyme-kinetic experiments · source_derived_draft · unverified_draft
### melatonin-night-light-s205 Nighttime light exposure decreased ovine AANAT Ser205 phosphorylation. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Light can alter the enzyme-regulation state, not merely the amount of starting amino acid. organism: Sheep AANAT and 14-3-3 biochemical systems tissue_or_cell_type: Pineal enzyme regulation experimental_model: Phosphorylation, binding and enzyme-kinetic experiments limitations: Residue numbering and kinetic states refer to ovine enzyme. Two-site and one-site binding have different effects; not a universal activation rule for all phosphorylation. exposure: Thr31 and Ser205 phosphorylation; night versus light exposure evidence_span: {"source_cache": "artifacts/melatonin-research/15644438.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d8be6407faaad634dbbe950dcc278cfcbe12aa24c08caafcc0ff740e8945b552", "start_char": 0, "end_char": 1693, "text_sha256": "d8be6407faaad634dbbe950dcc278cfcbe12aa24c08caafcc0ff740e8945b552"} [melatonin-p15644438] Melatonin synthesis: 14-3-3-dependent activation and inhibition of arylalkylamine N-acetyltransferase mediated by phosphoserine-205. (2005). https://pubmed.ncbi.nlm.nih.gov/15644438/ DOI: 10.1073/pnas.0406871102
Complete structured claim and evidence
The tested retinoic-acid stereoisomer increased HIOMT mRNA and enzyme activity in Y79 cells.
All-trans-retinoic acid → Human ASMT mRNA abundance source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/8752109.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d7a80b7b4106efe1c01849e3842ba968626d3a8c5401a5097b617da4d96ce83b", "start_char": 0, "end_char": 650, "text_sha256": "d7a80b7b4106efe1c01849e3842ba968626d3a8c5401a5097b617da4d96ce83b"}
experimental_model
Retinoid treatment and enzyme/mRNA measurements
exposure
All-trans, 13-cis and 9-cis retinoic acid exposure
limitations
Tumor-derived cell model. Retinoic acid is not synonymous with dietary vitamin A; no clinical vitamin A repletion or insomnia-treatment inference.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human Y79 retinoblastoma-derived cells
plain_language
A vitamin-A-derived signaling molecule can regulate this synthetic enzyme in a specific cell model.
primary_references
[melatonin-p8752109] Retinoic acid increases hydroxyindole-O-methyltransferase activity and mRNA in human Y-79 retinoblastoma cells. (1996). https://pubmed.ncbi.nlm.nih.gov/8752109/ DOI: 10.1046/j.1471-4159.1996.67031032.x
tissue_or_cell_type
ASMT/HIOMT expression
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 292–303
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Retinoid treatment and enzyme/mRNA measurements · source_derived_draft · unverified_draft
### melatonin-retinoid-atra The tested retinoic-acid stereoisomer increased HIOMT mRNA and enzyme activity in Y79 cells. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A vitamin-A-derived signaling molecule can regulate this synthetic enzyme in a specific cell model. organism: Human Y79 retinoblastoma-derived cells tissue_or_cell_type: ASMT/HIOMT expression experimental_model: Retinoid treatment and enzyme/mRNA measurements limitations: Tumor-derived cell model. Retinoic acid is not synonymous with dietary vitamin A; no clinical vitamin A repletion or insomnia-treatment inference. exposure: All-trans, 13-cis and 9-cis retinoic acid exposure evidence_span: {"source_cache": "artifacts/melatonin-research/8752109.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d7a80b7b4106efe1c01849e3842ba968626d3a8c5401a5097b617da4d96ce83b", "start_char": 0, "end_char": 650, "text_sha256": "d7a80b7b4106efe1c01849e3842ba968626d3a8c5401a5097b617da4d96ce83b"} [melatonin-p8752109] Retinoic acid increases hydroxyindole-O-methyltransferase activity and mRNA in human Y-79 retinoblastoma cells. (1996). https://pubmed.ncbi.nlm.nih.gov/8752109/ DOI: 10.1046/j.1471-4159.1996.67031032.x
Complete structured claim and evidence
The tested retinoic-acid stereoisomer increased HIOMT mRNA and enzyme activity in Y79 cells.
13-cis-Retinoic acid / isotretinoin → Human ASMT mRNA abundance source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/8752109.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d7a80b7b4106efe1c01849e3842ba968626d3a8c5401a5097b617da4d96ce83b", "start_char": 0, "end_char": 650, "text_sha256": "d7a80b7b4106efe1c01849e3842ba968626d3a8c5401a5097b617da4d96ce83b"}
experimental_model
Retinoid treatment and enzyme/mRNA measurements
exposure
All-trans, 13-cis and 9-cis retinoic acid exposure
limitations
Tumor-derived cell model. Retinoic acid is not synonymous with dietary vitamin A; no clinical vitamin A repletion or insomnia-treatment inference.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human Y79 retinoblastoma-derived cells
plain_language
A vitamin-A-derived signaling molecule can regulate this synthetic enzyme in a specific cell model.
primary_references
[melatonin-p8752109] Retinoic acid increases hydroxyindole-O-methyltransferase activity and mRNA in human Y-79 retinoblastoma cells. (1996). https://pubmed.ncbi.nlm.nih.gov/8752109/ DOI: 10.1046/j.1471-4159.1996.67031032.x
tissue_or_cell_type
ASMT/HIOMT expression
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 305–316
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Retinoid treatment and enzyme/mRNA measurements · source_derived_draft · unverified_draft
### melatonin-retinoid-13cis The tested retinoic-acid stereoisomer increased HIOMT mRNA and enzyme activity in Y79 cells. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A vitamin-A-derived signaling molecule can regulate this synthetic enzyme in a specific cell model. organism: Human Y79 retinoblastoma-derived cells tissue_or_cell_type: ASMT/HIOMT expression experimental_model: Retinoid treatment and enzyme/mRNA measurements limitations: Tumor-derived cell model. Retinoic acid is not synonymous with dietary vitamin A; no clinical vitamin A repletion or insomnia-treatment inference. exposure: All-trans, 13-cis and 9-cis retinoic acid exposure evidence_span: {"source_cache": "artifacts/melatonin-research/8752109.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d7a80b7b4106efe1c01849e3842ba968626d3a8c5401a5097b617da4d96ce83b", "start_char": 0, "end_char": 650, "text_sha256": "d7a80b7b4106efe1c01849e3842ba968626d3a8c5401a5097b617da4d96ce83b"} [melatonin-p8752109] Retinoic acid increases hydroxyindole-O-methyltransferase activity and mRNA in human Y-79 retinoblastoma cells. (1996). https://pubmed.ncbi.nlm.nih.gov/8752109/ DOI: 10.1046/j.1471-4159.1996.67031032.x
Complete structured claim and evidence
The tested retinoic-acid stereoisomer increased HIOMT mRNA and enzyme activity in Y79 cells.
9-cis-retinoic acid → Human ASMT mRNA abundance source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/8752109.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d7a80b7b4106efe1c01849e3842ba968626d3a8c5401a5097b617da4d96ce83b", "start_char": 0, "end_char": 650, "text_sha256": "d7a80b7b4106efe1c01849e3842ba968626d3a8c5401a5097b617da4d96ce83b"}
experimental_model
Retinoid treatment and enzyme/mRNA measurements
exposure
All-trans, 13-cis and 9-cis retinoic acid exposure
limitations
Tumor-derived cell model. Retinoic acid is not synonymous with dietary vitamin A; no clinical vitamin A repletion or insomnia-treatment inference.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human Y79 retinoblastoma-derived cells
plain_language
A vitamin-A-derived signaling molecule can regulate this synthetic enzyme in a specific cell model.
primary_references
[melatonin-p8752109] Retinoic acid increases hydroxyindole-O-methyltransferase activity and mRNA in human Y-79 retinoblastoma cells. (1996). https://pubmed.ncbi.nlm.nih.gov/8752109/ DOI: 10.1046/j.1471-4159.1996.67031032.x
tissue_or_cell_type
ASMT/HIOMT expression
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 318–329
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Retinoid treatment and enzyme/mRNA measurements · source_derived_draft · unverified_draft
### melatonin-retinoid-9cis The tested retinoic-acid stereoisomer increased HIOMT mRNA and enzyme activity in Y79 cells. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A vitamin-A-derived signaling molecule can regulate this synthetic enzyme in a specific cell model. organism: Human Y79 retinoblastoma-derived cells tissue_or_cell_type: ASMT/HIOMT expression experimental_model: Retinoid treatment and enzyme/mRNA measurements limitations: Tumor-derived cell model. Retinoic acid is not synonymous with dietary vitamin A; no clinical vitamin A repletion or insomnia-treatment inference. exposure: All-trans, 13-cis and 9-cis retinoic acid exposure evidence_span: {"source_cache": "artifacts/melatonin-research/8752109.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d7a80b7b4106efe1c01849e3842ba968626d3a8c5401a5097b617da4d96ce83b", "start_char": 0, "end_char": 650, "text_sha256": "d7a80b7b4106efe1c01849e3842ba968626d3a8c5401a5097b617da4d96ce83b"} [melatonin-p8752109] Retinoic acid increases hydroxyindole-O-methyltransferase activity and mRNA in human Y-79 retinoblastoma cells. (1996). https://pubmed.ncbi.nlm.nih.gov/8752109/ DOI: 10.1046/j.1471-4159.1996.67031032.x
Complete structured claim and evidence
Restoring HIOMT298 in A549 cells restored 5-methoxytryptophan production.
Human HIOMT298 / ASMT 298-amino-acid splice isoform → 5-Methoxytryptophan / 5-MTP source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/29794137.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "051e28814382bea96e610c4cc406e7bc1d4d705d245b43dea0bba61050ae341e", "start_char": 0, "end_char": 1575, "text_sha256": "051e28814382bea96e610c4cc406e7bc1d4d705d245b43dea0bba61050ae341e"}
experimental_model
Isoform expression, transfection and metabolic measurements
exposure
HIOMT298 expression versus pineal HIOMT345
limitations
The 298-aa isoform was studied for 5-MTP production. Do not assign its anti-tumor findings to melatonin or assume all ASMT isoforms have identical products.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human fibroblasts, A549 cancer cells and mouse xenografts
plain_language
An alternatively spliced form connects to a different tryptophan product.
primary_references
[melatonin-p29794137] Restoration of hydroxyindole O-methyltransferase levels in human cancer cells induces a tryptophan-metabolic switch and attenuates cancer progression. (2018). https://pubmed.ncbi.nlm.nih.gov/29794137/ DOI: 10.1074/jbc.ra117.000597
tissue_or_cell_type
Alternative tryptophan metabolism
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 331–342
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isoform expression, transfection and metabolic measurements · source_derived_draft · unverified_draft
### melatonin-asmt-isoform-5mtp Restoring HIOMT298 in A549 cells restored 5-methoxytryptophan production. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: An alternatively spliced form connects to a different tryptophan product. organism: Human fibroblasts, A549 cancer cells and mouse xenografts tissue_or_cell_type: Alternative tryptophan metabolism experimental_model: Isoform expression, transfection and metabolic measurements limitations: The 298-aa isoform was studied for 5-MTP production. Do not assign its anti-tumor findings to melatonin or assume all ASMT isoforms have identical products. exposure: HIOMT298 expression versus pineal HIOMT345 evidence_span: {"source_cache": "artifacts/melatonin-research/29794137.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "051e28814382bea96e610c4cc406e7bc1d4d705d245b43dea0bba61050ae341e", "start_char": 0, "end_char": 1575, "text_sha256": "051e28814382bea96e610c4cc406e7bc1d4d705d245b43dea0bba61050ae341e"} [melatonin-p29794137] Restoration of hydroxyindole O-methyltransferase levels in human cancer cells induces a tryptophan-metabolic switch and attenuates cancer progression. (2018). https://pubmed.ncbi.nlm.nih.gov/29794137/ DOI: 10.1074/jbc.ra117.000597
Complete structured claim and evidence
HIOMT298 expression shifted the measured tryptophan metabolism from serotonin toward 5-MTP production.
Human HIOMT298 / ASMT 298-amino-acid splice isoform → Serotonin source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/29794137.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "051e28814382bea96e610c4cc406e7bc1d4d705d245b43dea0bba61050ae341e", "start_char": 0, "end_char": 1575, "text_sha256": "051e28814382bea96e610c4cc406e7bc1d4d705d245b43dea0bba61050ae341e"}
experimental_model
Isoform expression, transfection and metabolic measurements
exposure
HIOMT298 expression versus pineal HIOMT345
limitations
The 298-aa isoform was studied for 5-MTP production. Do not assign its anti-tumor findings to melatonin or assume all ASMT isoforms have identical products.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human fibroblasts, A549 cancer cells and mouse xenografts
plain_language
A shared enzyme name does not mean every isoform feeds the melatonin branch.
primary_references
[melatonin-p29794137] Restoration of hydroxyindole O-methyltransferase levels in human cancer cells induces a tryptophan-metabolic switch and attenuates cancer progression. (2018). https://pubmed.ncbi.nlm.nih.gov/29794137/ DOI: 10.1074/jbc.ra117.000597
tissue_or_cell_type
Alternative tryptophan metabolism
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 344–355
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isoform expression, transfection and metabolic measurements · source_derived_draft · unverified_draft
### melatonin-asmt-isoform-serotonin-switch HIOMT298 expression shifted the measured tryptophan metabolism from serotonin toward 5-MTP production. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A shared enzyme name does not mean every isoform feeds the melatonin branch. organism: Human fibroblasts, A549 cancer cells and mouse xenografts tissue_or_cell_type: Alternative tryptophan metabolism experimental_model: Isoform expression, transfection and metabolic measurements limitations: The 298-aa isoform was studied for 5-MTP production. Do not assign its anti-tumor findings to melatonin or assume all ASMT isoforms have identical products. exposure: HIOMT298 expression versus pineal HIOMT345 evidence_span: {"source_cache": "artifacts/melatonin-research/29794137.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "051e28814382bea96e610c4cc406e7bc1d4d705d245b43dea0bba61050ae341e", "start_char": 0, "end_char": 1575, "text_sha256": "051e28814382bea96e610c4cc406e7bc1d4d705d245b43dea0bba61050ae341e"} [melatonin-p29794137] Restoration of hydroxyindole O-methyltransferase levels in human cancer cells induces a tryptophan-metabolic switch and attenuates cancer progression. (2018). https://pubmed.ncbi.nlm.nih.gov/29794137/ DOI: 10.1074/jbc.ra117.000597
Complete structured claim and evidence
Expressed human MT1 showed high-affinity iodinated-melatonin binding.
Human melatonin receptor 1A / MT1 / MTNR1A → MT1 high-affinity agonist binding source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/7946354.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4eed36768519d1c02ed67434eb3dc08eb561de445d3532113e7eaeb2827e021f", "start_char": 0, "end_char": 1054, "text_sha256": "4eed36768519d1c02ed67434eb3dc08eb561de445d3532113e7eaeb2827e021f"}
experimental_model
Receptor cloning, radioligand binding and functional expression
exposure
Heterologous COS-7 binding and NIH3T3 functional assays
limitations
Species differ across experiments. High-affinity radioligand binding is separated from the sheep functional assay.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human and sheep MT1 in cells; functional cyclase assay used sheep receptor
plain_language
MT1 has its own molecular identity; it is not interchangeable with MT2.
primary_references
[melatonin-p7946354] Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses. (1994). https://pubmed.ncbi.nlm.nih.gov/7946354/ DOI: 10.1016/0896-6273(94)90055-8
tissue_or_cell_type
Melatonin receptor identification
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 357–368
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Receptor cloning, radioligand binding and functional expression · source_derived_draft · unverified_draft
### melatonin-mt1-human-binding Expressed human MT1 showed high-affinity iodinated-melatonin binding. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: MT1 has its own molecular identity; it is not interchangeable with MT2. organism: Human and sheep MT1 in cells; functional cyclase assay used sheep receptor tissue_or_cell_type: Melatonin receptor identification experimental_model: Receptor cloning, radioligand binding and functional expression limitations: Species differ across experiments. High-affinity radioligand binding is separated from the sheep functional assay. exposure: Heterologous COS-7 binding and NIH3T3 functional assays evidence_span: {"source_cache": "artifacts/melatonin-research/7946354.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4eed36768519d1c02ed67434eb3dc08eb561de445d3532113e7eaeb2827e021f", "start_char": 0, "end_char": 1054, "text_sha256": "4eed36768519d1c02ed67434eb3dc08eb561de445d3532113e7eaeb2827e021f"} [melatonin-p7946354] Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses. (1994). https://pubmed.ncbi.nlm.nih.gov/7946354/ DOI: 10.1016/0896-6273(94)90055-8
Complete structured claim and evidence
The sheep MT1 receptor inhibited adenylyl cyclase through a pertussis-toxin-sensitive mechanism in transfected cells.
Sheep melatonin MT1 receptor / MTNR1A → Adenylyl cyclase catalytic activity, model specified source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/7946354.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4eed36768519d1c02ed67434eb3dc08eb561de445d3532113e7eaeb2827e021f", "start_char": 0, "end_char": 1054, "text_sha256": "4eed36768519d1c02ed67434eb3dc08eb561de445d3532113e7eaeb2827e021f"}
experimental_model
Receptor cloning, radioligand binding and functional expression
exposure
Heterologous COS-7 binding and NIH3T3 functional assays
limitations
Species differ across experiments. High-affinity radioligand binding is separated from the sheep functional assay.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human and sheep MT1 in cells; functional cyclase assay used sheep receptor
plain_language
The receptor connects to an inhibitory signaling system.
primary_references
[melatonin-p7946354] Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses. (1994). https://pubmed.ncbi.nlm.nih.gov/7946354/ DOI: 10.1016/0896-6273(94)90055-8
tissue_or_cell_type
Melatonin receptor identification
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 370–381
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Receptor cloning, radioligand binding and functional expression · source_derived_draft · unverified_draft
### melatonin-mt1-sheep-cyclase The sheep MT1 receptor inhibited adenylyl cyclase through a pertussis-toxin-sensitive mechanism in transfected cells. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The receptor connects to an inhibitory signaling system. organism: Human and sheep MT1 in cells; functional cyclase assay used sheep receptor tissue_or_cell_type: Melatonin receptor identification experimental_model: Receptor cloning, radioligand binding and functional expression limitations: Species differ across experiments. High-affinity radioligand binding is separated from the sheep functional assay. exposure: Heterologous COS-7 binding and NIH3T3 functional assays evidence_span: {"source_cache": "artifacts/melatonin-research/7946354.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4eed36768519d1c02ed67434eb3dc08eb561de445d3532113e7eaeb2827e021f", "start_char": 0, "end_char": 1054, "text_sha256": "4eed36768519d1c02ed67434eb3dc08eb561de445d3532113e7eaeb2827e021f"} [melatonin-p7946354] Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses. (1994). https://pubmed.ncbi.nlm.nih.gov/7946354/ DOI: 10.1016/0896-6273(94)90055-8
Complete structured claim and evidence
Human MT2 expression supported melatonin-receptor-mediated inhibition of adenylyl cyclase.
Human melatonin receptor 1B / MT2 / MTNR1B → Adenylyl cyclase catalytic activity, model specified source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/7568007.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1873168e5fa570a1dec0bc112045a3bcffda494e92b52f3349c8b1afebbb505f", "start_char": 0, "end_char": 1269, "text_sha256": "1873168e5fa570a1dec0bc112045a3bcffda494e92b52f3349c8b1afebbb505f"}
experimental_model
Human receptor cloning and functional expression
exposure
Radioligand binding and adenylyl cyclase measurements
limitations
Receptor overexpression system; no claim a given oral dose produces the same occupancy in every human tissue.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human MT2 expressed in COS-1 and NIH3T3 cells
plain_language
The second receptor can also reduce the signal that generates cAMP.
primary_references
[melatonin-p7568007] Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor. (1995). https://pubmed.ncbi.nlm.nih.gov/7568007/ DOI: 10.1073/pnas.92.19.8734
tissue_or_cell_type
Second melatonin receptor subtype
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 383–394
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human receptor cloning and functional expression · source_derived_draft · unverified_draft
### melatonin-mt2-cyclase Human MT2 expression supported melatonin-receptor-mediated inhibition of adenylyl cyclase. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The second receptor can also reduce the signal that generates cAMP. organism: Human MT2 expressed in COS-1 and NIH3T3 cells tissue_or_cell_type: Second melatonin receptor subtype experimental_model: Human receptor cloning and functional expression limitations: Receptor overexpression system; no claim a given oral dose produces the same occupancy in every human tissue. exposure: Radioligand binding and adenylyl cyclase measurements evidence_span: {"source_cache": "artifacts/melatonin-research/7568007.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1873168e5fa570a1dec0bc112045a3bcffda494e92b52f3349c8b1afebbb505f", "start_char": 0, "end_char": 1269, "text_sha256": "1873168e5fa570a1dec0bc112045a3bcffda494e92b52f3349c8b1afebbb505f"} [melatonin-p7568007] Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor. (1995). https://pubmed.ncbi.nlm.nih.gov/7568007/ DOI: 10.1073/pnas.92.19.8734
Complete structured claim and evidence
Agonist-bound human MT1 was structurally resolved in a Gi signaling complex.
Human melatonin receptor 1A / MT1 / MTNR1A → Inhibitory heterotrimeric G protein / Gi, assay-specified subunits source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/35075127.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "08af0c72228d7c72723f238e83eeabef1ca9196833c7e385ed0c75577c97024b", "start_char": 0, "end_char": 1239, "text_sha256": "08af0c72228d7c72723f238e83eeabef1ca9196833c7e385ed0c75577c97024b"}
experimental_model
Cryo-EM structures and functional receptor assays
exposure
2-iodomelatonin/ramelteon for MT1; ramelteon for MT2
limitations
Structures used agonists, not native melatonin in every complex. Receptor structure does not itself prove clinical effects or subtype-selective supplement actions.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human MT1 and MT2 signaling complexes
plain_language
The receptor and its signaling partner are separate searchable components.
primary_references
[melatonin-p35075127] Structural basis of the ligand binding and signaling mechanism of melatonin receptors. (2022). https://pubmed.ncbi.nlm.nih.gov/35075127/ DOI: 10.1038/s41467-022-28111-3
tissue_or_cell_type
Agonist-bound receptor-Gi coupling
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 396–407
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM structures and functional receptor assays · source_derived_draft · unverified_draft
### melatonin-mt1-gi-structure Agonist-bound human MT1 was structurally resolved in a Gi signaling complex. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The receptor and its signaling partner are separate searchable components. organism: Human MT1 and MT2 signaling complexes tissue_or_cell_type: Agonist-bound receptor-Gi coupling experimental_model: Cryo-EM structures and functional receptor assays limitations: Structures used agonists, not native melatonin in every complex. Receptor structure does not itself prove clinical effects or subtype-selective supplement actions. exposure: 2-iodomelatonin/ramelteon for MT1; ramelteon for MT2 evidence_span: {"source_cache": "artifacts/melatonin-research/35075127.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "08af0c72228d7c72723f238e83eeabef1ca9196833c7e385ed0c75577c97024b", "start_char": 0, "end_char": 1239, "text_sha256": "08af0c72228d7c72723f238e83eeabef1ca9196833c7e385ed0c75577c97024b"} [melatonin-p35075127] Structural basis of the ligand binding and signaling mechanism of melatonin receptors. (2022). https://pubmed.ncbi.nlm.nih.gov/35075127/ DOI: 10.1038/s41467-022-28111-3
Complete structured claim and evidence
Agonist-bound human MT2 was structurally resolved in a Gi signaling complex.
Human melatonin receptor 1B / MT2 / MTNR1B → Inhibitory heterotrimeric G protein / Gi, assay-specified subunits source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/35075127.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "08af0c72228d7c72723f238e83eeabef1ca9196833c7e385ed0c75577c97024b", "start_char": 0, "end_char": 1239, "text_sha256": "08af0c72228d7c72723f238e83eeabef1ca9196833c7e385ed0c75577c97024b"}
experimental_model
Cryo-EM structures and functional receptor assays
exposure
2-iodomelatonin/ramelteon for MT1; ramelteon for MT2
limitations
Structures used agonists, not native melatonin in every complex. Receptor structure does not itself prove clinical effects or subtype-selective supplement actions.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human MT1 and MT2 signaling complexes
plain_language
The receptor and its signaling partner are separate searchable components.
primary_references
[melatonin-p35075127] Structural basis of the ligand binding and signaling mechanism of melatonin receptors. (2022). https://pubmed.ncbi.nlm.nih.gov/35075127/ DOI: 10.1038/s41467-022-28111-3
tissue_or_cell_type
Agonist-bound receptor-Gi coupling
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 409–420
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM structures and functional receptor assays · source_derived_draft · unverified_draft
### melatonin-mt2-gi-structure Agonist-bound human MT2 was structurally resolved in a Gi signaling complex. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The receptor and its signaling partner are separate searchable components. organism: Human MT1 and MT2 signaling complexes tissue_or_cell_type: Agonist-bound receptor-Gi coupling experimental_model: Cryo-EM structures and functional receptor assays limitations: Structures used agonists, not native melatonin in every complex. Receptor structure does not itself prove clinical effects or subtype-selective supplement actions. exposure: 2-iodomelatonin/ramelteon for MT1; ramelteon for MT2 evidence_span: {"source_cache": "artifacts/melatonin-research/35075127.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "08af0c72228d7c72723f238e83eeabef1ca9196833c7e385ed0c75577c97024b", "start_char": 0, "end_char": 1239, "text_sha256": "08af0c72228d7c72723f238e83eeabef1ca9196833c7e385ed0c75577c97024b"} [melatonin-p35075127] Structural basis of the ligand binding and signaling mechanism of melatonin receptors. (2022). https://pubmed.ncbi.nlm.nih.gov/35075127/ DOI: 10.1038/s41467-022-28111-3
Complete structured claim and evidence
GPR50 formed heterodimers with MT1 in the tested cell systems.
Human melatonin-related orphan receptor / GPR50 → Human melatonin receptor 1A / MT1 / MTNR1A source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/16778767.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19c9ae903fb7926bb21cc3bda0a610612b16a899f850b8e787581b72ac434135", "start_char": 0, "end_char": 1204, "text_sha256": "19c9ae903fb7926bb21cc3bda0a610612b16a899f850b8e787581b72ac434135"}
experimental_model
Biochemical and biophysical receptor heteromer experiments
exposure
Full-length versus C-terminally truncated GPR50
limitations
Cell-system regulation; does not establish that a person with poor sleep has excess GPR50 or that more melatonin overcomes it.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human receptors in cultured cells
plain_language
A receptor partner can alter access to a signaling route.
primary_references
[melatonin-p16778767] The orphan GPR50 receptor specifically inhibits MT1 melatonin receptor function through heterodimerization. (2006). https://pubmed.ncbi.nlm.nih.gov/16778767/ DOI: 10.1038/sj.emboj.7601193
tissue_or_cell_type
GPR50-MT1/MT2 interactions
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 422–433
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemical and biophysical receptor heteromer experiments · source_derived_draft · unverified_draft
### melatonin-gpr50-mt1-heteromer GPR50 formed heterodimers with MT1 in the tested cell systems. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A receptor partner can alter access to a signaling route. organism: Human receptors in cultured cells tissue_or_cell_type: GPR50-MT1/MT2 interactions experimental_model: Biochemical and biophysical receptor heteromer experiments limitations: Cell-system regulation; does not establish that a person with poor sleep has excess GPR50 or that more melatonin overcomes it. exposure: Full-length versus C-terminally truncated GPR50 evidence_span: {"source_cache": "artifacts/melatonin-research/16778767.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19c9ae903fb7926bb21cc3bda0a610612b16a899f850b8e787581b72ac434135", "start_char": 0, "end_char": 1204, "text_sha256": "19c9ae903fb7926bb21cc3bda0a610612b16a899f850b8e787581b72ac434135"} [melatonin-p16778767] The orphan GPR50 receptor specifically inhibits MT1 melatonin receptor function through heterodimerization. (2006). https://pubmed.ncbi.nlm.nih.gov/16778767/ DOI: 10.1038/sj.emboj.7601193
Complete structured claim and evidence
GPR50 formed heterodimers with MT2 in the same study.
Human melatonin-related orphan receptor / GPR50 → Human melatonin receptor 1B / MT2 / MTNR1B source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/16778767.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19c9ae903fb7926bb21cc3bda0a610612b16a899f850b8e787581b72ac434135", "start_char": 0, "end_char": 1204, "text_sha256": "19c9ae903fb7926bb21cc3bda0a610612b16a899f850b8e787581b72ac434135"}
experimental_model
Biochemical and biophysical receptor heteromer experiments
exposure
Full-length versus C-terminally truncated GPR50
limitations
Cell-system regulation; does not establish that a person with poor sleep has excess GPR50 or that more melatonin overcomes it.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human receptors in cultured cells
plain_language
Physical partnership alone does not establish functional inhibition.
primary_references
[melatonin-p16778767] The orphan GPR50 receptor specifically inhibits MT1 melatonin receptor function through heterodimerization. (2006). https://pubmed.ncbi.nlm.nih.gov/16778767/ DOI: 10.1038/sj.emboj.7601193
tissue_or_cell_type
GPR50-MT1/MT2 interactions
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 435–446
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemical and biophysical receptor heteromer experiments · source_derived_draft · unverified_draft
### melatonin-gpr50-mt2-heteromer GPR50 formed heterodimers with MT2 in the same study. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Physical partnership alone does not establish functional inhibition. organism: Human receptors in cultured cells tissue_or_cell_type: GPR50-MT1/MT2 interactions experimental_model: Biochemical and biophysical receptor heteromer experiments limitations: Cell-system regulation; does not establish that a person with poor sleep has excess GPR50 or that more melatonin overcomes it. exposure: Full-length versus C-terminally truncated GPR50 evidence_span: {"source_cache": "artifacts/melatonin-research/16778767.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19c9ae903fb7926bb21cc3bda0a610612b16a899f850b8e787581b72ac434135", "start_char": 0, "end_char": 1204, "text_sha256": "19c9ae903fb7926bb21cc3bda0a610612b16a899f850b8e787581b72ac434135"} [melatonin-p16778767] The orphan GPR50 receptor specifically inhibits MT1 melatonin receptor function through heterodimerization. (2006). https://pubmed.ncbi.nlm.nih.gov/16778767/ DOI: 10.1038/sj.emboj.7601193
Complete structured claim and evidence
GPR50 abolished MT1 high-affinity agonist binding within the heterodimer.
Human melatonin-related orphan receptor / GPR50 → MT1 high-affinity agonist binding source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/melatonin-research/16778767.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19c9ae903fb7926bb21cc3bda0a610612b16a899f850b8e787581b72ac434135", "start_char": 0, "end_char": 1204, "text_sha256": "19c9ae903fb7926bb21cc3bda0a610612b16a899f850b8e787581b72ac434135"}
experimental_model
Biochemical and biophysical receptor heteromer experiments
exposure
Full-length versus C-terminally truncated GPR50
limitations
Cell-system regulation; does not establish that a person with poor sleep has excess GPR50 or that more melatonin overcomes it.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human receptors in cultured cells
plain_language
Available hormone and functional receptor machinery are different requirements.
primary_references
[melatonin-p16778767] The orphan GPR50 receptor specifically inhibits MT1 melatonin receptor function through heterodimerization. (2006). https://pubmed.ncbi.nlm.nih.gov/16778767/ DOI: 10.1038/sj.emboj.7601193
tissue_or_cell_type
GPR50-MT1/MT2 interactions
trigger_kind
machinery_impairment Imported condition classification; unverified.
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 448–459
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemical and biophysical receptor heteromer experiments · source_derived_draft · unverified_draft
### melatonin-gpr50-mt1-binding GPR50 abolished MT1 high-affinity agonist binding within the heterodimer. Condition category: machinery_impairment nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Available hormone and functional receptor machinery are different requirements. organism: Human receptors in cultured cells tissue_or_cell_type: GPR50-MT1/MT2 interactions experimental_model: Biochemical and biophysical receptor heteromer experiments limitations: Cell-system regulation; does not establish that a person with poor sleep has excess GPR50 or that more melatonin overcomes it. exposure: Full-length versus C-terminally truncated GPR50 evidence_span: {"source_cache": "artifacts/melatonin-research/16778767.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19c9ae903fb7926bb21cc3bda0a610612b16a899f850b8e787581b72ac434135", "start_char": 0, "end_char": 1204, "text_sha256": "19c9ae903fb7926bb21cc3bda0a610612b16a899f850b8e787581b72ac434135"} [melatonin-p16778767] The orphan GPR50 receptor specifically inhibits MT1 melatonin receptor function through heterodimerization. (2006). https://pubmed.ncbi.nlm.nih.gov/16778767/ DOI: 10.1038/sj.emboj.7601193
Complete structured claim and evidence
Association with GPR50 did not modify MT2 function in the experiment.
Human melatonin-related orphan receptor / GPR50 → MT2 agonist binding and signaling in heteromer experiments source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/16778767.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19c9ae903fb7926bb21cc3bda0a610612b16a899f850b8e787581b72ac434135", "start_char": 0, "end_char": 1204, "text_sha256": "19c9ae903fb7926bb21cc3bda0a610612b16a899f850b8e787581b72ac434135"}
experimental_model
Biochemical and biophysical receptor heteromer experiments
exposure
Full-length versus C-terminally truncated GPR50
limitations
Cell-system regulation; does not establish that a person with poor sleep has excess GPR50 or that more melatonin overcomes it.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human receptors in cultured cells
plain_language
The inhibition was receptor-subtype-specific.
primary_references
[melatonin-p16778767] The orphan GPR50 receptor specifically inhibits MT1 melatonin receptor function through heterodimerization. (2006). https://pubmed.ncbi.nlm.nih.gov/16778767/ DOI: 10.1038/sj.emboj.7601193
tissue_or_cell_type
GPR50-MT1/MT2 interactions
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 474–485
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemical and biophysical receptor heteromer experiments · source_derived_draft · unverified_draft
### melatonin-gpr50-mt2-null Association with GPR50 did not modify MT2 function in the experiment. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The inhibition was receptor-subtype-specific. organism: Human receptors in cultured cells tissue_or_cell_type: GPR50-MT1/MT2 interactions experimental_model: Biochemical and biophysical receptor heteromer experiments limitations: Cell-system regulation; does not establish that a person with poor sleep has excess GPR50 or that more melatonin overcomes it. exposure: Full-length versus C-terminally truncated GPR50 evidence_span: {"source_cache": "artifacts/melatonin-research/16778767.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19c9ae903fb7926bb21cc3bda0a610612b16a899f850b8e787581b72ac434135", "start_char": 0, "end_char": 1204, "text_sha256": "19c9ae903fb7926bb21cc3bda0a610612b16a899f850b8e787581b72ac434135"} [melatonin-p16778767] The orphan GPR50 receptor specifically inhibits MT1 melatonin receptor function through heterodimerization. (2006). https://pubmed.ncbi.nlm.nih.gov/16778767/ DOI: 10.1038/sj.emboj.7601193
Complete structured claim and evidence
Melatonin competitively inhibited NQO2 with respect to N-methyldihydronicotinamide, with Ki about 7.2 micromolar.
Melatonin → Human quinone reductase 2 / NQO2 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/18254726.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4b99428e7457cd7b67c75ef01b056609dcdf6d5d36cf1c0e933607e2be485c18", "start_char": 0, "end_char": 1724, "text_sha256": "4b99428e7457cd7b67c75ef01b056609dcdf6d5d36cf1c0e933607e2be485c18"}
experimental_model
Kinetics, calorimetry and crystal structures
exposure
Melatonin versus N-methyldihydronicotinamide or menadione in enzyme assays
limitations
NQO2 is the historically named MT3 binding site, not a third MT1/MT2-like GPCR. Micromolar inhibition does not establish the dominant effect at physiological blood concentrations.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Purified human NQO2/QR2
plain_language
A redox enzyme is a distinct target from the high-affinity membrane receptors.
primary_references
[melatonin-p18254726] Kinetic, thermodynamic and X-ray structural insights into the interaction of melatonin and analogues with quinone reductase 2. (2008). https://pubmed.ncbi.nlm.nih.gov/18254726/ DOI: 10.1042/bj20071373
tissue_or_cell_type
Cytosolic quinone-reductase active site
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 487–498
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Kinetics, calorimetry and crystal structures · source_derived_draft · unverified_draft
### melatonin-nqo2-cosubstrate-competition Melatonin competitively inhibited NQO2 with respect to N-methyldihydronicotinamide, with Ki about 7.2 micromolar. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A redox enzyme is a distinct target from the high-affinity membrane receptors. organism: Purified human NQO2/QR2 tissue_or_cell_type: Cytosolic quinone-reductase active site experimental_model: Kinetics, calorimetry and crystal structures limitations: NQO2 is the historically named MT3 binding site, not a third MT1/MT2-like GPCR. Micromolar inhibition does not establish the dominant effect at physiological blood concentrations. exposure: Melatonin versus N-methyldihydronicotinamide or menadione in enzyme assays evidence_span: {"source_cache": "artifacts/melatonin-research/18254726.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4b99428e7457cd7b67c75ef01b056609dcdf6d5d36cf1c0e933607e2be485c18", "start_char": 0, "end_char": 1724, "text_sha256": "4b99428e7457cd7b67c75ef01b056609dcdf6d5d36cf1c0e933607e2be485c18"} [melatonin-p18254726] Kinetic, thermodynamic and X-ray structural insights into the interaction of melatonin and analogues with quinone reductase 2. (2008). https://pubmed.ncbi.nlm.nih.gov/18254726/ DOI: 10.1042/bj20071373
Complete structured claim and evidence
Against menadione, melatonin showed uncompetitive NQO2 inhibition with Ki about 92 micromolar.
Melatonin → Human quinone reductase 2 / NQO2 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/18254726.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4b99428e7457cd7b67c75ef01b056609dcdf6d5d36cf1c0e933607e2be485c18", "start_char": 0, "end_char": 1724, "text_sha256": "4b99428e7457cd7b67c75ef01b056609dcdf6d5d36cf1c0e933607e2be485c18"}
experimental_model
Kinetics, calorimetry and crystal structures
exposure
Melatonin versus N-methyldihydronicotinamide or menadione in enzyme assays
limitations
NQO2 is the historically named MT3 binding site, not a third MT1/MT2-like GPCR. Micromolar inhibition does not establish the dominant effect at physiological blood concentrations.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Purified human NQO2/QR2
plain_language
The inhibition pattern depends on which reaction participant is varied.
primary_references
[melatonin-p18254726] Kinetic, thermodynamic and X-ray structural insights into the interaction of melatonin and analogues with quinone reductase 2. (2008). https://pubmed.ncbi.nlm.nih.gov/18254726/ DOI: 10.1042/bj20071373
tissue_or_cell_type
Cytosolic quinone-reductase active site
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 500–511
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Kinetics, calorimetry and crystal structures · source_derived_draft · unverified_draft
### melatonin-nqo2-menadione-kinetics Against menadione, melatonin showed uncompetitive NQO2 inhibition with Ki about 92 micromolar. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The inhibition pattern depends on which reaction participant is varied. organism: Purified human NQO2/QR2 tissue_or_cell_type: Cytosolic quinone-reductase active site experimental_model: Kinetics, calorimetry and crystal structures limitations: NQO2 is the historically named MT3 binding site, not a third MT1/MT2-like GPCR. Micromolar inhibition does not establish the dominant effect at physiological blood concentrations. exposure: Melatonin versus N-methyldihydronicotinamide or menadione in enzyme assays evidence_span: {"source_cache": "artifacts/melatonin-research/18254726.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4b99428e7457cd7b67c75ef01b056609dcdf6d5d36cf1c0e933607e2be485c18", "start_char": 0, "end_char": 1724, "text_sha256": "4b99428e7457cd7b67c75ef01b056609dcdf6d5d36cf1c0e933607e2be485c18"} [melatonin-p18254726] Kinetic, thermodynamic and X-ray structural insights into the interaction of melatonin and analogues with quinone reductase 2. (2008). https://pubmed.ncbi.nlm.nih.gov/18254726/ DOI: 10.1042/bj20071373
Complete structured claim and evidence
Oxidation of melatonin by singlet oxygen produced AFMK, verified by chemical and spectroscopic analyses.
Melatonin → N1-Acetyl-N2-formyl-5-methoxykynuramine / AFMK source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/12887657.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3d221b752cc6b59d719b21fd8ec2236bd75232ff34789f544a88e37bc270e8a5", "start_char": 0, "end_char": 1108, "text_sha256": "3d221b752cc6b59d719b21fd8ec2236bd75232ff34789f544a88e37bc270e8a5"}
experimental_model
Isotope-labeled chemical oxidation and product identification
exposure
Photosensitized or chemically generated singlet oxygen
limitations
Chemical scavenging/product formation is not proof that normal blood melatonin provides a clinically meaningful antioxidant flux or replaces vitamin C, E or selenium enzymes.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Cell-free chemical systems
plain_language
An antioxidant reaction changes melatonin into another molecule that is recorded separately.
primary_references
[melatonin-p12887657] Oxidation of melatonin by singlet molecular oxygen (O2(1deltag)) produces N1-acetyl-N2-formyl-5-methoxykynurenine. (2003). https://pubmed.ncbi.nlm.nih.gov/12887657/ DOI: 10.1034/j.1600-079x.2003.00066.x
tissue_or_cell_type
Melatonin oxidation chemistry
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 513–524
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isotope-labeled chemical oxidation and product identification · source_derived_draft · unverified_draft
### melatonin-singlet-oxygen-afmk Oxidation of melatonin by singlet oxygen produced AFMK, verified by chemical and spectroscopic analyses. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: An antioxidant reaction changes melatonin into another molecule that is recorded separately. organism: Cell-free chemical systems tissue_or_cell_type: Melatonin oxidation chemistry experimental_model: Isotope-labeled chemical oxidation and product identification limitations: Chemical scavenging/product formation is not proof that normal blood melatonin provides a clinically meaningful antioxidant flux or replaces vitamin C, E or selenium enzymes. exposure: Photosensitized or chemically generated singlet oxygen evidence_span: {"source_cache": "artifacts/melatonin-research/12887657.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3d221b752cc6b59d719b21fd8ec2236bd75232ff34789f544a88e37bc270e8a5", "start_char": 0, "end_char": 1108, "text_sha256": "3d221b752cc6b59d719b21fd8ec2236bd75232ff34789f544a88e37bc270e8a5"} [melatonin-p12887657] Oxidation of melatonin by singlet molecular oxygen (O2(1deltag)) produces N1-acetyl-N2-formyl-5-methoxykynurenine. (2003). https://pubmed.ncbi.nlm.nih.gov/12887657/ DOI: 10.1034/j.1600-079x.2003.00066.x
Complete structured claim and evidence
The study detected melatonin synthesis in the mitochondrial matrix of the tested neuronal system.
Melatonin synthesis in experimental neuronal mitochondria → Melatonin source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/28874589.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f20a034160c8e4d6022d0334d4ad9177591046f78a397ded41c90165b8847ade", "start_char": 0, "end_char": 1091, "text_sha256": "f20a034160c8e4d6022d0334d4ad9177591046f78a397ded41c90165b8847ade"}
experimental_model
Neuronal mitochondrial fractionation, signaling and injury experiments
exposure
Organelle synthesis and MT1 signaling; MT1 overexpression in mouse ischemia
limitations
Claims remain within the studied neuronal system; do not infer all human melatonin is mitochondrial or that oral supplements reproduce local synthesis. Transgene expression and endogenous protein identity are not merged.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Experimental neuronal systems and mice
plain_language
Local intracellular production is distinct from the circulating night signal.
primary_references
[melatonin-p28874589] Dual role of mitochondria in producing melatonin and driving GPCR signaling to block cytochrome c release. (2017). https://pubmed.ncbi.nlm.nih.gov/28874589/ DOI: 10.1073/pnas.1705768114
tissue_or_cell_type
Mitochondrial melatonin/MT1 pathway
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 526–537
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Neuronal mitochondrial fractionation, signaling and injury experiments · source_derived_draft · unverified_draft
### melatonin-mitochondrial-synthesis The study detected melatonin synthesis in the mitochondrial matrix of the tested neuronal system. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Local intracellular production is distinct from the circulating night signal. organism: Experimental neuronal systems and mice tissue_or_cell_type: Mitochondrial melatonin/MT1 pathway experimental_model: Neuronal mitochondrial fractionation, signaling and injury experiments limitations: Claims remain within the studied neuronal system; do not infer all human melatonin is mitochondrial or that oral supplements reproduce local synthesis. Transgene expression and endogenous protein identity are not merged. exposure: Organelle synthesis and MT1 signaling; MT1 overexpression in mouse ischemia evidence_span: {"source_cache": "artifacts/melatonin-research/28874589.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f20a034160c8e4d6022d0334d4ad9177591046f78a397ded41c90165b8847ade", "start_char": 0, "end_char": 1091, "text_sha256": "f20a034160c8e4d6022d0334d4ad9177591046f78a397ded41c90165b8847ade"} [melatonin-p28874589] Dual role of mitochondria in producing melatonin and driving GPCR signaling to block cytochrome c release. (2017). https://pubmed.ncbi.nlm.nih.gov/28874589/ DOI: 10.1073/pnas.1705768114
Complete structured claim and evidence
The reported mitochondrial MT1 pathway inhibited stress-associated cytochrome c release.
MT1-associated signaling in experimental neuronal mitochondria → Stress-associated mitochondrial cytochrome c release source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/28874589.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f20a034160c8e4d6022d0334d4ad9177591046f78a397ded41c90165b8847ade", "start_char": 0, "end_char": 1091, "text_sha256": "f20a034160c8e4d6022d0334d4ad9177591046f78a397ded41c90165b8847ade"}
experimental_model
Neuronal mitochondrial fractionation, signaling and injury experiments
exposure
Organelle synthesis and MT1 signaling; MT1 overexpression in mouse ischemia
limitations
Claims remain within the studied neuronal system; do not infer all human melatonin is mitochondrial or that oral supplements reproduce local synthesis. Transgene expression and endogenous protein identity are not merged.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Experimental neuronal systems and mice
plain_language
A locally studied receptor pathway connected to a mitochondrial injury step.
primary_references
[melatonin-p28874589] Dual role of mitochondria in producing melatonin and driving GPCR signaling to block cytochrome c release. (2017). https://pubmed.ncbi.nlm.nih.gov/28874589/ DOI: 10.1073/pnas.1705768114
tissue_or_cell_type
Mitochondrial melatonin/MT1 pathway
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 539–550
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Neuronal mitochondrial fractionation, signaling and injury experiments · source_derived_draft · unverified_draft
### melatonin-mitochondrial-cytochrome-c The reported mitochondrial MT1 pathway inhibited stress-associated cytochrome c release. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A locally studied receptor pathway connected to a mitochondrial injury step. organism: Experimental neuronal systems and mice tissue_or_cell_type: Mitochondrial melatonin/MT1 pathway experimental_model: Neuronal mitochondrial fractionation, signaling and injury experiments limitations: Claims remain within the studied neuronal system; do not infer all human melatonin is mitochondrial or that oral supplements reproduce local synthesis. Transgene expression and endogenous protein identity are not merged. exposure: Organelle synthesis and MT1 signaling; MT1 overexpression in mouse ischemia evidence_span: {"source_cache": "artifacts/melatonin-research/28874589.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f20a034160c8e4d6022d0334d4ad9177591046f78a397ded41c90165b8847ade", "start_char": 0, "end_char": 1091, "text_sha256": "f20a034160c8e4d6022d0334d4ad9177591046f78a397ded41c90165b8847ade"} [melatonin-p28874589] Dual role of mitochondria in producing melatonin and driving GPCR signaling to block cytochrome c release. (2017). https://pubmed.ncbi.nlm.nih.gov/28874589/ DOI: 10.1073/pnas.1705768114
Complete structured claim and evidence
The same experimental mitochondrial pathway reduced downstream caspase activation.
MT1-associated signaling in experimental neuronal mitochondria → Caspase activation in experimental neuronal injury source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/28874589.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f20a034160c8e4d6022d0334d4ad9177591046f78a397ded41c90165b8847ade", "start_char": 0, "end_char": 1091, "text_sha256": "f20a034160c8e4d6022d0334d4ad9177591046f78a397ded41c90165b8847ade"}
experimental_model
Neuronal mitochondrial fractionation, signaling and injury experiments
exposure
Organelle synthesis and MT1 signaling; MT1 overexpression in mouse ischemia
limitations
Claims remain within the studied neuronal system; do not infer all human melatonin is mitochondrial or that oral supplements reproduce local synthesis. Transgene expression and endogenous protein identity are not merged.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Experimental neuronal systems and mice
plain_language
This preclinical injury endpoint is not a demonstrated stroke treatment.
primary_references
[melatonin-p28874589] Dual role of mitochondria in producing melatonin and driving GPCR signaling to block cytochrome c release. (2017). https://pubmed.ncbi.nlm.nih.gov/28874589/ DOI: 10.1073/pnas.1705768114
tissue_or_cell_type
Mitochondrial melatonin/MT1 pathway
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 552–563
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Neuronal mitochondrial fractionation, signaling and injury experiments · source_derived_draft · unverified_draft
### melatonin-mitochondrial-caspase The same experimental mitochondrial pathway reduced downstream caspase activation. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This preclinical injury endpoint is not a demonstrated stroke treatment. organism: Experimental neuronal systems and mice tissue_or_cell_type: Mitochondrial melatonin/MT1 pathway experimental_model: Neuronal mitochondrial fractionation, signaling and injury experiments limitations: Claims remain within the studied neuronal system; do not infer all human melatonin is mitochondrial or that oral supplements reproduce local synthesis. Transgene expression and endogenous protein identity are not merged. exposure: Organelle synthesis and MT1 signaling; MT1 overexpression in mouse ischemia evidence_span: {"source_cache": "artifacts/melatonin-research/28874589.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f20a034160c8e4d6022d0334d4ad9177591046f78a397ded41c90165b8847ade", "start_char": 0, "end_char": 1091, "text_sha256": "f20a034160c8e4d6022d0334d4ad9177591046f78a397ded41c90165b8847ade"} [melatonin-p28874589] Dual role of mitochondria in producing melatonin and driving GPCR signaling to block cytochrome c release. (2017). https://pubmed.ncbi.nlm.nih.gov/28874589/ DOI: 10.1073/pnas.1705768114
Complete structured claim and evidence
Recombinant human CYP1A1 catalyzed melatonin 6-hydroxylation.
Human cytochrome P450 1A1 → 6-Hydroxymelatonin source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/15616152.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "482334074e10503323360f236e00b5b837c5b082a7cda4df000a23d491bff8a2", "start_char": 0, "end_char": 1733, "text_sha256": "482334074e10503323360f236e00b5b837c5b082a7cda4df000a23d491bff8a2"}
experimental_model
Recombinant P450 screen and mouse brain comparisons
exposure
Eleven P450 isozymes; NADPH-dependent 6-hydroxylation/O-demethylation
limitations
Catalytic capacity in an enzyme assay is not whole-body contribution. CYP1B1 is an extrahepatic route; human proteins are not substituted for mouse knockout identity.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human recombinant enzymes; separate mouse knockout experiment
plain_language
Melatonin has multiple metabolic routes whose importance depends on enzyme and tissue.
primary_references
[melatonin-p15616152] Metabolism of melatonin by human cytochromes p450. (2005). https://pubmed.ncbi.nlm.nih.gov/15616152/ DOI: 10.1124/dmd.104.002410
tissue_or_cell_type
Oxidative melatonin metabolism
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 565–576
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant P450 screen and mouse brain comparisons · source_derived_draft · unverified_draft
### melatonin-cyp-1a1-hydroxylation Recombinant human CYP1A1 catalyzed melatonin 6-hydroxylation. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Melatonin has multiple metabolic routes whose importance depends on enzyme and tissue. organism: Human recombinant enzymes; separate mouse knockout experiment tissue_or_cell_type: Oxidative melatonin metabolism experimental_model: Recombinant P450 screen and mouse brain comparisons limitations: Catalytic capacity in an enzyme assay is not whole-body contribution. CYP1B1 is an extrahepatic route; human proteins are not substituted for mouse knockout identity. exposure: Eleven P450 isozymes; NADPH-dependent 6-hydroxylation/O-demethylation evidence_span: {"source_cache": "artifacts/melatonin-research/15616152.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "482334074e10503323360f236e00b5b837c5b082a7cda4df000a23d491bff8a2", "start_char": 0, "end_char": 1733, "text_sha256": "482334074e10503323360f236e00b5b837c5b082a7cda4df000a23d491bff8a2"} [melatonin-p15616152] Metabolism of melatonin by human cytochromes p450. (2005). https://pubmed.ncbi.nlm.nih.gov/15616152/ DOI: 10.1124/dmd.104.002410
Complete structured claim and evidence
Recombinant human CYP1B1 catalyzed melatonin 6-hydroxylation.
Human cytochrome P450 1B1 / CYP1B1 → 6-Hydroxymelatonin source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/15616152.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "482334074e10503323360f236e00b5b837c5b082a7cda4df000a23d491bff8a2", "start_char": 0, "end_char": 1733, "text_sha256": "482334074e10503323360f236e00b5b837c5b082a7cda4df000a23d491bff8a2"}
experimental_model
Recombinant P450 screen and mouse brain comparisons
exposure
Eleven P450 isozymes; NADPH-dependent 6-hydroxylation/O-demethylation
limitations
Catalytic capacity in an enzyme assay is not whole-body contribution. CYP1B1 is an extrahepatic route; human proteins are not substituted for mouse knockout identity.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human recombinant enzymes; separate mouse knockout experiment
plain_language
Melatonin has multiple metabolic routes whose importance depends on enzyme and tissue.
primary_references
[melatonin-p15616152] Metabolism of melatonin by human cytochromes p450. (2005). https://pubmed.ncbi.nlm.nih.gov/15616152/ DOI: 10.1124/dmd.104.002410
tissue_or_cell_type
Oxidative melatonin metabolism
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 578–589
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant P450 screen and mouse brain comparisons · source_derived_draft · unverified_draft
### melatonin-cyp-1b1-hydroxylation Recombinant human CYP1B1 catalyzed melatonin 6-hydroxylation. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Melatonin has multiple metabolic routes whose importance depends on enzyme and tissue. organism: Human recombinant enzymes; separate mouse knockout experiment tissue_or_cell_type: Oxidative melatonin metabolism experimental_model: Recombinant P450 screen and mouse brain comparisons limitations: Catalytic capacity in an enzyme assay is not whole-body contribution. CYP1B1 is an extrahepatic route; human proteins are not substituted for mouse knockout identity. exposure: Eleven P450 isozymes; NADPH-dependent 6-hydroxylation/O-demethylation evidence_span: {"source_cache": "artifacts/melatonin-research/15616152.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "482334074e10503323360f236e00b5b837c5b082a7cda4df000a23d491bff8a2", "start_char": 0, "end_char": 1733, "text_sha256": "482334074e10503323360f236e00b5b837c5b082a7cda4df000a23d491bff8a2"} [melatonin-p15616152] Metabolism of melatonin by human cytochromes p450. (2005). https://pubmed.ncbi.nlm.nih.gov/15616152/ DOI: 10.1124/dmd.104.002410
Complete structured claim and evidence
Recombinant human CYP2C19 catalyzed melatonin 6-hydroxylation to a minor extent in this screen.
Human cytochrome P450 2C19 → 6-Hydroxymelatonin source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/15616152.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "482334074e10503323360f236e00b5b837c5b082a7cda4df000a23d491bff8a2", "start_char": 0, "end_char": 1733, "text_sha256": "482334074e10503323360f236e00b5b837c5b082a7cda4df000a23d491bff8a2"}
experimental_model
Recombinant P450 screen and mouse brain comparisons
exposure
Eleven P450 isozymes; NADPH-dependent 6-hydroxylation/O-demethylation
limitations
Catalytic capacity in an enzyme assay is not whole-body contribution. CYP1B1 is an extrahepatic route; human proteins are not substituted for mouse knockout identity.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human recombinant enzymes; separate mouse knockout experiment
plain_language
Melatonin has multiple metabolic routes whose importance depends on enzyme and tissue.
primary_references
[melatonin-p15616152] Metabolism of melatonin by human cytochromes p450. (2005). https://pubmed.ncbi.nlm.nih.gov/15616152/ DOI: 10.1124/dmd.104.002410
tissue_or_cell_type
Oxidative melatonin metabolism
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 591–602
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant P450 screen and mouse brain comparisons · source_derived_draft · unverified_draft
### melatonin-cyp-2c19-hydroxylation Recombinant human CYP2C19 catalyzed melatonin 6-hydroxylation to a minor extent in this screen. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Melatonin has multiple metabolic routes whose importance depends on enzyme and tissue. organism: Human recombinant enzymes; separate mouse knockout experiment tissue_or_cell_type: Oxidative melatonin metabolism experimental_model: Recombinant P450 screen and mouse brain comparisons limitations: Catalytic capacity in an enzyme assay is not whole-body contribution. CYP1B1 is an extrahepatic route; human proteins are not substituted for mouse knockout identity. exposure: Eleven P450 isozymes; NADPH-dependent 6-hydroxylation/O-demethylation evidence_span: {"source_cache": "artifacts/melatonin-research/15616152.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "482334074e10503323360f236e00b5b837c5b082a7cda4df000a23d491bff8a2", "start_char": 0, "end_char": 1733, "text_sha256": "482334074e10503323360f236e00b5b837c5b082a7cda4df000a23d491bff8a2"} [melatonin-p15616152] Metabolism of melatonin by human cytochromes p450. (2005). https://pubmed.ncbi.nlm.nih.gov/15616152/ DOI: 10.1124/dmd.104.002410
Complete structured claim and evidence
Human CYP2C19 catalyzed melatonin O-demethylation.
Human cytochrome P450 2C19 → N-Acetylserotonin source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/15616152.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "482334074e10503323360f236e00b5b837c5b082a7cda4df000a23d491bff8a2", "start_char": 0, "end_char": 1733, "text_sha256": "482334074e10503323360f236e00b5b837c5b082a7cda4df000a23d491bff8a2"}
experimental_model
Recombinant P450 screen and mouse brain comparisons
exposure
Eleven P450 isozymes; NADPH-dependent 6-hydroxylation/O-demethylation
limitations
Catalytic capacity in an enzyme assay is not whole-body contribution. CYP1B1 is an extrahepatic route; human proteins are not substituted for mouse knockout identity.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human recombinant enzymes; separate mouse knockout experiment
plain_language
Removing the methyl group returns a molecule with the identity of a synthetic precursor.
primary_references
[melatonin-p15616152] Metabolism of melatonin by human cytochromes p450. (2005). https://pubmed.ncbi.nlm.nih.gov/15616152/ DOI: 10.1124/dmd.104.002410
tissue_or_cell_type
Oxidative melatonin metabolism
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 604–615
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant P450 screen and mouse brain comparisons · source_derived_draft · unverified_draft
### melatonin-cyp-2c19-demethylation Human CYP2C19 catalyzed melatonin O-demethylation. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing the methyl group returns a molecule with the identity of a synthetic precursor. organism: Human recombinant enzymes; separate mouse knockout experiment tissue_or_cell_type: Oxidative melatonin metabolism experimental_model: Recombinant P450 screen and mouse brain comparisons limitations: Catalytic capacity in an enzyme assay is not whole-body contribution. CYP1B1 is an extrahepatic route; human proteins are not substituted for mouse knockout identity. exposure: Eleven P450 isozymes; NADPH-dependent 6-hydroxylation/O-demethylation evidence_span: {"source_cache": "artifacts/melatonin-research/15616152.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "482334074e10503323360f236e00b5b837c5b082a7cda4df000a23d491bff8a2", "start_char": 0, "end_char": 1733, "text_sha256": "482334074e10503323360f236e00b5b837c5b082a7cda4df000a23d491bff8a2"} [melatonin-p15616152] Metabolism of melatonin by human cytochromes p450. (2005). https://pubmed.ncbi.nlm.nih.gov/15616152/ DOI: 10.1124/dmd.104.002410
Complete structured claim and evidence
Human CYP1A2 catalyzed melatonin O-demethylation to a lesser extent than CYP2C19 in the study.
Human cytochrome P450 1A2 → N-Acetylserotonin source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/15616152.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "482334074e10503323360f236e00b5b837c5b082a7cda4df000a23d491bff8a2", "start_char": 0, "end_char": 1733, "text_sha256": "482334074e10503323360f236e00b5b837c5b082a7cda4df000a23d491bff8a2"}
experimental_model
Recombinant P450 screen and mouse brain comparisons
exposure
Eleven P450 isozymes; NADPH-dependent 6-hydroxylation/O-demethylation
limitations
Catalytic capacity in an enzyme assay is not whole-body contribution. CYP1B1 is an extrahepatic route; human proteins are not substituted for mouse knockout identity.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human recombinant enzymes; separate mouse knockout experiment
plain_language
Removing the methyl group returns a molecule with the identity of a synthetic precursor.
primary_references
[melatonin-p15616152] Metabolism of melatonin by human cytochromes p450. (2005). https://pubmed.ncbi.nlm.nih.gov/15616152/ DOI: 10.1124/dmd.104.002410
tissue_or_cell_type
Oxidative melatonin metabolism
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 617–628
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant P450 screen and mouse brain comparisons · source_derived_draft · unverified_draft
### melatonin-cyp-1a2-demethylation Human CYP1A2 catalyzed melatonin O-demethylation to a lesser extent than CYP2C19 in the study. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing the methyl group returns a molecule with the identity of a synthetic precursor. organism: Human recombinant enzymes; separate mouse knockout experiment tissue_or_cell_type: Oxidative melatonin metabolism experimental_model: Recombinant P450 screen and mouse brain comparisons limitations: Catalytic capacity in an enzyme assay is not whole-body contribution. CYP1B1 is an extrahepatic route; human proteins are not substituted for mouse knockout identity. exposure: Eleven P450 isozymes; NADPH-dependent 6-hydroxylation/O-demethylation evidence_span: {"source_cache": "artifacts/melatonin-research/15616152.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "482334074e10503323360f236e00b5b837c5b082a7cda4df000a23d491bff8a2", "start_char": 0, "end_char": 1733, "text_sha256": "482334074e10503323360f236e00b5b837c5b082a7cda4df000a23d491bff8a2"} [melatonin-p15616152] Metabolism of melatonin by human cytochromes p450. (2005). https://pubmed.ncbi.nlm.nih.gov/15616152/ DOI: 10.1124/dmd.104.002410
Complete structured claim and evidence
SULT1A1 had the strongest tested sulfating activity toward 6-hydroxymelatonin.
Human sulfotransferase 1A1 / SULT1A1 → 6-Sulfatoxymelatonin / aMT6s source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/26577053.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ab887dc7012d5f393de52ecf842b67282d51b61bac705b9ab187c1a3e24331d5", "start_char": 0, "end_char": 1378, "text_sha256": "ab887dc7012d5f393de52ecf842b67282d51b61bac705b9ab187c1a3e24331d5"}
experimental_model
Thirteen human SULT enzymes, labeled cells and tissue cytosols
exposure
6-hydroxymelatonin and N-acetylserotonin substrates; sulfate metabolic labeling
limitations
Enzyme ranking applies to tested conditions. Sulfation is a separate step from P450 hydroxylation; no dietary sulfur threshold was established.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human recombinant enzymes, HepG2 and Caco-2 cells
plain_language
The hydroxylated metabolite undergoes another reaction before common urinary measurement.
primary_references
[melatonin-p26577053] Sulfation of 6-hydroxymelatonin, N-acetylserotonin and 4-hydroxyramelteon by the human cytosolic sulfotransferases (SULTs). (2016). https://pubmed.ncbi.nlm.nih.gov/26577053/ DOI: 10.3109/00498254.2015.1107656
tissue_or_cell_type
Sulfate conjugation
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 630–641
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Thirteen human SULT enzymes, labeled cells and tissue cytosols · source_derived_draft · unverified_draft
### melatonin-sult1a1 SULT1A1 had the strongest tested sulfating activity toward 6-hydroxymelatonin. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The hydroxylated metabolite undergoes another reaction before common urinary measurement. organism: Human recombinant enzymes, HepG2 and Caco-2 cells tissue_or_cell_type: Sulfate conjugation experimental_model: Thirteen human SULT enzymes, labeled cells and tissue cytosols limitations: Enzyme ranking applies to tested conditions. Sulfation is a separate step from P450 hydroxylation; no dietary sulfur threshold was established. exposure: 6-hydroxymelatonin and N-acetylserotonin substrates; sulfate metabolic labeling evidence_span: {"source_cache": "artifacts/melatonin-research/26577053.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ab887dc7012d5f393de52ecf842b67282d51b61bac705b9ab187c1a3e24331d5", "start_char": 0, "end_char": 1378, "text_sha256": "ab887dc7012d5f393de52ecf842b67282d51b61bac705b9ab187c1a3e24331d5"} [melatonin-p26577053] Sulfation of 6-hydroxymelatonin, N-acetylserotonin and 4-hydroxyramelteon by the human cytosolic sulfotransferases (SULTs). (2016). https://pubmed.ncbi.nlm.nih.gov/26577053/ DOI: 10.3109/00498254.2015.1107656
Complete structured claim and evidence
SULT1C4 had the strongest tested sulfating activity toward N-acetylserotonin.
Human sulfotransferase 1C4 / SULT1C4 → N-Acetylserotonin sulfate source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/26577053.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ab887dc7012d5f393de52ecf842b67282d51b61bac705b9ab187c1a3e24331d5", "start_char": 0, "end_char": 1378, "text_sha256": "ab887dc7012d5f393de52ecf842b67282d51b61bac705b9ab187c1a3e24331d5"}
experimental_model
Thirteen human SULT enzymes, labeled cells and tissue cytosols
exposure
6-hydroxymelatonin and N-acetylserotonin substrates; sulfate metabolic labeling
limitations
Enzyme ranking applies to tested conditions. Sulfation is a separate step from P450 hydroxylation; no dietary sulfur threshold was established.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human recombinant enzymes, HepG2 and Caco-2 cells
plain_language
The precursor has its own conjugation route, separate from melatonin methylation.
primary_references
[melatonin-p26577053] Sulfation of 6-hydroxymelatonin, N-acetylserotonin and 4-hydroxyramelteon by the human cytosolic sulfotransferases (SULTs). (2016). https://pubmed.ncbi.nlm.nih.gov/26577053/ DOI: 10.3109/00498254.2015.1107656
tissue_or_cell_type
Sulfate conjugation
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 643–654
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Thirteen human SULT enzymes, labeled cells and tissue cytosols · source_derived_draft · unverified_draft
### melatonin-sult1c4 SULT1C4 had the strongest tested sulfating activity toward N-acetylserotonin. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The precursor has its own conjugation route, separate from melatonin methylation. organism: Human recombinant enzymes, HepG2 and Caco-2 cells tissue_or_cell_type: Sulfate conjugation experimental_model: Thirteen human SULT enzymes, labeled cells and tissue cytosols limitations: Enzyme ranking applies to tested conditions. Sulfation is a separate step from P450 hydroxylation; no dietary sulfur threshold was established. exposure: 6-hydroxymelatonin and N-acetylserotonin substrates; sulfate metabolic labeling evidence_span: {"source_cache": "artifacts/melatonin-research/26577053.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ab887dc7012d5f393de52ecf842b67282d51b61bac705b9ab187c1a3e24331d5", "start_char": 0, "end_char": 1378, "text_sha256": "ab887dc7012d5f393de52ecf842b67282d51b61bac705b9ab187c1a3e24331d5"} [melatonin-p26577053] Sulfation of 6-hydroxymelatonin, N-acetylserotonin and 4-hydroxyramelteon by the human cytosolic sulfotransferases (SULTs). (2016). https://pubmed.ncbi.nlm.nih.gov/26577053/ DOI: 10.3109/00498254.2015.1107656
Complete structured claim and evidence
Median absolute oral bioavailability was 2.5% in the 10 mg crossover study.
Melatonin → Absolute oral melatonin bioavailability 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
The swallowed amount and the amount reaching circulation are very different quantities.
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 656–667
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-bioavailability Median absolute oral bioavailability was 2.5% in the 10 mg crossover study. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The swallowed amount and the amount reaching circulation are very different quantities. 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
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
Mean elimination half-life was about 54 minutes after oral dosing and 39 minutes after intravenous dosing.
Melatonin → Melatonin plasma elimination half-life 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
The hormone blood half-life is not the same as the duration of a shifted body clock.
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 682–693
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-half-life Mean elimination half-life was about 54 minutes after oral dosing and 39 minutes after intravenous dosing. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The hormone blood half-life is not the same as the duration of a shifted body clock. 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
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
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
Endogenous overnight melatonin AUC was similar during smoking and after abstinence.
Abstinence from cigarette smoking → Nocturnal circulating melatonin concentration 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
The supplement result cannot be generalized to the natural night signal.
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 747–758
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-endogenous-null Endogenous overnight melatonin AUC was similar during smoking and after abstinence. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The supplement result cannot be generalized to the natural night signal. 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
Sleep amount and architecture were similar after pyridoxine and placebo.
Pyridoxine → Polysomnographic total sleep time source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/12080281.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "04727c17cd3152a4749ec25ff15b36b827efb885501ce058d436fbbea1e9e7a9", "start_char": 0, "end_char": 1222, "text_sha256": "04727c17cd3152a4749ec25ff15b36b827efb885501ce058d436fbbea1e9e7a9"}
experimental_model
Placebo-controlled evening pyridoxine experiment
exposure
100 mg pyridoxine at 17:00; evening/night sampling
limitations
Acute exposure in healthy men. Null supplementation response does not negate the enzymatic requirement for PLP or settle effects in B6 deficiency.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Twelve healthy men
plain_language
A plausible precursor pathway did not guarantee an observable sleep improvement.
primary_references
[melatonin-p12080281] The effect of pyridoxine administration on melatonin secretion in normal men. (2002). https://pubmed.ncbi.nlm.nih.gov/12080281/
tissue_or_cell_type
Melatonin secretion, temperature and polysomnography
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 786–797
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Placebo-controlled evening pyridoxine experiment · source_derived_draft · unverified_draft
### melatonin-b6-sleep-null Sleep amount and architecture were similar after pyridoxine and placebo. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A plausible precursor pathway did not guarantee an observable sleep improvement. organism: Twelve healthy men tissue_or_cell_type: Melatonin secretion, temperature and polysomnography experimental_model: Placebo-controlled evening pyridoxine experiment limitations: Acute exposure in healthy men. Null supplementation response does not negate the enzymatic requirement for PLP or settle effects in B6 deficiency. exposure: 100 mg pyridoxine at 17:00; evening/night sampling evidence_span: {"source_cache": "artifacts/melatonin-research/12080281.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "04727c17cd3152a4749ec25ff15b36b827efb885501ce058d436fbbea1e9e7a9", "start_char": 0, "end_char": 1222, "text_sha256": "04727c17cd3152a4749ec25ff15b36b827efb885501ce058d436fbbea1e9e7a9"} [melatonin-p12080281] The effect of pyridoxine administration on melatonin secretion in normal men. (2002). https://pubmed.ncbi.nlm.nih.gov/12080281/
Complete structured claim and evidence
The morning bright-light exposure advanced melatonin phase significantly during the B12 condition but not placebo.
Methylcobalamin → Circadian phase shift after bright-light exposure source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/8981490.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0079778f8efe44c1538b9c85d56b12a3a766b734aab19660419fd461ec22792", "start_char": 0, "end_char": 895, "text_sha256": "d0079778f8efe44c1538b9c85d56b12a3a766b734aab19660419fd461ec22792"}
experimental_model
Single-blind crossover light-response experiment
exposure
Methylcobalamin IV 0.5 mg/day for 11 days then oral 6 mg/day for seven; morning 2500-lux light for three hours
limitations
Small pharmacological B12 study, not B12-deficient participants. Does not establish a routine sleep treatment or increased melatonin production.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Eight young men
plain_language
A vitamin-related intervention affected timing of the signal rather than simply increasing its amount.
primary_references
[melatonin-p8981490] Vitamin B12 enhances the phase-response of circadian melatonin rhythm to a single bright light exposure in humans. (1996). https://pubmed.ncbi.nlm.nih.gov/8981490/ DOI: 10.1016/s0304-3940(96)13247-x
tissue_or_cell_type
Circadian melatonin rhythm
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 799–810
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-blind crossover light-response experiment · source_derived_draft · unverified_draft
### melatonin-b12-phase-response The morning bright-light exposure advanced melatonin phase significantly during the B12 condition but not placebo. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A vitamin-related intervention affected timing of the signal rather than simply increasing its amount. organism: Eight young men tissue_or_cell_type: Circadian melatonin rhythm experimental_model: Single-blind crossover light-response experiment limitations: Small pharmacological B12 study, not B12-deficient participants. Does not establish a routine sleep treatment or increased melatonin production. exposure: Methylcobalamin IV 0.5 mg/day for 11 days then oral 6 mg/day for seven; morning 2500-lux light for three hours evidence_span: {"source_cache": "artifacts/melatonin-research/8981490.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0079778f8efe44c1538b9c85d56b12a3a766b734aab19660419fd461ec22792", "start_char": 0, "end_char": 895, "text_sha256": "d0079778f8efe44c1538b9c85d56b12a3a766b734aab19660419fd461ec22792"} [melatonin-p8981490] Vitamin B12 enhances the phase-response of circadian melatonin rhythm to a single bright light exposure in humans. (1996). https://pubmed.ncbi.nlm.nih.gov/8981490/ DOI: 10.1016/s0304-3940(96)13247-x
Complete structured claim and evidence
Melatonin rhythm amplitude before the light exposure was smaller during the B12 condition.
Methylcobalamin → Amplitude of endogenous melatonin rhythm source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/8981490.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0079778f8efe44c1538b9c85d56b12a3a766b734aab19660419fd461ec22792", "start_char": 0, "end_char": 895, "text_sha256": "d0079778f8efe44c1538b9c85d56b12a3a766b734aab19660419fd461ec22792"}
experimental_model
Single-blind crossover light-response experiment
exposure
Methylcobalamin IV 0.5 mg/day for 11 days then oral 6 mg/day for seven; morning 2500-lux light for three hours
limitations
Small pharmacological B12 study, not B12-deficient participants. Does not establish a routine sleep treatment or increased melatonin production.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Eight young men
plain_language
A lower amplitude and a shifted clock are separate measurements.
primary_references
[melatonin-p8981490] Vitamin B12 enhances the phase-response of circadian melatonin rhythm to a single bright light exposure in humans. (1996). https://pubmed.ncbi.nlm.nih.gov/8981490/ DOI: 10.1016/s0304-3940(96)13247-x
tissue_or_cell_type
Circadian melatonin rhythm
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 812–823
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-blind crossover light-response experiment · source_derived_draft · unverified_draft
### melatonin-b12-amplitude Melatonin rhythm amplitude before the light exposure was smaller during the B12 condition. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A lower amplitude and a shifted clock are separate measurements. organism: Eight young men tissue_or_cell_type: Circadian melatonin rhythm experimental_model: Single-blind crossover light-response experiment limitations: Small pharmacological B12 study, not B12-deficient participants. Does not establish a routine sleep treatment or increased melatonin production. exposure: Methylcobalamin IV 0.5 mg/day for 11 days then oral 6 mg/day for seven; morning 2500-lux light for three hours evidence_span: {"source_cache": "artifacts/melatonin-research/8981490.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0079778f8efe44c1538b9c85d56b12a3a766b734aab19660419fd461ec22792", "start_char": 0, "end_char": 895, "text_sha256": "d0079778f8efe44c1538b9c85d56b12a3a766b734aab19660419fd461ec22792"} [melatonin-p8981490] Vitamin B12 enhances the phase-response of circadian melatonin rhythm to a single bright light exposure in humans. (1996). https://pubmed.ncbi.nlm.nih.gov/8981490/ DOI: 10.1016/s0304-3940(96)13247-x
Complete structured claim and evidence
The combination improved global PSQI sleep-quality scores compared with placebo.
Melatonin, magnesium and zinc study mixture → Global subjective sleep quality on PSQI source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/21226679.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2381a465728ea91061029d1d1d565623a15bdb941acf0cc9dbd2ed872fda32cf", "start_char": 0, "end_char": 1911, "text_sha256": "2381a465728ea91061029d1d1d565623a15bdb941acf0cc9dbd2ed872fda32cf"}
experimental_model
Double-blind placebo-controlled mixture trial
exposure
5 mg melatonin, 225 mg magnesium and 11.25 mg zinc nightly for eight weeks
limitations
Three active ingredients without separate ingredient arms; cannot demonstrate synergy or identify which ingredient caused the improvement. Single facility and short duration.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
43 elderly long-term-care residents with primary insomnia
plain_language
The tested product helped this outcome, but it does not isolate magnesium, zinc or melatonin.
primary_references
[melatonin-p21226679] The effect of melatonin, magnesium, and zinc on primary insomnia in long-term care facility residents in Italy: a double-blind, placebo-controlled clinical trial. (2011). https://pubmed.ncbi.nlm.nih.gov/21226679/ DOI: 10.1111/j.1532-5415.2010.03232.x
tissue_or_cell_type
Subjective and device-estimated sleep
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 825–836
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind placebo-controlled mixture trial · source_derived_draft · unverified_draft
### melatonin-mg-zinc-mixture-sleep The combination improved global PSQI sleep-quality scores compared with placebo. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The tested product helped this outcome, but it does not isolate magnesium, zinc or melatonin. organism: 43 elderly long-term-care residents with primary insomnia tissue_or_cell_type: Subjective and device-estimated sleep experimental_model: Double-blind placebo-controlled mixture trial limitations: Three active ingredients without separate ingredient arms; cannot demonstrate synergy or identify which ingredient caused the improvement. Single facility and short duration. exposure: 5 mg melatonin, 225 mg magnesium and 11.25 mg zinc nightly for eight weeks evidence_span: {"source_cache": "artifacts/melatonin-research/21226679.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2381a465728ea91061029d1d1d565623a15bdb941acf0cc9dbd2ed872fda32cf", "start_char": 0, "end_char": 1911, "text_sha256": "2381a465728ea91061029d1d1d565623a15bdb941acf0cc9dbd2ed872fda32cf"} [melatonin-p21226679] The effect of melatonin, magnesium, and zinc on primary insomnia in long-term care facility residents in Italy: a double-blind, placebo-controlled clinical trial. (2011). https://pubmed.ncbi.nlm.nih.gov/21226679/ DOI: 10.1111/j.1532-5415.2010.03232.x
Complete structured claim and evidence
The first half of habitual sleep corresponded to a region of minimal phase shifts in this protocol.
Melatonin → Phase of the endogenous melatonin circadian rhythm source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/18006583.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9eb1409f6e4c58eadfaf1554930378e03860dc9dc1201de6d104b6de784758ea", "start_char": 0, "end_char": 1518, "text_sha256": "9eb1409f6e4c58eadfaf1554930378e03860dc9dc1201de6d104b6de784758ea"}
experimental_model
Double-blind counterbalanced phase-response experiment
exposure
3 mg once daily for three days at different circadian times; dim-light onset measured
limitations
Timing is relative to individual biological phase, not a universal clock hour. This experimental schedule is not a dosing instruction.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
27 healthy young adults
plain_language
A sleep-promoting effect is not identical to resetting the clock.
primary_references
[melatonin-p18006583] A three pulse phase response curve to three milligrams of melatonin in humans. (2008). https://pubmed.ncbi.nlm.nih.gov/18006583/ DOI: 10.1113/jphysiol.2007.143180
tissue_or_cell_type
Circadian melatonin timing
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 864–875
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind counterbalanced phase-response experiment · source_derived_draft · unverified_draft
### melatonin-phase-dead-zone The first half of habitual sleep corresponded to a region of minimal phase shifts in this protocol. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A sleep-promoting effect is not identical to resetting the clock. organism: 27 healthy young adults tissue_or_cell_type: Circadian melatonin timing experimental_model: Double-blind counterbalanced phase-response experiment limitations: Timing is relative to individual biological phase, not a universal clock hour. This experimental schedule is not a dosing instruction. exposure: 3 mg once daily for three days at different circadian times; dim-light onset measured evidence_span: {"source_cache": "artifacts/melatonin-research/18006583.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9eb1409f6e4c58eadfaf1554930378e03860dc9dc1201de6d104b6de784758ea", "start_char": 0, "end_char": 1518, "text_sha256": "9eb1409f6e4c58eadfaf1554930378e03860dc9dc1201de6d104b6de784758ea"} [melatonin-p18006583] A three pulse phase response curve to three milligrams of melatonin in humans. (2008). https://pubmed.ncbi.nlm.nih.gov/18006583/ DOI: 10.1113/jphysiol.2007.143180
Complete structured claim and evidence
Prebed room light shortened melatonin duration by about 90 minutes in the analysis.
Evening room-light exposure compared with dim light → Duration of endogenous melatonin secretion source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/melatonin-research/21193540.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "899cae7b15ef3be8a3d4660202e8f675722295da9cb69a0eef3bdcf2470aeb23", "start_char": 0, "end_char": 1666, "text_sha256": "899cae7b15ef3be8a3d4660202e8f675722295da9cb69a0eef3bdcf2470aeb23"}
experimental_model
Controlled-light profiles analyzed retrospectively
exposure
Room light below 200 lux versus dim light below 3 lux before bed; light during usual sleep hours
limitations
Study light conditions are not universal thresholds for all eyes, spectra or exposure durations. Suppression is not dietary deficiency.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
116 healthy adults aged 18-30
plain_language
The duration of the signal changed, not just its peak.
primary_references
[melatonin-p21193540] Exposure to room light before bedtime suppresses melatonin onset and shortens melatonin duration in humans. (2011). https://pubmed.ncbi.nlm.nih.gov/21193540/ DOI: 10.1210/jc.2010-2098
tissue_or_cell_type
Circulating melatonin under different light conditions
trigger_kind
biomarker_context Imported condition classification; unverified.
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 890–901
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled-light profiles analyzed retrospectively · source_derived_draft · unverified_draft
### melatonin-light-duration Prebed room light shortened melatonin duration by about 90 minutes in the analysis. Condition category: biomarker_context nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The duration of the signal changed, not just its peak. organism: 116 healthy adults aged 18-30 tissue_or_cell_type: Circulating melatonin under different light conditions experimental_model: Controlled-light profiles analyzed retrospectively limitations: Study light conditions are not universal thresholds for all eyes, spectra or exposure durations. Suppression is not dietary deficiency. exposure: Room light below 200 lux versus dim light below 3 lux before bed; light during usual sleep hours evidence_span: {"source_cache": "artifacts/melatonin-research/21193540.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "899cae7b15ef3be8a3d4660202e8f675722295da9cb69a0eef3bdcf2470aeb23", "start_char": 0, "end_char": 1666, "text_sha256": "899cae7b15ef3be8a3d4660202e8f675722295da9cb69a0eef3bdcf2470aeb23"} [melatonin-p21193540] Exposure to room light before bedtime suppresses melatonin onset and shortens melatonin duration in humans. (2011). https://pubmed.ncbi.nlm.nih.gov/21193540/ DOI: 10.1210/jc.2010-2098
Complete structured claim and evidence
Light during usual sleep hours suppressed melatonin by more than 50% in most trials.
Light exposure during biological night → Nocturnal circulating melatonin concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/melatonin-research/21193540.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "899cae7b15ef3be8a3d4660202e8f675722295da9cb69a0eef3bdcf2470aeb23", "start_char": 0, "end_char": 1666, "text_sha256": "899cae7b15ef3be8a3d4660202e8f675722295da9cb69a0eef3bdcf2470aeb23"}
experimental_model
Controlled-light profiles analyzed retrospectively
exposure
Room light below 200 lux versus dim light below 3 lux before bed; light during usual sleep hours
limitations
Study light conditions are not universal thresholds for all eyes, spectra or exposure durations. Suppression is not dietary deficiency.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
116 healthy adults aged 18-30
plain_language
A low sample can have an environmental explanation.
primary_references
[melatonin-p21193540] Exposure to room light before bedtime suppresses melatonin onset and shortens melatonin duration in humans. (2011). https://pubmed.ncbi.nlm.nih.gov/21193540/ DOI: 10.1210/jc.2010-2098
tissue_or_cell_type
Circulating melatonin under different light conditions
trigger_kind
biomarker_context Imported condition classification; unverified.
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 903–914
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled-light profiles analyzed retrospectively · source_derived_draft · unverified_draft
### melatonin-light-night-level Light during usual sleep hours suppressed melatonin by more than 50% in most trials. Condition category: biomarker_context nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A low sample can have an environmental explanation. organism: 116 healthy adults aged 18-30 tissue_or_cell_type: Circulating melatonin under different light conditions experimental_model: Controlled-light profiles analyzed retrospectively limitations: Study light conditions are not universal thresholds for all eyes, spectra or exposure durations. Suppression is not dietary deficiency. exposure: Room light below 200 lux versus dim light below 3 lux before bed; light during usual sleep hours evidence_span: {"source_cache": "artifacts/melatonin-research/21193540.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "899cae7b15ef3be8a3d4660202e8f675722295da9cb69a0eef3bdcf2470aeb23", "start_char": 0, "end_char": 1666, "text_sha256": "899cae7b15ef3be8a3d4660202e8f675722295da9cb69a0eef3bdcf2470aeb23"} [melatonin-p21193540] Exposure to room light before bedtime suppresses melatonin onset and shortens melatonin duration in humans. (2011). https://pubmed.ncbi.nlm.nih.gov/21193540/ DOI: 10.1210/jc.2010-2098
Complete structured claim and evidence
Six of seven participants entrained to a 24-hour rhythm during melatonin treatment, unlike placebo.
Melatonin → Entrainment of a free-running circadian rhythm to 24 hours source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/11027741.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ef0d484e68b993c88b611d48f4cd8dc16db62056baa76f41f508818cccf78641", "start_char": 0, "end_char": 1749, "text_sha256": "ef0d484e68b993c88b611d48f4cd8dc16db62056baa76f41f508818cccf78641"}
experimental_model
Placebo crossover entrainment study
exposure
10 mg daily before preferred bedtime; three participants later tapered to 0.5 mg after entrainment
limitations
Small selected population. Not all blindness causes free-running rhythms; these findings do not establish general insomnia efficacy.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Seven totally blind people with free-running rhythms
plain_language
An external timing signal can synchronize a free-running clock.
primary_references
[melatonin-p11027741] Entrainment of free-running circadian rhythms by melatonin in blind people. (2000). https://pubmed.ncbi.nlm.nih.gov/11027741/ DOI: 10.1056/nejm200010123431503
tissue_or_cell_type
Circadian phase and polysomnography
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 916–927
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Placebo crossover entrainment study · source_derived_draft · unverified_draft
### melatonin-blind-entrainment Six of seven participants entrained to a 24-hour rhythm during melatonin treatment, unlike placebo. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: An external timing signal can synchronize a free-running clock. organism: Seven totally blind people with free-running rhythms tissue_or_cell_type: Circadian phase and polysomnography experimental_model: Placebo crossover entrainment study limitations: Small selected population. Not all blindness causes free-running rhythms; these findings do not establish general insomnia efficacy. exposure: 10 mg daily before preferred bedtime; three participants later tapered to 0.5 mg after entrainment evidence_span: {"source_cache": "artifacts/melatonin-research/11027741.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ef0d484e68b993c88b611d48f4cd8dc16db62056baa76f41f508818cccf78641", "start_char": 0, "end_char": 1749, "text_sha256": "ef0d484e68b993c88b611d48f4cd8dc16db62056baa76f41f508818cccf78641"} [melatonin-p11027741] Entrainment of free-running circadian rhythms by melatonin in blind people. (2000). https://pubmed.ncbi.nlm.nih.gov/11027741/ DOI: 10.1056/nejm200010123431503
Complete structured claim and evidence
Sleep onset occurred 34 minutes earlier than placebo in the melatonin-plus-scheduling group.
Melatonin → Clock time of actigraphic sleep onset source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/29912983.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fd415c3cd95238c53759d8e28260e8e33e934391d3e2e160074c56e18613cb4c", "start_char": 0, "end_char": 3360, "text_sha256": "fd415c3cd95238c53759d8e28260e8e33e934391d3e2e160074c56e18613cb4c"}
experimental_model
Randomized double-blind placebo-controlled trial
exposure
0.5 mg fast-release one hour before desired bedtime, plus behavioral scheduling in both arms, four weeks
limitations
Selected delayed-phase population, not all people reporting insomnia. Post-treatment DLMO subset did not differ significantly; long-term effects were not tested.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
116 people with delayed sleep-wake phase disorder and delayed endogenous phase
plain_language
The tested treatment combined a small dose with a planned sleep schedule.
primary_references
[melatonin-p29912983] Efficacy of melatonin with behavioural sleep-wake scheduling for delayed sleep-wake phase disorder: A double-blind, randomised clinical trial. (2018). https://pubmed.ncbi.nlm.nih.gov/29912983/ DOI: 10.1371/journal.pmed.1002587
tissue_or_cell_type
Sleep timing and daytime impairment
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 929–940
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled trial · source_derived_draft · unverified_draft
### melatonin-dswpd-sleep-onset Sleep onset occurred 34 minutes earlier than placebo in the melatonin-plus-scheduling group. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The tested treatment combined a small dose with a planned sleep schedule. organism: 116 people with delayed sleep-wake phase disorder and delayed endogenous phase tissue_or_cell_type: Sleep timing and daytime impairment experimental_model: Randomized double-blind placebo-controlled trial limitations: Selected delayed-phase population, not all people reporting insomnia. Post-treatment DLMO subset did not differ significantly; long-term effects were not tested. exposure: 0.5 mg fast-release one hour before desired bedtime, plus behavioral scheduling in both arms, four weeks evidence_span: {"source_cache": "artifacts/melatonin-research/29912983.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fd415c3cd95238c53759d8e28260e8e33e934391d3e2e160074c56e18613cb4c", "start_char": 0, "end_char": 3360, "text_sha256": "fd415c3cd95238c53759d8e28260e8e33e934391d3e2e160074c56e18613cb4c"} [melatonin-p29912983] Efficacy of melatonin with behavioural sleep-wake scheduling for delayed sleep-wake phase disorder: A double-blind, randomised clinical trial. (2018). https://pubmed.ncbi.nlm.nih.gov/29912983/ DOI: 10.1371/journal.pmed.1002587
Complete structured claim and evidence
Patient-reported sleep-related impairment improved compared with placebo plus scheduling.
Melatonin → Patient-reported sleep-related daytime impairment source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/29912983.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fd415c3cd95238c53759d8e28260e8e33e934391d3e2e160074c56e18613cb4c", "start_char": 0, "end_char": 3360, "text_sha256": "fd415c3cd95238c53759d8e28260e8e33e934391d3e2e160074c56e18613cb4c"}
experimental_model
Randomized double-blind placebo-controlled trial
exposure
0.5 mg fast-release one hour before desired bedtime, plus behavioral scheduling in both arms, four weeks
limitations
Selected delayed-phase population, not all people reporting insomnia. Post-treatment DLMO subset did not differ significantly; long-term effects were not tested.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
116 people with delayed sleep-wake phase disorder and delayed endogenous phase
plain_language
The trial measured daytime consequences as well as sleep onset.
primary_references
[melatonin-p29912983] Efficacy of melatonin with behavioural sleep-wake scheduling for delayed sleep-wake phase disorder: A double-blind, randomised clinical trial. (2018). https://pubmed.ncbi.nlm.nih.gov/29912983/ DOI: 10.1371/journal.pmed.1002587
tissue_or_cell_type
Sleep timing and daytime impairment
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 942–953
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled trial · source_derived_draft · unverified_draft
### melatonin-dswpd-daytime Patient-reported sleep-related impairment improved compared with placebo plus scheduling. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The trial measured daytime consequences as well as sleep onset. organism: 116 people with delayed sleep-wake phase disorder and delayed endogenous phase tissue_or_cell_type: Sleep timing and daytime impairment experimental_model: Randomized double-blind placebo-controlled trial limitations: Selected delayed-phase population, not all people reporting insomnia. Post-treatment DLMO subset did not differ significantly; long-term effects were not tested. exposure: 0.5 mg fast-release one hour before desired bedtime, plus behavioral scheduling in both arms, four weeks evidence_span: {"source_cache": "artifacts/melatonin-research/29912983.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fd415c3cd95238c53759d8e28260e8e33e934391d3e2e160074c56e18613cb4c", "start_char": 0, "end_char": 3360, "text_sha256": "fd415c3cd95238c53759d8e28260e8e33e934391d3e2e160074c56e18613cb4c"} [melatonin-p29912983] Efficacy of melatonin with behavioural sleep-wake scheduling for delayed sleep-wake phase disorder: A double-blind, randomised clinical trial. (2018). https://pubmed.ncbi.nlm.nih.gov/29912983/ DOI: 10.1371/journal.pmed.1002587
Complete structured claim and evidence
Post-treatment dim-light melatonin onset did not differ significantly between groups in the measured subset of 43 patients.
Melatonin → Circadian onset of endogenous melatonin secretion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/29912983.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fd415c3cd95238c53759d8e28260e8e33e934391d3e2e160074c56e18613cb4c", "start_char": 0, "end_char": 3360, "text_sha256": "fd415c3cd95238c53759d8e28260e8e33e934391d3e2e160074c56e18613cb4c"}
experimental_model
Randomized double-blind placebo-controlled trial
exposure
0.5 mg fast-release one hour before desired bedtime, plus behavioral scheduling in both arms, four weeks
limitations
Selected delayed-phase population, not all people reporting insomnia. Post-treatment DLMO subset did not differ significantly; long-term effects were not tested.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
116 people with delayed sleep-wake phase disorder and delayed endogenous phase
plain_language
Earlier sleep in this trial did not prove a measured shift in the circadian hormone onset.
primary_references
[melatonin-p29912983] Efficacy of melatonin with behavioural sleep-wake scheduling for delayed sleep-wake phase disorder: A double-blind, randomised clinical trial. (2018). https://pubmed.ncbi.nlm.nih.gov/29912983/ DOI: 10.1371/journal.pmed.1002587
tissue_or_cell_type
Sleep timing and daytime impairment
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 955–966
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled trial · source_derived_draft · unverified_draft
### melatonin-dswpd-phase-null Post-treatment dim-light melatonin onset did not differ significantly between groups in the measured subset of 43 patients. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Earlier sleep in this trial did not prove a measured shift in the circadian hormone onset. organism: 116 people with delayed sleep-wake phase disorder and delayed endogenous phase tissue_or_cell_type: Sleep timing and daytime impairment experimental_model: Randomized double-blind placebo-controlled trial limitations: Selected delayed-phase population, not all people reporting insomnia. Post-treatment DLMO subset did not differ significantly; long-term effects were not tested. exposure: 0.5 mg fast-release one hour before desired bedtime, plus behavioral scheduling in both arms, four weeks evidence_span: {"source_cache": "artifacts/melatonin-research/29912983.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fd415c3cd95238c53759d8e28260e8e33e934391d3e2e160074c56e18613cb4c", "start_char": 0, "end_char": 3360, "text_sha256": "fd415c3cd95238c53759d8e28260e8e33e934391d3e2e160074c56e18613cb4c"} [melatonin-p29912983] Efficacy of melatonin with behavioural sleep-wake scheduling for delayed sleep-wake phase disorder: A double-blind, randomised clinical trial. (2018). https://pubmed.ncbi.nlm.nih.gov/29912983/ DOI: 10.1371/journal.pmed.1002587
Complete structured claim and evidence
All tested atenolol doses reduced nocturnal melatonin relative to placebo, with a dose-dependent pattern.
Atenolol → Nocturnal circulating melatonin concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/melatonin-research/9406983.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7d3fe9b237757bb5797ed40bbc26931a04868f9160ea458dd1264671c77e0718", "start_char": 0, "end_char": 1175, "text_sha256": "7d3fe9b237757bb5797ed40bbc26931a04868f9160ea458dd1264671c77e0718"}
experimental_model
Randomized single-blind dose-response study
exposure
Atenolol 12.5, 25, 37.5 or 50 mg versus placebo; week washouts
limitations
Acute beta1 blockade and small sample. A lower concentration does not by itself establish symptomatic deficiency or a need for replacement.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Six healthy humans
plain_language
A medicine can weaken the normal secretion signal even when synthetic nutrients are available.
primary_references
[melatonin-p9406983] The effect of atenolol, a beta1-adrenergic antagonist, on nocturnal plasma melatonin secretion: evidence for a dose-response relationship in humans. (1997). https://pubmed.ncbi.nlm.nih.gov/9406983/ DOI: 10.1111/j.1600-079x.1997.tb00345.x
tissue_or_cell_type
Nocturnal melatonin secretion
trigger_kind
machinery_impairment Imported condition classification; unverified.
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 968–979
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized single-blind dose-response study · source_derived_draft · unverified_draft
### melatonin-atenolol-suppression All tested atenolol doses reduced nocturnal melatonin relative to placebo, with a dose-dependent pattern. Condition category: machinery_impairment nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A medicine can weaken the normal secretion signal even when synthetic nutrients are available. organism: Six healthy humans tissue_or_cell_type: Nocturnal melatonin secretion experimental_model: Randomized single-blind dose-response study limitations: Acute beta1 blockade and small sample. A lower concentration does not by itself establish symptomatic deficiency or a need for replacement. exposure: Atenolol 12.5, 25, 37.5 or 50 mg versus placebo; week washouts evidence_span: {"source_cache": "artifacts/melatonin-research/9406983.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7d3fe9b237757bb5797ed40bbc26931a04868f9160ea458dd1264671c77e0718", "start_char": 0, "end_char": 1175, "text_sha256": "7d3fe9b237757bb5797ed40bbc26931a04868f9160ea458dd1264671c77e0718"} [melatonin-p9406983] The effect of atenolol, a beta1-adrenergic antagonist, on nocturnal plasma melatonin secretion: evidence for a dose-response relationship in humans. (1997). https://pubmed.ncbi.nlm.nih.gov/9406983/ DOI: 10.1111/j.1600-079x.1997.tb00345.x
Complete structured claim and evidence
Total sleep time increased by about 36 minutes compared with placebo in beta-blocker-treated patients.
Melatonin → Polysomnographic total sleep time source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/23024438.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f886545db45f7067ce68991935dcc3715082dbe31898c939eb64b015d3581f3", "start_char": 0, "end_char": 2402, "text_sha256": "0f886545db45f7067ce68991935dcc3715082dbe31898c939eb64b015d3581f3"}
experimental_model
Randomized double-blind placebo-controlled trial
exposure
2.5 mg melatonin nightly for three weeks
limitations
Small selected group; does not prove every beta-blocker user is deficient or that all low-melatonin states respond identically.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Hypertensive patients taking atenolol or metoprolol; 15 analyzed
plain_language
This is a measured sleep outcome in a specific medication context.
primary_references
[melatonin-p23024438] Repeated melatonin supplementation improves sleep in hypertensive patients treated with beta-blockers: a randomized controlled trial. (2012). https://pubmed.ncbi.nlm.nih.gov/23024438/ DOI: 10.5665/sleep.2122
tissue_or_cell_type
Polysomnographic sleep
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 981–992
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled trial · source_derived_draft · unverified_draft
### melatonin-beta-blocker-sleep-duration Total sleep time increased by about 36 minutes compared with placebo in beta-blocker-treated patients. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This is a measured sleep outcome in a specific medication context. organism: Hypertensive patients taking atenolol or metoprolol; 15 analyzed tissue_or_cell_type: Polysomnographic sleep experimental_model: Randomized double-blind placebo-controlled trial limitations: Small selected group; does not prove every beta-blocker user is deficient or that all low-melatonin states respond identically. exposure: 2.5 mg melatonin nightly for three weeks evidence_span: {"source_cache": "artifacts/melatonin-research/23024438.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f886545db45f7067ce68991935dcc3715082dbe31898c939eb64b015d3581f3", "start_char": 0, "end_char": 2402, "text_sha256": "0f886545db45f7067ce68991935dcc3715082dbe31898c939eb64b015d3581f3"} [melatonin-p23024438] Repeated melatonin supplementation improves sleep in hypertensive patients treated with beta-blockers: a randomized controlled trial. (2012). https://pubmed.ncbi.nlm.nih.gov/23024438/ DOI: 10.5665/sleep.2122
Complete structured claim and evidence
Sleep efficiency increased by about 7.6 percentage points compared with placebo in beta-blocker-treated patients.
Melatonin → Polysomnographic sleep efficiency source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/23024438.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f886545db45f7067ce68991935dcc3715082dbe31898c939eb64b015d3581f3", "start_char": 0, "end_char": 2402, "text_sha256": "0f886545db45f7067ce68991935dcc3715082dbe31898c939eb64b015d3581f3"}
experimental_model
Randomized double-blind placebo-controlled trial
exposure
2.5 mg melatonin nightly for three weeks
limitations
Small selected group; does not prove every beta-blocker user is deficient or that all low-melatonin states respond identically.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Hypertensive patients taking atenolol or metoprolol; 15 analyzed
plain_language
This is a measured sleep outcome in a specific medication context.
primary_references
[melatonin-p23024438] Repeated melatonin supplementation improves sleep in hypertensive patients treated with beta-blockers: a randomized controlled trial. (2012). https://pubmed.ncbi.nlm.nih.gov/23024438/ DOI: 10.5665/sleep.2122
tissue_or_cell_type
Polysomnographic sleep
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 994–1005
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled trial · source_derived_draft · unverified_draft
### melatonin-beta-blocker-sleep-efficiency Sleep efficiency increased by about 7.6 percentage points compared with placebo in beta-blocker-treated patients. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This is a measured sleep outcome in a specific medication context. organism: Hypertensive patients taking atenolol or metoprolol; 15 analyzed tissue_or_cell_type: Polysomnographic sleep experimental_model: Randomized double-blind placebo-controlled trial limitations: Small selected group; does not prove every beta-blocker user is deficient or that all low-melatonin states respond identically. exposure: 2.5 mg melatonin nightly for three weeks evidence_span: {"source_cache": "artifacts/melatonin-research/23024438.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f886545db45f7067ce68991935dcc3715082dbe31898c939eb64b015d3581f3", "start_char": 0, "end_char": 2402, "text_sha256": "0f886545db45f7067ce68991935dcc3715082dbe31898c939eb64b015d3581f3"} [melatonin-p23024438] Repeated melatonin supplementation improves sleep in hypertensive patients treated with beta-blockers: a randomized controlled trial. (2012). https://pubmed.ncbi.nlm.nih.gov/23024438/ DOI: 10.5665/sleep.2122
Complete structured claim and evidence
Stage 2 sleep increased by about 41 minutes compared with placebo in beta-blocker-treated patients.
Melatonin → Polysomnographic stage 2 sleep duration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/23024438.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f886545db45f7067ce68991935dcc3715082dbe31898c939eb64b015d3581f3", "start_char": 0, "end_char": 2402, "text_sha256": "0f886545db45f7067ce68991935dcc3715082dbe31898c939eb64b015d3581f3"}
experimental_model
Randomized double-blind placebo-controlled trial
exposure
2.5 mg melatonin nightly for three weeks
limitations
Small selected group; does not prove every beta-blocker user is deficient or that all low-melatonin states respond identically.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Hypertensive patients taking atenolol or metoprolol; 15 analyzed
plain_language
This is a measured sleep outcome in a specific medication context.
primary_references
[melatonin-p23024438] Repeated melatonin supplementation improves sleep in hypertensive patients treated with beta-blockers: a randomized controlled trial. (2012). https://pubmed.ncbi.nlm.nih.gov/23024438/ DOI: 10.5665/sleep.2122
tissue_or_cell_type
Polysomnographic sleep
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 1007–1018
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled trial · source_derived_draft · unverified_draft
### melatonin-beta-blocker-sleep-stage2 Stage 2 sleep increased by about 41 minutes compared with placebo in beta-blocker-treated patients. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This is a measured sleep outcome in a specific medication context. organism: Hypertensive patients taking atenolol or metoprolol; 15 analyzed tissue_or_cell_type: Polysomnographic sleep experimental_model: Randomized double-blind placebo-controlled trial limitations: Small selected group; does not prove every beta-blocker user is deficient or that all low-melatonin states respond identically. exposure: 2.5 mg melatonin nightly for three weeks evidence_span: {"source_cache": "artifacts/melatonin-research/23024438.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f886545db45f7067ce68991935dcc3715082dbe31898c939eb64b015d3581f3", "start_char": 0, "end_char": 2402, "text_sha256": "0f886545db45f7067ce68991935dcc3715082dbe31898c939eb64b015d3581f3"} [melatonin-p23024438] Repeated melatonin supplementation improves sleep in hypertensive patients treated with beta-blockers: a randomized controlled trial. (2012). https://pubmed.ncbi.nlm.nih.gov/23024438/ DOI: 10.5665/sleep.2122
Complete structured claim and evidence
Latency to stage 2 sleep decreased by about 14 minutes compared with placebo.
Melatonin → Sleep latency, measurement specified by study source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/23024438.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f886545db45f7067ce68991935dcc3715082dbe31898c939eb64b015d3581f3", "start_char": 0, "end_char": 2402, "text_sha256": "0f886545db45f7067ce68991935dcc3715082dbe31898c939eb64b015d3581f3"}
experimental_model
Randomized double-blind placebo-controlled trial
exposure
2.5 mg melatonin nightly for three weeks
limitations
Small selected group; does not prove every beta-blocker user is deficient or that all low-melatonin states respond identically.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Hypertensive patients taking atenolol or metoprolol; 15 analyzed
plain_language
The study measured a specific polysomnographic endpoint.
primary_references
[melatonin-p23024438] Repeated melatonin supplementation improves sleep in hypertensive patients treated with beta-blockers: a randomized controlled trial. (2012). https://pubmed.ncbi.nlm.nih.gov/23024438/ DOI: 10.5665/sleep.2122
tissue_or_cell_type
Polysomnographic sleep
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 1020–1031
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled trial · source_derived_draft · unverified_draft
### melatonin-beta-blocker-latency Latency to stage 2 sleep decreased by about 14 minutes compared with placebo. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The study measured a specific polysomnographic endpoint. organism: Hypertensive patients taking atenolol or metoprolol; 15 analyzed tissue_or_cell_type: Polysomnographic sleep experimental_model: Randomized double-blind placebo-controlled trial limitations: Small selected group; does not prove every beta-blocker user is deficient or that all low-melatonin states respond identically. exposure: 2.5 mg melatonin nightly for three weeks evidence_span: {"source_cache": "artifacts/melatonin-research/23024438.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f886545db45f7067ce68991935dcc3715082dbe31898c939eb64b015d3581f3", "start_char": 0, "end_char": 2402, "text_sha256": "0f886545db45f7067ce68991935dcc3715082dbe31898c939eb64b015d3581f3"} [melatonin-p23024438] Repeated melatonin supplementation improves sleep in hypertensive patients treated with beta-blockers: a randomized controlled trial. (2012). https://pubmed.ncbi.nlm.nih.gov/23024438/ DOI: 10.5665/sleep.2122
Complete structured claim and evidence
With nifedipine therapy, melatonin increased 24-hour systolic/diastolic pressure by about 6.5/4.9 mmHg.
Melatonin → Arterial blood pressure source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/10792199.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "71e8d66126f1339089c1fda1bee67e6ceaf0afb4001d547741056521babf881b", "start_char": 0, "end_char": 1482, "text_sha256": "71e8d66126f1339089c1fda1bee67e6ceaf0afb4001d547741056521babf881b"}
experimental_model
Double-blind crossover drug-context trial
exposure
5 mg melatonin nightly for four weeks; nifedipine GITS 30 or 60 mg daily
limitations
Observed drug-context effect. The authors proposed competition, but a specific transporter, CYP interaction or calcium-channel mechanism was not proven.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
47 hypertensive patients stable on nifedipine
plain_language
A favorable reputation for one pathway does not guarantee the same response with a particular medicine.
primary_references
[melatonin-p10792199] Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine: a 24-hour study. (2000). https://pubmed.ncbi.nlm.nih.gov/10792199/ DOI: 10.1046/j.1365-2125.2000.00195.x
tissue_or_cell_type
Ambulatory blood pressure and heart rate
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 1033–1044
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind crossover drug-context trial · source_derived_draft · unverified_draft
### melatonin-nifedipine-pressure With nifedipine therapy, melatonin increased 24-hour systolic/diastolic pressure by about 6.5/4.9 mmHg. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A favorable reputation for one pathway does not guarantee the same response with a particular medicine. organism: 47 hypertensive patients stable on nifedipine tissue_or_cell_type: Ambulatory blood pressure and heart rate experimental_model: Double-blind crossover drug-context trial limitations: Observed drug-context effect. The authors proposed competition, but a specific transporter, CYP interaction or calcium-channel mechanism was not proven. exposure: 5 mg melatonin nightly for four weeks; nifedipine GITS 30 or 60 mg daily evidence_span: {"source_cache": "artifacts/melatonin-research/10792199.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "71e8d66126f1339089c1fda1bee67e6ceaf0afb4001d547741056521babf881b", "start_char": 0, "end_char": 1482, "text_sha256": "71e8d66126f1339089c1fda1bee67e6ceaf0afb4001d547741056521babf881b"} [melatonin-p10792199] Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine: a 24-hour study. (2000). https://pubmed.ncbi.nlm.nih.gov/10792199/ DOI: 10.1046/j.1365-2125.2000.00195.x
Complete structured claim and evidence
Heart rate increased by about 3.9 beats/minute during the melatonin period.
Melatonin → Heart rate source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/10792199.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "71e8d66126f1339089c1fda1bee67e6ceaf0afb4001d547741056521babf881b", "start_char": 0, "end_char": 1482, "text_sha256": "71e8d66126f1339089c1fda1bee67e6ceaf0afb4001d547741056521babf881b"}
experimental_model
Double-blind crossover drug-context trial
exposure
5 mg melatonin nightly for four weeks; nifedipine GITS 30 or 60 mg daily
limitations
Observed drug-context effect. The authors proposed competition, but a specific transporter, CYP interaction or calcium-channel mechanism was not proven.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
47 hypertensive patients stable on nifedipine
plain_language
This outcome is retained separately from the blood-pressure finding.
primary_references
[melatonin-p10792199] Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine: a 24-hour study. (2000). https://pubmed.ncbi.nlm.nih.gov/10792199/ DOI: 10.1046/j.1365-2125.2000.00195.x
tissue_or_cell_type
Ambulatory blood pressure and heart rate
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 1046–1057
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind crossover drug-context trial · source_derived_draft · unverified_draft
### melatonin-nifedipine-heart-rate Heart rate increased by about 3.9 beats/minute during the melatonin period. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This outcome is retained separately from the blood-pressure finding. organism: 47 hypertensive patients stable on nifedipine tissue_or_cell_type: Ambulatory blood pressure and heart rate experimental_model: Double-blind crossover drug-context trial limitations: Observed drug-context effect. The authors proposed competition, but a specific transporter, CYP interaction or calcium-channel mechanism was not proven. exposure: 5 mg melatonin nightly for four weeks; nifedipine GITS 30 or 60 mg daily evidence_span: {"source_cache": "artifacts/melatonin-research/10792199.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "71e8d66126f1339089c1fda1bee67e6ceaf0afb4001d547741056521babf881b", "start_char": 0, "end_char": 1482, "text_sha256": "71e8d66126f1339089c1fda1bee67e6ceaf0afb4001d547741056521babf881b"} [melatonin-p10792199] Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine: a 24-hour study. (2000). https://pubmed.ncbi.nlm.nih.gov/10792199/ DOI: 10.1046/j.1365-2125.2000.00195.x
Complete structured claim and evidence
Melatonin impaired glucose tolerance during both morning and evening challenges.
Melatonin → Glucose tolerance source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/25197811.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a2ed431f069ffbe6ace434aba258b90c154b1d07e4c6b92816cba26bb3b31c04", "start_char": 0, "end_char": 1466, "text_sha256": "a2ed431f069ffbe6ace434aba258b90c154b1d07e4c6b92816cba26bb3b31c04"}
experimental_model
Single-blind placebo-controlled glucose challenges
exposure
5 mg melatonin 15 minutes before 75 g OGTT at 09:00 or 21:00
limitations
Acute high-exposure challenge; not evidence that every bedtime regimen causes diabetes. Estimated mechanisms varied by time of day.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
21 healthy young women
plain_language
Melatonin exposure close to carbohydrate intake can matter metabolically.
primary_references
[melatonin-p25197811] Acute melatonin administration in humans impairs glucose tolerance in both the morning and evening. (2014). https://pubmed.ncbi.nlm.nih.gov/25197811/ DOI: 10.5665/sleep.4088
tissue_or_cell_type
Oral glucose tolerance in morning and evening
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 1059–1070
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-blind placebo-controlled glucose challenges · source_derived_draft · unverified_draft
### melatonin-acute-glucose Melatonin impaired glucose tolerance during both morning and evening challenges. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Melatonin exposure close to carbohydrate intake can matter metabolically. organism: 21 healthy young women tissue_or_cell_type: Oral glucose tolerance in morning and evening experimental_model: Single-blind placebo-controlled glucose challenges limitations: Acute high-exposure challenge; not evidence that every bedtime regimen causes diabetes. Estimated mechanisms varied by time of day. exposure: 5 mg melatonin 15 minutes before 75 g OGTT at 09:00 or 21:00 evidence_span: {"source_cache": "artifacts/melatonin-research/25197811.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a2ed431f069ffbe6ace434aba258b90c154b1d07e4c6b92816cba26bb3b31c04", "start_char": 0, "end_char": 1466, "text_sha256": "a2ed431f069ffbe6ace434aba258b90c154b1d07e4c6b92816cba26bb3b31c04"} [melatonin-p25197811] Acute melatonin administration in humans impairs glucose tolerance in both the morning and evening. (2014). https://pubmed.ncbi.nlm.nih.gov/25197811/ DOI: 10.5665/sleep.4088
Complete structured claim and evidence
The morning impairment was attributed primarily to reduced insulin release.
Melatonin → Insulin secretion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/25197811.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a2ed431f069ffbe6ace434aba258b90c154b1d07e4c6b92816cba26bb3b31c04", "start_char": 0, "end_char": 1466, "text_sha256": "a2ed431f069ffbe6ace434aba258b90c154b1d07e4c6b92816cba26bb3b31c04"}
experimental_model
Single-blind placebo-controlled glucose challenges
exposure
5 mg melatonin 15 minutes before 75 g OGTT at 09:00 or 21:00
limitations
Acute high-exposure challenge; not evidence that every bedtime regimen causes diabetes. Estimated mechanisms varied by time of day.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
21 healthy young women
plain_language
Timing changes which part of glucose regulation appears affected.
primary_references
[melatonin-p25197811] Acute melatonin administration in humans impairs glucose tolerance in both the morning and evening. (2014). https://pubmed.ncbi.nlm.nih.gov/25197811/ DOI: 10.5665/sleep.4088
tissue_or_cell_type
Oral glucose tolerance in morning and evening
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 1072–1083
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-blind placebo-controlled glucose challenges · source_derived_draft · unverified_draft
### melatonin-morning-insulin The morning impairment was attributed primarily to reduced insulin release. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Timing changes which part of glucose regulation appears affected. organism: 21 healthy young women tissue_or_cell_type: Oral glucose tolerance in morning and evening experimental_model: Single-blind placebo-controlled glucose challenges limitations: Acute high-exposure challenge; not evidence that every bedtime regimen causes diabetes. Estimated mechanisms varied by time of day. exposure: 5 mg melatonin 15 minutes before 75 g OGTT at 09:00 or 21:00 evidence_span: {"source_cache": "artifacts/melatonin-research/25197811.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a2ed431f069ffbe6ace434aba258b90c154b1d07e4c6b92816cba26bb3b31c04", "start_char": 0, "end_char": 1466, "text_sha256": "a2ed431f069ffbe6ace434aba258b90c154b1d07e4c6b92816cba26bb3b31c04"} [melatonin-p25197811] Acute melatonin administration in humans impairs glucose tolerance in both the morning and evening. (2014). https://pubmed.ncbi.nlm.nih.gov/25197811/ DOI: 10.5665/sleep.4088
Complete structured claim and evidence
The evening impairment was attributed primarily to lower insulin sensitivity in this study.
Melatonin → Insulin sensitivity source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/25197811.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a2ed431f069ffbe6ace434aba258b90c154b1d07e4c6b92816cba26bb3b31c04", "start_char": 0, "end_char": 1466, "text_sha256": "a2ed431f069ffbe6ace434aba258b90c154b1d07e4c6b92816cba26bb3b31c04"}
experimental_model
Single-blind placebo-controlled glucose challenges
exposure
5 mg melatonin 15 minutes before 75 g OGTT at 09:00 or 21:00
limitations
Acute high-exposure challenge; not evidence that every bedtime regimen causes diabetes. Estimated mechanisms varied by time of day.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
21 healthy young women
plain_language
The same exposure can have different physiological components at another time.
primary_references
[melatonin-p25197811] Acute melatonin administration in humans impairs glucose tolerance in both the morning and evening. (2014). https://pubmed.ncbi.nlm.nih.gov/25197811/ DOI: 10.5665/sleep.4088
tissue_or_cell_type
Oral glucose tolerance in morning and evening
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 1085–1096
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-blind placebo-controlled glucose challenges · source_derived_draft · unverified_draft
### melatonin-evening-sensitivity The evening impairment was attributed primarily to lower insulin sensitivity in this study. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same exposure can have different physiological components at another time. organism: 21 healthy young women tissue_or_cell_type: Oral glucose tolerance in morning and evening experimental_model: Single-blind placebo-controlled glucose challenges limitations: Acute high-exposure challenge; not evidence that every bedtime regimen causes diabetes. Estimated mechanisms varied by time of day. exposure: 5 mg melatonin 15 minutes before 75 g OGTT at 09:00 or 21:00 evidence_span: {"source_cache": "artifacts/melatonin-research/25197811.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a2ed431f069ffbe6ace434aba258b90c154b1d07e4c6b92816cba26bb3b31c04", "start_char": 0, "end_char": 1466, "text_sha256": "a2ed431f069ffbe6ace434aba258b90c154b1d07e4c6b92816cba26bb3b31c04"} [melatonin-p25197811] Acute melatonin administration in humans impairs glucose tolerance in both the morning and evening. (2014). https://pubmed.ncbi.nlm.nih.gov/25197811/ DOI: 10.5665/sleep.4088
Complete structured claim and evidence
Risk G-allele carriers had increased MTNR1B expression in human islets.
Human MTNR1B rs10830963 G risk allele → Human islet MTNR1B expression source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/27185156.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "61fcf7c730c1349e5b306e5c9cfcabcb2905290d7f8762cbfba06f2b5fccaded", "start_char": 0, "end_char": 1043, "text_sha256": "61fcf7c730c1349e5b306e5c9cfcabcb2905290d7f8762cbfba06f2b5fccaded"}
experimental_model
Human islet genetics, cell experiments and recall-by-genotype intervention
exposure
Risk G allele, receptor overexpression and melatonin exposure
limitations
Genotype associations, cultured-cell manipulation and human intervention are separate evidence types. Do not generalize islet signaling to every tissue.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human islets and volunteers; separate insulin-cell and mouse experiments
plain_language
A receptor-gene variant can change the strength of a hormone response.
primary_references
[melatonin-p27185156] Increased Melatonin Signaling Is a Risk Factor for Type 2 Diabetes. (2016). https://pubmed.ncbi.nlm.nih.gov/27185156/ DOI: 10.1016/j.cmet.2016.04.009
tissue_or_cell_type
MTNR1B signaling and insulin secretion
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 1098–1109
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human islet genetics, cell experiments and recall-by-genotype intervention · source_derived_draft · unverified_draft
### melatonin-mtnr1b-risk-expression Risk G-allele carriers had increased MTNR1B expression in human islets. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A receptor-gene variant can change the strength of a hormone response. organism: Human islets and volunteers; separate insulin-cell and mouse experiments tissue_or_cell_type: MTNR1B signaling and insulin secretion experimental_model: Human islet genetics, cell experiments and recall-by-genotype intervention limitations: Genotype associations, cultured-cell manipulation and human intervention are separate evidence types. Do not generalize islet signaling to every tissue. exposure: Risk G allele, receptor overexpression and melatonin exposure evidence_span: {"source_cache": "artifacts/melatonin-research/27185156.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "61fcf7c730c1349e5b306e5c9cfcabcb2905290d7f8762cbfba06f2b5fccaded", "start_char": 0, "end_char": 1043, "text_sha256": "61fcf7c730c1349e5b306e5c9cfcabcb2905290d7f8762cbfba06f2b5fccaded"} [melatonin-p27185156] Increased Melatonin Signaling Is a Risk Factor for Type 2 Diabetes. (2016). https://pubmed.ncbi.nlm.nih.gov/27185156/ DOI: 10.1016/j.cmet.2016.04.009
Complete structured claim and evidence
Melatonin lowered cAMP in the insulin-secreting cells in the study.
Melatonin → Intracellular cyclic AMP content source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/27185156.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "61fcf7c730c1349e5b306e5c9cfcabcb2905290d7f8762cbfba06f2b5fccaded", "start_char": 0, "end_char": 1043, "text_sha256": "61fcf7c730c1349e5b306e5c9cfcabcb2905290d7f8762cbfba06f2b5fccaded"}
experimental_model
Human islet genetics, cell experiments and recall-by-genotype intervention
exposure
Risk G allele, receptor overexpression and melatonin exposure
limitations
Genotype associations, cultured-cell manipulation and human intervention are separate evidence types. Do not generalize islet signaling to every tissue.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human islets and volunteers; separate insulin-cell and mouse experiments
plain_language
The receptor signal meets a messenger involved in insulin release.
primary_references
[melatonin-p27185156] Increased Melatonin Signaling Is a Risk Factor for Type 2 Diabetes. (2016). https://pubmed.ncbi.nlm.nih.gov/27185156/ DOI: 10.1016/j.cmet.2016.04.009
tissue_or_cell_type
MTNR1B signaling and insulin secretion
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 1111–1122
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human islet genetics, cell experiments and recall-by-genotype intervention · source_derived_draft · unverified_draft
### melatonin-islet-camp Melatonin lowered cAMP in the insulin-secreting cells in the study. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The receptor signal meets a messenger involved in insulin release. organism: Human islets and volunteers; separate insulin-cell and mouse experiments tissue_or_cell_type: MTNR1B signaling and insulin secretion experimental_model: Human islet genetics, cell experiments and recall-by-genotype intervention limitations: Genotype associations, cultured-cell manipulation and human intervention are separate evidence types. Do not generalize islet signaling to every tissue. exposure: Risk G allele, receptor overexpression and melatonin exposure evidence_span: {"source_cache": "artifacts/melatonin-research/27185156.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "61fcf7c730c1349e5b306e5c9cfcabcb2905290d7f8762cbfba06f2b5fccaded", "start_char": 0, "end_char": 1043, "text_sha256": "61fcf7c730c1349e5b306e5c9cfcabcb2905290d7f8762cbfba06f2b5fccaded"} [melatonin-p27185156] Increased Melatonin Signaling Is a Risk Factor for Type 2 Diabetes. (2016). https://pubmed.ncbi.nlm.nih.gov/27185156/ DOI: 10.1016/j.cmet.2016.04.009
Complete structured claim and evidence
MTNR1B overexpression exaggerated melatonin-associated inhibition of insulin release in cells.
MTNR1B overexpression in experimental insulin-secreting cells → Insulin secretion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/27185156.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "61fcf7c730c1349e5b306e5c9cfcabcb2905290d7f8762cbfba06f2b5fccaded", "start_char": 0, "end_char": 1043, "text_sha256": "61fcf7c730c1349e5b306e5c9cfcabcb2905290d7f8762cbfba06f2b5fccaded"}
experimental_model
Human islet genetics, cell experiments and recall-by-genotype intervention
exposure
Risk G allele, receptor overexpression and melatonin exposure
limitations
Genotype associations, cultured-cell manipulation and human intervention are separate evidence types. Do not generalize islet signaling to every tissue.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human islets and volunteers; separate insulin-cell and mouse experiments
plain_language
More receptor can strengthen this inhibitory response.
primary_references
[melatonin-p27185156] Increased Melatonin Signaling Is a Risk Factor for Type 2 Diabetes. (2016). https://pubmed.ncbi.nlm.nih.gov/27185156/ DOI: 10.1016/j.cmet.2016.04.009
tissue_or_cell_type
MTNR1B signaling and insulin secretion
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 1124–1135
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human islet genetics, cell experiments and recall-by-genotype intervention · source_derived_draft · unverified_draft
### melatonin-islet-overexpression MTNR1B overexpression exaggerated melatonin-associated inhibition of insulin release in cells. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: More receptor can strengthen this inhibitory response. organism: Human islets and volunteers; separate insulin-cell and mouse experiments tissue_or_cell_type: MTNR1B signaling and insulin secretion experimental_model: Human islet genetics, cell experiments and recall-by-genotype intervention limitations: Genotype associations, cultured-cell manipulation and human intervention are separate evidence types. Do not generalize islet signaling to every tissue. exposure: Risk G allele, receptor overexpression and melatonin exposure evidence_span: {"source_cache": "artifacts/melatonin-research/27185156.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "61fcf7c730c1349e5b306e5c9cfcabcb2905290d7f8762cbfba06f2b5fccaded", "start_char": 0, "end_char": 1043, "text_sha256": "61fcf7c730c1349e5b306e5c9cfcabcb2905290d7f8762cbfba06f2b5fccaded"} [melatonin-p27185156] Increased Melatonin Signaling Is a Risk Factor for Type 2 Diabetes. (2016). https://pubmed.ncbi.nlm.nih.gov/27185156/ DOI: 10.1016/j.cmet.2016.04.009
Complete structured claim and evidence
The human recall-by-genotype study found greater insulin-secretion reduction and glucose elevation in G-allele carriers.
Melatonin → Insulin secretion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/27185156.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "61fcf7c730c1349e5b306e5c9cfcabcb2905290d7f8762cbfba06f2b5fccaded", "start_char": 0, "end_char": 1043, "text_sha256": "61fcf7c730c1349e5b306e5c9cfcabcb2905290d7f8762cbfba06f2b5fccaded"}
experimental_model
Human islet genetics, cell experiments and recall-by-genotype intervention
exposure
Risk G allele, receptor overexpression and melatonin exposure
limitations
Genotype associations, cultured-cell manipulation and human intervention are separate evidence types. Do not generalize islet signaling to every tissue.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
Human islets and volunteers; separate insulin-cell and mouse experiments
plain_language
A response can vary with receptor genotype.
primary_references
[melatonin-p27185156] Increased Melatonin Signaling Is a Risk Factor for Type 2 Diabetes. (2016). https://pubmed.ncbi.nlm.nih.gov/27185156/ DOI: 10.1016/j.cmet.2016.04.009
tissue_or_cell_type
MTNR1B signaling and insulin secretion
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 1137–1148
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human islet genetics, cell experiments and recall-by-genotype intervention · source_derived_draft · unverified_draft
### melatonin-genotype-human-insulin The human recall-by-genotype study found greater insulin-secretion reduction and glucose elevation in G-allele carriers. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A response can vary with receptor genotype. organism: Human islets and volunteers; separate insulin-cell and mouse experiments tissue_or_cell_type: MTNR1B signaling and insulin secretion experimental_model: Human islet genetics, cell experiments and recall-by-genotype intervention limitations: Genotype associations, cultured-cell manipulation and human intervention are separate evidence types. Do not generalize islet signaling to every tissue. exposure: Risk G allele, receptor overexpression and melatonin exposure evidence_span: {"source_cache": "artifacts/melatonin-research/27185156.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "61fcf7c730c1349e5b306e5c9cfcabcb2905290d7f8762cbfba06f2b5fccaded", "start_char": 0, "end_char": 1043, "text_sha256": "61fcf7c730c1349e5b306e5c9cfcabcb2905290d7f8762cbfba06f2b5fccaded"} [melatonin-p27185156] Increased Melatonin Signaling Is a Risk Factor for Type 2 Diabetes. (2016). https://pubmed.ncbi.nlm.nih.gov/27185156/ DOI: 10.1016/j.cmet.2016.04.009
Complete structured claim and evidence
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
Glucose AUC was about 8.3% higher in the late condition, with greater impairment in MTNR1B risk carriers.
Late-evening glucose challenge relative to habitual bedtime → Glucose area under the curve after glucose challenge 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
A meal-timing comparison can reveal susceptibility without proving melatonin is the only mediator.
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 1163–1174
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-glucose Glucose AUC was about 8.3% higher in the late condition, with greater impairment in MTNR1B risk carriers. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A meal-timing comparison can reveal susceptibility without proving melatonin is the only mediator. 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
Insulin AUC was about 6.7% lower in the late condition.
Late-evening glucose challenge relative to habitual bedtime → Plasma insulin response to glucose challenge 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
The glucose rise accompanied a weaker insulin response.
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 1176–1187
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-insulin Insulin AUC was about 6.7% lower in the late condition. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The glucose rise accompanied a weaker insulin response. 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
Melatonin worsened glucose tolerance in MTNR1B risk carriers, while the corresponding impairment was not significant in noncarriers.
Melatonin → Glucose tolerance source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/42346809.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8e4b84650338084b0a878a3b06138c9ef65502d7f9b119877434421b5131bc6", "start_char": 0, "end_char": 1941, "text_sha256": "a8e4b84650338084b0a878a3b06138c9ef65502d7f9b119877434421b5131bc6"}
experimental_model
Randomized double-blind placebo-controlled crossover physiology trial
exposure
5 mg oral melatonin; five-day laboratory protocol
limitations
Small genotype-stratified acute study published in 2026. Stronger carrier findings are not a population-wide diabetes risk estimate or evidence about all chronic formulations.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
21 healthy European-ancestry participants: 10 risk carriers, 11 noncarriers
plain_language
The recent controlled study found a genotype-dependent response.
primary_references
[melatonin-p42346809] Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With MTNR1B Diabetes Risk Variant. (2026). https://pubmed.ncbi.nlm.nih.gov/42346809/ DOI: 10.2337/dc26-0164
tissue_or_cell_type
Insulin-modified IV glucose test and beta-cell modeling
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 1189–1200
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled crossover physiology trial · source_derived_draft · unverified_draft
### melatonin-2026-glucose-carriers Melatonin worsened glucose tolerance in MTNR1B risk carriers, while the corresponding impairment was not significant in noncarriers. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The recent controlled study found a genotype-dependent response. organism: 21 healthy European-ancestry participants: 10 risk carriers, 11 noncarriers tissue_or_cell_type: Insulin-modified IV glucose test and beta-cell modeling experimental_model: Randomized double-blind placebo-controlled crossover physiology trial limitations: Small genotype-stratified acute study published in 2026. Stronger carrier findings are not a population-wide diabetes risk estimate or evidence about all chronic formulations. exposure: 5 mg oral melatonin; five-day laboratory protocol evidence_span: {"source_cache": "artifacts/melatonin-research/42346809.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8e4b84650338084b0a878a3b06138c9ef65502d7f9b119877434421b5131bc6", "start_char": 0, "end_char": 1941, "text_sha256": "a8e4b84650338084b0a878a3b06138c9ef65502d7f9b119877434421b5131bc6"} [melatonin-p42346809] Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With MTNR1B Diabetes Risk Variant. (2026). https://pubmed.ncbi.nlm.nih.gov/42346809/ DOI: 10.2337/dc26-0164
Complete structured claim and evidence
Risk carriers showed a slower insulin-induced decline in second-phase insulin secretion during melatonin exposure.
Melatonin → Suppression of insulin secretion by exogenous insulin source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/42346809.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8e4b84650338084b0a878a3b06138c9ef65502d7f9b119877434421b5131bc6", "start_char": 0, "end_char": 1941, "text_sha256": "a8e4b84650338084b0a878a3b06138c9ef65502d7f9b119877434421b5131bc6"}
experimental_model
Randomized double-blind placebo-controlled crossover physiology trial
exposure
5 mg oral melatonin; five-day laboratory protocol
limitations
Small genotype-stratified acute study published in 2026. Stronger carrier findings are not a population-wide diabetes risk estimate or evidence about all chronic formulations.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
21 healthy European-ancestry participants: 10 risk carriers, 11 noncarriers
plain_language
Regulation by insulin itself changed as well as the response to glucose.
primary_references
[melatonin-p42346809] Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With MTNR1B Diabetes Risk Variant. (2026). https://pubmed.ncbi.nlm.nih.gov/42346809/ DOI: 10.2337/dc26-0164
tissue_or_cell_type
Insulin-modified IV glucose test and beta-cell modeling
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 1215–1226
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled crossover physiology trial · source_derived_draft · unverified_draft
### melatonin-2026-insulin-feedback Risk carriers showed a slower insulin-induced decline in second-phase insulin secretion during melatonin exposure. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Regulation by insulin itself changed as well as the response to glucose. organism: 21 healthy European-ancestry participants: 10 risk carriers, 11 noncarriers tissue_or_cell_type: Insulin-modified IV glucose test and beta-cell modeling experimental_model: Randomized double-blind placebo-controlled crossover physiology trial limitations: Small genotype-stratified acute study published in 2026. Stronger carrier findings are not a population-wide diabetes risk estimate or evidence about all chronic formulations. exposure: 5 mg oral melatonin; five-day laboratory protocol evidence_span: {"source_cache": "artifacts/melatonin-research/42346809.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8e4b84650338084b0a878a3b06138c9ef65502d7f9b119877434421b5131bc6", "start_char": 0, "end_char": 1941, "text_sha256": "a8e4b84650338084b0a878a3b06138c9ef65502d7f9b119877434421b5131bc6"} [melatonin-p42346809] Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With MTNR1B Diabetes Risk Variant. (2026). https://pubmed.ncbi.nlm.nih.gov/42346809/ DOI: 10.2337/dc26-0164
Complete structured claim and evidence
Risk carriers had no insulin-induced hypoglycemia events with melatonin versus seven with placebo in the test.
Melatonin → Hypoglycemia during an insulin-modified glucose test source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/42346809.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8e4b84650338084b0a878a3b06138c9ef65502d7f9b119877434421b5131bc6", "start_char": 0, "end_char": 1941, "text_sha256": "a8e4b84650338084b0a878a3b06138c9ef65502d7f9b119877434421b5131bc6"}
experimental_model
Randomized double-blind placebo-controlled crossover physiology trial
exposure
5 mg oral melatonin; five-day laboratory protocol
limitations
Small genotype-stratified acute study published in 2026. Stronger carrier findings are not a population-wide diabetes risk estimate or evidence about all chronic formulations.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
21 healthy European-ancestry participants: 10 risk carriers, 11 noncarriers
plain_language
This experimental observation is not evidence to use melatonin as a hypoglycemia treatment.
primary_references
[melatonin-p42346809] Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With MTNR1B Diabetes Risk Variant. (2026). https://pubmed.ncbi.nlm.nih.gov/42346809/ DOI: 10.2337/dc26-0164
tissue_or_cell_type
Insulin-modified IV glucose test and beta-cell modeling
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 1228–1239
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled crossover physiology trial · source_derived_draft · unverified_draft
### melatonin-2026-hypoglycemia Risk carriers had no insulin-induced hypoglycemia events with melatonin versus seven with placebo in the test. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This experimental observation is not evidence to use melatonin as a hypoglycemia treatment. organism: 21 healthy European-ancestry participants: 10 risk carriers, 11 noncarriers tissue_or_cell_type: Insulin-modified IV glucose test and beta-cell modeling experimental_model: Randomized double-blind placebo-controlled crossover physiology trial limitations: Small genotype-stratified acute study published in 2026. Stronger carrier findings are not a population-wide diabetes risk estimate or evidence about all chronic formulations. exposure: 5 mg oral melatonin; five-day laboratory protocol evidence_span: {"source_cache": "artifacts/melatonin-research/42346809.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8e4b84650338084b0a878a3b06138c9ef65502d7f9b119877434421b5131bc6", "start_char": 0, "end_char": 1941, "text_sha256": "a8e4b84650338084b0a878a3b06138c9ef65502d7f9b119877434421b5131bc6"} [melatonin-p42346809] Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With MTNR1B Diabetes Risk Variant. (2026). https://pubmed.ncbi.nlm.nih.gov/42346809/ DOI: 10.2337/dc26-0164
Complete structured claim and evidence
Atenolol treatment was associated with lower urinary aMT6s and a small increase in blood glucose.
Atenolol → Urinary 6-sulfatoxymelatonin excretion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/26946962.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ad9bf60e8f57ef2ec9fe9e4b74b848b9cc0711fe00cf5a9959bf489dd9c8f992", "start_char": 0, "end_char": 1191, "text_sha256": "ad9bf60e8f57ef2ec9fe9e4b74b848b9cc0711fe00cf5a9959bf489dd9c8f992"}
experimental_model
Nine-week antihypertensive pharmacogenetic cohort analysis
exposure
Atenolol treatment; urinary aMT6s normalized to creatinine
limitations
Association study; absence of correlation is not proof of no biological role. It does not support a simple linear explanation of atenolol-related glucose changes by lost melatonin.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
232 hypertensive participants reported as Caucasian in PEAR
plain_language
Metabolite excretion and glucose changed during the same treatment.
primary_references
[melatonin-p26946962] Melatonin Pathway and Atenolol-Related Glucose Dysregulation: Is There a Correlation? (2016). https://pubmed.ncbi.nlm.nih.gov/26946962/ DOI: 10.1111/cts.12389
tissue_or_cell_type
Urinary melatonin metabolite and blood glucose
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 1241–1252
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nine-week antihypertensive pharmacogenetic cohort analysis · source_derived_draft · unverified_draft
### melatonin-atenolol-metabolite Atenolol treatment was associated with lower urinary aMT6s and a small increase in blood glucose. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Metabolite excretion and glucose changed during the same treatment. organism: 232 hypertensive participants reported as Caucasian in PEAR tissue_or_cell_type: Urinary melatonin metabolite and blood glucose experimental_model: Nine-week antihypertensive pharmacogenetic cohort analysis limitations: Association study; absence of correlation is not proof of no biological role. It does not support a simple linear explanation of atenolol-related glucose changes by lost melatonin. exposure: Atenolol treatment; urinary aMT6s normalized to creatinine evidence_span: {"source_cache": "artifacts/melatonin-research/26946962.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ad9bf60e8f57ef2ec9fe9e4b74b848b9cc0711fe00cf5a9959bf489dd9c8f992", "start_char": 0, "end_char": 1191, "text_sha256": "ad9bf60e8f57ef2ec9fe9e4b74b848b9cc0711fe00cf5a9959bf489dd9c8f992"} [melatonin-p26946962] Melatonin Pathway and Atenolol-Related Glucose Dysregulation: Is There a Correlation? (2016). https://pubmed.ncbi.nlm.nih.gov/26946962/ DOI: 10.1111/cts.12389
Complete structured claim and evidence
The aMT6s change did not correlate with the post-atenolol blood-glucose change.
Urinary 6-sulfatoxymelatonin excretion → Fasting plasma glucose source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/melatonin-research/26946962.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ad9bf60e8f57ef2ec9fe9e4b74b848b9cc0711fe00cf5a9959bf489dd9c8f992", "start_char": 0, "end_char": 1191, "text_sha256": "ad9bf60e8f57ef2ec9fe9e4b74b848b9cc0711fe00cf5a9959bf489dd9c8f992"}
experimental_model
Nine-week antihypertensive pharmacogenetic cohort analysis
exposure
Atenolol treatment; urinary aMT6s normalized to creatinine
limitations
Association study; absence of correlation is not proof of no biological role. It does not support a simple linear explanation of atenolol-related glucose changes by lost melatonin.
nutrient_topic
Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
organism
232 hypertensive participants reported as Caucasian in PEAR
plain_language
Two effects occurring together do not show that one caused the other.
primary_references
[melatonin-p26946962] Melatonin Pathway and Atenolol-Related Glucose Dysregulation: Is There a Correlation? (2016). https://pubmed.ncbi.nlm.nih.gov/26946962/ DOI: 10.1111/cts.12389
tissue_or_cell_type
Fasting blood glucose change, not an OGTT-derived tolerance index
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 1254–1265
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nine-week antihypertensive pharmacogenetic cohort analysis · source_derived_draft · unverified_draft
### melatonin-atenolol-correlation-null The aMT6s change did not correlate with the post-atenolol blood-glucose change. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Two effects occurring together do not show that one caused the other. organism: 232 hypertensive participants reported as Caucasian in PEAR tissue_or_cell_type: Fasting blood glucose change, not an OGTT-derived tolerance index experimental_model: Nine-week antihypertensive pharmacogenetic cohort analysis limitations: Association study; absence of correlation is not proof of no biological role. It does not support a simple linear explanation of atenolol-related glucose changes by lost melatonin. exposure: Atenolol treatment; urinary aMT6s normalized to creatinine evidence_span: {"source_cache": "artifacts/melatonin-research/26946962.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ad9bf60e8f57ef2ec9fe9e4b74b848b9cc0711fe00cf5a9959bf489dd9c8f992", "start_char": 0, "end_char": 1191, "text_sha256": "ad9bf60e8f57ef2ec9fe9e4b74b848b9cc0711fe00cf5a9959bf489dd9c8f992"} [melatonin-p26946962] Melatonin Pathway and Atenolol-Related Glucose Dysregulation: Is There a Correlation? (2016). https://pubmed.ncbi.nlm.nih.gov/26946962/ DOI: 10.1111/cts.12389
Complete structured claim and evidence
Expressed human DDC decarboxylated 5-hydroxy-L-tryptophan; added PLP enhanced the measured activity.
Human aromatic L-amino acid decarboxylase / DDC → Serotonin source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human DDC expressed in monkey COS cells; enzyme assays
exposure
PLP addition to transfected COS-cell enzyme incubations.
limitations
An expression-system response is not proof that supplements increase brain monoamines.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Human DDC expressed in monkey COS cells
plain_language
B6 cofactor supports this monoamine-producing step.
primary_references
[sumi-1990-ddc] Characterization of recombinant human aromatic L-amino acid decarboxylase expressed in COS cells (1990). https://doi.org/10.1111/j.1471-4159.1990.tb04601.x DOI: 10.1111/j.1471-4159.1990.tb04601.x
tissue_or_cell_type
COS-cell expression system
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1011–1021
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human DDC expressed in monkey COS cells; enzyme assays · source_derived_draft · unverified_draft
### b6-neuro-ddc-serotonin Expressed human DDC decarboxylated 5-hydroxy-L-tryptophan; added PLP enhanced the measured activity. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: B6 cofactor supports this monoamine-producing step. organism: Human DDC expressed in monkey COS cells tissue_or_cell_type: COS-cell expression system experimental_model: Human DDC expressed in monkey COS cells; enzyme assays limitations: An expression-system response is not proof that supplements increase brain monoamines. exposure: PLP addition to transfected COS-cell enzyme incubations. [sumi-1990-ddc] Characterization of recombinant human aromatic L-amino acid decarboxylase expressed in COS cells (1990). https://doi.org/10.1111/j.1471-4159.1990.tb04601.x DOI: 10.1111/j.1471-4159.1990.tb04601.x
Complete structured claim and evidence
Human holoDDC crystallography resolved an internal PLP aldimine at 1.9 angstrom resolution.
PLP → Human aromatic L-amino acid decarboxylase / DDC source_derived_draftungraded
Experimental context and source evidence
experimental_model
Recombinant human DDC structures, SAXS and molecular dynamics
exposure
Crystallized purified holoenzyme.
limitations
Structure describes a catalytic state, not a dietary dose requirement.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The active B6 cofactor is chemically attached inside DDC.
primary_references
[bisello-2023-ddc] Human aromatic amino acid decarboxylase is an asymmetric and flexible enzyme: Implication in aromatic amino acid decarboxylase deficiency (2023). https://pmc.ncbi.nlm.nih.gov/articles/PMC10382914/ DOI: 10.1002/pro.4732
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1035–1045
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human DDC structures, SAXS and molecular dynamics · source_derived_draft · unverified_draft
### b6-neuro-ddc-internal-aldimine Human holoDDC crystallography resolved an internal PLP aldimine at 1.9 angstrom resolution. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The active B6 cofactor is chemically attached inside DDC. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human DDC structures, SAXS and molecular dynamics limitations: Structure describes a catalytic state, not a dietary dose requirement. exposure: Crystallized purified holoenzyme. [bisello-2023-ddc] Human aromatic amino acid decarboxylase is an asymmetric and flexible enzyme: Implication in aromatic amino acid decarboxylase deficiency (2023). https://pmc.ncbi.nlm.nih.gov/articles/PMC10382914/ DOI: 10.1002/pro.4732
Complete structured claim and evidence
Human PANK3 catalyzes ATP-dependent conversion of pantothenate to 4′-phosphopantothenate.
Human pantothenate kinase 3 / PANK3 → Pantothenate (vitamin B5) source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Purified recombinant human PANK3, crystallography and biochemical ligand-binding/heterodimer experiments
exposure
In-vitro biochemical exposure; concentrations not extracted.
limitations
Abstract-level structural and biochemical findings; no diet or Mg-repletion experiment. Substrate concentrations not established here.
nutrient_topic
Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
organism
Homo sapiens
plain_language
PANK3 starts vitamin B5 activation by adding phosphate.
primary_references
[b5-bio-pank3allosteric] Allosteric Regulation of Mammalian Pantothenate Kinase. (2016). https://pubmed.ncbi.nlm.nih.gov/27555321/ DOI: 10.1074/jbc.m116.748061
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 483–494
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human PANK3, crystallography and biochemical ligand-binding/heterodimer experiments · source_derived_draft · unverified_draft
### b5-bio-pank3-phosphorylation Human PANK3 catalyzes ATP-dependent conversion of pantothenate to 4′-phosphopantothenate. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: PANK3 starts vitamin B5 activation by adding phosphate. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified recombinant human PANK3, crystallography and biochemical ligand-binding/heterodimer experiments limitations: Abstract-level structural and biochemical findings; no diet or Mg-repletion experiment. Substrate concentrations not established here. exposure: In-vitro biochemical exposure; concentrations not extracted. cross_nutrient: true [b5-bio-pank3allosteric] Allosteric Regulation of Mammalian Pantothenate Kinase. (2016). https://pubmed.ncbi.nlm.nih.gov/27555321/ DOI: 10.1074/jbc.m116.748061
Complete structured claim and evidence
Reconstituted human MTR transfers methylfolate-derived methyl groups through cobalamin to homocysteine, producing methionine and THF.
Cobalamin-dependent methionine synthase / MTR → L-Methionine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Folate methyl transfer requires B12.
experimental_model
Human MTR/MTRR expressed in insect cells; purified enzymes and extracts.
limitations
Chemistry, not dietary response.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Homo sapiens
plain_language
B12-dependent MTR recycles both homocysteine and folate.
primary_references
[yamada-2006] Human methionine synthase reductase is a molecular chaperone for human methionine synthase (2006). https://pubmed.ncbi.nlm.nih.gov/16769880/ DOI: 10.1073/pnas.0603694103
tissue_or_cell_type
Purified protein
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 482–492
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human MTR/MTRR expressed in insect cells; purified enzymes and extracts. · source_derived_draft · unverified_draft
### folate-methyl-mtr-methyl-transfer Reconstituted human MTR transfers methylfolate-derived methyl groups through cobalamin to homocysteine, producing methionine and THF. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: B12-dependent MTR recycles both homocysteine and folate. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Human MTR/MTRR expressed in insect cells; purified enzymes and extracts. limitations: Chemistry, not dietary response. cross_nutrient: Folate methyl transfer requires B12. [yamada-2006] Human methionine synthase reductase is a molecular chaperone for human methionine synthase (2006). https://pubmed.ncbi.nlm.nih.gov/16769880/ DOI: 10.1073/pnas.0603694103
Complete structured claim and evidence
Methionine adenosylation supplies SAM, the methyl donor consumed when guanidinoacetate is converted to creatine.
L-Methionine → S-Adenosyl-L-methionine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/11595668.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b195a8b17815bf7d9223831374e2f85ae2f90d8d74117ad7aa8d94af7a9e94b0", "start_char": 0, "end_char": 1687, "text_sha256": "b195a8b17815bf7d9223831374e2f85ae2f90d8d74117ad7aa8d94af7a9e94b0"}
experimental_model
Rat methyl-demand feeding and hepatocyte experiments; reaction context from the primary report
exposure
Guanidinoacetate, creatine and methionine exposures
limitations
The reaction record preserves the biochemical context of this primary experiment; it does not establish a universal fraction of human methylation demand.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Rats
plain_language
Methionine must first be activated into SAM before its methyl group can finish creatine synthesis.
primary_references
[creatine-p11595668] Methylation demand and homocysteine metabolism: effects of dietary provision of creatine and guanidinoacetate. (2001). https://pubmed.ncbi.nlm.nih.gov/11595668/ DOI: 10.1152/ajpendo.2001.281.5.e1095
tissue_or_cell_type
Liver and isolated hepatocytes
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 217–228
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat methyl-demand feeding and hepatocyte experiments; reaction context from the primary report · source_derived_draft · unverified_draft
### creatine-methionine-sam-supply Methionine adenosylation supplies SAM, the methyl donor consumed when guanidinoacetate is converted to creatine. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Methionine must first be activated into SAM before its methyl group can finish creatine synthesis. organism: Rats tissue_or_cell_type: Liver and isolated hepatocytes experimental_model: Rat methyl-demand feeding and hepatocyte experiments; reaction context from the primary report limitations: The reaction record preserves the biochemical context of this primary experiment; it does not establish a universal fraction of human methylation demand. exposure: Guanidinoacetate, creatine and methionine exposures evidence_span: {"source_cache": "artifacts/creatine-research/11595668.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b195a8b17815bf7d9223831374e2f85ae2f90d8d74117ad7aa8d94af7a9e94b0", "start_char": 0, "end_char": 1687, "text_sha256": "b195a8b17815bf7d9223831374e2f85ae2f90d8d74117ad7aa8d94af7a9e94b0"} [creatine-p11595668] Methylation demand and homocysteine metabolism: effects of dietary provision of creatine and guanidinoacetate. (2001). https://pubmed.ncbi.nlm.nih.gov/11595668/ DOI: 10.1152/ajpendo.2001.281.5.e1095
Complete structured claim and evidence
CYP1A2 was the principal high-affinity, but not exclusive, enzyme for melatonin 6-hydroxylation.
Human cytochrome P450 1A2 → Melatonin source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/11317475.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "503f4e9d299c6c978aa1e867a32cdc7b4f5c191290b74415f0f152d3b2f0d87d", "start_char": 0, "end_char": 1580, "text_sha256": "503f4e9d299c6c978aa1e867a32cdc7b4f5c191290b74415f0f152d3b2f0d87d"}
experimental_model
Human microsomes, expressed enzymes and inhibition assays
exposure
Substrate range 1-1000 micromolar
limitations
In-vitro pathway identification; no DIM coadministration, sleep outcome or proof that DIM lowers nighttime melatonin.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human liver CYP systems
plain_language
Melatonin shares the enzyme; a DIM effect on sleep cannot be read directly from this edge.
primary_references
[dim-p11317475] Cytochrome P450 isoforms involved in melatonin metabolism in human liver microsomes. (2001). https://pubmed.ncbi.nlm.nih.gov/11317475/ DOI: 10.1007/s002280000245
tissue_or_cell_type
Melatonin 6-hydroxylation
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 818–829
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human microsomes, expressed enzymes and inhibition assays · source_derived_draft · unverified_draft
### dim-melatonin-1a2 CYP1A2 was the principal high-affinity, but not exclusive, enzyme for melatonin 6-hydroxylation. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Melatonin shares the enzyme; a DIM effect on sleep cannot be read directly from this edge. organism: Human liver CYP systems tissue_or_cell_type: Melatonin 6-hydroxylation experimental_model: Human microsomes, expressed enzymes and inhibition assays limitations: In-vitro pathway identification; no DIM coadministration, sleep outcome or proof that DIM lowers nighttime melatonin. exposure: Substrate range 1-1000 micromolar evidence_span: {"source_cache": "artifacts/dim-research/11317475.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "503f4e9d299c6c978aa1e867a32cdc7b4f5c191290b74415f0f152d3b2f0d87d", "start_char": 0, "end_char": 1580, "text_sha256": "503f4e9d299c6c978aa1e867a32cdc7b4f5c191290b74415f0f152d3b2f0d87d"} [dim-p11317475] Cytochrome P450 isoforms involved in melatonin metabolism in human liver microsomes. (2001). https://pubmed.ncbi.nlm.nih.gov/11317475/ DOI: 10.1007/s002280000245
Complete structured claim and evidence
The CYP1A2 structure places its ligand above the heme prosthetic group.
Human cytochrome P450 1A2 → Heme source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dim-research/17311915.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4c3f047d0ee4583ca15aae2c7059d2237b02105371fda21bf32639cbaad2d318", "start_char": 0, "end_char": 1400, "text_sha256": "4c3f047d0ee4583ca15aae2c7059d2237b02105371fda21bf32639cbaad2d318"}
experimental_model
X-ray crystallography
exposure
Alpha-naphthoflavone-bound structure at 1.95 angstrom resolution
limitations
Structural enzyme requirement; not proof that DIM depletes iron or that iron supplementation changes DIM response.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Purified human CYP1A2
plain_language
The induced enzyme still needs its iron-containing catalytic machinery.
primary_references
[dim-p17311915] Adaptations for the oxidation of polycyclic aromatic hydrocarbons exhibited by the structure of human P450 1A2. (2007). https://pubmed.ncbi.nlm.nih.gov/17311915/ DOI: 10.1074/jbc.m611692200
tissue_or_cell_type
Catalytic pocket
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 259–270
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray crystallography · source_derived_draft · unverified_draft
### dim-cyp1a2-heme The CYP1A2 structure places its ligand above the heme prosthetic group. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The induced enzyme still needs its iron-containing catalytic machinery. organism: Purified human CYP1A2 tissue_or_cell_type: Catalytic pocket experimental_model: X-ray crystallography limitations: Structural enzyme requirement; not proof that DIM depletes iron or that iron supplementation changes DIM response. exposure: Alpha-naphthoflavone-bound structure at 1.95 angstrom resolution evidence_span: {"source_cache": "artifacts/dim-research/17311915.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4c3f047d0ee4583ca15aae2c7059d2237b02105371fda21bf32639cbaad2d318", "start_char": 0, "end_char": 1400, "text_sha256": "4c3f047d0ee4583ca15aae2c7059d2237b02105371fda21bf32639cbaad2d318"} [dim-p17311915] Adaptations for the oxidation of polycyclic aromatic hydrocarbons exhibited by the structure of human P450 1A2. (2007). https://pubmed.ncbi.nlm.nih.gov/17311915/ DOI: 10.1074/jbc.m611692200
Complete structured claim and evidence
POR Y181D lacked bound FMN and poorly supported CYP1A2-catalyzed reactions despite retaining FAD binding and NADPH utilization.
Human POR Y181D variant → Human cytochrome P450 1A2 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/dim-research/19884324.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3f702cc9af1528241d8572b8bcafc23dacb5ed3cacf6bb77403e8aa40d21a214", "start_char": 0, "end_char": 1738, "text_sha256": "3f702cc9af1528241d8572b8bcafc23dacb5ed3cacf6bb77403e8aa40d21a214"}
experimental_model
Recombinant protein and engineered bacterial coexpression
exposure
POR mutation and added FMN
limitations
In-vitro rescue of one mutant; not a dietary-riboflavin deficiency experiment or evidence that FMN reverses a DIM-drug interaction.
nutrient_topic
Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
organism
Human POR Y181D and human CYP1A2 in engineered systems
plain_language
Inducing an enzyme is not enough if its electron-supply machinery fails.
primary_references
[dim-p19884324] Human cytochrome P450 oxidoreductase deficiency caused by the Y181D mutation: molecular consequences and rescue of defect. (2010). https://pubmed.ncbi.nlm.nih.gov/19884324/ DOI: 10.1124/dmd.109.030445
tissue_or_cell_type
FMN-dependent electron transfer
trigger_kind
machinery_impairment Imported condition classification; unverified.
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 272–283
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant protein and engineered bacterial coexpression · source_derived_draft · unverified_draft
### dim-por-fmn-loss POR Y181D lacked bound FMN and poorly supported CYP1A2-catalyzed reactions despite retaining FAD binding and NADPH utilization. Condition category: machinery_impairment nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Inducing an enzyme is not enough if its electron-supply machinery fails. organism: Human POR Y181D and human CYP1A2 in engineered systems tissue_or_cell_type: FMN-dependent electron transfer experimental_model: Recombinant protein and engineered bacterial coexpression limitations: In-vitro rescue of one mutant; not a dietary-riboflavin deficiency experiment or evidence that FMN reverses a DIM-drug interaction. exposure: POR mutation and added FMN evidence_span: {"source_cache": "artifacts/dim-research/19884324.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3f702cc9af1528241d8572b8bcafc23dacb5ed3cacf6bb77403e8aa40d21a214", "start_char": 0, "end_char": 1738, "text_sha256": "3f702cc9af1528241d8572b8bcafc23dacb5ed3cacf6bb77403e8aa40d21a214"} [dim-p19884324] Human cytochrome P450 oxidoreductase deficiency caused by the Y181D mutation: molecular consequences and rescue of defect. (2010). https://pubmed.ncbi.nlm.nih.gov/19884324/ DOI: 10.1124/dmd.109.030445
Complete structured claim and evidence
Human COASY dephospho-CoA kinase activity phosphorylated dephospho-CoA to CoA using ATP; deleting the C-terminal domain retained PPAT but removed DPCK activity.
Coenzyme A synthase / COASY → 3′-Dephospho-coenzyme A source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution
exposure
DPCK assay: 5–100 micromolar dephospho-CoA, 1 mM ATP; coupled ADP readout and direct HPLC product analysis.
limitations
Recombinant enzyme and truncation studies define two distinct COASY activities; no whole-body nutritional threshold is measured.
nutrient_topic
Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
organism
Homo sapiens
plain_language
The final COASY reaction completes CoA.
primary_references
[b5-bio-daugherty2002] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 587–598
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution · source_derived_draft · unverified_draft
### b5-bio-coasy-phosphorylation Human COASY dephospho-CoA kinase activity phosphorylated dephospho-CoA to CoA using ATP; deleting the C-terminal domain retained PPAT but removed DPCK activity. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The final COASY reaction completes CoA. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution limitations: Recombinant enzyme and truncation studies define two distinct COASY activities; no whole-body nutritional threshold is measured. exposure: DPCK assay: 5–100 micromolar dephospho-CoA, 1 mM ATP; coupled ADP readout and direct HPLC product analysis. cross_nutrient: false [b5-bio-daugherty2002] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200
Complete structured claim and evidence

Availability and dependencies

Each situation shows the normal role first, then what the sources report under a specific condition. A shortfall in the diet, a fault in the machinery, and a low blood reading are kept separate because they are not the same thing.

A synthetic enzyme can be impaired even when precursor supply is adequate

Condition: machinery_impairment · An experimentally impaired ASMT variant

Normal role: ASMT methylates N-acetylserotonin using SAM.

Recorded consequence: Reduced enzyme activity can constrain the terminal synthetic step.

Scope: Human recombinant variants; not a dietary melatonin deficiency

A receptor partner can block signaling despite available hormone

Condition: machinery_impairment · GPR50 heterodimerization involving its C-terminal tail

Normal role: MT1 can bind agonist and couple to G proteins.

Recorded consequence: Loss of high-affinity binding and G-protein coupling in the paired MT1 receptor.

Scope: Cultured-cell receptor regulation; not a melatonin dietary shortfall

A low measured night signal can reflect light exposure

Condition: biomarker_context · Evening or night room-light exposure

Normal role: Endogenous secretion normally has a biological-night pattern.

Recorded consequence: Later measured onset, shorter secretion duration and lower levels.

Scope: Human light-exposure context; low biomarker does not establish missing nutrient intake

Medication can suppress the endogenous night signal

Condition: machinery_impairment · Atenolol beta1-receptor blockade

Normal role: Pineal beta1-adrenergic signaling participates in nighttime secretion.

Recorded consequence: Dose-dependent suppression of plasma melatonin.

Scope: Human acute drug exposure; separate from dietary shortage

The sources

Every document behind this chapter is preserved word for word. Open one to read it in full with its recorded conflicts marked in place.

Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source

Recorded disagreements

Where two sources say different things, both are kept and the difference is explained. You can discuss a disagreement or propose a mechanism that might account for it.

Open questions in this collection

Questions the curators could not answer from the sources in front of them, kept here with the reason each one is still open. These are gaps in this collection, not findings or proof that no one has studied them.

Which precursor or cofactor actually limits pineal melatonin synthesis in a specific human context?Biochemical requirements for tryptophan, iron/BH4, PLP, acetyl-CoA and SAM are not clinical thresholds or proof that supplementation increases secretion.
Which timing and exposure best balance sleep outcomes against metabolic effects for different people?Short trials, circadian phase, meal proximity, formulation and MTNR1B genotype differ. These records do not supply an individual dosing algorithm or prove that every nightly regimen raises diabetes risk.
Are long-term effects in pregnancy, childhood and complex medication combinations established by these studies?They are not. Selected adult short-term trials and laboratory mechanisms cannot settle all long-term or population-specific questions; this collection is not exhaustive.
Do DIM, berberine or other supplements change melatonin exposure in people?Their shared CYP nodes identify testable routes. Enzyme induction and direct inhibition can coexist; no measured clinical combination effect is inferred here from graph traversal.
Can B5, folate, B12, magnesium, B6 or zinc repletion reliably restore low melatonin in humans?Nutrient-deficient animals, high-dose vitamin studies, biochemical reactions and multicomponent trials answer different questions. A general rescue rule is unproven.
How much do direct antioxidant chemistry, NQO2 binding and local mitochondrial synthesis contribute at ordinary human exposures?Separate chemical, receptor and organelle experiments do not establish their relative contributions in intact humans. Local levels cannot be inferred from a blood sample.
Does melatonin directly bind nuclear ROR receptors with physiological relevance?Direct ROR agonism is disputed and is not encoded as established here. Changes in ROR expression or reporter activity would not by themselves demonstrate ligand binding.

Chapters are assembled from supplied drafts and curated literature summaries. Statements remain unverified against the primary studies, and the ledger is not medical advice.

Evidence, AI assistance and curation standards

Melatonin

The mechanisms

Purified human pineal TPH catalyzed tryptophan hydroxylation to 5-hydroxytryptophan.

Human AANAT transferred an acetyl group from acetyl-CoA to serotonin, producing N-acetylserotonin.

Human ASMT catalyzes the terminal methylation step converting N-acetylserotonin to melatonin using SAM.

The phase-advance response peaked about five hours before dim-light melatonin onset in the three-pulse experiment.

The phase-delay response peaked about eleven hours after dim-light melatonin onset.

Room light delayed measured melatonin onset in 99% of participants relative to dim light.

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

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

Mean plasma melatonin was about 50 versus 75 pg/mL in magnesium-deficient versus adequate-diet rats.

Evening pyridoxine did not significantly change melatonin onset, peak, mean or AUC relative to placebo.

First-phase beta-cell glucose responsiveness was suppressed by about 40% in risk carriers.

GPR50 abolished MT1 G-protein coupling within the heterodimer.

Human pineal TPH activity was measured with BH4, and a transient 4alpha-hydroxytetrahydrobiopterin intermediate was detected.

The human TPH catalytic domain positioned tryptophan and a pterin analogue near its catalytic non-heme iron.

The human AANAT assay used acetyl-CoA as the acetyl donor in N-acetylserotonin formation.

Human ASMT has a SAM-dependent O-methyltransferase catalytic domain.

The N17K ASMT variant was among variants with reduced or abolished activity in the radioenzymatic screen.

Binding involving both phosphorylated Thr31 and Ser205 lowered ovine AANAT substrate Km to about 30 micromolar.

Binding through Ser205 alone raised substrate Km to about 1200 micromolar in the ovine AANAT system.

Nighttime light exposure decreased ovine AANAT Thr31 phosphorylation.

Nighttime light exposure decreased ovine AANAT Ser205 phosphorylation.

The tested retinoic-acid stereoisomer increased HIOMT mRNA and enzyme activity in Y79 cells.

The tested retinoic-acid stereoisomer increased HIOMT mRNA and enzyme activity in Y79 cells.

The tested retinoic-acid stereoisomer increased HIOMT mRNA and enzyme activity in Y79 cells.

Restoring HIOMT298 in A549 cells restored 5-methoxytryptophan production.

HIOMT298 expression shifted the measured tryptophan metabolism from serotonin toward 5-MTP production.

Expressed human MT1 showed high-affinity iodinated-melatonin binding.

The sheep MT1 receptor inhibited adenylyl cyclase through a pertussis-toxin-sensitive mechanism in transfected cells.

Human MT2 expression supported melatonin-receptor-mediated inhibition of adenylyl cyclase.

Agonist-bound human MT1 was structurally resolved in a Gi signaling complex.

Agonist-bound human MT2 was structurally resolved in a Gi signaling complex.

GPR50 formed heterodimers with MT1 in the tested cell systems.

GPR50 formed heterodimers with MT2 in the same study.

GPR50 abolished MT1 high-affinity agonist binding within the heterodimer.

Association with GPR50 did not modify MT2 function in the experiment.

Melatonin competitively inhibited NQO2 with respect to N-methyldihydronicotinamide, with Ki about 7.2 micromolar.

Against menadione, melatonin showed uncompetitive NQO2 inhibition with Ki about 92 micromolar.

Oxidation of melatonin by singlet oxygen produced AFMK, verified by chemical and spectroscopic analyses.

The study detected melatonin synthesis in the mitochondrial matrix of the tested neuronal system.

The reported mitochondrial MT1 pathway inhibited stress-associated cytochrome c release.

The same experimental mitochondrial pathway reduced downstream caspase activation.

Recombinant human CYP1A1 catalyzed melatonin 6-hydroxylation.

Recombinant human CYP1B1 catalyzed melatonin 6-hydroxylation.

Recombinant human CYP2C19 catalyzed melatonin 6-hydroxylation to a minor extent in this screen.

Human CYP2C19 catalyzed melatonin O-demethylation.

Human CYP1A2 catalyzed melatonin O-demethylation to a lesser extent than CYP2C19 in the study.

SULT1A1 had the strongest tested sulfating activity toward 6-hydroxymelatonin.

SULT1C4 had the strongest tested sulfating activity toward N-acetylserotonin.

Median absolute oral bioavailability was 2.5% in the 10 mg crossover study.

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

Mean elimination half-life was about 54 minutes after oral dosing and 39 minutes after intravenous dosing.

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

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

Endogenous overnight melatonin AUC was similar during smoking and after abstinence.

Sleep amount and architecture were similar after pyridoxine and placebo.

The morning bright-light exposure advanced melatonin phase significantly during the B12 condition but not placebo.

Melatonin rhythm amplitude before the light exposure was smaller during the B12 condition.

The combination improved global PSQI sleep-quality scores compared with placebo.

The first half of habitual sleep corresponded to a region of minimal phase shifts in this protocol.

Prebed room light shortened melatonin duration by about 90 minutes in the analysis.

Light during usual sleep hours suppressed melatonin by more than 50% in most trials.

Six of seven participants entrained to a 24-hour rhythm during melatonin treatment, unlike placebo.

Sleep onset occurred 34 minutes earlier than placebo in the melatonin-plus-scheduling group.

Patient-reported sleep-related impairment improved compared with placebo plus scheduling.

Post-treatment dim-light melatonin onset did not differ significantly between groups in the measured subset of 43 patients.

All tested atenolol doses reduced nocturnal melatonin relative to placebo, with a dose-dependent pattern.

Total sleep time increased by about 36 minutes compared with placebo in beta-blocker-treated patients.

Sleep efficiency increased by about 7.6 percentage points compared with placebo in beta-blocker-treated patients.

Stage 2 sleep increased by about 41 minutes compared with placebo in beta-blocker-treated patients.

Latency to stage 2 sleep decreased by about 14 minutes compared with placebo.

With nifedipine therapy, melatonin increased 24-hour systolic/diastolic pressure by about 6.5/4.9 mmHg.

Heart rate increased by about 3.9 beats/minute during the melatonin period.

Melatonin impaired glucose tolerance during both morning and evening challenges.

The morning impairment was attributed primarily to reduced insulin release.

The evening impairment was attributed primarily to lower insulin sensitivity in this study.

Risk G-allele carriers had increased MTNR1B expression in human islets.

Melatonin lowered cAMP in the insulin-secreting cells in the study.

MTNR1B overexpression exaggerated melatonin-associated inhibition of insulin release in cells.