Component
Melatonin
Melatonin. Species, exposure and limitations are retained in each linked claim.
60 recorded relationships. Experimental role, claim status and evidence remain attached to each record.
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How nutrients influence it
Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.
Other things that act on it
Enzymes, hormones, genes, and other components with a recorded effect. These are not nutrients, so they do not count toward the arrows above. Each finding names the chapter that recorded it.
How nutrients reach it in more than one step
Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.
Tracing routes…
What it does
Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.
What it acts on
First-phase beta-cell glucose responsiveness was suppressed by about 40% in risk carriers.
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 evidenceMelatonin worsened glucose tolerance in MTNR1B risk carriers, while the corresponding impairment was not significant in noncarriers.
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 evidenceRisk carriers had no insulin-induced hypoglycemia events with melatonin versus seven with placebo in the test.
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 evidenceRisk carriers showed a slower insulin-induced decline in second-phase insulin secretion during melatonin exposure.
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 evidenceMelatonin impaired glucose tolerance during both morning and evening challenges.
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 evidenceLatency to stage 2 sleep decreased by about 14 minutes compared with placebo.
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 evidenceTotal sleep time increased by about 36 minutes compared with placebo in beta-blocker-treated patients.
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 evidenceSleep efficiency increased by about 7.6 percentage points compared with placebo in beta-blocker-treated patients.
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 evidenceStage 2 sleep increased by about 41 minutes compared with placebo in beta-blocker-treated patients.
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 evidenceSix of seven participants entrained to a 24-hour rhythm during melatonin treatment, unlike placebo.
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 evidencePatient-reported sleep-related impairment improved compared with placebo plus scheduling.
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 evidencePost-treatment dim-light melatonin onset did not differ significantly between groups in the measured subset of 43 patients.
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 evidenceSleep onset occurred 34 minutes earlier than placebo in the melatonin-plus-scheduling group.
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 evidenceThe evening impairment was attributed primarily to lower insulin sensitivity in this study.
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 evidenceThe human recall-by-genotype study found greater insulin-secretion reduction and glucose elevation in G-allele carriers.
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 evidenceMelatonin lowered cAMP in the insulin-secreting cells in the study.
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 evidenceThe morning impairment was attributed primarily to reduced insulin release.
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 evidenceHeart rate increased by about 3.9 beats/minute during the melatonin period.
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 evidenceWith nifedipine therapy, melatonin increased 24-hour systolic/diastolic pressure by about 6.5/4.9 mmHg.
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 evidenceMelatonin competitively inhibited NQO2 with respect to N-methyldihydronicotinamide, with Ki about 7.2 micromolar.
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 evidenceAgainst menadione, melatonin showed uncompetitive NQO2 inhibition with Ki about 92 micromolar.
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 evidenceMedian absolute oral bioavailability was 2.5% in the 10 mg crossover study.
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 evidenceMean elimination half-life was about 54 minutes after oral dosing and 39 minutes after intravenous dosing.
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 evidenceMean time to peak concentration was about 41 minutes after the tested oral dose.
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 evidenceThe phase-advance response peaked about five hours before dim-light melatonin onset in the three-pulse experiment.
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 evidenceThe first half of habitual sleep corresponded to a region of minimal phase shifts in this protocol.
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 evidenceThe phase-delay response peaked about eleven hours after dim-light melatonin onset.
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 evidenceOxidation of melatonin by singlet oxygen produced AFMK, verified by chemical and spectroscopic analyses.
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 evidenceMelatonin pretreatment reduced sulfanilic-acid-associated impairment of trypsin secretion.
Experimental context and source evidence
- dose
- Sulfanilic acid exposure; melatonin pretreatment 100 micromolar; exact CCK-8 series not in abstract
- duration
- Pretreatment interval not specified in accessed abstract
- evidence_access
- Primary PubMed abstract; unrecovered method details explicitly retained.
- evidence_scope
- literature_reviewed; source-specific experimental curation
- experimental_model
- Rat AR42J pancreatic cells
- limitations
- Pharmacological antioxidant rescue does not establish a clinical melatonin regimen or a specific melatonin receptor mechanism.
- nutrient_topic
- Tartrazine food-colorant chapter; nutrient, drug and peptide interactions retain their models and limits. · Tartrazine
- organism
- Rat AR42J pancreatic cells
- plain_language
- Melatonin pretreatment reduced sulfanilic-acid-associated impairment of trypsin secretion.
- primary_references
- Sulfanilic acid increases intracellular free-calcium concentration, induces reactive oxygen species production and impairs trypsin secretion in pancreatic AR42J cells. (2018). https://pubmed.ncbi.nlm.nih.gov/29986830/ DOI: 10.1016/j.fct.2018.07.001
- route
- In vitro pretreatment and secretagogue challenge
- tissue
- CCK-8-stimulated secretion
Tartrazine: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 204–213
Original AI-assisted curation of eighteen primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Rat AR42J pancreatic cells · source_derived_draft · unverified_draft
## tartrazine-melatonin-rescue Melatonin pretreatment reduced sulfanilic-acid-associated impairment of trypsin secretion. Model/species: Rat AR42J pancreatic cells Tissue: CCK-8-stimulated secretion Exposure: Sulfanilic acid exposure; melatonin pretreatment 100 micromolar; exact CCK-8 series not in abstract Route: In vitro pretreatment and secretagogue challenge Duration: Pretreatment interval not specified in accessed abstract Limits: Pharmacological antioxidant rescue does not establish a clinical melatonin regimen or a specific melatonin receptor mechanism. Primary reference: Sulfanilic acid increases intracellular free-calcium concentration, induces reactive oxygen species production and impairs trypsin secretion in pancreatic AR42J cells. (2018). https://pubmed.ncbi.nlm.nih.gov/29986830/ DOI: 10.1016/j.fct.2018.07.001 Access: Primary PubMed abstract; unrecovered method details explicitly retained.
Complete structured claim and evidence
What acts on it
CYP1A2 was the principal high-affinity, but not exclusive, enzyme for melatonin 6-hydroxylation.
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 evidenceHuman ASMT catalyzes the terminal methylation step converting N-acetylserotonin to melatonin using SAM.
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 evidenceThe study detected melatonin synthesis in the mitochondrial matrix of the tested neuronal system.
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 evidenceD-aspartate inhibited norepinephrine-stimulated melatonin production in rat pineal preparations, with approximately 75 micromolar required for half-maximal inhibition.
Experimental context and source evidence
- evidence_access
- Primary abstract
- experimental_model
- Rat pineal gland/pinealocyte incubation.
- limitations
- Not a human sleep trial or a demonstrated interaction with a melatonin supplement.
- nutrient_topic
- D-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · D-Aspartate
- plain_language
- The compound can reduce stimulated melatonin production in this tissue model.
- primary_references
- D-aspartate modulates melatonin synthesis in rat pinealocytes. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9682837/ · DOI 10.1016/s0304-3940(98)00414-5
D-Aspartate: synthesis, clearance, neural and endocrine mechanisms (2026-09-19) · lines 176–182
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat pineal gland/pinealocyte incubation. · source_derived_draft · unverified_draft
## d-aspartate-pineal-melatonin The compound can reduce stimulated melatonin production in this tissue model. D-aspartate inhibited norepinephrine-stimulated melatonin production in rat pineal preparations, with approximately 75 micromolar required for half-maximal inhibition. Model: Rat pineal gland/pinealocyte incubation. Limitations: Not a human sleep trial or a demonstrated interaction with a melatonin supplement. Evidence access: Primary abstract D-aspartate modulates melatonin synthesis in rat pinealocytes. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9682837/ · DOI 10.1016/s0304-3940(98)00414-5
Complete structured claim and evidence
Where it participates (unsigned role)
The N17K ASMT variant was among variants with reduced or abolished activity in the radioenzymatic screen.
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 evidenceAll tested atenolol doses reduced nocturnal melatonin relative to placebo, with a dose-dependent pattern.
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 evidenceConcurrent caffeine raised melatonin peak concentration by 142% and AUC by 120% on average.
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 evidenceMelatonin AUC and peak concentrations were about four- to fivefold higher in oral-contraceptive users than nonusers.
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 evidenceRecombinant human CYP1A1 catalyzed melatonin 6-hydroxylation.
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 evidenceHuman CYP1A2 catalyzed melatonin O-demethylation to a lesser extent than CYP2C19 in the study.
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 evidenceRecombinant human CYP1B1 catalyzed melatonin 6-hydroxylation.
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 evidenceHuman CYP2C19 catalyzed melatonin O-demethylation.
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 evidenceRecombinant human CYP2C19 catalyzed melatonin 6-hydroxylation to a minor extent in this screen.
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 evidenceFluvoxamine increased melatonin AUC about 17-fold and peak concentration about 12-fold on average.
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 evidenceGPR50 abolished MT1 high-affinity agonist binding within the heterodimer.
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 evidenceGPR50 abolished MT1 G-protein coupling within the heterodimer.
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 evidenceMTNR1B overexpression exaggerated melatonin-associated inhibition of insulin release in cells.
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 evidenceEndogenous melatonin was about 3.5-fold higher in the late condition.
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 evidencePrebed room light shortened melatonin duration by about 90 minutes in the analysis.
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 evidenceLight during usual sleep hours suppressed melatonin by more than 50% in most trials.
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 evidenceRoom light delayed measured melatonin onset in 99% of participants relative to dim light.
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 evidenceMean plasma melatonin was about 50 versus 75 pg/mL in magnesium-deficient versus adequate-diet rats.
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 evidenceThe combination improved global PSQI sleep-quality scores compared with placebo.
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 evidenceThe same experimental mitochondrial pathway reduced downstream caspase activation.
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 evidenceThe reported mitochondrial MT1 pathway inhibited stress-associated cytochrome c release.
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 evidenceExpressed human MT1 showed high-affinity iodinated-melatonin binding.
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 evidenceThe sheep MT1 receptor inhibited adenylyl cyclase through a pertussis-toxin-sensitive mechanism in transfected cells.
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 evidenceHuman MT2 expression supported melatonin-receptor-mediated inhibition of adenylyl cyclase.
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 evidenceOral melatonin AUC was higher after seven days of smoking abstinence than during smoking.
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 evidenceMyricetin treatment lowered nocturnal serum melatonin in rats.
Experimental context and source evidence
- evidence_access
- Primary abstract
- experimental_model
- Rat circadian experiment.
- limitations
- No established human sleep effect or melatonin supplement interaction.
- nutrient_topic
- Myricetin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Myricetin
- plain_language
- A biochemical pathway change was accompanied by a hormone measurement.
- primary_references
- The flavonoid myricetin reduces nocturnal melatonin levels in the blood through the inhibition of serotonin N-acetyltransferase. · 2013 · https://pubmed.ncbi.nlm.nih.gov/24076393/ · DOI 10.1016/j.bbrc.2013.09.076
Myricetin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 572–578
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat circadian experiment. · source_derived_draft · unverified_draft
## myricetin-rat-melatonin A biochemical pathway change was accompanied by a hormone measurement. Myricetin treatment lowered nocturnal serum melatonin in rats. Model: Rat circadian experiment. Limitations: No established human sleep effect or melatonin supplement interaction. Evidence access: Primary abstract The flavonoid myricetin reduces nocturnal melatonin levels in the blood through the inhibition of serotonin N-acetyltransferase. · 2013 · https://pubmed.ncbi.nlm.nih.gov/24076393/ · DOI 10.1016/j.bbrc.2013.09.076
Complete structured claim and evidenceThe pineal melatonin reduction was partly attributed to lower norepinephrine-stimulated serotonin N-acetyltransferase activity.
Experimental context and source evidence
- evidence_access
- Primary abstract
- experimental_model
- Rat pineal preparation enzyme-activity measurements.
- limitations
- Partial mediation; does not establish direct binding of D-aspartate to AANAT.
- nutrient_topic
- D-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · D-Aspartate
- plain_language
- A step in converting serotonin toward melatonin was less active.
- primary_references
- D-aspartate modulates melatonin synthesis in rat pinealocytes. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9682837/ · DOI 10.1016/s0304-3940(98)00414-5
D-Aspartate: synthesis, clearance, neural and endocrine mechanisms (2026-09-19) · lines 184–190
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat pineal preparation enzyme-activity measurements. · source_derived_draft · unverified_draft
## d-aspartate-pineal-aanat A step in converting serotonin toward melatonin was less active. The pineal melatonin reduction was partly attributed to lower norepinephrine-stimulated serotonin N-acetyltransferase activity. Model: Rat pineal preparation enzyme-activity measurements. Limitations: Partial mediation; does not establish direct binding of D-aspartate to AANAT. Evidence access: Primary abstract D-aspartate modulates melatonin synthesis in rat pinealocytes. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9682837/ · DOI 10.1016/s0304-3940(98)00414-5
Complete structured claim and evidence
The events it takes part in
A mechanism often involves more than two components. These are the full events, with every participant and its role.
Situations it appears in
Low-supply and faulty-machinery situations recorded in the chapters where this component plays a part.
In the sources
Preserved passages that mention this component, quoted exactly. Open one to read it in context.
Open hypotheses
Proposed ideas that involve this component. They are labeled as hypotheses and do not change any recorded statement.
This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.