Nutrient chapter

Choline

Independent biological entity. Read linked claims for experimental scope and context.

116 recorded mechanisms · 13 availability situations · 14 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

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

ChAT catalyzes reversible acetylcholine synthesis from choline and acetyl-CoA.
Human choline acetyltransferase / CHAT → Acetylcholine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/11172068.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "691b96b9c5c149c554b99d8e1532ffee25084a8970f8deb23f0991dfd6013d39", "start_char": 0, "end_char": 1231, "text_sha256": "691b96b9c5c149c554b99d8e1532ffee25084a8970f8deb23f0991dfd6013d39"}
experimental_model
Human CHAT genetics, recombinant expression and enzyme kinetics
exposure
Ten recessive variants in five patients; nine mutant proteins assayed
limitations
Inherited enzyme defects, not a dietary choline-deficiency model. Acetyl-CoA and choline are distinct substrates.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human CHAT proteins; COS-cell and bacterial expression systems
plain_language
The neurotransmitter needs both the choline headgroup and an acetyl group supplied by acetyl-CoA.
primary_references
[choline-p11172068] Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans. (2001). https://pubmed.ncbi.nlm.nih.gov/11172068/ DOI: 10.1073/pnas.98.4.2017
tissue_or_cell_type
Neuromuscular acetylcholine resynthesis
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 412–423
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CHAT genetics, recombinant expression and enzyme kinetics · source_derived_draft · unverified_draft
### choline-chat-acetylcholine ChAT catalyzes reversible acetylcholine synthesis from choline and acetyl-CoA. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The neurotransmitter needs both the choline headgroup and an acetyl group supplied by acetyl-CoA. organism: Human CHAT proteins; COS-cell and bacterial expression systems tissue_or_cell_type: Neuromuscular acetylcholine resynthesis experimental_model: Human CHAT genetics, recombinant expression and enzyme kinetics limitations: Inherited enzyme defects, not a dietary choline-deficiency model. Acetyl-CoA and choline are distinct substrates. exposure: Ten recessive variants in five patients; nine mutant proteins assayed evidence_span: {"source_cache": "artifacts/choline-research/11172068.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "691b96b9c5c149c554b99d8e1532ffee25084a8970f8deb23f0991dfd6013d39", "start_char": 0, "end_char": 1231, "text_sha256": "691b96b9c5c149c554b99d8e1532ffee25084a8970f8deb23f0991dfd6013d39"} [choline-p11172068] Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans. (2001). https://pubmed.ncbi.nlm.nih.gov/11172068/ DOI: 10.1073/pnas.98.4.2017
Complete structured claim and evidence
PEMT converts PE to PC through three sequential SAM-dependent methylation reactions.
Human phosphatidylethanolamine N-methyltransferase / PEMT → Phosphatidylethanolamine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/12431977.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7c299a547408772f2f24bdd77f2f22dc8ea9e5aaf8179150f2d8b59c9713306a", "start_char": 0, "end_char": 1380, "text_sha256": "7c299a547408772f2f24bdd77f2f22dc8ea9e5aaf8179150f2d8b59c9713306a"}
experimental_model
Human liver fractionation and recombinant PEMT membrane-topology experiments
exposure
Protein cleavage mapping and methyltransferase localization
limitations
Three methyl transfers make a choline-containing phospholipid; PEMT does not directly synthesize free choline from nothing.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human enzyme
plain_language
The body can build a choline headgroup in a membrane lipid by spending methyl groups.
primary_references
[choline-p12431977] Membrane topography of human phosphatidylethanolamine N-methyltransferase. (2003). https://pubmed.ncbi.nlm.nih.gov/12431977/ DOI: 10.1074/jbc.m210904200
tissue_or_cell_type
ER and mitochondria-associated membranes
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 802–813
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human liver fractionation and recombinant PEMT membrane-topology experiments · source_derived_draft · unverified_draft
### choline-pemt-pc PEMT converts PE to PC through three sequential SAM-dependent methylation reactions. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The body can build a choline headgroup in a membrane lipid by spending methyl groups. organism: Human enzyme tissue_or_cell_type: ER and mitochondria-associated membranes experimental_model: Human liver fractionation and recombinant PEMT membrane-topology experiments limitations: Three methyl transfers make a choline-containing phospholipid; PEMT does not directly synthesize free choline from nothing. exposure: Protein cleavage mapping and methyltransferase localization evidence_span: {"source_cache": "artifacts/choline-research/12431977.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7c299a547408772f2f24bdd77f2f22dc8ea9e5aaf8179150f2d8b59c9713306a", "start_char": 0, "end_char": 1380, "text_sha256": "7c299a547408772f2f24bdd77f2f22dc8ea9e5aaf8179150f2d8b59c9713306a"} [choline-p12431977] Membrane topography of human phosphatidylethanolamine N-methyltransferase. (2003). https://pubmed.ncbi.nlm.nih.gov/12431977/ DOI: 10.1074/jbc.m210904200
Complete structured claim and evidence
SLC25A48 loss impaired choline-derived betaine production in human-cell mitochondrial metabolism experiments.
SLC25A48-deficient human cells in the 2024 transport studies → Human mitochondrial choline-derived betaine synthesis source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/choline-research/39111307.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f", "start_char": 0, "end_char": 1201, "text_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f"}
experimental_model
Slc25a48 knockout, rescue, mitochondrial assays and isotope tracing
exposure
Germline mouse knockout; human-cell SLC25A48 loss; labeled choline
limitations
Transport, energy and one-carbon outcomes are model-specific; normal intake cannot be assumed to correct a carrier defect.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human HEK293T cells
plain_language
A transport defect can restrict methyl-donor production upstream of betaine.
primary_references
[choline-p39111307] SLC25A48 controls mitochondrial choline import and metabolism. (2024). https://pubmed.ncbi.nlm.nih.gov/39111307/ DOI: 10.1016/j.cmet.2024.07.010
tissue_or_cell_type
Brown adipose tissue and human HEK293T cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 490–501
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Slc25a48 knockout, rescue, mitochondrial assays and isotope tracing · source_derived_draft · unverified_draft
### choline-slc25a48-betaine SLC25A48 loss impaired choline-derived betaine production in human-cell mitochondrial metabolism experiments. Condition category: machinery_impairment nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: A transport defect can restrict methyl-donor production upstream of betaine. organism: Human HEK293T cells tissue_or_cell_type: Brown adipose tissue and human HEK293T cells experimental_model: Slc25a48 knockout, rescue, mitochondrial assays and isotope tracing limitations: Transport, energy and one-carbon outcomes are model-specific; normal intake cannot be assumed to correct a carrier defect. exposure: Germline mouse knockout; human-cell SLC25A48 loss; labeled choline evidence_span: {"source_cache": "artifacts/choline-research/39111307.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f", "start_char": 0, "end_char": 1201, "text_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f"} [choline-p39111307] SLC25A48 controls mitochondrial choline import and metabolism. (2024). https://pubmed.ncbi.nlm.nih.gov/39111307/ DOI: 10.1016/j.cmet.2024.07.010
Complete structured claim and evidence
Human choline kinase alpha1 catalyzes ATP-dependent phosphorylation of choline, producing phosphocholine and ADP in magnesium-containing conditions.
Human choline kinase alpha1 / CHKA alpha1 → Phosphocholine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/25515750.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "742dc604629df5eae2bb6cfc0ef0a13cbd69f5e318a2f3292e98f2e707958aeb", "start_char": 0, "end_char": 1321, "text_sha256": "742dc604629df5eae2bb6cfc0ef0a13cbd69f5e318a2f3292e98f2e707958aeb"}
experimental_model
Human choline kinase alpha1 and pathogen-enzyme biochemical comparison
exposure
ATP-dependent choline phosphorylation in magnesium-containing assays
limitations
The shared enzyme requirement is not a clinical magnesium threshold or proof of a general supplement rescue.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human alpha1 isoform; pathogen comparators remain separate
plain_language
Choline enters membrane synthesis through an ATP-powered phosphorylation step.
primary_references
[choline-p25515750] Choline kinase active site provides features for designing versatile inhibitors. (2014). https://pubmed.ncbi.nlm.nih.gov/25515750/ DOI: 10.2174/1568026614666141216093337
tissue_or_cell_type
Purified choline kinase active site
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 698–709
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human choline kinase alpha1 and pathogen-enzyme biochemical comparison · source_derived_draft · unverified_draft
### choline-chka-phosphocholine Human choline kinase alpha1 catalyzes ATP-dependent phosphorylation of choline, producing phosphocholine and ADP in magnesium-containing conditions. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Choline enters membrane synthesis through an ATP-powered phosphorylation step. organism: Human alpha1 isoform; pathogen comparators remain separate tissue_or_cell_type: Purified choline kinase active site experimental_model: Human choline kinase alpha1 and pathogen-enzyme biochemical comparison limitations: The shared enzyme requirement is not a clinical magnesium threshold or proof of a general supplement rescue. exposure: ATP-dependent choline phosphorylation in magnesium-containing assays evidence_span: {"source_cache": "artifacts/choline-research/25515750.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "742dc604629df5eae2bb6cfc0ef0a13cbd69f5e318a2f3292e98f2e707958aeb", "start_char": 0, "end_char": 1321, "text_sha256": "742dc604629df5eae2bb6cfc0ef0a13cbd69f5e318a2f3292e98f2e707958aeb"} [choline-p25515750] Choline kinase active site provides features for designing versatile inhibitors. (2014). https://pubmed.ncbi.nlm.nih.gov/25515750/ DOI: 10.2174/1568026614666141216093337
Complete structured claim and evidence
Randomized folic acid supplementation at 400 micrograms/day did not alter the response to the choline-depletion diet.
Folic acid → Fatty liver or muscle damage during controlled human choline depletion source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/choline-research/17490963.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "28d18f06c2deb6f384ef2b5e84238b05deb076778619c21ee9682d49e34ae824", "start_char": 0, "end_char": 1758, "text_sha256": "28d18f06c2deb6f384ef2b5e84238b05deb076778619c21ee9682d49e34ae824"}
experimental_model
Controlled depletion/repletion with randomized folic acid supplementation
exposure
550 mg choline/70 kg/day for 10 days, then less than 50 mg/70 kg/day up to 42 days; graded repletion
limitations
Supervised experimental depletion, not a recommended intake protocol. Liver/muscle endpoints and susceptibility differed; one cohort underlies related genetic publications.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
Folic acid did not substitute for choline in preventing these liver or muscle endpoints.
primary_references
[choline-p17490963] Sex and menopausal status influence human dietary requirements for the nutrient choline. (2007). https://pubmed.ncbi.nlm.nih.gov/17490963/ DOI: 10.1093/ajcn/85.5.1275
tissue_or_cell_type
57 adults: 26 men, 16 premenopausal and 15 postmenopausal women
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1023–1034
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled depletion/repletion with randomized folic acid supplementation · source_derived_draft · unverified_draft
### choline-folate-no-organ-rescue Randomized folic acid supplementation at 400 micrograms/day did not alter the response to the choline-depletion diet. Condition category: nutrient_deficiency nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Folic acid did not substitute for choline in preventing these liver or muscle endpoints. organism: Human tissue_or_cell_type: 57 adults: 26 men, 16 premenopausal and 15 postmenopausal women experimental_model: Controlled depletion/repletion with randomized folic acid supplementation limitations: Supervised experimental depletion, not a recommended intake protocol. Liver/muscle endpoints and susceptibility differed; one cohort underlies related genetic publications. exposure: 550 mg choline/70 kg/day for 10 days, then less than 50 mg/70 kg/day up to 42 days; graded repletion evidence_span: {"source_cache": "artifacts/choline-research/17490963.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "28d18f06c2deb6f384ef2b5e84238b05deb076778619c21ee9682d49e34ae824", "start_char": 0, "end_char": 1758, "text_sha256": "28d18f06c2deb6f384ef2b5e84238b05deb076778619c21ee9682d49e34ae824"} [choline-p17490963] Sex and menopausal status influence human dietary requirements for the nutrient choline. (2007). https://pubmed.ncbi.nlm.nih.gov/17490963/ DOI: 10.1093/ajcn/85.5.1275
Complete structured claim and evidence
Purified recombinant human ALDH7A1 metabolized betaine aldehyde.
Antiquitin / ALDH7A1 → Betaine aldehyde source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/20207735.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "510558afae2825079b269c8a4ee3f16114ab8d7f6c357c1a085ec14f1924e5e5", "start_char": 0, "end_char": 1582, "text_sha256": "510558afae2825079b269c8a4ee3f16114ab8d7f6c357c1a085ec14f1924e5e5"}
experimental_model
Purified recombinant human enzyme and CHO-cell expression
exposure
Betaine aldehyde substrate; increased extracellular sucrose or NaCl
limitations
ALDH7A1 accepts several aldehydes. Cell protection was not proved to be mediated exclusively by betaine or to predict benefit in pyridoxine-dependent epilepsy.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human ALDH7A1; Chinese hamster ovary expression host
plain_language
The lysine-pathway enzyme already in the ledger also has activity on a choline-derived aldehyde.
primary_references
[choline-p20207735] Aldehyde dehydrogenase 7A1 (ALDH7A1) is a novel enzyme involved in cellular defense against hyperosmotic stress. (2010). https://pubmed.ncbi.nlm.nih.gov/20207735/ DOI: 10.1074/jbc.m109.077925
tissue_or_cell_type
Purified enzyme and osmotic-stress cell assays
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 633–644
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human enzyme and CHO-cell expression · source_derived_draft · unverified_draft
### choline-aldh7-betaine Purified recombinant human ALDH7A1 metabolized betaine aldehyde. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The lysine-pathway enzyme already in the ledger also has activity on a choline-derived aldehyde. organism: Human ALDH7A1; Chinese hamster ovary expression host tissue_or_cell_type: Purified enzyme and osmotic-stress cell assays experimental_model: Purified recombinant human enzyme and CHO-cell expression limitations: ALDH7A1 accepts several aldehydes. Cell protection was not proved to be mediated exclusively by betaine or to predict benefit in pyridoxine-dependent epilepsy. exposure: Betaine aldehyde substrate; increased extracellular sucrose or NaCl evidence_span: {"source_cache": "artifacts/choline-research/20207735.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "510558afae2825079b269c8a4ee3f16114ab8d7f6c357c1a085ec14f1924e5e5", "start_char": 0, "end_char": 1582, "text_sha256": "510558afae2825079b269c8a4ee3f16114ab8d7f6c357c1a085ec14f1924e5e5"} [choline-p20207735] Aldehyde dehydrogenase 7A1 (ALDH7A1) is a novel enzyme involved in cellular defense against hyperosmotic stress. (2010). https://pubmed.ncbi.nlm.nih.gov/20207735/ DOI: 10.1074/jbc.m109.077925
Complete structured claim and evidence
Human CHT1-mediated choline uptake depended on Na+ in the oocyte assay.
Sodium ion → Human CHT1-mediated choline uptake in expression assays source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/11068039.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5", "start_char": 0, "end_char": 1088, "text_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5"}
experimental_model
Human CHT1 expression in Xenopus oocytes
exposure
Choline, sodium and chloride titrations; hemicholinium-3 inhibition
limitations
Assay EC50 values and Hill coefficients are not dietary requirements or exact ion-coupling stoichiometry.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human transporter; Xenopus oocyte host
plain_language
Na+ was part of the transport requirement, not just a background nutrient.
primary_references
[choline-p11068039] Functional characterization of the human high-affinity choline transporter. (2000). https://pubmed.ncbi.nlm.nih.gov/11068039/ DOI: 10.1016/s0014-5793(00)02134-7
tissue_or_cell_type
Plasma-membrane transport assay
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 295–306
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CHT1 expression in Xenopus oocytes · source_derived_draft · unverified_draft
### choline-cht1-sodium Human CHT1-mediated choline uptake depended on Na+ in the oocyte assay. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Na+ was part of the transport requirement, not just a background nutrient. organism: Human transporter; Xenopus oocyte host tissue_or_cell_type: Plasma-membrane transport assay experimental_model: Human CHT1 expression in Xenopus oocytes limitations: Assay EC50 values and Hill coefficients are not dietary requirements or exact ion-coupling stoichiometry. exposure: Choline, sodium and chloride titrations; hemicholinium-3 inhibition evidence_span: {"source_cache": "artifacts/choline-research/11068039.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5", "start_char": 0, "end_char": 1088, "text_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5"} [choline-p11068039] Functional characterization of the human high-affinity choline transporter. (2000). https://pubmed.ncbi.nlm.nih.gov/11068039/ DOI: 10.1016/s0014-5793(00)02134-7
Complete structured claim and evidence
Mfsd2a transported DHA carried by lysophosphatidylcholine rather than unesterified DHA in the tested system.
Mouse lysophosphatidylcholine transporter Mfsd2a → Lysophosphatidylcholine 22:6 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/24828044.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3ec710edae591ed103960d73b49918a61b0260b22702926792e7133337b93695", "start_char": 0, "end_char": 1689, "text_sha256": "3ec710edae591ed103960d73b49918a61b0260b22702926792e7133337b93695"}
experimental_model
Mouse knockout and cell transport experiments
exposure
LPC-bound versus unesterified DHA; sodium-dependent transport
limitations
LPC-DHA is a choline-containing lipid, not free choline. No claim that oral choline necessarily raises brain DHA.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Mouse Mfsd2a and experimental expression system
plain_language
The chemical package used to carry DHA mattered.
primary_references
[choline-p24828044] Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid. (2014). https://pubmed.ncbi.nlm.nih.gov/24828044/ DOI: 10.1038/nature13241
tissue_or_cell_type
Blood-brain-barrier endothelium
transport_effect
raises Mfsd2a is recorded as the influx route carrying DHA as lysophosphatidylcholine.
transport_pool
the brain-endothelial cell interior Mfsd2a is recorded as the influx route carrying DHA as lysophosphatidylcholine.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 945–956
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse knockout and cell transport experiments · source_derived_draft · unverified_draft
### choline-mfsd2a-lpc Mfsd2a transported DHA carried by lysophosphatidylcholine rather than unesterified DHA in the tested system. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The chemical package used to carry DHA mattered. organism: Mouse Mfsd2a and experimental expression system tissue_or_cell_type: Blood-brain-barrier endothelium experimental_model: Mouse knockout and cell transport experiments limitations: LPC-DHA is a choline-containing lipid, not free choline. No claim that oral choline necessarily raises brain DHA. exposure: LPC-bound versus unesterified DHA; sodium-dependent transport evidence_span: {"source_cache": "artifacts/choline-research/24828044.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3ec710edae591ed103960d73b49918a61b0260b22702926792e7133337b93695", "start_char": 0, "end_char": 1689, "text_sha256": "3ec710edae591ed103960d73b49918a61b0260b22702926792e7133337b93695"} [choline-p24828044] Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid. (2014). https://pubmed.ncbi.nlm.nih.gov/24828044/ DOI: 10.1038/nature13241
Complete structured claim and evidence
All three bitartrate-containing arms increased fasting TMAO, p<0.0001.
Choline bitartrate → Circulating trimethylamine N-oxide concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/33872583.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac", "start_char": 0, "end_char": 1740, "text_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac"}
experimental_model
Five-arm randomized four-week choline-form intervention
exposure
Eggs, choline bitartrate, eggs plus bitartrate, egg whites plus bitartrate, or PC supplements
limitations
Fasting TMAO and platelet assays, not cardiovascular events. Acute post-meal tracing and four-week fasting results are not the same endpoint.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
Free-choline salt supplementation raised this marker in the trial.
primary_references
[choline-p33872583] Dietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in Participants with Normal Renal Function: A Randomized Clinical Trial. (2021). https://pubmed.ncbi.nlm.nih.gov/33872583/ DOI: 10.1016/j.amjmed.2021.03.016
tissue_or_cell_type
82 healthy volunteers with normal renal function
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1179–1190
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five-arm randomized four-week choline-form intervention · source_derived_draft · unverified_draft
### choline-bitartrate-tmao All three bitartrate-containing arms increased fasting TMAO, p<0.0001. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Free-choline salt supplementation raised this marker in the trial. organism: Human tissue_or_cell_type: 82 healthy volunteers with normal renal function experimental_model: Five-arm randomized four-week choline-form intervention limitations: Fasting TMAO and platelet assays, not cardiovascular events. Acute post-meal tracing and four-week fasting results are not the same endpoint. exposure: Eggs, choline bitartrate, eggs plus bitartrate, egg whites plus bitartrate, or PC supplements evidence_span: {"source_cache": "artifacts/choline-research/33872583.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac", "start_char": 0, "end_char": 1740, "text_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac"} [choline-p33872583] Dietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in Participants with Normal Renal Function: A Randomized Clinical Trial. (2021). https://pubmed.ncbi.nlm.nih.gov/33872583/ DOI: 10.1016/j.amjmed.2021.03.016
Complete structured claim and evidence
PC supplements did not significantly raise fasting TMAO, p=0.27.
Study-specific phosphatidylcholine supplements → Circulating trimethylamine N-oxide concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/33872583.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac", "start_char": 0, "end_char": 1740, "text_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac"}
experimental_model
Five-arm randomized four-week choline-form intervention
exposure
Eggs, choline bitartrate, eggs plus bitartrate, egg whites plus bitartrate, or PC supplements
limitations
Fasting TMAO and platelet assays, not cardiovascular events. Acute post-meal tracing and four-week fasting results are not the same endpoint.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
A phospholipid form behaved differently from bitartrate in this setting.
primary_references
[choline-p33872583] Dietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in Participants with Normal Renal Function: A Randomized Clinical Trial. (2021). https://pubmed.ncbi.nlm.nih.gov/33872583/ DOI: 10.1016/j.amjmed.2021.03.016
tissue_or_cell_type
82 healthy volunteers with normal renal function
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1231–1242
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five-arm randomized four-week choline-form intervention · source_derived_draft · unverified_draft
### choline-pc-tmao-null PC supplements did not significantly raise fasting TMAO, p=0.27. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: A phospholipid form behaved differently from bitartrate in this setting. organism: Human tissue_or_cell_type: 82 healthy volunteers with normal renal function experimental_model: Five-arm randomized four-week choline-form intervention limitations: Fasting TMAO and platelet assays, not cardiovascular events. Acute post-meal tracing and four-week fasting results are not the same endpoint. exposure: Eggs, choline bitartrate, eggs plus bitartrate, egg whites plus bitartrate, or PC supplements evidence_span: {"source_cache": "artifacts/choline-research/33872583.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac", "start_char": 0, "end_char": 1740, "text_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac"} [choline-p33872583] Dietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in Participants with Normal Renal Function: A Randomized Clinical Trial. (2021). https://pubmed.ncbi.nlm.nih.gov/33872583/ DOI: 10.1016/j.amjmed.2021.03.016
Complete structured claim and evidence
Human FLVCR1 facilitated concentration-driven choline transport across the plasma membrane.
Human FLVCR1 / SLC49A1 → Choline source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/38778100.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0c0c95f81ece7f339f1b92631ced5244c053d1b4a4cbfd9ef964ff0640b5aed4", "start_char": 0, "end_char": 1367, "text_sha256": "0c0c95f81ece7f339f1b92631ced5244c053d1b4a4cbfd9ef964ff0640b5aed4"}
experimental_model
Human transporter expression, uptake, cryo-EM and mutagenesis
exposure
Choline/ethanolamine substrate challenges and purified transporter structures
limitations
Concentration-driven transport in these preparations; not proof that a single transporter supplies every tissue. Historical heme assignments are not copied as established choline mechanisms.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human proteins in experimental systems
plain_language
FLVCR1 can move choline across the cell boundary.
primary_references
[choline-p38778100] Molecular mechanism of choline and ethanolamine transport in humans. (2024). https://pubmed.ncbi.nlm.nih.gov/38778100/ DOI: 10.1038/s41586-024-07444-7
tissue_or_cell_type
Plasma-membrane transport
transport_effect
depends Recorded as concentration-driven transport, so the net direction follows the gradient.
transport_pool
the cytosol across the plasma membrane Recorded as concentration-driven transport, so the net direction follows the gradient.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 217–228
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human transporter expression, uptake, cryo-EM and mutagenesis · source_derived_draft · unverified_draft
### choline-flvcr1-choline Human FLVCR1 facilitated concentration-driven choline transport across the plasma membrane. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: FLVCR1 can move choline across the cell boundary. organism: Human proteins in experimental systems tissue_or_cell_type: Plasma-membrane transport experimental_model: Human transporter expression, uptake, cryo-EM and mutagenesis limitations: Concentration-driven transport in these preparations; not proof that a single transporter supplies every tissue. Historical heme assignments are not copied as established choline mechanisms. exposure: Choline/ethanolamine substrate challenges and purified transporter structures evidence_span: {"source_cache": "artifacts/choline-research/38778100.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0c0c95f81ece7f339f1b92631ced5244c053d1b4a4cbfd9ef964ff0640b5aed4", "start_char": 0, "end_char": 1367, "text_sha256": "0c0c95f81ece7f339f1b92631ced5244c053d1b4a4cbfd9ef964ff0640b5aed4"} [choline-p38778100] Molecular mechanism of choline and ethanolamine transport in humans. (2024). https://pubmed.ncbi.nlm.nih.gov/38778100/ DOI: 10.1038/s41586-024-07444-7
Complete structured claim and evidence
Human FLVCR1 facilitated concentration-driven ethanolamine transport across the plasma membrane.
Human FLVCR1 / SLC49A1 → Ethanolamine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/38778100.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0c0c95f81ece7f339f1b92631ced5244c053d1b4a4cbfd9ef964ff0640b5aed4", "start_char": 0, "end_char": 1367, "text_sha256": "0c0c95f81ece7f339f1b92631ced5244c053d1b4a4cbfd9ef964ff0640b5aed4"}
experimental_model
Human transporter expression, uptake, cryo-EM and mutagenesis
exposure
Choline/ethanolamine substrate challenges and purified transporter structures
limitations
Concentration-driven transport in these preparations; not proof that a single transporter supplies every tissue. Historical heme assignments are not copied as established choline mechanisms.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human proteins in experimental systems
plain_language
FLVCR1 can move ethanolamine across the cell boundary.
primary_references
[choline-p38778100] Molecular mechanism of choline and ethanolamine transport in humans. (2024). https://pubmed.ncbi.nlm.nih.gov/38778100/ DOI: 10.1038/s41586-024-07444-7
tissue_or_cell_type
Plasma-membrane transport
transport_effect
depends Recorded as concentration-driven transport, so the net direction follows the gradient.
transport_pool
the cytosol across the plasma membrane Recorded as concentration-driven transport, so the net direction follows the gradient.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 230–241
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human transporter expression, uptake, cryo-EM and mutagenesis · source_derived_draft · unverified_draft
### choline-flvcr1-ethanolamine Human FLVCR1 facilitated concentration-driven ethanolamine transport across the plasma membrane. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: FLVCR1 can move ethanolamine across the cell boundary. organism: Human proteins in experimental systems tissue_or_cell_type: Plasma-membrane transport experimental_model: Human transporter expression, uptake, cryo-EM and mutagenesis limitations: Concentration-driven transport in these preparations; not proof that a single transporter supplies every tissue. Historical heme assignments are not copied as established choline mechanisms. exposure: Choline/ethanolamine substrate challenges and purified transporter structures evidence_span: {"source_cache": "artifacts/choline-research/38778100.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0c0c95f81ece7f339f1b92631ced5244c053d1b4a4cbfd9ef964ff0640b5aed4", "start_char": 0, "end_char": 1367, "text_sha256": "0c0c95f81ece7f339f1b92631ced5244c053d1b4a4cbfd9ef964ff0640b5aed4"} [choline-p38778100] Molecular mechanism of choline and ethanolamine transport in humans. (2024). https://pubmed.ncbi.nlm.nih.gov/38778100/ DOI: 10.1038/s41586-024-07444-7
Complete structured claim and evidence
Human FLVCR2 facilitated concentration-driven choline transport across the plasma membrane.
Human FLVCR2 / SLC49A2 → Choline source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/38778100.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0c0c95f81ece7f339f1b92631ced5244c053d1b4a4cbfd9ef964ff0640b5aed4", "start_char": 0, "end_char": 1367, "text_sha256": "0c0c95f81ece7f339f1b92631ced5244c053d1b4a4cbfd9ef964ff0640b5aed4"}
experimental_model
Human transporter expression, uptake, cryo-EM and mutagenesis
exposure
Choline/ethanolamine substrate challenges and purified transporter structures
limitations
Concentration-driven transport in these preparations; not proof that a single transporter supplies every tissue. Historical heme assignments are not copied as established choline mechanisms.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human proteins in experimental systems
plain_language
FLVCR2 can move choline across the cell boundary.
primary_references
[choline-p38778100] Molecular mechanism of choline and ethanolamine transport in humans. (2024). https://pubmed.ncbi.nlm.nih.gov/38778100/ DOI: 10.1038/s41586-024-07444-7
tissue_or_cell_type
Plasma-membrane transport
transport_effect
depends Recorded as concentration-driven transport, so the net direction follows the gradient.
transport_pool
the cytosol across the plasma membrane Recorded as concentration-driven transport, so the net direction follows the gradient.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 243–254
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human transporter expression, uptake, cryo-EM and mutagenesis · source_derived_draft · unverified_draft
### choline-flvcr2-choline Human FLVCR2 facilitated concentration-driven choline transport across the plasma membrane. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: FLVCR2 can move choline across the cell boundary. organism: Human proteins in experimental systems tissue_or_cell_type: Plasma-membrane transport experimental_model: Human transporter expression, uptake, cryo-EM and mutagenesis limitations: Concentration-driven transport in these preparations; not proof that a single transporter supplies every tissue. Historical heme assignments are not copied as established choline mechanisms. exposure: Choline/ethanolamine substrate challenges and purified transporter structures evidence_span: {"source_cache": "artifacts/choline-research/38778100.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0c0c95f81ece7f339f1b92631ced5244c053d1b4a4cbfd9ef964ff0640b5aed4", "start_char": 0, "end_char": 1367, "text_sha256": "0c0c95f81ece7f339f1b92631ced5244c053d1b4a4cbfd9ef964ff0640b5aed4"} [choline-p38778100] Molecular mechanism of choline and ethanolamine transport in humans. (2024). https://pubmed.ncbi.nlm.nih.gov/38778100/ DOI: 10.1038/s41586-024-07444-7
Complete structured claim and evidence
Human FLVCR2 facilitated concentration-driven ethanolamine transport across the plasma membrane.
Human FLVCR2 / SLC49A2 → Ethanolamine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/38778100.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0c0c95f81ece7f339f1b92631ced5244c053d1b4a4cbfd9ef964ff0640b5aed4", "start_char": 0, "end_char": 1367, "text_sha256": "0c0c95f81ece7f339f1b92631ced5244c053d1b4a4cbfd9ef964ff0640b5aed4"}
experimental_model
Human transporter expression, uptake, cryo-EM and mutagenesis
exposure
Choline/ethanolamine substrate challenges and purified transporter structures
limitations
Concentration-driven transport in these preparations; not proof that a single transporter supplies every tissue. Historical heme assignments are not copied as established choline mechanisms.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human proteins in experimental systems
plain_language
FLVCR2 can move ethanolamine across the cell boundary.
primary_references
[choline-p38778100] Molecular mechanism of choline and ethanolamine transport in humans. (2024). https://pubmed.ncbi.nlm.nih.gov/38778100/ DOI: 10.1038/s41586-024-07444-7
tissue_or_cell_type
Plasma-membrane transport
transport_effect
depends Recorded as concentration-driven transport, so the net direction follows the gradient.
transport_pool
the cytosol across the plasma membrane Recorded as concentration-driven transport, so the net direction follows the gradient.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 256–267
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human transporter expression, uptake, cryo-EM and mutagenesis · source_derived_draft · unverified_draft
### choline-flvcr2-ethanolamine Human FLVCR2 facilitated concentration-driven ethanolamine transport across the plasma membrane. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: FLVCR2 can move ethanolamine across the cell boundary. organism: Human proteins in experimental systems tissue_or_cell_type: Plasma-membrane transport experimental_model: Human transporter expression, uptake, cryo-EM and mutagenesis limitations: Concentration-driven transport in these preparations; not proof that a single transporter supplies every tissue. Historical heme assignments are not copied as established choline mechanisms. exposure: Choline/ethanolamine substrate challenges and purified transporter structures evidence_span: {"source_cache": "artifacts/choline-research/38778100.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0c0c95f81ece7f339f1b92631ced5244c053d1b4a4cbfd9ef964ff0640b5aed4", "start_char": 0, "end_char": 1367, "text_sha256": "0c0c95f81ece7f339f1b92631ced5244c053d1b4a4cbfd9ef964ff0640b5aed4"} [choline-p38778100] Molecular mechanism of choline and ethanolamine transport in humans. (2024). https://pubmed.ncbi.nlm.nih.gov/38778100/ DOI: 10.1038/s41586-024-07444-7
Complete structured claim and evidence
The in-vivo experiments identified Flvcr2 as a major route for blood-to-brain choline uptake.
Mouse blood-brain-barrier Flvcr2 → Mouse blood-to-brain choline uptake source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/38693257.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "39822712c47b19d59930fdb695e57814c795431132b6d8118c619dad2e1566b3", "start_char": 0, "end_char": 1335, "text_sha256": "39822712c47b19d59930fdb695e57814c795431132b6d8118c619dad2e1566b3"}
experimental_model
BBB expression, mouse physiology and transporter structural analysis
exposure
Flvcr2 perturbation and choline uptake
limitations
The majority-contribution result is a model result, not a universal percentage in humans. This is free-choline transport, distinct from LPC-DHA transport.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Mouse in-vivo BBB experiments; construct-specific structural work
plain_language
Getting choline into the brain is a separate transport step from getting it into a neuron.
primary_references
[choline-p38693257] Structural and molecular basis of choline uptake into the brain by FLVCR2. (2024). https://pubmed.ncbi.nlm.nih.gov/38693257/ DOI: 10.1038/s41586-024-07326-y
tissue_or_cell_type
Blood-brain barrier endothelium
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 269–280
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · BBB expression, mouse physiology and transporter structural analysis · source_derived_draft · unverified_draft
### choline-flvcr2-brain The in-vivo experiments identified Flvcr2 as a major route for blood-to-brain choline uptake. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Getting choline into the brain is a separate transport step from getting it into a neuron. organism: Mouse in-vivo BBB experiments; construct-specific structural work tissue_or_cell_type: Blood-brain barrier endothelium experimental_model: BBB expression, mouse physiology and transporter structural analysis limitations: The majority-contribution result is a model result, not a universal percentage in humans. This is free-choline transport, distinct from LPC-DHA transport. exposure: Flvcr2 perturbation and choline uptake evidence_span: {"source_cache": "artifacts/choline-research/38693257.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "39822712c47b19d59930fdb695e57814c795431132b6d8118c619dad2e1566b3", "start_char": 0, "end_char": 1335, "text_sha256": "39822712c47b19d59930fdb695e57814c795431132b6d8118c619dad2e1566b3"} [choline-p38693257] Structural and molecular basis of choline uptake into the brain by FLVCR2. (2024). https://pubmed.ncbi.nlm.nih.gov/38693257/ DOI: 10.1038/s41586-024-07326-y
Complete structured claim and evidence
Human CHT1 expression produced high-affinity choline uptake in Xenopus oocytes.
Human high-affinity choline transporter CHT1 / SLC5A7 → Human CHT1-mediated choline uptake in expression assays source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/11068039.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5", "start_char": 0, "end_char": 1088, "text_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5"}
experimental_model
Human CHT1 expression in Xenopus oocytes
exposure
Choline, sodium and chloride titrations; hemicholinium-3 inhibition
limitations
Assay EC50 values and Hill coefficients are not dietary requirements or exact ion-coupling stoichiometry.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human transporter; Xenopus oocyte host
plain_language
This transporter supplies choline for the neuronal recycling route.
primary_references
[choline-p11068039] Functional characterization of the human high-affinity choline transporter. (2000). https://pubmed.ncbi.nlm.nih.gov/11068039/ DOI: 10.1016/s0014-5793(00)02134-7
tissue_or_cell_type
Plasma-membrane transport assay
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 282–293
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CHT1 expression in Xenopus oocytes · source_derived_draft · unverified_draft
### choline-cht1-uptake Human CHT1 expression produced high-affinity choline uptake in Xenopus oocytes. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: This transporter supplies choline for the neuronal recycling route. organism: Human transporter; Xenopus oocyte host tissue_or_cell_type: Plasma-membrane transport assay experimental_model: Human CHT1 expression in Xenopus oocytes limitations: Assay EC50 values and Hill coefficients are not dietary requirements or exact ion-coupling stoichiometry. exposure: Choline, sodium and chloride titrations; hemicholinium-3 inhibition evidence_span: {"source_cache": "artifacts/choline-research/11068039.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5", "start_char": 0, "end_char": 1088, "text_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5"} [choline-p11068039] Functional characterization of the human high-affinity choline transporter. (2000). https://pubmed.ncbi.nlm.nih.gov/11068039/ DOI: 10.1016/s0014-5793(00)02134-7
Complete structured claim and evidence
Human CHT1-mediated choline uptake depended on Cl− in the oocyte assay.
Chloride ion → Human CHT1-mediated choline uptake in expression assays source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/11068039.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5", "start_char": 0, "end_char": 1088, "text_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5"}
experimental_model
Human CHT1 expression in Xenopus oocytes
exposure
Choline, sodium and chloride titrations; hemicholinium-3 inhibition
limitations
Assay EC50 values and Hill coefficients are not dietary requirements or exact ion-coupling stoichiometry.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human transporter; Xenopus oocyte host
plain_language
Cl− was part of the transport requirement, not just a background nutrient.
primary_references
[choline-p11068039] Functional characterization of the human high-affinity choline transporter. (2000). https://pubmed.ncbi.nlm.nih.gov/11068039/ DOI: 10.1016/s0014-5793(00)02134-7
tissue_or_cell_type
Plasma-membrane transport assay
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 308–319
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CHT1 expression in Xenopus oocytes · source_derived_draft · unverified_draft
### choline-cht1-chloride Human CHT1-mediated choline uptake depended on Cl− in the oocyte assay. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cl− was part of the transport requirement, not just a background nutrient. organism: Human transporter; Xenopus oocyte host tissue_or_cell_type: Plasma-membrane transport assay experimental_model: Human CHT1 expression in Xenopus oocytes limitations: Assay EC50 values and Hill coefficients are not dietary requirements or exact ion-coupling stoichiometry. exposure: Choline, sodium and chloride titrations; hemicholinium-3 inhibition evidence_span: {"source_cache": "artifacts/choline-research/11068039.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5", "start_char": 0, "end_char": 1088, "text_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5"} [choline-p11068039] Functional characterization of the human high-affinity choline transporter. (2000). https://pubmed.ncbi.nlm.nih.gov/11068039/ DOI: 10.1016/s0014-5793(00)02134-7
Complete structured claim and evidence
Hemicholinium-3 inhibited human CHT1-mediated uptake with a reported Ki of 1.3 nM.
Hemicholinium-3 → Human CHT1-mediated choline uptake in expression assays source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/11068039.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5", "start_char": 0, "end_char": 1088, "text_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5"}
experimental_model
Human CHT1 expression in Xenopus oocytes
exposure
Choline, sodium and chloride titrations; hemicholinium-3 inhibition
limitations
Assay EC50 values and Hill coefficients are not dietary requirements or exact ion-coupling stoichiometry.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human transporter; Xenopus oocyte host
plain_language
Blocking entry can limit choline availability even when choline is outside the cell.
primary_references
[choline-p11068039] Functional characterization of the human high-affinity choline transporter. (2000). https://pubmed.ncbi.nlm.nih.gov/11068039/ DOI: 10.1016/s0014-5793(00)02134-7
tissue_or_cell_type
Plasma-membrane transport assay
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 321–332
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CHT1 expression in Xenopus oocytes · source_derived_draft · unverified_draft
### choline-cht1-inhibitor Hemicholinium-3 inhibited human CHT1-mediated uptake with a reported Ki of 1.3 nM. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Blocking entry can limit choline availability even when choline is outside the cell. organism: Human transporter; Xenopus oocyte host tissue_or_cell_type: Plasma-membrane transport assay experimental_model: Human CHT1 expression in Xenopus oocytes limitations: Assay EC50 values and Hill coefficients are not dietary requirements or exact ion-coupling stoichiometry. exposure: Choline, sodium and chloride titrations; hemicholinium-3 inhibition evidence_span: {"source_cache": "artifacts/choline-research/11068039.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5", "start_char": 0, "end_char": 1088, "text_sha256": "f9885c7f9525456b2c9eac0865a1f86cda2cf8f26cd6a8e34c212218f3a22bd5"} [choline-p11068039] Functional characterization of the human high-affinity choline transporter. (2000). https://pubmed.ncbi.nlm.nih.gov/11068039/ DOI: 10.1016/s0014-5793(00)02134-7
Complete structured claim and evidence
CHT1 supports reutilization of choline liberated by synaptic acetylcholine hydrolysis, sustaining presynaptic acetylcholine synthesis.
Human high-affinity choline transporter CHT1 / SLC5A7 → Choline source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/38589607.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3cf951acec5056180aacccf73a96951c54fa40be5446cd778bd90eb23b43fd3a", "start_char": 0, "end_char": 1090, "text_sha256": "3cf951acec5056180aacccf73a96951c54fa40be5446cd778bd90eb23b43fd3a"}
experimental_model
Human CHT1 cryo-EM and functional characterization
exposure
Choline-bound, inhibitor-bound and apo conformations
limitations
Structural transport cycle; no claim of cognitive benefit from increasing intake.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human CHT1 protein
plain_language
After acetylcholine is broken down, choline can be taken back up and reused.
primary_references
[choline-p38589607] Transport mechanism of presynaptic high-affinity choline uptake by CHT1. (2024). https://pubmed.ncbi.nlm.nih.gov/38589607/ DOI: 10.1038/s41594-024-01259-w
tissue_or_cell_type
Presynaptic uptake mechanism and experimental structures
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 334–345
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CHT1 cryo-EM and functional characterization · source_derived_draft · unverified_draft
### choline-cht1-recycling CHT1 supports reutilization of choline liberated by synaptic acetylcholine hydrolysis, sustaining presynaptic acetylcholine synthesis. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: After acetylcholine is broken down, choline can be taken back up and reused. organism: Human CHT1 protein tissue_or_cell_type: Presynaptic uptake mechanism and experimental structures experimental_model: Human CHT1 cryo-EM and functional characterization limitations: Structural transport cycle; no claim of cognitive benefit from increasing intake. exposure: Choline-bound, inhibitor-bound and apo conformations evidence_span: {"source_cache": "artifacts/choline-research/38589607.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3cf951acec5056180aacccf73a96951c54fa40be5446cd778bd90eb23b43fd3a", "start_char": 0, "end_char": 1090, "text_sha256": "3cf951acec5056180aacccf73a96951c54fa40be5446cd778bd90eb23b43fd3a"} [choline-p38589607] Transport mechanism of presynaptic high-affinity choline uptake by CHT1. (2024). https://pubmed.ncbi.nlm.nih.gov/38589607/ DOI: 10.1038/s41594-024-01259-w
Complete structured claim and evidence
Tested SLC5A7 missense variants caused a near-complete loss of CHT transport activity in cell models.
Human SLC5A7 missense variants tested in the 2016 CMS study → Human CHT1-mediated choline uptake in expression assays source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/choline-research/27569547.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8f8b3acd919795de1aa33ccb5a616ccaaffc27e619990562f1bb69add7836d3d", "start_char": 0, "end_char": 1723, "text_sha256": "8f8b3acd919795de1aa33ccb5a616ccaaffc27e619990562f1bb69add7836d3d"}
experimental_model
Six-family genetics, expression assays and NMJ examination
exposure
Eleven recessive SLC5A7 mutations; missense variants tested functionally
limitations
Rare inherited disease with variant-specific effects; not a dietary-deficiency diagnosis or evidence that supplements repair the transporter.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human variants; cell expression systems
plain_language
A damaged transporter can interrupt acetylcholine supply upstream of the synthesis enzyme.
primary_references
[choline-p27569547] Impaired Presynaptic High-Affinity Choline Transporter Causes a Congenital Myasthenic Syndrome with Episodic Apnea. (2016). https://pubmed.ncbi.nlm.nih.gov/27569547/ DOI: 10.1016/j.ajhg.2016.06.033
tissue_or_cell_type
Neuromuscular junction and choline transport
trigger_kind
machinery_impairment Imported condition classification; unverified.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 347–358
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six-family genetics, expression assays and NMJ examination · source_derived_draft · unverified_draft
### choline-cht1-mutants Tested SLC5A7 missense variants caused a near-complete loss of CHT transport activity in cell models. Condition category: machinery_impairment nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: A damaged transporter can interrupt acetylcholine supply upstream of the synthesis enzyme. organism: Human variants; cell expression systems tissue_or_cell_type: Neuromuscular junction and choline transport experimental_model: Six-family genetics, expression assays and NMJ examination limitations: Rare inherited disease with variant-specific effects; not a dietary-deficiency diagnosis or evidence that supplements repair the transporter. exposure: Eleven recessive SLC5A7 mutations; missense variants tested functionally evidence_span: {"source_cache": "artifacts/choline-research/27569547.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8f8b3acd919795de1aa33ccb5a616ccaaffc27e619990562f1bb69add7836d3d", "start_char": 0, "end_char": 1723, "text_sha256": "8f8b3acd919795de1aa33ccb5a616ccaaffc27e619990562f1bb69add7836d3d"} [choline-p27569547] Impaired Presynaptic High-Affinity Choline Transporter Causes a Congenital Myasthenic Syndrome with Episodic Apnea. (2016). https://pubmed.ncbi.nlm.nih.gov/27569547/ DOI: 10.1016/j.ajhg.2016.06.033
Complete structured claim and evidence
Patient fibroblasts had diminished choline transport.
SLC44A1 frameshift-mutant patient fibroblasts in the 2020 study → Human cellular choline uptake source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/choline-research/31855247.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "34cbef18c0e83c0bcd06954a1d81d7329825171b5ecac31f8ea19b2457543f19", "start_char": 0, "end_char": 1785, "text_sha256": "34cbef18c0e83c0bcd06954a1d81d7329825171b5ecac31f8ea19b2457543f19"}
experimental_model
Four individuals, three families; patient-fibroblast transport and rescue
exposure
SLC44A1 frameshift genotypes, chronic choline treatment and acute iron challenge
limitations
Cell rescue is not a demonstrated clinical treatment. Preserved PC content coexisted with disturbed other lipids and organelles. The linked issue-wide erratum corrected publication year to 2020, not these biological findings (PMID 32333675; doi:10.1093/brain/awaa007).
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
Transport failed even though not every downstream concentration fell.
primary_references
[choline-p31855247] Choline transporter-like 1 deficiency causes a new type of childhood-onset neurodegeneration. (2020). https://pubmed.ncbi.nlm.nih.gov/31855247/ DOI: 10.1093/brain/awz376
tissue_or_cell_type
Patient fibroblasts; clinical neurodegeneration
trigger_kind
machinery_impairment Imported condition classification; unverified.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 360–371
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four individuals, three families; patient-fibroblast transport and rescue · source_derived_draft · unverified_draft
### choline-ctl1-uptake Patient fibroblasts had diminished choline transport. Condition category: machinery_impairment nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Transport failed even though not every downstream concentration fell. organism: Human tissue_or_cell_type: Patient fibroblasts; clinical neurodegeneration experimental_model: Four individuals, three families; patient-fibroblast transport and rescue limitations: Cell rescue is not a demonstrated clinical treatment. Preserved PC content coexisted with disturbed other lipids and organelles. The linked issue-wide erratum corrected publication year to 2020, not these biological findings (PMID 32333675; doi:10.1093/brain/awaa007). exposure: SLC44A1 frameshift genotypes, chronic choline treatment and acute iron challenge evidence_span: {"source_cache": "artifacts/choline-research/31855247.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "34cbef18c0e83c0bcd06954a1d81d7329825171b5ecac31f8ea19b2457543f19", "start_char": 0, "end_char": 1785, "text_sha256": "34cbef18c0e83c0bcd06954a1d81d7329825171b5ecac31f8ea19b2457543f19"} [choline-p31855247] Choline transporter-like 1 deficiency causes a new type of childhood-onset neurodegeneration. (2020). https://pubmed.ncbi.nlm.nih.gov/31855247/ DOI: 10.1093/brain/awz376
Complete structured claim and evidence
Membrane phosphatidylcholine content remained unchanged in the mutant fibroblasts.
SLC44A1 frameshift-mutant patient fibroblasts in the 2020 study → Membrane phosphatidylcholine content in SLC44A1 patient fibroblasts source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/choline-research/31855247.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "34cbef18c0e83c0bcd06954a1d81d7329825171b5ecac31f8ea19b2457543f19", "start_char": 0, "end_char": 1785, "text_sha256": "34cbef18c0e83c0bcd06954a1d81d7329825171b5ecac31f8ea19b2457543f19"}
experimental_model
Four individuals, three families; patient-fibroblast transport and rescue
exposure
SLC44A1 frameshift genotypes, chronic choline treatment and acute iron challenge
limitations
Cell rescue is not a demonstrated clinical treatment. Preserved PC content coexisted with disturbed other lipids and organelles. The linked issue-wide erratum corrected publication year to 2020, not these biological findings (PMID 32333675; doi:10.1093/brain/awaa007).
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
A preserved membrane PC measurement did not exclude a choline-handling defect.
primary_references
[choline-p31855247] Choline transporter-like 1 deficiency causes a new type of childhood-onset neurodegeneration. (2020). https://pubmed.ncbi.nlm.nih.gov/31855247/ DOI: 10.1093/brain/awz376
tissue_or_cell_type
Patient fibroblasts; clinical neurodegeneration
trigger_kind
machinery_impairment Imported condition classification; unverified.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 373–384
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four individuals, three families; patient-fibroblast transport and rescue · source_derived_draft · unverified_draft
### choline-ctl1-pc-preserved Membrane phosphatidylcholine content remained unchanged in the mutant fibroblasts. Condition category: machinery_impairment nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: A preserved membrane PC measurement did not exclude a choline-handling defect. organism: Human tissue_or_cell_type: Patient fibroblasts; clinical neurodegeneration experimental_model: Four individuals, three families; patient-fibroblast transport and rescue limitations: Cell rescue is not a demonstrated clinical treatment. Preserved PC content coexisted with disturbed other lipids and organelles. The linked issue-wide erratum corrected publication year to 2020, not these biological findings (PMID 32333675; doi:10.1093/brain/awaa007). exposure: SLC44A1 frameshift genotypes, chronic choline treatment and acute iron challenge evidence_span: {"source_cache": "artifacts/choline-research/31855247.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "34cbef18c0e83c0bcd06954a1d81d7329825171b5ecac31f8ea19b2457543f19", "start_char": 0, "end_char": 1785, "text_sha256": "34cbef18c0e83c0bcd06954a1d81d7329825171b5ecac31f8ea19b2457543f19"} [choline-p31855247] Choline transporter-like 1 deficiency causes a new type of childhood-onset neurodegeneration. (2020). https://pubmed.ncbi.nlm.nih.gov/31855247/ DOI: 10.1093/brain/awz376
Complete structured claim and evidence
Chronic choline treatment made mutant fibroblast ultrastructure resemble healthy control cells.
Choline → Organelle abnormalities in SLC44A1 patient fibroblasts source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/choline-research/31855247.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "34cbef18c0e83c0bcd06954a1d81d7329825171b5ecac31f8ea19b2457543f19", "start_char": 0, "end_char": 1785, "text_sha256": "34cbef18c0e83c0bcd06954a1d81d7329825171b5ecac31f8ea19b2457543f19"}
experimental_model
Four individuals, three families; patient-fibroblast transport and rescue
exposure
SLC44A1 frameshift genotypes, chronic choline treatment and acute iron challenge
limitations
Cell rescue is not a demonstrated clinical treatment. Preserved PC content coexisted with disturbed other lipids and organelles. The linked issue-wide erratum corrected publication year to 2020, not these biological findings (PMID 32333675; doi:10.1093/brain/awaa007).
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
Extra choline improved the cell phenotype in this experiment.
primary_references
[choline-p31855247] Choline transporter-like 1 deficiency causes a new type of childhood-onset neurodegeneration. (2020). https://pubmed.ncbi.nlm.nih.gov/31855247/ DOI: 10.1093/brain/awz376
tissue_or_cell_type
Patient fibroblasts; clinical neurodegeneration
trigger_kind
machinery_impairment Imported condition classification; unverified.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 386–397
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four individuals, three families; patient-fibroblast transport and rescue · source_derived_draft · unverified_draft
### choline-ctl1-cell-rescue Chronic choline treatment made mutant fibroblast ultrastructure resemble healthy control cells. Condition category: machinery_impairment nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Extra choline improved the cell phenotype in this experiment. organism: Human tissue_or_cell_type: Patient fibroblasts; clinical neurodegeneration experimental_model: Four individuals, three families; patient-fibroblast transport and rescue limitations: Cell rescue is not a demonstrated clinical treatment. Preserved PC content coexisted with disturbed other lipids and organelles. The linked issue-wide erratum corrected publication year to 2020, not these biological findings (PMID 32333675; doi:10.1093/brain/awaa007). exposure: SLC44A1 frameshift genotypes, chronic choline treatment and acute iron challenge evidence_span: {"source_cache": "artifacts/choline-research/31855247.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "34cbef18c0e83c0bcd06954a1d81d7329825171b5ecac31f8ea19b2457543f19", "start_char": 0, "end_char": 1785, "text_sha256": "34cbef18c0e83c0bcd06954a1d81d7329825171b5ecac31f8ea19b2457543f19"} [choline-p31855247] Choline transporter-like 1 deficiency causes a new type of childhood-onset neurodegeneration. (2020). https://pubmed.ncbi.nlm.nih.gov/31855247/ DOI: 10.1093/brain/awz376
Complete structured claim and evidence
Choline treatment protected the mutant fibroblasts from acute iron overload.
Choline → Acute iron-overload injury in SLC44A1 patient fibroblasts source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/choline-research/31855247.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "34cbef18c0e83c0bcd06954a1d81d7329825171b5ecac31f8ea19b2457543f19", "start_char": 0, "end_char": 1785, "text_sha256": "34cbef18c0e83c0bcd06954a1d81d7329825171b5ecac31f8ea19b2457543f19"}
experimental_model
Four individuals, three families; patient-fibroblast transport and rescue
exposure
SLC44A1 frameshift genotypes, chronic choline treatment and acute iron challenge
limitations
Cultured-cell rescue under an acute challenge; does not establish clinical iron tolerance or a general choline–iron dosing rule.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
Choline handling and iron-stress resistance met in this cell model.
primary_references
[choline-p31855247] Choline transporter-like 1 deficiency causes a new type of childhood-onset neurodegeneration. (2020). https://pubmed.ncbi.nlm.nih.gov/31855247/ DOI: 10.1093/brain/awz376
tissue_or_cell_type
Patient fibroblasts; clinical neurodegeneration
trigger_kind
machinery_impairment Imported condition classification; unverified.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 399–410
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four individuals, three families; patient-fibroblast transport and rescue · source_derived_draft · unverified_draft
### choline-ctl1-iron-rescue Choline treatment protected the mutant fibroblasts from acute iron overload. Condition category: machinery_impairment nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Choline handling and iron-stress resistance met in this cell model. organism: Human tissue_or_cell_type: Patient fibroblasts; clinical neurodegeneration experimental_model: Four individuals, three families; patient-fibroblast transport and rescue limitations: Cultured-cell rescue under an acute challenge; does not establish clinical iron tolerance or a general choline–iron dosing rule. exposure: SLC44A1 frameshift genotypes, chronic choline treatment and acute iron challenge evidence_span: {"source_cache": "artifacts/choline-research/31855247.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "34cbef18c0e83c0bcd06954a1d81d7329825171b5ecac31f8ea19b2457543f19", "start_char": 0, "end_char": 1785, "text_sha256": "34cbef18c0e83c0bcd06954a1d81d7329825171b5ecac31f8ea19b2457543f19"} [choline-p31855247] Choline transporter-like 1 deficiency causes a new type of childhood-onset neurodegeneration. (2020). https://pubmed.ncbi.nlm.nih.gov/31855247/ DOI: 10.1093/brain/awz376
Complete structured claim and evidence
Bacterially expressed human ChAT E441K lacked catalytic activity in the reported kinetic experiment.
Human ChAT E441K construct in the 2001 study → Human ChAT acetylcholine synthesis activity source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/choline-research/11172068.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "691b96b9c5c149c554b99d8e1532ffee25084a8970f8deb23f0991dfd6013d39", "start_char": 0, "end_char": 1231, "text_sha256": "691b96b9c5c149c554b99d8e1532ffee25084a8970f8deb23f0991dfd6013d39"}
experimental_model
Human CHAT genetics, recombinant expression and enzyme kinetics
exposure
Ten recessive variants in five patients; nine mutant proteins assayed
limitations
Inherited enzyme defects, not a dietary choline-deficiency model. Acetyl-CoA and choline are distinct substrates.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human CHAT proteins; COS-cell and bacterial expression systems
plain_language
Having the nutrient present cannot by itself guarantee synthesis when the enzyme is inactive.
primary_references
[choline-p11172068] Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans. (2001). https://pubmed.ncbi.nlm.nih.gov/11172068/ DOI: 10.1073/pnas.98.4.2017
tissue_or_cell_type
Neuromuscular acetylcholine resynthesis
trigger_kind
machinery_impairment Imported condition classification; unverified.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 425–436
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CHAT genetics, recombinant expression and enzyme kinetics · source_derived_draft · unverified_draft
### choline-chat-e441k Bacterially expressed human ChAT E441K lacked catalytic activity in the reported kinetic experiment. Condition category: machinery_impairment nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Having the nutrient present cannot by itself guarantee synthesis when the enzyme is inactive. organism: Human CHAT proteins; COS-cell and bacterial expression systems tissue_or_cell_type: Neuromuscular acetylcholine resynthesis experimental_model: Human CHAT genetics, recombinant expression and enzyme kinetics limitations: Inherited enzyme defects, not a dietary choline-deficiency model. Acetyl-CoA and choline are distinct substrates. exposure: Ten recessive variants in five patients; nine mutant proteins assayed evidence_span: {"source_cache": "artifacts/choline-research/11172068.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "691b96b9c5c149c554b99d8e1532ffee25084a8970f8deb23f0991dfd6013d39", "start_char": 0, "end_char": 1231, "text_sha256": "691b96b9c5c149c554b99d8e1532ffee25084a8970f8deb23f0991dfd6013d39"} [choline-p11172068] Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans. (2001). https://pubmed.ncbi.nlm.nih.gov/11172068/ DOI: 10.1073/pnas.98.4.2017
Complete structured claim and evidence
VAChT recognizes acetylcholine and packages it into vesicles for subsequent release.
Human vesicular acetylcholine transporter VAChT / SLC18A3 → Human VAChT-mediated vesicular acetylcholine packaging source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/39806024.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e2c63d42f1864e1d9401293ec0c67d659eca8dbb0d571a8d1a328ec04883eb78", "start_char": 0, "end_char": 1047, "text_sha256": "e2c63d42f1864e1d9401293ec0c67d659eca8dbb0d571a8d1a328ec04883eb78"}
experimental_model
Human VAChT cryo-EM in apo, substrate-bound and inhibitor-bound states
exposure
Acetylcholine and vesamicol ligand binding
limitations
Packaging is distinct from synthesis and release. Structures support substrate recognition and protonation coupling, not a clinical effect of choline supplementation.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human VAChT protein
plain_language
Making acetylcholine and loading it into a release vesicle are separate steps.
primary_references
[choline-p39806024] Binding mechanism and antagonism of the vesicular acetylcholine transporter VAChT. (2025). https://pubmed.ncbi.nlm.nih.gov/39806024/ DOI: 10.1038/s41594-024-01462-9
tissue_or_cell_type
Synaptic-vesicle transporter
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 438–449
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human VAChT cryo-EM in apo, substrate-bound and inhibitor-bound states · source_derived_draft · unverified_draft
### choline-vacht-packaging VAChT recognizes acetylcholine and packages it into vesicles for subsequent release. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Making acetylcholine and loading it into a release vesicle are separate steps. organism: Human VAChT protein tissue_or_cell_type: Synaptic-vesicle transporter experimental_model: Human VAChT cryo-EM in apo, substrate-bound and inhibitor-bound states limitations: Packaging is distinct from synthesis and release. Structures support substrate recognition and protonation coupling, not a clinical effect of choline supplementation. exposure: Acetylcholine and vesamicol ligand binding evidence_span: {"source_cache": "artifacts/choline-research/39806024.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e2c63d42f1864e1d9401293ec0c67d659eca8dbb0d571a8d1a328ec04883eb78", "start_char": 0, "end_char": 1047, "text_sha256": "e2c63d42f1864e1d9401293ec0c67d659eca8dbb0d571a8d1a328ec04883eb78"} [choline-p39806024] Binding mechanism and antagonism of the vesicular acetylcholine transporter VAChT. (2025). https://pubmed.ncbi.nlm.nih.gov/39806024/ DOI: 10.1038/s41594-024-01462-9
Complete structured claim and evidence
The human VAChT structure captured vesamicol in its inhibitory binding site.
Vesamicol → Human vesicular acetylcholine transporter VAChT / SLC18A3 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/39806024.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e2c63d42f1864e1d9401293ec0c67d659eca8dbb0d571a8d1a328ec04883eb78", "start_char": 0, "end_char": 1047, "text_sha256": "e2c63d42f1864e1d9401293ec0c67d659eca8dbb0d571a8d1a328ec04883eb78"}
experimental_model
Human VAChT cryo-EM in apo, substrate-bound and inhibitor-bound states
exposure
Acetylcholine and vesamicol ligand binding
limitations
Packaging is distinct from synthesis and release. Structures support substrate recognition and protonation coupling, not a clinical effect of choline supplementation.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human VAChT protein
plain_language
A drug can interrupt packaging without being a choline shortage.
primary_references
[choline-p39806024] Binding mechanism and antagonism of the vesicular acetylcholine transporter VAChT. (2025). https://pubmed.ncbi.nlm.nih.gov/39806024/ DOI: 10.1038/s41594-024-01462-9
tissue_or_cell_type
Synaptic-vesicle transporter
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 451–462
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human VAChT cryo-EM in apo, substrate-bound and inhibitor-bound states · source_derived_draft · unverified_draft
### choline-vacht-vesamicol The human VAChT structure captured vesamicol in its inhibitory binding site. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: A drug can interrupt packaging without being a choline shortage. organism: Human VAChT protein tissue_or_cell_type: Synaptic-vesicle transporter experimental_model: Human VAChT cryo-EM in apo, substrate-bound and inhibitor-bound states limitations: Packaging is distinct from synthesis and release. Structures support substrate recognition and protonation coupling, not a clinical effect of choline supplementation. exposure: Acetylcholine and vesamicol ligand binding evidence_span: {"source_cache": "artifacts/choline-research/39806024.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e2c63d42f1864e1d9401293ec0c67d659eca8dbb0d571a8d1a328ec04883eb78", "start_char": 0, "end_char": 1047, "text_sha256": "e2c63d42f1864e1d9401293ec0c67d659eca8dbb0d571a8d1a328ec04883eb78"} [choline-p39806024] Binding mechanism and antagonism of the vesicular acetylcholine transporter VAChT. (2025). https://pubmed.ncbi.nlm.nih.gov/39806024/ DOI: 10.1038/s41594-024-01462-9
Complete structured claim and evidence
The pathway model identifies CHDH-mediated oxidation of choline to betaine aldehyde upstream of aldehyde-dehydrogenase-mediated betaine production.
Human choline dehydrogenase / CHDH → Betaine aldehyde source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/39111307.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "086a515ebf324a03baeb82e7fe21771eb7f819da09ef7a22372e06db25d3c571", "start_char": 3335, "end_char": 3656, "text_sha256": "580d72b54dac50ca5d1cfdb4e2ffe3719e957af76ac81d761422471424636d69"}
experimental_model
Slc25a48 knockout, rescue, mitochondrial assays and isotope tracing
exposure
Biochemical pathway described in the study introduction
limitations
Established pathway background in this carrier study, not a newly isolated human CHDH catalytic assay. No cofactor identity or exclusive downstream ALDH isoform is inferred.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Mammalian pathway background applied to the human-cell arm
plain_language
Choline oxidation has an aldehyde intermediate; it is not one undifferentiated jump to betaine.
primary_references
[choline-p39111307] SLC25A48 controls mitochondrial choline import and metabolism. (2024). https://pubmed.ncbi.nlm.nih.gov/39111307/ DOI: 10.1016/j.cmet.2024.07.010
tissue_or_cell_type
Mitochondrial choline metabolism
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 464–475
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Slc25a48 knockout, rescue, mitochondrial assays and isotope tracing · source_derived_draft · unverified_draft
### choline-chdh-aldehyde-step The pathway model identifies CHDH-mediated oxidation of choline to betaine aldehyde upstream of aldehyde-dehydrogenase-mediated betaine production. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Choline oxidation has an aldehyde intermediate; it is not one undifferentiated jump to betaine. organism: Mammalian pathway background applied to the human-cell arm tissue_or_cell_type: Mitochondrial choline metabolism experimental_model: Slc25a48 knockout, rescue, mitochondrial assays and isotope tracing limitations: Established pathway background in this carrier study, not a newly isolated human CHDH catalytic assay. No cofactor identity or exclusive downstream ALDH isoform is inferred. exposure: Biochemical pathway described in the study introduction evidence_span: {"source_cache": "artifacts/choline-research/39111307.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "086a515ebf324a03baeb82e7fe21771eb7f819da09ef7a22372e06db25d3c571", "start_char": 3335, "end_char": 3656, "text_sha256": "580d72b54dac50ca5d1cfdb4e2ffe3719e957af76ac81d761422471424636d69"} [choline-p39111307] SLC25A48 controls mitochondrial choline import and metabolism. (2024). https://pubmed.ncbi.nlm.nih.gov/39111307/ DOI: 10.1016/j.cmet.2024.07.010
Complete structured claim and evidence
Human-cell experiments identified SLC25A48 as necessary for efficient mitochondrial choline import.
Human mitochondrial choline carrier SLC25A48 → Human mitochondrial choline import source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/39111307.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f", "start_char": 0, "end_char": 1201, "text_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f"}
experimental_model
Slc25a48 knockout, rescue, mitochondrial assays and isotope tracing
exposure
Germline mouse knockout; human-cell SLC25A48 loss; labeled choline
limitations
Transport, energy and one-carbon outcomes are model-specific; normal intake cannot be assumed to correct a carrier defect.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human HEK293T cells
plain_language
Choline must cross another membrane to reach its mitochondrial metabolic route.
primary_references
[choline-p39111307] SLC25A48 controls mitochondrial choline import and metabolism. (2024). https://pubmed.ncbi.nlm.nih.gov/39111307/ DOI: 10.1016/j.cmet.2024.07.010
tissue_or_cell_type
Brown adipose tissue and human HEK293T cells
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 477–488
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Slc25a48 knockout, rescue, mitochondrial assays and isotope tracing · source_derived_draft · unverified_draft
### choline-slc25a48-import Human-cell experiments identified SLC25A48 as necessary for efficient mitochondrial choline import. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Choline must cross another membrane to reach its mitochondrial metabolic route. organism: Human HEK293T cells tissue_or_cell_type: Brown adipose tissue and human HEK293T cells experimental_model: Slc25a48 knockout, rescue, mitochondrial assays and isotope tracing limitations: Transport, energy and one-carbon outcomes are model-specific; normal intake cannot be assumed to correct a carrier defect. exposure: Germline mouse knockout; human-cell SLC25A48 loss; labeled choline evidence_span: {"source_cache": "artifacts/choline-research/39111307.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f", "start_char": 0, "end_char": 1201, "text_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f"} [choline-p39111307] SLC25A48 controls mitochondrial choline import and metabolism. (2024). https://pubmed.ncbi.nlm.nih.gov/39111307/ DOI: 10.1016/j.cmet.2024.07.010
Complete structured claim and evidence
SLC25A48 loss reduced the contribution of labeled choline to purine nucleotides in HEK293T cells.
SLC25A48-deficient human cells in the 2024 transport studies → Human HEK293T choline-derived purine nucleotide labeling source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/choline-research/39111307.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f", "start_char": 0, "end_char": 1201, "text_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f"}
experimental_model
Slc25a48 knockout, rescue, mitochondrial assays and isotope tracing
exposure
1 mM 13C2-choline for 24 hours in the study methods
limitations
Tracer contribution is not a claim that choline directly becomes a whole nucleotide or that dietary choline controls every purine pathway.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human HEK293T cells
plain_language
Choline-derived metabolism reached nucleotide production in the tracer experiment.
primary_references
[choline-p39111307] SLC25A48 controls mitochondrial choline import and metabolism. (2024). https://pubmed.ncbi.nlm.nih.gov/39111307/ DOI: 10.1016/j.cmet.2024.07.010
tissue_or_cell_type
Brown adipose tissue and human HEK293T cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 503–514
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Slc25a48 knockout, rescue, mitochondrial assays and isotope tracing · source_derived_draft · unverified_draft
### choline-slc25a48-purines SLC25A48 loss reduced the contribution of labeled choline to purine nucleotides in HEK293T cells. Condition category: machinery_impairment nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Choline-derived metabolism reached nucleotide production in the tracer experiment. organism: Human HEK293T cells tissue_or_cell_type: Brown adipose tissue and human HEK293T cells experimental_model: Slc25a48 knockout, rescue, mitochondrial assays and isotope tracing limitations: Tracer contribution is not a claim that choline directly becomes a whole nucleotide or that dietary choline controls every purine pathway. exposure: 1 mM 13C2-choline for 24 hours in the study methods evidence_span: {"source_cache": "artifacts/choline-research/39111307.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f", "start_char": 0, "end_char": 1201, "text_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f"} [choline-p39111307] SLC25A48 controls mitochondrial choline import and metabolism. (2024). https://pubmed.ncbi.nlm.nih.gov/39111307/ DOI: 10.1016/j.cmet.2024.07.010
Complete structured claim and evidence
Slc25a48-null mice had impaired brown-fat mitochondrial respiration.
Slc25a48-null mice and derived brown adipocytes in the 2024 study → Mouse brown-adipose mitochondrial respiration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/choline-research/39111307.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f", "start_char": 0, "end_char": 1201, "text_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f"}
experimental_model
Slc25a48 knockout, rescue, mitochondrial assays and isotope tracing
exposure
Germline mouse knockout; human-cell SLC25A48 loss; labeled choline
limitations
Transport, energy and one-carbon outcomes are model-specific; normal intake cannot be assumed to correct a carrier defect.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Mouse
plain_language
The carrier defect affected energy handling in brown fat.
primary_references
[choline-p39111307] SLC25A48 controls mitochondrial choline import and metabolism. (2024). https://pubmed.ncbi.nlm.nih.gov/39111307/ DOI: 10.1016/j.cmet.2024.07.010
tissue_or_cell_type
Brown adipose tissue and human HEK293T cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 516–527
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Slc25a48 knockout, rescue, mitochondrial assays and isotope tracing · source_derived_draft · unverified_draft
### choline-bat-respiration Slc25a48-null mice had impaired brown-fat mitochondrial respiration. Condition category: machinery_impairment nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The carrier defect affected energy handling in brown fat. organism: Mouse tissue_or_cell_type: Brown adipose tissue and human HEK293T cells experimental_model: Slc25a48 knockout, rescue, mitochondrial assays and isotope tracing limitations: Transport, energy and one-carbon outcomes are model-specific; normal intake cannot be assumed to correct a carrier defect. exposure: Germline mouse knockout; human-cell SLC25A48 loss; labeled choline evidence_span: {"source_cache": "artifacts/choline-research/39111307.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f", "start_char": 0, "end_char": 1201, "text_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f"} [choline-p39111307] SLC25A48 controls mitochondrial choline import and metabolism. (2024). https://pubmed.ncbi.nlm.nih.gov/39111307/ DOI: 10.1016/j.cmet.2024.07.010
Complete structured claim and evidence
Slc25a48-null brown-fat mitochondria emitted more hydrogen peroxide under the measured assay conditions.
Slc25a48-null mice and derived brown adipocytes in the 2024 study → Mouse brown-adipose mitochondrial hydrogen-peroxide emission source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/choline-research/39111307.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f", "start_char": 0, "end_char": 1201, "text_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f"}
experimental_model
Slc25a48 knockout, rescue, mitochondrial assays and isotope tracing
exposure
Germline mouse knockout; human-cell SLC25A48 loss; labeled choline
limitations
Transport, energy and one-carbon outcomes are model-specific; normal intake cannot be assumed to correct a carrier defect.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Mouse
plain_language
The defect also changed mitochondrial redox behavior.
primary_references
[choline-p39111307] SLC25A48 controls mitochondrial choline import and metabolism. (2024). https://pubmed.ncbi.nlm.nih.gov/39111307/ DOI: 10.1016/j.cmet.2024.07.010
tissue_or_cell_type
Brown adipose tissue and human HEK293T cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 529–540
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Slc25a48 knockout, rescue, mitochondrial assays and isotope tracing · source_derived_draft · unverified_draft
### choline-bat-peroxide Slc25a48-null brown-fat mitochondria emitted more hydrogen peroxide under the measured assay conditions. Condition category: machinery_impairment nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The defect also changed mitochondrial redox behavior. organism: Mouse tissue_or_cell_type: Brown adipose tissue and human HEK293T cells experimental_model: Slc25a48 knockout, rescue, mitochondrial assays and isotope tracing limitations: Transport, energy and one-carbon outcomes are model-specific; normal intake cannot be assumed to correct a carrier defect. exposure: Germline mouse knockout; human-cell SLC25A48 loss; labeled choline evidence_span: {"source_cache": "artifacts/choline-research/39111307.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f", "start_char": 0, "end_char": 1201, "text_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f"} [choline-p39111307] SLC25A48 controls mitochondrial choline import and metabolism. (2024). https://pubmed.ncbi.nlm.nih.gov/39111307/ DOI: 10.1016/j.cmet.2024.07.010
Complete structured claim and evidence
Slc25a48-null mice had impaired cold tolerance.
Slc25a48-null mice and derived brown adipocytes in the 2024 study → Mouse cold tolerance source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/choline-research/39111307.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f", "start_char": 0, "end_char": 1201, "text_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f"}
experimental_model
Slc25a48 knockout, rescue, mitochondrial assays and isotope tracing
exposure
Germline mouse knockout; human-cell SLC25A48 loss; labeled choline
limitations
Transport, energy and one-carbon outcomes are model-specific; normal intake cannot be assumed to correct a carrier defect.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Mouse
plain_language
The mouse whole-body response was consistent with impaired heat production.
primary_references
[choline-p39111307] SLC25A48 controls mitochondrial choline import and metabolism. (2024). https://pubmed.ncbi.nlm.nih.gov/39111307/ DOI: 10.1016/j.cmet.2024.07.010
tissue_or_cell_type
Brown adipose tissue and human HEK293T cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 542–553
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Slc25a48 knockout, rescue, mitochondrial assays and isotope tracing · source_derived_draft · unverified_draft
### choline-cold-tolerance Slc25a48-null mice had impaired cold tolerance. Condition category: machinery_impairment nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mouse whole-body response was consistent with impaired heat production. organism: Mouse tissue_or_cell_type: Brown adipose tissue and human HEK293T cells experimental_model: Slc25a48 knockout, rescue, mitochondrial assays and isotope tracing limitations: Transport, energy and one-carbon outcomes are model-specific; normal intake cannot be assumed to correct a carrier defect. exposure: Germline mouse knockout; human-cell SLC25A48 loss; labeled choline evidence_span: {"source_cache": "artifacts/choline-research/39111307.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f", "start_char": 0, "end_char": 1201, "text_sha256": "c0a9377732782bdaa55105cae0a0446afcfb1225e686d2b047a7fdf1ef67535f"} [choline-p39111307] SLC25A48 controls mitochondrial choline import and metabolism. (2024). https://pubmed.ncbi.nlm.nih.gov/39111307/ DOI: 10.1016/j.cmet.2024.07.010
Complete structured claim and evidence
An independent GeneMAP study found that SLC25A48 loss strongly impaired mitochondrial choline import.
Human mitochondrial choline carrier SLC25A48 → Human mitochondrial choline import source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/38977856.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "80a5e7038c33442cc887901558cb662b39fe4c54e3821f860c12a388c8a44c92", "start_char": 0, "end_char": 1169, "text_sha256": "80a5e7038c33442cc887901558cb662b39fe4c54e3821f860c12a388c8a44c92"}
experimental_model
Independent gene–metabolite mapping and mitochondrial experiments
exposure
SLC25A48 genetic association and loss-of-function experiments
limitations
Indexed abstract leaves individual construct details unresolved; no tissue-specific quantitative claim is made here.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human genetic data and experimental cells
plain_language
A second research group supported the same transport step.
primary_references
[choline-p38977856] Metabolic gene function discovery platform GeneMAP identifies SLC25A48 as necessary for mitochondrial choline import. (2024). https://pubmed.ncbi.nlm.nih.gov/38977856/ DOI: 10.1038/s41588-024-01827-2
tissue_or_cell_type
Plasma choline and mitochondrial import
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 555–566
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Independent gene–metabolite mapping and mitochondrial experiments · source_derived_draft · unverified_draft
### choline-slc25a48-independent An independent GeneMAP study found that SLC25A48 loss strongly impaired mitochondrial choline import. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second research group supported the same transport step. organism: Human genetic data and experimental cells tissue_or_cell_type: Plasma choline and mitochondrial import experimental_model: Independent gene–metabolite mapping and mitochondrial experiments limitations: Indexed abstract leaves individual construct details unresolved; no tissue-specific quantitative claim is made here. exposure: SLC25A48 genetic association and loss-of-function experiments evidence_span: {"source_cache": "artifacts/choline-research/38977856.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "80a5e7038c33442cc887901558cb662b39fe4c54e3821f860c12a388c8a44c92", "start_char": 0, "end_char": 1169, "text_sha256": "80a5e7038c33442cc887901558cb662b39fe4c54e3821f860c12a388c8a44c92"} [choline-p38977856] Metabolic gene function discovery platform GeneMAP identifies SLC25A48 as necessary for mitochondrial choline import. (2024). https://pubmed.ncbi.nlm.nih.gov/38977856/ DOI: 10.1038/s41588-024-01827-2
Complete structured claim and evidence
Chdh deletion lowered testicular betaine while choline and phosphocholine increased.
Experimental mouse Chdh-null genotype → Mouse testicular betaine concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/choline-research/20371614.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dce0c14d2eb09194040087e691053960d9e4f477a49099cdd9482ad9ab38dc48", "start_char": 0, "end_char": 1334, "text_sha256": "dce0c14d2eb09194040087e691053960d9e4f477a49099cdd9482ad9ab38dc48"}
experimental_model
Chdh-null mouse genetics and sperm biochemical assays
exposure
Chdh deletion versus wild type
limitations
Loss of an enzyme is not the same exposure as low dietary choline; mouse fertility results are not a human diagnostic rule. The 2018 correction replaces the original knockout exon diagram: exons 1–6 and much of exon 7 were deleted, not only exons 1–3 (PMID 29698116; doi:10.1096/fj.09-153718ERR).
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Mouse
plain_language
Choline accumulated upstream while a downstream product fell.
primary_references
[choline-p20371614] Deletion of murine choline dehydrogenase results in diminished sperm motility. (2010). https://pubmed.ncbi.nlm.nih.gov/20371614/ DOI: 10.1096/fj.09-153718
tissue_or_cell_type
Testis and sperm mitochondria
trigger_kind
machinery_impairment Imported condition classification; unverified.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 568–579
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chdh-null mouse genetics and sperm biochemical assays · source_derived_draft · unverified_draft
### choline-chdh-betaine Chdh deletion lowered testicular betaine while choline and phosphocholine increased. Condition category: machinery_impairment nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Choline accumulated upstream while a downstream product fell. organism: Mouse tissue_or_cell_type: Testis and sperm mitochondria experimental_model: Chdh-null mouse genetics and sperm biochemical assays limitations: Loss of an enzyme is not the same exposure as low dietary choline; mouse fertility results are not a human diagnostic rule. The 2018 correction replaces the original knockout exon diagram: exons 1–6 and much of exon 7 were deleted, not only exons 1–3 (PMID 29698116; doi:10.1096/fj.09-153718ERR). exposure: Chdh deletion versus wild type evidence_span: {"source_cache": "artifacts/choline-research/20371614.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dce0c14d2eb09194040087e691053960d9e4f477a49099cdd9482ad9ab38dc48", "start_char": 0, "end_char": 1334, "text_sha256": "dce0c14d2eb09194040087e691053960d9e4f477a49099cdd9482ad9ab38dc48"} [choline-p20371614] Deletion of murine choline dehydrogenase results in diminished sperm motility. (2010). https://pubmed.ncbi.nlm.nih.gov/20371614/ DOI: 10.1096/fj.09-153718
Complete structured claim and evidence
Sperm ATP content was significantly reduced in Chdh-null males.
Experimental mouse Chdh-null genotype → Mouse sperm ATP content source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/choline-research/20371614.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dce0c14d2eb09194040087e691053960d9e4f477a49099cdd9482ad9ab38dc48", "start_char": 0, "end_char": 1334, "text_sha256": "dce0c14d2eb09194040087e691053960d9e4f477a49099cdd9482ad9ab38dc48"}
experimental_model
Chdh-null mouse genetics and sperm biochemical assays
exposure
Chdh deletion versus wild type
limitations
Loss of an enzyme is not the same exposure as low dietary choline; mouse fertility results are not a human diagnostic rule. The 2018 correction replaces the original knockout exon diagram: exons 1–6 and much of exon 7 were deleted, not only exons 1–3 (PMID 29698116; doi:10.1096/fj.09-153718ERR).
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Mouse
plain_language
The enzyme defect was associated with impaired sperm energetics.
primary_references
[choline-p20371614] Deletion of murine choline dehydrogenase results in diminished sperm motility. (2010). https://pubmed.ncbi.nlm.nih.gov/20371614/ DOI: 10.1096/fj.09-153718
tissue_or_cell_type
Testis and sperm mitochondria
trigger_kind
machinery_impairment Imported condition classification; unverified.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 581–592
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chdh-null mouse genetics and sperm biochemical assays · source_derived_draft · unverified_draft
### choline-chdh-atp Sperm ATP content was significantly reduced in Chdh-null males. Condition category: machinery_impairment nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme defect was associated with impaired sperm energetics. organism: Mouse tissue_or_cell_type: Testis and sperm mitochondria experimental_model: Chdh-null mouse genetics and sperm biochemical assays limitations: Loss of an enzyme is not the same exposure as low dietary choline; mouse fertility results are not a human diagnostic rule. The 2018 correction replaces the original knockout exon diagram: exons 1–6 and much of exon 7 were deleted, not only exons 1–3 (PMID 29698116; doi:10.1096/fj.09-153718ERR). exposure: Chdh deletion versus wild type evidence_span: {"source_cache": "artifacts/choline-research/20371614.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dce0c14d2eb09194040087e691053960d9e4f477a49099cdd9482ad9ab38dc48", "start_char": 0, "end_char": 1334, "text_sha256": "dce0c14d2eb09194040087e691053960d9e4f477a49099cdd9482ad9ab38dc48"} [choline-p20371614] Deletion of murine choline dehydrogenase results in diminished sperm motility. (2010). https://pubmed.ncbi.nlm.nih.gov/20371614/ DOI: 10.1096/fj.09-153718
Complete structured claim and evidence
Chdh-null males produced comparable amounts of sperm but had diminished sperm motility.
Experimental mouse Chdh-null genotype → Mouse sperm motility source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/choline-research/20371614.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dce0c14d2eb09194040087e691053960d9e4f477a49099cdd9482ad9ab38dc48", "start_char": 0, "end_char": 1334, "text_sha256": "dce0c14d2eb09194040087e691053960d9e4f477a49099cdd9482ad9ab38dc48"}
experimental_model
Chdh-null mouse genetics and sperm biochemical assays
exposure
Chdh deletion versus wild type
limitations
Loss of an enzyme is not the same exposure as low dietary choline; mouse fertility results are not a human diagnostic rule. The 2018 correction replaces the original knockout exon diagram: exons 1–6 and much of exon 7 were deleted, not only exons 1–3 (PMID 29698116; doi:10.1096/fj.09-153718ERR).
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Mouse
plain_language
Sperm number and sperm movement were different outcomes.
primary_references
[choline-p20371614] Deletion of murine choline dehydrogenase results in diminished sperm motility. (2010). https://pubmed.ncbi.nlm.nih.gov/20371614/ DOI: 10.1096/fj.09-153718
tissue_or_cell_type
Testis and sperm mitochondria
trigger_kind
machinery_impairment Imported condition classification; unverified.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 594–605
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chdh-null mouse genetics and sperm biochemical assays · source_derived_draft · unverified_draft
### choline-chdh-motility Chdh-null males produced comparable amounts of sperm but had diminished sperm motility. Condition category: machinery_impairment nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Sperm number and sperm movement were different outcomes. organism: Mouse tissue_or_cell_type: Testis and sperm mitochondria experimental_model: Chdh-null mouse genetics and sperm biochemical assays limitations: Loss of an enzyme is not the same exposure as low dietary choline; mouse fertility results are not a human diagnostic rule. The 2018 correction replaces the original knockout exon diagram: exons 1–6 and much of exon 7 were deleted, not only exons 1–3 (PMID 29698116; doi:10.1096/fj.09-153718ERR). exposure: Chdh deletion versus wild type evidence_span: {"source_cache": "artifacts/choline-research/20371614.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dce0c14d2eb09194040087e691053960d9e4f477a49099cdd9482ad9ab38dc48", "start_char": 0, "end_char": 1334, "text_sha256": "dce0c14d2eb09194040087e691053960d9e4f477a49099cdd9482ad9ab38dc48"} [choline-p20371614] Deletion of murine choline dehydrogenase results in diminished sperm motility. (2010). https://pubmed.ncbi.nlm.nih.gov/20371614/ DOI: 10.1096/fj.09-153718
Complete structured claim and evidence
Purified human E3 aldehyde dehydrogenase showed betaine-aldehyde dehydrogenase activity, with the activities co-purifying across six columns.
ALDH9A1 → Betaine aldehyde source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/7646513.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "26a654f5b886888ad8c9de61fc59a9fcbaa08dce54a8bd2ba4be43ac637071dc", "start_char": 0, "end_char": 687, "text_sha256": "26a654f5b886888ad8c9de61fc59a9fcbaa08dce54a8bd2ba4be43ac637071dc"}
experimental_model
Purified human E3 aldehyde dehydrogenase substrate assays
exposure
Betaine aldehyde and 4-aminobutyraldehyde activity across six chromatography steps
limitations
E3/ALDH9A1 has demonstrated betaine-aldehyde activity; not an exclusive assignment of every tissue’s betaine synthesis to this enzyme.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human enzyme
plain_language
This enzyme can process the aldehyde intermediate in the betaine pathway.
primary_references
[choline-p7646513] Human aldehyde dehydrogenase E3 isozyme is a betaine aldehyde dehydrogenase. (1995). https://pubmed.ncbi.nlm.nih.gov/7646513/ DOI: 10.1006/bbrc.1995.2168
tissue_or_cell_type
Purified protein
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 607–618
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human E3 aldehyde dehydrogenase substrate assays · source_derived_draft · unverified_draft
### choline-aldh9-betaine Purified human E3 aldehyde dehydrogenase showed betaine-aldehyde dehydrogenase activity, with the activities co-purifying across six columns. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: This enzyme can process the aldehyde intermediate in the betaine pathway. organism: Human enzyme tissue_or_cell_type: Purified protein experimental_model: Purified human E3 aldehyde dehydrogenase substrate assays limitations: E3/ALDH9A1 has demonstrated betaine-aldehyde activity; not an exclusive assignment of every tissue’s betaine synthesis to this enzyme. exposure: Betaine aldehyde and 4-aminobutyraldehyde activity across six chromatography steps evidence_span: {"source_cache": "artifacts/choline-research/7646513.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "26a654f5b886888ad8c9de61fc59a9fcbaa08dce54a8bd2ba4be43ac637071dc", "start_char": 0, "end_char": 687, "text_sha256": "26a654f5b886888ad8c9de61fc59a9fcbaa08dce54a8bd2ba4be43ac637071dc"} [choline-p7646513] Human aldehyde dehydrogenase E3 isozyme is a betaine aldehyde dehydrogenase. (1995). https://pubmed.ncbi.nlm.nih.gov/7646513/ DOI: 10.1006/bbrc.1995.2168
Complete structured claim and evidence
ALDH9/E3 betaine-aldehyde activity was highest in liver, adrenal and kidney among the tested tissues; mRNA peaked in different tissues.
ALDH9A1 → Betaine aldehyde source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/9417993.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "67df6eb3c096ba09a314314ada97fc4c2b9ad555b28b316df3d17501b397c7d4", "start_char": 0, "end_char": 941, "text_sha256": "67df6eb3c096ba09a314314ada97fc4c2b9ad555b28b316df3d17501b397c7d4"}
experimental_model
Tissue enzyme activity, immunoblot and RNA comparison
exposure
Betaine-aldehyde activity compared with E3/ALDH9 protein and transcript
limitations
Transcript abundance differed from protein/activity distribution; RNA is not a universal proxy for flux.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
The enzyme’s measured activity did not simply track its RNA abundance.
primary_references
[choline-p9417993] Tissue distribution of human aldehyde dehydrogenase E3 (ALDH9): comparison of enzyme activity with E3 protein and mRNA distribution. (1997). https://pubmed.ncbi.nlm.nih.gov/9417993/ DOI: 10.1016/s0305-0491(97)00022-9
tissue_or_cell_type
Multiple tissues including liver, adrenal, kidney and muscle
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 620–631
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Tissue enzyme activity, immunoblot and RNA comparison · source_derived_draft · unverified_draft
### choline-aldh9-activity-distribution ALDH9/E3 betaine-aldehyde activity was highest in liver, adrenal and kidney among the tested tissues; mRNA peaked in different tissues. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme’s measured activity did not simply track its RNA abundance. organism: Human tissue_or_cell_type: Multiple tissues including liver, adrenal, kidney and muscle experimental_model: Tissue enzyme activity, immunoblot and RNA comparison limitations: Transcript abundance differed from protein/activity distribution; RNA is not a universal proxy for flux. exposure: Betaine-aldehyde activity compared with E3/ALDH9 protein and transcript evidence_span: {"source_cache": "artifacts/choline-research/9417993.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "67df6eb3c096ba09a314314ada97fc4c2b9ad555b28b316df3d17501b397c7d4", "start_char": 0, "end_char": 941, "text_sha256": "67df6eb3c096ba09a314314ada97fc4c2b9ad555b28b316df3d17501b397c7d4"} [choline-p9417993] Tissue distribution of human aldehyde dehydrogenase E3 (ALDH9): comparison of enzyme activity with E3 protein and mRNA distribution. (1997). https://pubmed.ncbi.nlm.nih.gov/9417993/ DOI: 10.1016/s0305-0491(97)00022-9
Complete structured claim and evidence
Human ALDH7A1 expression attenuated apoptosis caused by high extracellular sucrose or sodium chloride in CHO cells.
Antiquitin / ALDH7A1 → Hyperosmotic apoptosis in CHO cells expressing human ALDH7A1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/20207735.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "510558afae2825079b269c8a4ee3f16114ab8d7f6c357c1a085ec14f1924e5e5", "start_char": 0, "end_char": 1582, "text_sha256": "510558afae2825079b269c8a4ee3f16114ab8d7f6c357c1a085ec14f1924e5e5"}
experimental_model
Purified recombinant human enzyme and CHO-cell expression
exposure
Betaine aldehyde substrate; increased extracellular sucrose or NaCl
limitations
The enzyme also detoxifies other aldehydes; betaine is a proposed contributor, not an isolated mediator in this endpoint.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human ALDH7A1; Chinese hamster ovary expression host
plain_language
The enzyme protected these cells during osmotic stress.
primary_references
[choline-p20207735] Aldehyde dehydrogenase 7A1 (ALDH7A1) is a novel enzyme involved in cellular defense against hyperosmotic stress. (2010). https://pubmed.ncbi.nlm.nih.gov/20207735/ DOI: 10.1074/jbc.m109.077925
tissue_or_cell_type
Purified enzyme and osmotic-stress cell assays
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 646–657
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human enzyme and CHO-cell expression · source_derived_draft · unverified_draft
### choline-aldh7-osmotic Human ALDH7A1 expression attenuated apoptosis caused by high extracellular sucrose or sodium chloride in CHO cells. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme protected these cells during osmotic stress. organism: Human ALDH7A1; Chinese hamster ovary expression host tissue_or_cell_type: Purified enzyme and osmotic-stress cell assays experimental_model: Purified recombinant human enzyme and CHO-cell expression limitations: The enzyme also detoxifies other aldehydes; betaine is a proposed contributor, not an isolated mediator in this endpoint. exposure: Betaine aldehyde substrate; increased extracellular sucrose or NaCl evidence_span: {"source_cache": "artifacts/choline-research/20207735.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "510558afae2825079b269c8a4ee3f16114ab8d7f6c357c1a085ec14f1924e5e5", "start_char": 0, "end_char": 1582, "text_sha256": "510558afae2825079b269c8a4ee3f16114ab8d7f6c357c1a085ec14f1924e5e5"} [choline-p20207735] Aldehyde dehydrogenase 7A1 (ALDH7A1) is a novel enzyme involved in cellular defense against hyperosmotic stress. (2010). https://pubmed.ncbi.nlm.nih.gov/20207735/ DOI: 10.1074/jbc.m109.077925
Complete structured claim and evidence
Rat DMGDH catalyzes oxidative demethylation of dimethylglycine to sarcosine.
Rat dimethylglycine dehydrogenase / Dmgdh → Dimethylglycine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/24858690.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e00bbb8f1c2c805e9d7261c286bace5758abd277bc95b3e0a830bd9cdb82a34f", "start_char": 0, "end_char": 1506, "text_sha256": "e00bbb8f1c2c805e9d7261c286bace5758abd277bc95b3e0a830bd9cdb82a34f"}
experimental_model
Rat DMGDH crystallography and enzyme characterization
exposure
Dimethylglycine turnover and THF-bound structures
limitations
Species and assay context retained. The proposed intramolecular transfer route is not represented as a directly observed moving intermediate.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Rat recombinant enzyme
plain_language
After betaine donates one methyl group, another enzyme handles the remaining dimethylglycine.
primary_references
[choline-p24858690] Folate in demethylation: the crystal structure of the rat dimethylglycine dehydrogenase complexed with tetrahydrofolate. (2014). https://pubmed.ncbi.nlm.nih.gov/24858690/ DOI: 10.1016/j.bbrc.2014.05.064
tissue_or_cell_type
Mitochondrial-enzyme preparation
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 659–670
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat DMGDH crystallography and enzyme characterization · source_derived_draft · unverified_draft
### choline-dmgdh-sarcosine Rat DMGDH catalyzes oxidative demethylation of dimethylglycine to sarcosine. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: After betaine donates one methyl group, another enzyme handles the remaining dimethylglycine. organism: Rat recombinant enzyme tissue_or_cell_type: Mitochondrial-enzyme preparation experimental_model: Rat DMGDH crystallography and enzyme characterization limitations: Species and assay context retained. The proposed intramolecular transfer route is not represented as a directly observed moving intermediate. exposure: Dimethylglycine turnover and THF-bound structures evidence_span: {"source_cache": "artifacts/choline-research/24858690.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e00bbb8f1c2c805e9d7261c286bace5758abd277bc95b3e0a830bd9cdb82a34f", "start_char": 0, "end_char": 1506, "text_sha256": "e00bbb8f1c2c805e9d7261c286bace5758abd277bc95b3e0a830bd9cdb82a34f"} [choline-p24858690] Folate in demethylation: the crystal structure of the rat dimethylglycine dehydrogenase complexed with tetrahydrofolate. (2014). https://pubmed.ncbi.nlm.nih.gov/24858690/ DOI: 10.1016/j.bbrc.2014.05.064
Complete structured claim and evidence
Rat DMGDH structures located THF in a domain separated from the FAD-containing active center and connected by an internal channel.
Rat dimethylglycine dehydrogenase / Dmgdh → Tetrahydrofolate source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/24858690.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e00bbb8f1c2c805e9d7261c286bace5758abd277bc95b3e0a830bd9cdb82a34f", "start_char": 0, "end_char": 1506, "text_sha256": "e00bbb8f1c2c805e9d7261c286bace5758abd277bc95b3e0a830bd9cdb82a34f"}
experimental_model
Rat DMGDH crystallography and enzyme characterization
exposure
Dimethylglycine turnover and THF-bound structures
limitations
Species and assay context retained. The proposed intramolecular transfer route is not represented as a directly observed moving intermediate.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Rat recombinant enzyme
plain_language
Folate and a riboflavin-derived cofactor occupy distinct sites in the same enzyme.
primary_references
[choline-p24858690] Folate in demethylation: the crystal structure of the rat dimethylglycine dehydrogenase complexed with tetrahydrofolate. (2014). https://pubmed.ncbi.nlm.nih.gov/24858690/ DOI: 10.1016/j.bbrc.2014.05.064
tissue_or_cell_type
Mitochondrial-enzyme preparation
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 672–683
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat DMGDH crystallography and enzyme characterization · source_derived_draft · unverified_draft
### choline-dmgdh-thf Rat DMGDH structures located THF in a domain separated from the FAD-containing active center and connected by an internal channel. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Folate and a riboflavin-derived cofactor occupy distinct sites in the same enzyme. organism: Rat recombinant enzyme tissue_or_cell_type: Mitochondrial-enzyme preparation experimental_model: Rat DMGDH crystallography and enzyme characterization limitations: Species and assay context retained. The proposed intramolecular transfer route is not represented as a directly observed moving intermediate. exposure: Dimethylglycine turnover and THF-bound structures evidence_span: {"source_cache": "artifacts/choline-research/24858690.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e00bbb8f1c2c805e9d7261c286bace5758abd277bc95b3e0a830bd9cdb82a34f", "start_char": 0, "end_char": 1506, "text_sha256": "e00bbb8f1c2c805e9d7261c286bace5758abd277bc95b3e0a830bd9cdb82a34f"} [choline-p24858690] Folate in demethylation: the crystal structure of the rat dimethylglycine dehydrogenase complexed with tetrahydrofolate. (2014). https://pubmed.ncbi.nlm.nih.gov/24858690/ DOI: 10.1016/j.bbrc.2014.05.064
Complete structured claim and evidence
In the THF-coupled DMGDH pathway, a removed one-carbon unit is captured as 5,10-methylenetetrahydrofolate rather than released as free formaldehyde.
Tetrahydrofolate → 5,10-Methylenetetrahydrofolate source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/24858690.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e00bbb8f1c2c805e9d7261c286bace5758abd277bc95b3e0a830bd9cdb82a34f", "start_char": 0, "end_char": 1506, "text_sha256": "e00bbb8f1c2c805e9d7261c286bace5758abd277bc95b3e0a830bd9cdb82a34f"}
experimental_model
Rat DMGDH crystallography and enzyme characterization
exposure
Dimethylglycine turnover and THF-bound structures
limitations
Pathway chemistry interpreted with rat enzyme structures; not proof that dietary folate rescue restores every human choline-dependent function.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Rat recombinant enzyme
plain_language
Choline-derived methyl metabolism feeds the folate pool.
primary_references
[choline-p24858690] Folate in demethylation: the crystal structure of the rat dimethylglycine dehydrogenase complexed with tetrahydrofolate. (2014). https://pubmed.ncbi.nlm.nih.gov/24858690/ DOI: 10.1016/j.bbrc.2014.05.064
tissue_or_cell_type
Mitochondrial-enzyme preparation
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 685–696
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat DMGDH crystallography and enzyme characterization · source_derived_draft · unverified_draft
### choline-dmgdh-one-carbon In the THF-coupled DMGDH pathway, a removed one-carbon unit is captured as 5,10-methylenetetrahydrofolate rather than released as free formaldehyde. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Choline-derived methyl metabolism feeds the folate pool. organism: Rat recombinant enzyme tissue_or_cell_type: Mitochondrial-enzyme preparation experimental_model: Rat DMGDH crystallography and enzyme characterization limitations: Pathway chemistry interpreted with rat enzyme structures; not proof that dietary folate rescue restores every human choline-dependent function. exposure: Dimethylglycine turnover and THF-bound structures evidence_span: {"source_cache": "artifacts/choline-research/24858690.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e00bbb8f1c2c805e9d7261c286bace5758abd277bc95b3e0a830bd9cdb82a34f", "start_char": 0, "end_char": 1506, "text_sha256": "e00bbb8f1c2c805e9d7261c286bace5758abd277bc95b3e0a830bd9cdb82a34f"} [choline-p24858690] Folate in demethylation: the crystal structure of the rat dimethylglycine dehydrogenase complexed with tetrahydrofolate. (2014). https://pubmed.ncbi.nlm.nih.gov/24858690/ DOI: 10.1016/j.bbrc.2014.05.064
Complete structured claim and evidence
Choline kinase activity was undetectable in the three reported muscle samples with CHKB nonsense variants.
CHKB nonsense genotypes in the three 2011 muscle assays → Muscle choline kinase activity in CHKB-deficient individuals source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/choline-research/21665002.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ccd6913be10435c076cc81d7ea0509678751d445078c857bb977497a3754059f", "start_char": 0, "end_char": 1157, "text_sha256": "ccd6913be10435c076cc81d7ea0509678751d445078c857bb977497a3754059f"}
experimental_model
Fifteen affected individuals with CHKB variants; muscle assays in three
exposure
Biallelic CHKB variants; three nonsense-genotype muscle samples
limitations
A congenital enzyme defect, distinct from ordinary nutrient depletion; mitochondrial morphology does not prove one unique downstream lesion.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
The first phosphorylation step was severely impaired.
primary_references
[choline-p21665002] A congenital muscular dystrophy with mitochondrial structural abnormalities caused by defective de novo phosphatidylcholine biosynthesis. (2011). https://pubmed.ncbi.nlm.nih.gov/21665002/ DOI: 10.1016/j.ajhg.2011.05.010
tissue_or_cell_type
Skeletal muscle
trigger_kind
machinery_impairment Imported condition classification; unverified.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 711–722
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Fifteen affected individuals with CHKB variants; muscle assays in three · source_derived_draft · unverified_draft
### choline-chkb-activity Choline kinase activity was undetectable in the three reported muscle samples with CHKB nonsense variants. Condition category: machinery_impairment nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The first phosphorylation step was severely impaired. organism: Human tissue_or_cell_type: Skeletal muscle experimental_model: Fifteen affected individuals with CHKB variants; muscle assays in three limitations: A congenital enzyme defect, distinct from ordinary nutrient depletion; mitochondrial morphology does not prove one unique downstream lesion. exposure: Biallelic CHKB variants; three nonsense-genotype muscle samples evidence_span: {"source_cache": "artifacts/choline-research/21665002.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ccd6913be10435c076cc81d7ea0509678751d445078c857bb977497a3754059f", "start_char": 0, "end_char": 1157, "text_sha256": "ccd6913be10435c076cc81d7ea0509678751d445078c857bb977497a3754059f"} [choline-p21665002] A congenital muscular dystrophy with mitochondrial structural abnormalities caused by defective de novo phosphatidylcholine biosynthesis. (2011). https://pubmed.ncbi.nlm.nih.gov/21665002/ DOI: 10.1016/j.ajhg.2011.05.010
Complete structured claim and evidence
Phosphatidylcholine levels were reduced in those affected muscle samples.
CHKB nonsense genotypes in the three 2011 muscle assays → Muscle phosphatidylcholine content in CHKB-deficient individuals source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/choline-research/21665002.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ccd6913be10435c076cc81d7ea0509678751d445078c857bb977497a3754059f", "start_char": 0, "end_char": 1157, "text_sha256": "ccd6913be10435c076cc81d7ea0509678751d445078c857bb977497a3754059f"}
experimental_model
Fifteen affected individuals with CHKB variants; muscle assays in three
exposure
Biallelic CHKB variants; three nonsense-genotype muscle samples
limitations
A congenital enzyme defect, distinct from ordinary nutrient depletion; mitochondrial morphology does not prove one unique downstream lesion.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
The membrane-lipid product was lower in the sampled tissue.
primary_references
[choline-p21665002] A congenital muscular dystrophy with mitochondrial structural abnormalities caused by defective de novo phosphatidylcholine biosynthesis. (2011). https://pubmed.ncbi.nlm.nih.gov/21665002/ DOI: 10.1016/j.ajhg.2011.05.010
tissue_or_cell_type
Skeletal muscle
trigger_kind
machinery_impairment Imported condition classification; unverified.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 724–735
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Fifteen affected individuals with CHKB variants; muscle assays in three · source_derived_draft · unverified_draft
### choline-chkb-pc Phosphatidylcholine levels were reduced in those affected muscle samples. Condition category: machinery_impairment nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The membrane-lipid product was lower in the sampled tissue. organism: Human tissue_or_cell_type: Skeletal muscle experimental_model: Fifteen affected individuals with CHKB variants; muscle assays in three limitations: A congenital enzyme defect, distinct from ordinary nutrient depletion; mitochondrial morphology does not prove one unique downstream lesion. exposure: Biallelic CHKB variants; three nonsense-genotype muscle samples evidence_span: {"source_cache": "artifacts/choline-research/21665002.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ccd6913be10435c076cc81d7ea0509678751d445078c857bb977497a3754059f", "start_char": 0, "end_char": 1157, "text_sha256": "ccd6913be10435c076cc81d7ea0509678751d445078c857bb977497a3754059f"} [choline-p21665002] A congenital muscular dystrophy with mitochondrial structural abnormalities caused by defective de novo phosphatidylcholine biosynthesis. (2011). https://pubmed.ncbi.nlm.nih.gov/21665002/ DOI: 10.1016/j.ajhg.2011.05.010
Complete structured claim and evidence
The patient variants markedly reduced PCYT1A expression.
Biallelic PCYT1A loss-of-function genotypes in the 2014 patients → Human PCYT1A protein expression source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/choline-research/24889630.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2a370c0cdea7e750360683ff2fe878373965dc5f385e243fe6b0fce1a332ee99", "start_char": 0, "end_char": 1005, "text_sha256": "2a370c0cdea7e750360683ff2fe878373965dc5f385e243fe6b0fce1a332ee99"}
experimental_model
Two unrelated patients; PCYT1A expression and PC-synthesis experiments
exposure
Biallelic PCYT1A loss-of-function variants
limitations
Rare genetic disease does not establish choline intake as the cause of common fatty liver or diabetes.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
Less of the pathway enzyme was available.
primary_references
[choline-p24889630] Mutations disrupting the Kennedy phosphatidylcholine pathway in humans with congenital lipodystrophy and fatty liver disease. (2014). https://pubmed.ncbi.nlm.nih.gov/24889630/ DOI: 10.1073/pnas.1408523111
tissue_or_cell_type
Patient-derived material; liver/adipose phenotype
trigger_kind
machinery_impairment Imported condition classification; unverified.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 737–748
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two unrelated patients; PCYT1A expression and PC-synthesis experiments · source_derived_draft · unverified_draft
### choline-pcyt1a-expression The patient variants markedly reduced PCYT1A expression. Condition category: machinery_impairment nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Less of the pathway enzyme was available. organism: Human tissue_or_cell_type: Patient-derived material; liver/adipose phenotype experimental_model: Two unrelated patients; PCYT1A expression and PC-synthesis experiments limitations: Rare genetic disease does not establish choline intake as the cause of common fatty liver or diabetes. exposure: Biallelic PCYT1A loss-of-function variants evidence_span: {"source_cache": "artifacts/choline-research/24889630.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2a370c0cdea7e750360683ff2fe878373965dc5f385e243fe6b0fce1a332ee99", "start_char": 0, "end_char": 1005, "text_sha256": "2a370c0cdea7e750360683ff2fe878373965dc5f385e243fe6b0fce1a332ee99"} [choline-p24889630] Mutations disrupting the Kennedy phosphatidylcholine pathway in humans with congenital lipodystrophy and fatty liver disease. (2014). https://pubmed.ncbi.nlm.nih.gov/24889630/ DOI: 10.1073/pnas.1408523111
Complete structured claim and evidence
The PCYT1A defects markedly reduced phosphatidylcholine synthesis.
Biallelic PCYT1A loss-of-function genotypes in the 2014 patients → Human phosphatidylcholine synthesis source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/choline-research/24889630.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2a370c0cdea7e750360683ff2fe878373965dc5f385e243fe6b0fce1a332ee99", "start_char": 0, "end_char": 1005, "text_sha256": "2a370c0cdea7e750360683ff2fe878373965dc5f385e243fe6b0fce1a332ee99"}
experimental_model
Two unrelated patients; PCYT1A expression and PC-synthesis experiments
exposure
Biallelic PCYT1A loss-of-function variants
limitations
Rare genetic disease does not establish choline intake as the cause of common fatty liver or diabetes.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
Choline supply alone did not describe the impaired synthetic machinery.
primary_references
[choline-p24889630] Mutations disrupting the Kennedy phosphatidylcholine pathway in humans with congenital lipodystrophy and fatty liver disease. (2014). https://pubmed.ncbi.nlm.nih.gov/24889630/ DOI: 10.1073/pnas.1408523111
tissue_or_cell_type
Patient-derived material; liver/adipose phenotype
trigger_kind
machinery_impairment Imported condition classification; unverified.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 750–761
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two unrelated patients; PCYT1A expression and PC-synthesis experiments · source_derived_draft · unverified_draft
### choline-pcyt1a-pc The PCYT1A defects markedly reduced phosphatidylcholine synthesis. Condition category: machinery_impairment nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Choline supply alone did not describe the impaired synthetic machinery. organism: Human tissue_or_cell_type: Patient-derived material; liver/adipose phenotype experimental_model: Two unrelated patients; PCYT1A expression and PC-synthesis experiments limitations: Rare genetic disease does not establish choline intake as the cause of common fatty liver or diabetes. exposure: Biallelic PCYT1A loss-of-function variants evidence_span: {"source_cache": "artifacts/choline-research/24889630.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2a370c0cdea7e750360683ff2fe878373965dc5f385e243fe6b0fce1a332ee99", "start_char": 0, "end_char": 1005, "text_sha256": "2a370c0cdea7e750360683ff2fe878373965dc5f385e243fe6b0fce1a332ee99"} [choline-p24889630] Mutations disrupting the Kennedy phosphatidylcholine pathway in humans with congenital lipodystrophy and fatty liver disease. (2014). https://pubmed.ncbi.nlm.nih.gov/24889630/ DOI: 10.1073/pnas.1408523111
Complete structured claim and evidence
Human CHPT1 catalyzes the PC-producing final step of the Kennedy pathway with choline-headgroup substrate selectivity.
Human choline phosphotransferase 1 / CHPT1 → Phosphatidylcholine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/40435706.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d08b2ce68e8731e88e1204dc1b09d1301020452752a630a880ec3a2cdb0f2351", "start_char": 0, "end_char": 1339, "text_sha256": "d08b2ce68e8731e88e1204dc1b09d1301020452752a630a880ec3a2cdb0f2351"}
experimental_model
Human CHPT1 cryo-EM, sequence analysis and biochemical characterization
exposure
CDP-choline/CDP-ethanolamine substrate selectivity
limitations
Human CHPT1 and CEPT1 remain separate. Evolutionary suggestions about oviparous species are not asserted as human bifunctionality.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human proteins; evolutionary comparisons explicitly separate
plain_language
One terminal enzyme specializes in making phosphatidylcholine.
primary_references
[choline-p40435706] Structural basis for substrate selectivity and evolutionary insights into human choline phosphotransferase 1. (2025). https://pubmed.ncbi.nlm.nih.gov/40435706/ DOI: 10.1016/j.bbrc.2025.152082
tissue_or_cell_type
Membrane phospholipid synthesis
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 763–774
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CHPT1 cryo-EM, sequence analysis and biochemical characterization · source_derived_draft · unverified_draft
### choline-chpt1-pc Human CHPT1 catalyzes the PC-producing final step of the Kennedy pathway with choline-headgroup substrate selectivity. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: One terminal enzyme specializes in making phosphatidylcholine. organism: Human proteins; evolutionary comparisons explicitly separate tissue_or_cell_type: Membrane phospholipid synthesis experimental_model: Human CHPT1 cryo-EM, sequence analysis and biochemical characterization limitations: Human CHPT1 and CEPT1 remain separate. Evolutionary suggestions about oviparous species are not asserted as human bifunctionality. exposure: CDP-choline/CDP-ethanolamine substrate selectivity evidence_span: {"source_cache": "artifacts/choline-research/40435706.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d08b2ce68e8731e88e1204dc1b09d1301020452752a630a880ec3a2cdb0f2351", "start_char": 0, "end_char": 1339, "text_sha256": "d08b2ce68e8731e88e1204dc1b09d1301020452752a630a880ec3a2cdb0f2351"} [choline-p40435706] Structural basis for substrate selectivity and evolutionary insights into human choline phosphotransferase 1. (2025). https://pubmed.ncbi.nlm.nih.gov/40435706/ DOI: 10.1016/j.bbrc.2025.152082
Complete structured claim and evidence
CEPT1 can catalyze PC production as well as PE production.
Human choline/ethanolamine phosphotransferase 1 / CEPT1 → Phosphatidylcholine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/40435706.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d08b2ce68e8731e88e1204dc1b09d1301020452752a630a880ec3a2cdb0f2351", "start_char": 0, "end_char": 1339, "text_sha256": "d08b2ce68e8731e88e1204dc1b09d1301020452752a630a880ec3a2cdb0f2351"}
experimental_model
Human CHPT1 cryo-EM, sequence analysis and biochemical characterization
exposure
CDP-choline/CDP-ethanolamine substrate selectivity
limitations
Human CHPT1 and CEPT1 remain separate. Evolutionary suggestions about oviparous species are not asserted as human bifunctionality.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human proteins; evolutionary comparisons explicitly separate
plain_language
A separate terminal enzyme can serve both headgroup pathways.
primary_references
[choline-p40435706] Structural basis for substrate selectivity and evolutionary insights into human choline phosphotransferase 1. (2025). https://pubmed.ncbi.nlm.nih.gov/40435706/ DOI: 10.1016/j.bbrc.2025.152082
tissue_or_cell_type
Membrane phospholipid synthesis
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 776–787
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CHPT1 cryo-EM, sequence analysis and biochemical characterization · source_derived_draft · unverified_draft
### choline-cept1-pc CEPT1 can catalyze PC production as well as PE production. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: A separate terminal enzyme can serve both headgroup pathways. organism: Human proteins; evolutionary comparisons explicitly separate tissue_or_cell_type: Membrane phospholipid synthesis experimental_model: Human CHPT1 cryo-EM, sequence analysis and biochemical characterization limitations: Human CHPT1 and CEPT1 remain separate. Evolutionary suggestions about oviparous species are not asserted as human bifunctionality. exposure: CDP-choline/CDP-ethanolamine substrate selectivity evidence_span: {"source_cache": "artifacts/choline-research/40435706.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d08b2ce68e8731e88e1204dc1b09d1301020452752a630a880ec3a2cdb0f2351", "start_char": 0, "end_char": 1339, "text_sha256": "d08b2ce68e8731e88e1204dc1b09d1301020452752a630a880ec3a2cdb0f2351"} [choline-p40435706] Structural basis for substrate selectivity and evolutionary insights into human choline phosphotransferase 1. (2025). https://pubmed.ncbi.nlm.nih.gov/40435706/ DOI: 10.1016/j.bbrc.2025.152082
Complete structured claim and evidence
CEPT1 also catalyzes phosphatidylethanolamine production, unlike the human CHPT1 specificity described in the study.
Human choline/ethanolamine phosphotransferase 1 / CEPT1 → Phosphatidylethanolamine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/40435706.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d08b2ce68e8731e88e1204dc1b09d1301020452752a630a880ec3a2cdb0f2351", "start_char": 0, "end_char": 1339, "text_sha256": "d08b2ce68e8731e88e1204dc1b09d1301020452752a630a880ec3a2cdb0f2351"}
experimental_model
Human CHPT1 cryo-EM, sequence analysis and biochemical characterization
exposure
CDP-choline/CDP-ethanolamine substrate selectivity
limitations
Human CHPT1 and CEPT1 remain separate. Evolutionary suggestions about oviparous species are not asserted as human bifunctionality.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human proteins; evolutionary comparisons explicitly separate
plain_language
The related enzymes are not interchangeable in substrate preference.
primary_references
[choline-p40435706] Structural basis for substrate selectivity and evolutionary insights into human choline phosphotransferase 1. (2025). https://pubmed.ncbi.nlm.nih.gov/40435706/ DOI: 10.1016/j.bbrc.2025.152082
tissue_or_cell_type
Membrane phospholipid synthesis
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 789–800
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CHPT1 cryo-EM, sequence analysis and biochemical characterization · source_derived_draft · unverified_draft
### choline-cept1-pe CEPT1 also catalyzes phosphatidylethanolamine production, unlike the human CHPT1 specificity described in the study. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The related enzymes are not interchangeable in substrate preference. organism: Human proteins; evolutionary comparisons explicitly separate tissue_or_cell_type: Membrane phospholipid synthesis experimental_model: Human CHPT1 cryo-EM, sequence analysis and biochemical characterization limitations: Human CHPT1 and CEPT1 remain separate. Evolutionary suggestions about oviparous species are not asserted as human bifunctionality. exposure: CDP-choline/CDP-ethanolamine substrate selectivity evidence_span: {"source_cache": "artifacts/choline-research/40435706.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d08b2ce68e8731e88e1204dc1b09d1301020452752a630a880ec3a2cdb0f2351", "start_char": 0, "end_char": 1339, "text_sha256": "d08b2ce68e8731e88e1204dc1b09d1301020452752a630a880ec3a2cdb0f2351"} [choline-p40435706] Structural basis for substrate selectivity and evolutionary insights into human choline phosphotransferase 1. (2025). https://pubmed.ncbi.nlm.nih.gov/40435706/ DOI: 10.1016/j.bbrc.2025.152082
Complete structured claim and evidence
SAM supplies the methyl groups for each of the three PEMT-catalyzed transfers.
S-Adenosyl-L-methionine → Human phosphatidylethanolamine N-methyltransferase / PEMT source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/12431977.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7c299a547408772f2f24bdd77f2f22dc8ea9e5aaf8179150f2d8b59c9713306a", "start_char": 0, "end_char": 1380, "text_sha256": "7c299a547408772f2f24bdd77f2f22dc8ea9e5aaf8179150f2d8b59c9713306a"}
experimental_model
Human liver fractionation and recombinant PEMT membrane-topology experiments
exposure
Protein cleavage mapping and methyltransferase localization
limitations
Three methyl transfers make a choline-containing phospholipid; PEMT does not directly synthesize free choline from nothing.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human enzyme
plain_language
Membrane PC synthesis and the methyl-donor pool are connected.
primary_references
[choline-p12431977] Membrane topography of human phosphatidylethanolamine N-methyltransferase. (2003). https://pubmed.ncbi.nlm.nih.gov/12431977/ DOI: 10.1074/jbc.m210904200
tissue_or_cell_type
ER and mitochondria-associated membranes
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 815–826
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human liver fractionation and recombinant PEMT membrane-topology experiments · source_derived_draft · unverified_draft
### choline-pemt-sam SAM supplies the methyl groups for each of the three PEMT-catalyzed transfers. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Membrane PC synthesis and the methyl-donor pool are connected. organism: Human enzyme tissue_or_cell_type: ER and mitochondria-associated membranes experimental_model: Human liver fractionation and recombinant PEMT membrane-topology experiments limitations: Three methyl transfers make a choline-containing phospholipid; PEMT does not directly synthesize free choline from nothing. exposure: Protein cleavage mapping and methyltransferase localization evidence_span: {"source_cache": "artifacts/choline-research/12431977.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7c299a547408772f2f24bdd77f2f22dc8ea9e5aaf8179150f2d8b59c9713306a", "start_char": 0, "end_char": 1380, "text_sha256": "7c299a547408772f2f24bdd77f2f22dc8ea9e5aaf8179150f2d8b59c9713306a"} [choline-p12431977] Membrane topography of human phosphatidylethanolamine N-methyltransferase. (2003). https://pubmed.ncbi.nlm.nih.gov/12431977/ DOI: 10.1074/jbc.m210904200
Complete structured claim and evidence
Estradiol increased PEMT transcription in primary human hepatocytes in a dose-dependent manner.
17-beta-Estradiol → Human hepatocyte PEMT transcription source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/17456783.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d3585209a8c4db7cfe8b93aa2587fdd570f5e5c42bd3ea8f6195feb60b23b9da", "start_char": 0, "end_char": 1399, "text_sha256": "d3585209a8c4db7cfe8b93aa2587fdd570f5e5c42bd3ea8f6195feb60b23b9da"}
experimental_model
Primary-hepatocyte estrogen exposure
exposure
17-beta-estradiol treatment for 24 hours
limitations
Culture regulation supports a mechanism but does not set requirements for every person or justify hormone treatment.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human primary hepatocytes
plain_language
Hormone status can affect endogenous choline-headgroup synthesis.
primary_references
[choline-p17456783] Phosphatidylethanolamine N-methyltransferase (PEMT) gene expression is induced by estrogen in human and mouse primary hepatocytes. (2007). https://pubmed.ncbi.nlm.nih.gov/17456783/ DOI: 10.1096/fj.07-8227com
tissue_or_cell_type
Primary hepatocytes
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 828–839
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary-hepatocyte estrogen exposure · source_derived_draft · unverified_draft
### choline-estrogen-pemt-transcription Estradiol increased PEMT transcription in primary human hepatocytes in a dose-dependent manner. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Hormone status can affect endogenous choline-headgroup synthesis. organism: Human primary hepatocytes tissue_or_cell_type: Primary hepatocytes experimental_model: Primary-hepatocyte estrogen exposure limitations: Culture regulation supports a mechanism but does not set requirements for every person or justify hormone treatment. exposure: 17-beta-estradiol treatment for 24 hours evidence_span: {"source_cache": "artifacts/choline-research/17456783.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d3585209a8c4db7cfe8b93aa2587fdd570f5e5c42bd3ea8f6195feb60b23b9da", "start_char": 0, "end_char": 1399, "text_sha256": "d3585209a8c4db7cfe8b93aa2587fdd570f5e5c42bd3ea8f6195feb60b23b9da"} [choline-p17456783] Phosphatidylethanolamine N-methyltransferase (PEMT) gene expression is induced by estrogen in human and mouse primary hepatocytes. (2007). https://pubmed.ncbi.nlm.nih.gov/17456783/ DOI: 10.1096/fj.07-8227com
Complete structured claim and evidence
The increased PEMT message was accompanied by higher protein expression and enzyme activity in the hepatocyte study.
17-beta-Estradiol → Human hepatocyte PEMT enzyme activity source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/17456783.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d3585209a8c4db7cfe8b93aa2587fdd570f5e5c42bd3ea8f6195feb60b23b9da", "start_char": 0, "end_char": 1399, "text_sha256": "d3585209a8c4db7cfe8b93aa2587fdd570f5e5c42bd3ea8f6195feb60b23b9da"}
experimental_model
Primary-hepatocyte estrogen exposure
exposure
17-beta-estradiol treatment for 24 hours
limitations
Culture regulation supports a mechanism but does not set requirements for every person or justify hormone treatment.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human primary hepatocytes
plain_language
The response extended beyond an RNA measurement.
primary_references
[choline-p17456783] Phosphatidylethanolamine N-methyltransferase (PEMT) gene expression is induced by estrogen in human and mouse primary hepatocytes. (2007). https://pubmed.ncbi.nlm.nih.gov/17456783/ DOI: 10.1096/fj.07-8227com
tissue_or_cell_type
Primary hepatocytes
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 841–852
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary-hepatocyte estrogen exposure · source_derived_draft · unverified_draft
### choline-estrogen-pemt-activity The increased PEMT message was accompanied by higher protein expression and enzyme activity in the hepatocyte study. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The response extended beyond an RNA measurement. organism: Human primary hepatocytes tissue_or_cell_type: Primary hepatocytes experimental_model: Primary-hepatocyte estrogen exposure limitations: Culture regulation supports a mechanism but does not set requirements for every person or justify hormone treatment. exposure: 17-beta-estradiol treatment for 24 hours evidence_span: {"source_cache": "artifacts/choline-research/17456783.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d3585209a8c4db7cfe8b93aa2587fdd570f5e5c42bd3ea8f6195feb60b23b9da", "start_char": 0, "end_char": 1399, "text_sha256": "d3585209a8c4db7cfe8b93aa2587fdd570f5e5c42bd3ea8f6195feb60b23b9da"} [choline-p17456783] Phosphatidylethanolamine N-methyltransferase (PEMT) gene expression is induced by estrogen in human and mouse primary hepatocytes. (2007). https://pubmed.ncbi.nlm.nih.gov/17456783/ DOI: 10.1096/fj.07-8227com
Complete structured claim and evidence
The studied risk allele failed to bind estrogen receptor at the critical PEMT regulatory region.
PEMT estrogen-response risk haplotype in the 2011 study → Estrogen-receptor binding at the PEMT risk haplotype source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/choline-research/21059658.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e2906288f8d608133ab4c746793ac5939f8c9fb157dbfd92c0af7b85064310d4", "start_char": 0, "end_char": 1380, "text_sha256": "e2906288f8d608133ab4c746793ac5939f8c9fb157dbfd92c0af7b85064310d4"}
experimental_model
Transcript-specific expression, haplotype and chromatin-binding analyses
exposure
Estrogen stimulation across PEMT haplotypes
limitations
Risk is allele/haplotype-specific; not every PEMT variant or every woman has the same response.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
The hormone signal could not engage this regulatory site normally.
primary_references
[choline-p21059658] Aberrant estrogen regulation of PEMT results in choline deficiency-associated liver dysfunction. (2011). https://pubmed.ncbi.nlm.nih.gov/21059658/ DOI: 10.1074/jbc.m110.106922
tissue_or_cell_type
Primary hepatocytes and PEMT regulatory locus
trigger_kind
machinery_impairment Imported condition classification; unverified.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 854–865
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transcript-specific expression, haplotype and chromatin-binding analyses · source_derived_draft · unverified_draft
### choline-pemt-esr-binding The studied risk allele failed to bind estrogen receptor at the critical PEMT regulatory region. Condition category: machinery_impairment nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The hormone signal could not engage this regulatory site normally. organism: Human tissue_or_cell_type: Primary hepatocytes and PEMT regulatory locus experimental_model: Transcript-specific expression, haplotype and chromatin-binding analyses limitations: Risk is allele/haplotype-specific; not every PEMT variant or every woman has the same response. exposure: Estrogen stimulation across PEMT haplotypes evidence_span: {"source_cache": "artifacts/choline-research/21059658.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e2906288f8d608133ab4c746793ac5939f8c9fb157dbfd92c0af7b85064310d4", "start_char": 0, "end_char": 1380, "text_sha256": "e2906288f8d608133ab4c746793ac5939f8c9fb157dbfd92c0af7b85064310d4"} [choline-p21059658] Aberrant estrogen regulation of PEMT results in choline deficiency-associated liver dysfunction. (2011). https://pubmed.ncbi.nlm.nih.gov/21059658/ DOI: 10.1074/jbc.m110.106922
Complete structured claim and evidence
The risk allele also failed to bind the pioneer factor FOXA1.
PEMT estrogen-response risk haplotype in the 2011 study → FOXA1 binding at the PEMT risk haplotype source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/choline-research/21059658.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e2906288f8d608133ab4c746793ac5939f8c9fb157dbfd92c0af7b85064310d4", "start_char": 0, "end_char": 1380, "text_sha256": "e2906288f8d608133ab4c746793ac5939f8c9fb157dbfd92c0af7b85064310d4"}
experimental_model
Transcript-specific expression, haplotype and chromatin-binding analyses
exposure
Estrogen stimulation across PEMT haplotypes
limitations
Risk is allele/haplotype-specific; not every PEMT variant or every woman has the same response.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
A second regulatory protein was affected at the same locus.
primary_references
[choline-p21059658] Aberrant estrogen regulation of PEMT results in choline deficiency-associated liver dysfunction. (2011). https://pubmed.ncbi.nlm.nih.gov/21059658/ DOI: 10.1074/jbc.m110.106922
tissue_or_cell_type
Primary hepatocytes and PEMT regulatory locus
trigger_kind
machinery_impairment Imported condition classification; unverified.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 867–878
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transcript-specific expression, haplotype and chromatin-binding analyses · source_derived_draft · unverified_draft
### choline-pemt-foxa-binding The risk allele also failed to bind the pioneer factor FOXA1. Condition category: machinery_impairment nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second regulatory protein was affected at the same locus. organism: Human tissue_or_cell_type: Primary hepatocytes and PEMT regulatory locus experimental_model: Transcript-specific expression, haplotype and chromatin-binding analyses limitations: Risk is allele/haplotype-specific; not every PEMT variant or every woman has the same response. exposure: Estrogen stimulation across PEMT haplotypes evidence_span: {"source_cache": "artifacts/choline-research/21059658.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e2906288f8d608133ab4c746793ac5939f8c9fb157dbfd92c0af7b85064310d4", "start_char": 0, "end_char": 1380, "text_sha256": "e2906288f8d608133ab4c746793ac5939f8c9fb157dbfd92c0af7b85064310d4"} [choline-p21059658] Aberrant estrogen regulation of PEMT results in choline deficiency-associated liver dysfunction. (2011). https://pubmed.ncbi.nlm.nih.gov/21059658/ DOI: 10.1074/jbc.m110.106922
Complete structured claim and evidence
The risk-associated haplotype lost hormone-inducible PEMT expression.
PEMT estrogen-response risk haplotype in the 2011 study → Hormone-inducible PEMT expression source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/choline-research/21059658.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e2906288f8d608133ab4c746793ac5939f8c9fb157dbfd92c0af7b85064310d4", "start_char": 0, "end_char": 1380, "text_sha256": "e2906288f8d608133ab4c746793ac5939f8c9fb157dbfd92c0af7b85064310d4"}
experimental_model
Transcript-specific expression, haplotype and chromatin-binding analyses
exposure
Estrogen stimulation across PEMT haplotypes
limitations
Risk is allele/haplotype-specific; not every PEMT variant or every woman has the same response.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
The expected increase in endogenous synthesis machinery was impaired.
primary_references
[choline-p21059658] Aberrant estrogen regulation of PEMT results in choline deficiency-associated liver dysfunction. (2011). https://pubmed.ncbi.nlm.nih.gov/21059658/ DOI: 10.1074/jbc.m110.106922
tissue_or_cell_type
Primary hepatocytes and PEMT regulatory locus
trigger_kind
machinery_impairment Imported condition classification; unverified.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 880–891
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transcript-specific expression, haplotype and chromatin-binding analyses · source_derived_draft · unverified_draft
### choline-pemt-hormone-induction The risk-associated haplotype lost hormone-inducible PEMT expression. Condition category: machinery_impairment nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The expected increase in endogenous synthesis machinery was impaired. organism: Human tissue_or_cell_type: Primary hepatocytes and PEMT regulatory locus experimental_model: Transcript-specific expression, haplotype and chromatin-binding analyses limitations: Risk is allele/haplotype-specific; not every PEMT variant or every woman has the same response. exposure: Estrogen stimulation across PEMT haplotypes evidence_span: {"source_cache": "artifacts/choline-research/21059658.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e2906288f8d608133ab4c746793ac5939f8c9fb157dbfd92c0af7b85064310d4", "start_char": 0, "end_char": 1380, "text_sha256": "e2906288f8d608133ab4c746793ac5939f8c9fb157dbfd92c0af7b85064310d4"} [choline-p21059658] Aberrant estrogen regulation of PEMT results in choline deficiency-associated liver dysfunction. (2011). https://pubmed.ncbi.nlm.nih.gov/21059658/ DOI: 10.1074/jbc.m110.106922
Complete structured claim and evidence
Choline-deficient Pemt-null mice developed a low hepatic PC/PE ratio.
Choline-deficient diet in mouse PEMT experiments → Mouse hepatic phosphatidylcholine/phosphatidylethanolamine ratio source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/choline-research/16679290.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "656910ebe959c2867cac5d7cb75341ba3974ff922e584274829161326f10cf4d", "start_char": 0, "end_char": 1016, "text_sha256": "656910ebe959c2867cac5d7cb75341ba3974ff922e584274829161326f10cf4d"}
experimental_model
Dietary depletion and Pemt/Mdr2 mouse genetics
exposure
Choline-deficient feeding in Pemt-null and double-null mice
limitations
A combined diet/genotype model; total PC amount, PC/PE ratio and membrane damage are not interchangeable measurements.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Mouse, with separate human tissue comparison in the paper
plain_language
Both dietary input and endogenous synthesis were compromised.
primary_references
[choline-p16679290] The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis. (2006). https://pubmed.ncbi.nlm.nih.gov/16679290/ DOI: 10.1016/j.cmet.2006.03.007
tissue_or_cell_type
Hepatic membranes
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 893–904
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary depletion and Pemt/Mdr2 mouse genetics · source_derived_draft · unverified_draft
### choline-pemt-low-ratio Choline-deficient Pemt-null mice developed a low hepatic PC/PE ratio. Condition category: nutrient_deficiency nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Both dietary input and endogenous synthesis were compromised. organism: Mouse, with separate human tissue comparison in the paper tissue_or_cell_type: Hepatic membranes experimental_model: Dietary depletion and Pemt/Mdr2 mouse genetics limitations: A combined diet/genotype model; total PC amount, PC/PE ratio and membrane damage are not interchangeable measurements. exposure: Choline-deficient feeding in Pemt-null and double-null mice evidence_span: {"source_cache": "artifacts/choline-research/16679290.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "656910ebe959c2867cac5d7cb75341ba3974ff922e584274829161326f10cf4d", "start_char": 0, "end_char": 1016, "text_sha256": "656910ebe959c2867cac5d7cb75341ba3974ff922e584274829161326f10cf4d"} [choline-p16679290] The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis. (2006). https://pubmed.ncbi.nlm.nih.gov/16679290/ DOI: 10.1016/j.cmet.2006.03.007
Complete structured claim and evidence
Experimental manipulation supported a causal role for the lowered PC/PE ratio in loss of hepatocyte membrane integrity.
Mouse hepatic phosphatidylcholine/phosphatidylethanolamine ratio → Mouse hepatocyte membrane integrity source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/choline-research/16679290.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "656910ebe959c2867cac5d7cb75341ba3974ff922e584274829161326f10cf4d", "start_char": 0, "end_char": 1016, "text_sha256": "656910ebe959c2867cac5d7cb75341ba3974ff922e584274829161326f10cf4d"}
experimental_model
Dietary depletion and Pemt/Mdr2 mouse genetics
exposure
Choline-deficient feeding in Pemt-null and double-null mice
limitations
A combined diet/genotype model; total PC amount, PC/PE ratio and membrane damage are not interchangeable measurements.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Mouse, with separate human tissue comparison in the paper
plain_language
The balance between two membrane lipids mattered, not just one concentration.
primary_references
[choline-p16679290] The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis. (2006). https://pubmed.ncbi.nlm.nih.gov/16679290/ DOI: 10.1016/j.cmet.2006.03.007
tissue_or_cell_type
Hepatic membranes
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 906–917
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary depletion and Pemt/Mdr2 mouse genetics · source_derived_draft · unverified_draft
### choline-pc-pe-membrane Experimental manipulation supported a causal role for the lowered PC/PE ratio in loss of hepatocyte membrane integrity. Condition category: nutrient_deficiency nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The balance between two membrane lipids mattered, not just one concentration. organism: Mouse, with separate human tissue comparison in the paper tissue_or_cell_type: Hepatic membranes experimental_model: Dietary depletion and Pemt/Mdr2 mouse genetics limitations: A combined diet/genotype model; total PC amount, PC/PE ratio and membrane damage are not interchangeable measurements. exposure: Choline-deficient feeding in Pemt-null and double-null mice evidence_span: {"source_cache": "artifacts/choline-research/16679290.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "656910ebe959c2867cac5d7cb75341ba3974ff922e584274829161326f10cf4d", "start_char": 0, "end_char": 1016, "text_sha256": "656910ebe959c2867cac5d7cb75341ba3974ff922e584274829161326f10cf4d"} [choline-p16679290] The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis. (2006). https://pubmed.ncbi.nlm.nih.gov/16679290/ DOI: 10.1016/j.cmet.2006.03.007
Complete structured claim and evidence
Choline-deficient Pemt/Mdr2 double-null mice maintained a normal PC/PE ratio and escaped liver failure despite steatosis.
Experimental mouse Pemt/Mdr2 double-knockout genotype → Liver failure in choline-deficient Pemt-null mice source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/choline-research/16679290.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "656910ebe959c2867cac5d7cb75341ba3974ff922e584274829161326f10cf4d", "start_char": 0, "end_char": 1016, "text_sha256": "656910ebe959c2867cac5d7cb75341ba3974ff922e584274829161326f10cf4d"}
experimental_model
Dietary depletion and Pemt/Mdr2 mouse genetics
exposure
Choline-deficient feeding in Pemt-null and double-null mice
limitations
Additional loss of biliary PC secretion modifies this mouse model; not a treatment suggestion or contradiction of choline essentiality.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Mouse, with separate human tissue comparison in the paper
plain_language
Changing another route of PC loss changed the outcome.
primary_references
[choline-p16679290] The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis. (2006). https://pubmed.ncbi.nlm.nih.gov/16679290/ DOI: 10.1016/j.cmet.2006.03.007
tissue_or_cell_type
Hepatic membranes
trigger_kind
machinery_impairment Imported condition classification; unverified.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 919–930
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary depletion and Pemt/Mdr2 mouse genetics · source_derived_draft · unverified_draft
### choline-double-knockout-protection Choline-deficient Pemt/Mdr2 double-null mice maintained a normal PC/PE ratio and escaped liver failure despite steatosis. Condition category: machinery_impairment nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Changing another route of PC loss changed the outcome. organism: Mouse, with separate human tissue comparison in the paper tissue_or_cell_type: Hepatic membranes experimental_model: Dietary depletion and Pemt/Mdr2 mouse genetics limitations: Additional loss of biliary PC secretion modifies this mouse model; not a treatment suggestion or contradiction of choline essentiality. exposure: Choline-deficient feeding in Pemt-null and double-null mice evidence_span: {"source_cache": "artifacts/choline-research/16679290.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "656910ebe959c2867cac5d7cb75341ba3974ff922e584274829161326f10cf4d", "start_char": 0, "end_char": 1016, "text_sha256": "656910ebe959c2867cac5d7cb75341ba3974ff922e584274829161326f10cf4d"} [choline-p16679290] The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis. (2006). https://pubmed.ncbi.nlm.nih.gov/16679290/ DOI: 10.1016/j.cmet.2006.03.007
Complete structured claim and evidence
Pemt deletion modestly reduced hepatic VLDL secretion in Ldlr-null mice.
Experimental mouse Pemt-null genotype → Mouse hepatic VLDL secretion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/19520976.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "57c952bdb4e387632c90b6dcc00ab5f0c600047b7e78bb179c08f6ccd62704d0", "start_char": 0, "end_char": 1537, "text_sha256": "57c952bdb4e387632c90b6dcc00ab5f0c600047b7e78bb179c08f6ccd62704d0"}
experimental_model
Pemt/Ldlr mouse knockout under a high-fat/high-cholesterol diet
exposure
Sixteen weeks of the specified diet; Pemt-null/Ldlr-null versus Pemt-intact/Ldlr-null
limitations
A lipid-export mechanism in a specific genetic model; lower plasma lipids do not establish healthier liver tissue or dietary benefit.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Mouse
plain_language
PC synthesis is connected to how the liver exports lipid.
primary_references
[choline-p19520976] Lack of phosphatidylethanolamine N-methyltransferase alters plasma VLDL phospholipids and attenuates atherosclerosis in mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19520976/ DOI: 10.1161/atvbaha.109.188672
tissue_or_cell_type
Liver and circulating VLDL
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 932–943
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pemt/Ldlr mouse knockout under a high-fat/high-cholesterol diet · source_derived_draft · unverified_draft
### choline-pemt-vldl Pemt deletion modestly reduced hepatic VLDL secretion in Ldlr-null mice. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: PC synthesis is connected to how the liver exports lipid. organism: Mouse tissue_or_cell_type: Liver and circulating VLDL experimental_model: Pemt/Ldlr mouse knockout under a high-fat/high-cholesterol diet limitations: A lipid-export mechanism in a specific genetic model; lower plasma lipids do not establish healthier liver tissue or dietary benefit. exposure: Sixteen weeks of the specified diet; Pemt-null/Ldlr-null versus Pemt-intact/Ldlr-null evidence_span: {"source_cache": "artifacts/choline-research/19520976.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "57c952bdb4e387632c90b6dcc00ab5f0c600047b7e78bb179c08f6ccd62704d0", "start_char": 0, "end_char": 1537, "text_sha256": "57c952bdb4e387632c90b6dcc00ab5f0c600047b7e78bb179c08f6ccd62704d0"} [choline-p19520976] Lack of phosphatidylethanolamine N-methyltransferase alters plasma VLDL phospholipids and attenuates atherosclerosis in mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19520976/ DOI: 10.1161/atvbaha.109.188672
Complete structured claim and evidence
Mfsd2a-mediated LPC transport was sodium-dependent.
Sodium ion → Mouse lysophosphatidylcholine transporter Mfsd2a source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/24828044.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3ec710edae591ed103960d73b49918a61b0260b22702926792e7133337b93695", "start_char": 0, "end_char": 1689, "text_sha256": "3ec710edae591ed103960d73b49918a61b0260b22702926792e7133337b93695"}
experimental_model
Mouse knockout and cell transport experiments
exposure
LPC-bound versus unesterified DHA; sodium-dependent transport
limitations
LPC-DHA is a choline-containing lipid, not free choline. No claim that oral choline necessarily raises brain DHA.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Mouse Mfsd2a and experimental expression system
plain_language
This lipid transport route also depends on an ion gradient.
primary_references
[choline-p24828044] Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid. (2014). https://pubmed.ncbi.nlm.nih.gov/24828044/ DOI: 10.1038/nature13241
tissue_or_cell_type
Blood-brain-barrier endothelium
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 958–969
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse knockout and cell transport experiments · source_derived_draft · unverified_draft
### choline-mfsd2a-sodium Mfsd2a-mediated LPC transport was sodium-dependent. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: This lipid transport route also depends on an ion gradient. organism: Mouse Mfsd2a and experimental expression system tissue_or_cell_type: Blood-brain-barrier endothelium experimental_model: Mouse knockout and cell transport experiments limitations: LPC-DHA is a choline-containing lipid, not free choline. No claim that oral choline necessarily raises brain DHA. exposure: LPC-bound versus unesterified DHA; sodium-dependent transport evidence_span: {"source_cache": "artifacts/choline-research/24828044.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3ec710edae591ed103960d73b49918a61b0260b22702926792e7133337b93695", "start_char": 0, "end_char": 1689, "text_sha256": "3ec710edae591ed103960d73b49918a61b0260b22702926792e7133337b93695"} [choline-p24828044] Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid. (2014). https://pubmed.ncbi.nlm.nih.gov/24828044/ DOI: 10.1038/nature13241
Complete structured claim and evidence
Mfsd2a-null mice had markedly reduced uptake of plasma-labeled LPC-DHA into the brain.
Experimental mouse Mfsd2a-null genotype → Mouse plasma-to-brain LPC-DHA uptake source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/choline-research/24828044.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3ec710edae591ed103960d73b49918a61b0260b22702926792e7133337b93695", "start_char": 0, "end_char": 1689, "text_sha256": "3ec710edae591ed103960d73b49918a61b0260b22702926792e7133337b93695"}
experimental_model
Mouse knockout and cell transport experiments
exposure
LPC-bound versus unesterified DHA; sodium-dependent transport
limitations
LPC-DHA is a choline-containing lipid, not free choline. No claim that oral choline necessarily raises brain DHA.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Mouse Mfsd2a and experimental expression system
plain_language
Less of the carrier lipid reached the brain.
primary_references
[choline-p24828044] Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid. (2014). https://pubmed.ncbi.nlm.nih.gov/24828044/ DOI: 10.1038/nature13241
tissue_or_cell_type
Blood-brain-barrier endothelium
trigger_kind
machinery_impairment Imported condition classification; unverified.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 971–982
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse knockout and cell transport experiments · source_derived_draft · unverified_draft
### choline-mfsd2a-uptake Mfsd2a-null mice had markedly reduced uptake of plasma-labeled LPC-DHA into the brain. Condition category: machinery_impairment nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Less of the carrier lipid reached the brain. organism: Mouse Mfsd2a and experimental expression system tissue_or_cell_type: Blood-brain-barrier endothelium experimental_model: Mouse knockout and cell transport experiments limitations: LPC-DHA is a choline-containing lipid, not free choline. No claim that oral choline necessarily raises brain DHA. exposure: LPC-bound versus unesterified DHA; sodium-dependent transport evidence_span: {"source_cache": "artifacts/choline-research/24828044.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3ec710edae591ed103960d73b49918a61b0260b22702926792e7133337b93695", "start_char": 0, "end_char": 1689, "text_sha256": "3ec710edae591ed103960d73b49918a61b0260b22702926792e7133337b93695"} [choline-p24828044] Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid. (2014). https://pubmed.ncbi.nlm.nih.gov/24828044/ DOI: 10.1038/nature13241
Complete structured claim and evidence
Mfsd2a-null mice had markedly reduced brain DHA abundance.
Experimental mouse Mfsd2a-null genotype → Mouse brain DHA abundance source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/choline-research/24828044.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3ec710edae591ed103960d73b49918a61b0260b22702926792e7133337b93695", "start_char": 0, "end_char": 1689, "text_sha256": "3ec710edae591ed103960d73b49918a61b0260b22702926792e7133337b93695"}
experimental_model
Mouse knockout and cell transport experiments
exposure
LPC-bound versus unesterified DHA; sodium-dependent transport
limitations
LPC-DHA is a choline-containing lipid, not free choline. No claim that oral choline necessarily raises brain DHA.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Mouse Mfsd2a and experimental expression system
plain_language
The tissue fatty-acid pool changed downstream of the transport defect.
primary_references
[choline-p24828044] Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid. (2014). https://pubmed.ncbi.nlm.nih.gov/24828044/ DOI: 10.1038/nature13241
tissue_or_cell_type
Blood-brain-barrier endothelium
trigger_kind
machinery_impairment Imported condition classification; unverified.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 984–995
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse knockout and cell transport experiments · source_derived_draft · unverified_draft
### choline-mfsd2a-dha Mfsd2a-null mice had markedly reduced brain DHA abundance. Condition category: machinery_impairment nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The tissue fatty-acid pool changed downstream of the transport defect. organism: Mouse Mfsd2a and experimental expression system tissue_or_cell_type: Blood-brain-barrier endothelium experimental_model: Mouse knockout and cell transport experiments limitations: LPC-DHA is a choline-containing lipid, not free choline. No claim that oral choline necessarily raises brain DHA. exposure: LPC-bound versus unesterified DHA; sodium-dependent transport evidence_span: {"source_cache": "artifacts/choline-research/24828044.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3ec710edae591ed103960d73b49918a61b0260b22702926792e7133337b93695", "start_char": 0, "end_char": 1689, "text_sha256": "3ec710edae591ed103960d73b49918a61b0260b22702926792e7133337b93695"} [choline-p24828044] Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid. (2014). https://pubmed.ncbi.nlm.nih.gov/24828044/ DOI: 10.1038/nature13241
Complete structured claim and evidence
During deprivation, fatty liver or muscle damage developed in 77% of men, 80% of postmenopausal women and 44% of premenopausal women.
Controlled low-choline diet in the 2006–2007 human depletion cohort → Fatty liver or muscle damage during controlled human choline depletion source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/choline-research/17490963.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "28d18f06c2deb6f384ef2b5e84238b05deb076778619c21ee9682d49e34ae824", "start_char": 0, "end_char": 1758, "text_sha256": "28d18f06c2deb6f384ef2b5e84238b05deb076778619c21ee9682d49e34ae824"}
experimental_model
Controlled depletion/repletion with randomized folic acid supplementation
exposure
550 mg choline/70 kg/day for 10 days, then less than 50 mg/70 kg/day up to 42 days; graded repletion
limitations
Supervised experimental depletion, not a recommended intake protocol. Liver/muscle endpoints and susceptibility differed; one cohort underlies related genetic publications.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
The response to low choline differed across people.
primary_references
[choline-p17490963] Sex and menopausal status influence human dietary requirements for the nutrient choline. (2007). https://pubmed.ncbi.nlm.nih.gov/17490963/ DOI: 10.1093/ajcn/85.5.1275
tissue_or_cell_type
57 adults: 26 men, 16 premenopausal and 15 postmenopausal women
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 997–1008
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled depletion/repletion with randomized folic acid supplementation · source_derived_draft · unverified_draft
### choline-depletion-organs During deprivation, fatty liver or muscle damage developed in 77% of men, 80% of postmenopausal women and 44% of premenopausal women. Condition category: nutrient_deficiency nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The response to low choline differed across people. organism: Human tissue_or_cell_type: 57 adults: 26 men, 16 premenopausal and 15 postmenopausal women experimental_model: Controlled depletion/repletion with randomized folic acid supplementation limitations: Supervised experimental depletion, not a recommended intake protocol. Liver/muscle endpoints and susceptibility differed; one cohort underlies related genetic publications. exposure: 550 mg choline/70 kg/day for 10 days, then less than 50 mg/70 kg/day up to 42 days; graded repletion evidence_span: {"source_cache": "artifacts/choline-research/17490963.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "28d18f06c2deb6f384ef2b5e84238b05deb076778619c21ee9682d49e34ae824", "start_char": 0, "end_char": 1758, "text_sha256": "28d18f06c2deb6f384ef2b5e84238b05deb076778619c21ee9682d49e34ae824"} [choline-p17490963] Sex and menopausal status influence human dietary requirements for the nutrient choline. (2007). https://pubmed.ncbi.nlm.nih.gov/17490963/ DOI: 10.1093/ajcn/85.5.1275
Complete structured claim and evidence
Participants who developed organ dysfunction recovered normal organ function after incremental choline repletion.
Graded choline repletion after experimental human depletion → Organ-function recovery after controlled choline repletion source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/choline-research/17490963.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "28d18f06c2deb6f384ef2b5e84238b05deb076778619c21ee9682d49e34ae824", "start_char": 0, "end_char": 1758, "text_sha256": "28d18f06c2deb6f384ef2b5e84238b05deb076778619c21ee9682d49e34ae824"}
experimental_model
Controlled depletion/repletion with randomized folic acid supplementation
exposure
550 mg choline/70 kg/day for 10 days, then less than 50 mg/70 kg/day up to 42 days; graded repletion
limitations
Supervised experimental depletion, not a recommended intake protocol. Liver/muscle endpoints and susceptibility differed; one cohort underlies related genetic publications.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
The experimentally induced signs were reversible with choline restoration.
primary_references
[choline-p17490963] Sex and menopausal status influence human dietary requirements for the nutrient choline. (2007). https://pubmed.ncbi.nlm.nih.gov/17490963/ DOI: 10.1093/ajcn/85.5.1275
tissue_or_cell_type
57 adults: 26 men, 16 premenopausal and 15 postmenopausal women
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1010–1021
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled depletion/repletion with randomized folic acid supplementation · source_derived_draft · unverified_draft
### choline-depletion-recovery Participants who developed organ dysfunction recovered normal organ function after incremental choline repletion. Condition category: nutrient_deficiency nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The experimentally induced signs were reversible with choline restoration. organism: Human tissue_or_cell_type: 57 adults: 26 men, 16 premenopausal and 15 postmenopausal women experimental_model: Controlled depletion/repletion with randomized folic acid supplementation limitations: Supervised experimental depletion, not a recommended intake protocol. Liver/muscle endpoints and susceptibility differed; one cohort underlies related genetic publications. exposure: 550 mg choline/70 kg/day for 10 days, then less than 50 mg/70 kg/day up to 42 days; graded repletion evidence_span: {"source_cache": "artifacts/choline-research/17490963.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "28d18f06c2deb6f384ef2b5e84238b05deb076778619c21ee9682d49e34ae824", "start_char": 0, "end_char": 1758, "text_sha256": "28d18f06c2deb6f384ef2b5e84238b05deb076778619c21ee9682d49e34ae824"} [choline-p17490963] Sex and menopausal status influence human dietary requirements for the nutrient choline. (2007). https://pubmed.ncbi.nlm.nih.gov/17490963/ DOI: 10.1093/ajcn/85.5.1275
Complete structured claim and evidence
Among women, 18 of 23 PEMT rs12325817 C-allele carriers developed organ dysfunction during depletion; reported odds ratio 25, p=0.002.
PEMT rs12325817 C allele in the 2006 depletion study → Fatty liver or muscle damage during controlled human choline depletion source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/choline-research/16816108.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "555f2ace5850ed1fce7061ce91c5133cac7d92c29fdab192b0aa595f9dd390b1", "start_char": 0, "end_char": 1424, "text_sha256": "555f2ace5850ed1fce7061ce91c5133cac7d92c29fdab192b0aa595f9dd390b1"}
experimental_model
Genotype association within the controlled depletion cohort
exposure
Common PEMT/CHDH/BHMT variants during low-choline feeding
limitations
Small candidate-gene study; does not support deterministic recommendations from one SNP. Shares participants with related depletion publications.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
This variant marked higher susceptibility in the small study.
primary_references
[choline-p16816108] Common genetic polymorphisms affect the human requirement for the nutrient choline. (2006). https://pubmed.ncbi.nlm.nih.gov/16816108/ DOI: 10.1096/fj.06-5734com
tissue_or_cell_type
57 participants; liver and muscle endpoints
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1036–1047
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genotype association within the controlled depletion cohort · source_derived_draft · unverified_draft
### choline-pemt-snp-risk Among women, 18 of 23 PEMT rs12325817 C-allele carriers developed organ dysfunction during depletion; reported odds ratio 25, p=0.002. Condition category: nutrient_deficiency nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: This variant marked higher susceptibility in the small study. organism: Human tissue_or_cell_type: 57 participants; liver and muscle endpoints experimental_model: Genotype association within the controlled depletion cohort limitations: Small candidate-gene study; does not support deterministic recommendations from one SNP. Shares participants with related depletion publications. exposure: Common PEMT/CHDH/BHMT variants during low-choline feeding evidence_span: {"source_cache": "artifacts/choline-research/16816108.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "555f2ace5850ed1fce7061ce91c5133cac7d92c29fdab192b0aa595f9dd390b1", "start_char": 0, "end_char": 1424, "text_sha256": "555f2ace5850ed1fce7061ce91c5133cac7d92c29fdab192b0aa595f9dd390b1"} [choline-p16816108] Common genetic polymorphisms affect the human requirement for the nutrient choline. (2006). https://pubmed.ncbi.nlm.nih.gov/16816108/ DOI: 10.1096/fj.06-5734com
Complete structured claim and evidence
The PEMT rs7946 comparison did not show an association with susceptibility in this depletion study.
PEMT rs7946 genotype comparison in the 2006 depletion study → Fatty liver or muscle damage during controlled human choline depletion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/16816108.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "555f2ace5850ed1fce7061ce91c5133cac7d92c29fdab192b0aa595f9dd390b1", "start_char": 0, "end_char": 1424, "text_sha256": "555f2ace5850ed1fce7061ce91c5133cac7d92c29fdab192b0aa595f9dd390b1"}
experimental_model
Genotype association within the controlled depletion cohort
exposure
Common PEMT/CHDH/BHMT variants during low-choline feeding
limitations
Small candidate-gene study; does not support deterministic recommendations from one SNP. Shares participants with related depletion publications.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
Not every tested variant predicted the clinical response.
primary_references
[choline-p16816108] Common genetic polymorphisms affect the human requirement for the nutrient choline. (2006). https://pubmed.ncbi.nlm.nih.gov/16816108/ DOI: 10.1096/fj.06-5734com
tissue_or_cell_type
57 participants; liver and muscle endpoints
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1049–1060
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genotype association within the controlled depletion cohort · source_derived_draft · unverified_draft
### choline-pemt-rs7946-null The PEMT rs7946 comparison did not show an association with susceptibility in this depletion study. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Not every tested variant predicted the clinical response. organism: Human tissue_or_cell_type: 57 participants; liver and muscle endpoints experimental_model: Genotype association within the controlled depletion cohort limitations: Small candidate-gene study; does not support deterministic recommendations from one SNP. Shares participants with related depletion publications. exposure: Common PEMT/CHDH/BHMT variants during low-choline feeding evidence_span: {"source_cache": "artifacts/choline-research/16816108.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "555f2ace5850ed1fce7061ce91c5133cac7d92c29fdab192b0aa595f9dd390b1", "start_char": 0, "end_char": 1424, "text_sha256": "555f2ace5850ed1fce7061ce91c5133cac7d92c29fdab192b0aa595f9dd390b1"} [choline-p16816108] Common genetic polymorphisms affect the human requirement for the nutrient choline. (2006). https://pubmed.ncbi.nlm.nih.gov/16816108/ DOI: 10.1096/fj.06-5734com
Complete structured claim and evidence
The BHMT rs3733890 comparison did not show an association with susceptibility in this depletion study.
BHMT rs3733890 genotype comparison in the 2006 depletion study → Fatty liver or muscle damage during controlled human choline depletion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/16816108.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "555f2ace5850ed1fce7061ce91c5133cac7d92c29fdab192b0aa595f9dd390b1", "start_char": 0, "end_char": 1424, "text_sha256": "555f2ace5850ed1fce7061ce91c5133cac7d92c29fdab192b0aa595f9dd390b1"}
experimental_model
Genotype association within the controlled depletion cohort
exposure
Common PEMT/CHDH/BHMT variants during low-choline feeding
limitations
Small candidate-gene study; does not support deterministic recommendations from one SNP. Shares participants with related depletion publications.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
Not every tested variant predicted the clinical response.
primary_references
[choline-p16816108] Common genetic polymorphisms affect the human requirement for the nutrient choline. (2006). https://pubmed.ncbi.nlm.nih.gov/16816108/ DOI: 10.1096/fj.06-5734com
tissue_or_cell_type
57 participants; liver and muscle endpoints
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1062–1073
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genotype association within the controlled depletion cohort · source_derived_draft · unverified_draft
### choline-bhmt-snp-null The BHMT rs3733890 comparison did not show an association with susceptibility in this depletion study. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Not every tested variant predicted the clinical response. organism: Human tissue_or_cell_type: 57 participants; liver and muscle endpoints experimental_model: Genotype association within the controlled depletion cohort limitations: Small candidate-gene study; does not support deterministic recommendations from one SNP. Shares participants with related depletion publications. exposure: Common PEMT/CHDH/BHMT variants during low-choline feeding evidence_span: {"source_cache": "artifacts/choline-research/16816108.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "555f2ace5850ed1fce7061ce91c5133cac7d92c29fdab192b0aa595f9dd390b1", "start_char": 0, "end_char": 1424, "text_sha256": "555f2ace5850ed1fce7061ce91c5133cac7d92c29fdab192b0aa595f9dd390b1"} [choline-p16816108] Common genetic polymorphisms affect the human requirement for the nutrient choline. (2006). https://pubmed.ncbi.nlm.nih.gov/16816108/ DOI: 10.1096/fj.06-5734com
Complete structured claim and evidence
Two weeks of phosphatidylcholine supplementation reduced fasting total homocysteine by 18% relative to placebo.
Study-specific phosphatidylcholine supplements → Human fasting plasma total homocysteine concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/16002808.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ad206000c96c52d280ac135c03d531122121a82c436dce40c7d13e55d0976ae1", "start_char": 0, "end_char": 1797, "text_sha256": "ad206000c96c52d280ac135c03d531122121a82c436dce40c7d13e55d0976ae1"}
experimental_model
Randomized crossover feeding trial
exposure
About 2.6 g choline/day as PC versus matched placebo oil for two weeks; methionine-load testing
limitations
High experimental intake and biomarker endpoint; no cardiovascular-event benefit was tested.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
A choline-containing form changed a methyl-metabolism blood marker.
primary_references
[choline-p16002808] Choline supplemented as phosphatidylcholine decreases fasting and postmethionine-loading plasma homocysteine concentrations in healthy men. (2005). https://pubmed.ncbi.nlm.nih.gov/16002808/ DOI: 10.1093/ajcn.82.1.111
tissue_or_cell_type
26 men with mildly elevated plasma homocysteine
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1075–1086
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized crossover feeding trial · source_derived_draft · unverified_draft
### choline-pc-hcy-fasting Two weeks of phosphatidylcholine supplementation reduced fasting total homocysteine by 18% relative to placebo. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: A choline-containing form changed a methyl-metabolism blood marker. organism: Human tissue_or_cell_type: 26 men with mildly elevated plasma homocysteine experimental_model: Randomized crossover feeding trial limitations: High experimental intake and biomarker endpoint; no cardiovascular-event benefit was tested. exposure: About 2.6 g choline/day as PC versus matched placebo oil for two weeks; methionine-load testing evidence_span: {"source_cache": "artifacts/choline-research/16002808.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ad206000c96c52d280ac135c03d531122121a82c436dce40c7d13e55d0976ae1", "start_char": 0, "end_char": 1797, "text_sha256": "ad206000c96c52d280ac135c03d531122121a82c436dce40c7d13e55d0976ae1"} [choline-p16002808] Choline supplemented as phosphatidylcholine decreases fasting and postmethionine-loading plasma homocysteine concentrations in healthy men. (2005). https://pubmed.ncbi.nlm.nih.gov/16002808/ DOI: 10.1093/ajcn.82.1.111
Complete structured claim and evidence
After two weeks, the post-methionine-load homocysteine rise was 29% lower than with placebo.
Study-specific phosphatidylcholine supplements → Human post-methionine-load plasma total homocysteine response source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/16002808.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ad206000c96c52d280ac135c03d531122121a82c436dce40c7d13e55d0976ae1", "start_char": 0, "end_char": 1797, "text_sha256": "ad206000c96c52d280ac135c03d531122121a82c436dce40c7d13e55d0976ae1"}
experimental_model
Randomized crossover feeding trial
exposure
About 2.6 g choline/day as PC versus matched placebo oil for two weeks; methionine-load testing
limitations
High experimental intake and biomarker endpoint; no cardiovascular-event benefit was tested.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
The response to a methionine challenge also changed.
primary_references
[choline-p16002808] Choline supplemented as phosphatidylcholine decreases fasting and postmethionine-loading plasma homocysteine concentrations in healthy men. (2005). https://pubmed.ncbi.nlm.nih.gov/16002808/ DOI: 10.1093/ajcn.82.1.111
tissue_or_cell_type
26 men with mildly elevated plasma homocysteine
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1088–1099
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized crossover feeding trial · source_derived_draft · unverified_draft
### choline-pc-hcy-load After two weeks, the post-methionine-load homocysteine rise was 29% lower than with placebo. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The response to a methionine challenge also changed. organism: Human tissue_or_cell_type: 26 men with mildly elevated plasma homocysteine experimental_model: Randomized crossover feeding trial limitations: High experimental intake and biomarker endpoint; no cardiovascular-event benefit was tested. exposure: About 2.6 g choline/day as PC versus matched placebo oil for two weeks; methionine-load testing evidence_span: {"source_cache": "artifacts/choline-research/16002808.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ad206000c96c52d280ac135c03d531122121a82c436dce40c7d13e55d0976ae1", "start_char": 0, "end_char": 1797, "text_sha256": "ad206000c96c52d280ac135c03d531122121a82c436dce40c7d13e55d0976ae1"} [choline-p16002808] Choline supplemented as phosphatidylcholine decreases fasting and postmethionine-loading plasma homocysteine concentrations in healthy men. (2005). https://pubmed.ncbi.nlm.nih.gov/16002808/ DOI: 10.1093/ajcn.82.1.111
Complete structured claim and evidence
The characterized anaerobic choline-utilization pathway uses a glycyl-radical choline TMA-lyase to cleave the choline C–N bond and generate TMA.
Desulfovibrio desulfuricans CutC choline TMA-lyase → Trimethylamine / TMA source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/23151509.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "20246eb796db8ca7b3ff78f530e744bd8f3abe8beb617358b0a1a924166fb2d6", "start_char": 0, "end_char": 1160, "text_sha256": "20246eb796db8ca7b3ff78f530e744bd8f3abe8beb617358b0a1a924166fb2d6"}
experimental_model
Anaerobic bacterial genetics, heterologous expression and EPR
exposure
Genetic knockout and heterologous expression of choline-utilization genes
limitations
A bacterial enzyme pathway, not a direct human-enzyme reaction or evidence that every microbiome produces the same TMA amount.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Desulfovibrio desulfuricans; E. coli expression host
plain_language
Gut microbial machinery can divert choline into a different metabolic route.
primary_references
[choline-p23151509] Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme. (2012). https://pubmed.ncbi.nlm.nih.gov/23151509/ DOI: 10.1073/pnas.1215689109
tissue_or_cell_type
Microbial choline-utilization pathway
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1101–1112
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Anaerobic bacterial genetics, heterologous expression and EPR · source_derived_draft · unverified_draft
### choline-cutc-tma The characterized anaerobic choline-utilization pathway uses a glycyl-radical choline TMA-lyase to cleave the choline C–N bond and generate TMA. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Gut microbial machinery can divert choline into a different metabolic route. organism: Desulfovibrio desulfuricans; E. coli expression host tissue_or_cell_type: Microbial choline-utilization pathway experimental_model: Anaerobic bacterial genetics, heterologous expression and EPR limitations: A bacterial enzyme pathway, not a direct human-enzyme reaction or evidence that every microbiome produces the same TMA amount. exposure: Genetic knockout and heterologous expression of choline-utilization genes evidence_span: {"source_cache": "artifacts/choline-research/23151509.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "20246eb796db8ca7b3ff78f530e744bd8f3abe8beb617358b0a1a924166fb2d6", "start_char": 0, "end_char": 1160, "text_sha256": "20246eb796db8ca7b3ff78f530e744bd8f3abe8beb617358b0a1a924166fb2d6"} [choline-p23151509] Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme. (2012). https://pubmed.ncbi.nlm.nih.gov/23151509/ DOI: 10.1073/pnas.1215689109
Complete structured claim and evidence
The enzyme comparison demonstrated FMO3-mediated oxidation of TMA to TMAO.
Human flavin-containing monooxygenase 3 → Trimethylamine / TMA source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/23312283.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e7c2641ac478a43513c49a68d2ba21e40aa909b32269e91d106072a9028febae", "start_char": 0, "end_char": 1052, "text_sha256": "e7c2641ac478a43513c49a68d2ba21e40aa909b32269e91d106072a9028febae"}
experimental_model
Recombinant FMO comparison, mouse manipulation and human expression analyses
exposure
FMO1/FMO3 enzyme assays; mouse Fmo3 overexpression and silencing
limitations
Enzyme activity, circulating TMAO and clinical disease are different endpoints. Sex regulation is not assigned universally across species.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human recombinant FMO3 assay
plain_language
The liver-side enzyme processes a product generated by microbial metabolism.
primary_references
[choline-p23312283] Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. (2013). https://pubmed.ncbi.nlm.nih.gov/23312283/ DOI: 10.1016/j.cmet.2012.12.011
tissue_or_cell_type
Hepatic TMA oxidation
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1114–1125
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant FMO comparison, mouse manipulation and human expression analyses · source_derived_draft · unverified_draft
### choline-fmo3-tmao The enzyme comparison demonstrated FMO3-mediated oxidation of TMA to TMAO. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The liver-side enzyme processes a product generated by microbial metabolism. organism: Human recombinant FMO3 assay tissue_or_cell_type: Hepatic TMA oxidation experimental_model: Recombinant FMO comparison, mouse manipulation and human expression analyses limitations: Enzyme activity, circulating TMAO and clinical disease are different endpoints. Sex regulation is not assigned universally across species. exposure: FMO1/FMO3 enzyme assays; mouse Fmo3 overexpression and silencing evidence_span: {"source_cache": "artifacts/choline-research/23312283.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e7c2641ac478a43513c49a68d2ba21e40aa909b32269e91d106072a9028febae", "start_char": 0, "end_char": 1052, "text_sha256": "e7c2641ac478a43513c49a68d2ba21e40aa909b32269e91d106072a9028febae"} [choline-p23312283] Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. (2013). https://pubmed.ncbi.nlm.nih.gov/23312283/ DOI: 10.1016/j.cmet.2012.12.011
Complete structured claim and evidence
FMO1 also oxidized TMA in the comparison, with FMO3 showing about tenfold higher specific activity.
Human flavin-containing monooxygenase 1 / FMO1 → Trimethylamine / TMA source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/23312283.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e7c2641ac478a43513c49a68d2ba21e40aa909b32269e91d106072a9028febae", "start_char": 0, "end_char": 1052, "text_sha256": "e7c2641ac478a43513c49a68d2ba21e40aa909b32269e91d106072a9028febae"}
experimental_model
Recombinant FMO comparison, mouse manipulation and human expression analyses
exposure
FMO1/FMO3 enzyme assays; mouse Fmo3 overexpression and silencing
limitations
Enzyme activity, circulating TMAO and clinical disease are different endpoints. Sex regulation is not assigned universally across species.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human recombinant FMO1 assay
plain_language
The related enzymes differed quantitatively in this preparation.
primary_references
[choline-p23312283] Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. (2013). https://pubmed.ncbi.nlm.nih.gov/23312283/ DOI: 10.1016/j.cmet.2012.12.011
tissue_or_cell_type
Hepatic TMA oxidation
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1127–1138
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant FMO comparison, mouse manipulation and human expression analyses · source_derived_draft · unverified_draft
### choline-fmo1-tmao FMO1 also oxidized TMA in the comparison, with FMO3 showing about tenfold higher specific activity. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The related enzymes differed quantitatively in this preparation. organism: Human recombinant FMO1 assay tissue_or_cell_type: Hepatic TMA oxidation experimental_model: Recombinant FMO comparison, mouse manipulation and human expression analyses limitations: Enzyme activity, circulating TMAO and clinical disease are different endpoints. Sex regulation is not assigned universally across species. exposure: FMO1/FMO3 enzyme assays; mouse Fmo3 overexpression and silencing evidence_span: {"source_cache": "artifacts/choline-research/23312283.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e7c2641ac478a43513c49a68d2ba21e40aa909b32269e91d106072a9028febae", "start_char": 0, "end_char": 1052, "text_sha256": "e7c2641ac478a43513c49a68d2ba21e40aa909b32269e91d106072a9028febae"} [choline-p23312283] Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. (2013). https://pubmed.ncbi.nlm.nih.gov/23312283/ DOI: 10.1016/j.cmet.2012.12.011
Complete structured claim and evidence
The challenge produced time-dependent increases in TMAO and its d9-labeled isotopologue.
Two eggs plus d9-phosphatidylcholine challenge in the 2013 study → Circulating trimethylamine N-oxide concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/23614584.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9de33f54f0fce1c470cc96c18163574d26fc5c56802e60771c75fdacc5804e0a", "start_char": 0, "end_char": 2119, "text_sha256": "9de33f54f0fce1c470cc96c18163574d26fc5c56802e60771c75fdacc5804e0a"}
experimental_model
Human isotope challenge with antibiotics plus a separate observational cohort
exposure
Two eggs plus d9-PC before/after antibiotics; three-year event follow-up
limitations
The challenge establishes microbiota involvement; the outcome cohort establishes association, not that avoiding choline or eggs prevents events.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
A label on dietary PC appeared in the downstream microbial-host product.
primary_references
[choline-p23614584] Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. (2013). https://pubmed.ncbi.nlm.nih.gov/23614584/ DOI: 10.1056/nejmoa1109400
tissue_or_cell_type
Healthy challenge participants; 4007 angiography patients in the outcome cohort
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1140–1151
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human isotope challenge with antibiotics plus a separate observational cohort · source_derived_draft · unverified_draft
### choline-pc-tmao-tracing The challenge produced time-dependent increases in TMAO and its d9-labeled isotopologue. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: A label on dietary PC appeared in the downstream microbial-host product. organism: Human tissue_or_cell_type: Healthy challenge participants; 4007 angiography patients in the outcome cohort experimental_model: Human isotope challenge with antibiotics plus a separate observational cohort limitations: The challenge establishes microbiota involvement; the outcome cohort establishes association, not that avoiding choline or eggs prevents events. exposure: Two eggs plus d9-PC before/after antibiotics; three-year event follow-up evidence_span: {"source_cache": "artifacts/choline-research/23614584.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9de33f54f0fce1c470cc96c18163574d26fc5c56802e60771c75fdacc5804e0a", "start_char": 0, "end_char": 2119, "text_sha256": "9de33f54f0fce1c470cc96c18163574d26fc5c56802e60771c75fdacc5804e0a"} [choline-p23614584] Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. (2013). https://pubmed.ncbi.nlm.nih.gov/23614584/ DOI: 10.1056/nejmoa1109400
Complete structured claim and evidence
Antibiotics suppressed challenge-associated TMAO, which reappeared after antibiotic withdrawal.
Broad-spectrum antibiotic regimen in the 2013 phosphatidylcholine challenge study → Circulating trimethylamine N-oxide concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/23614584.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9de33f54f0fce1c470cc96c18163574d26fc5c56802e60771c75fdacc5804e0a", "start_char": 0, "end_char": 2119, "text_sha256": "9de33f54f0fce1c470cc96c18163574d26fc5c56802e60771c75fdacc5804e0a"}
experimental_model
Human isotope challenge with antibiotics plus a separate observational cohort
exposure
Two eggs plus d9-PC before/after antibiotics; three-year event follow-up
limitations
A mechanistic research intervention, not a recommendation to use antibiotics to manage TMAO.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
The challenge response depended on intestinal microbes.
primary_references
[choline-p23614584] Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. (2013). https://pubmed.ncbi.nlm.nih.gov/23614584/ DOI: 10.1056/nejmoa1109400
tissue_or_cell_type
Healthy challenge participants; 4007 angiography patients in the outcome cohort
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1153–1164
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human isotope challenge with antibiotics plus a separate observational cohort · source_derived_draft · unverified_draft
### choline-antibiotics-tmao Antibiotics suppressed challenge-associated TMAO, which reappeared after antibiotic withdrawal. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The challenge response depended on intestinal microbes. organism: Human tissue_or_cell_type: Healthy challenge participants; 4007 angiography patients in the outcome cohort experimental_model: Human isotope challenge with antibiotics plus a separate observational cohort limitations: A mechanistic research intervention, not a recommendation to use antibiotics to manage TMAO. exposure: Two eggs plus d9-PC before/after antibiotics; three-year event follow-up evidence_span: {"source_cache": "artifacts/choline-research/23614584.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9de33f54f0fce1c470cc96c18163574d26fc5c56802e60771c75fdacc5804e0a", "start_char": 0, "end_char": 2119, "text_sha256": "9de33f54f0fce1c470cc96c18163574d26fc5c56802e60771c75fdacc5804e0a"} [choline-p23614584] Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. (2013). https://pubmed.ncbi.nlm.nih.gov/23614584/ DOI: 10.1056/nejmoa1109400
Complete structured claim and evidence
The highest versus lowest TMAO quartile was associated with a three-year event hazard ratio of 2.54 (95% CI 1.96–3.28) in the angiography cohort.
Circulating trimethylamine N-oxide concentration → Major cardiovascular events source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/23614584.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9de33f54f0fce1c470cc96c18163574d26fc5c56802e60771c75fdacc5804e0a", "start_char": 0, "end_char": 2119, "text_sha256": "9de33f54f0fce1c470cc96c18163574d26fc5c56802e60771c75fdacc5804e0a"}
experimental_model
Human isotope challenge with antibiotics plus a separate observational cohort
exposure
Two eggs plus d9-PC before/after antibiotics; three-year event follow-up
limitations
The challenge establishes microbiota involvement; the outcome cohort establishes association, not that avoiding choline or eggs prevents events.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
A blood marker predicted risk in this clinical cohort; that alone does not prove a dietary cause.
primary_references
[choline-p23614584] Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. (2013). https://pubmed.ncbi.nlm.nih.gov/23614584/ DOI: 10.1056/nejmoa1109400
tissue_or_cell_type
Healthy challenge participants; 4007 angiography patients in the outcome cohort
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1166–1177
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human isotope challenge with antibiotics plus a separate observational cohort · source_derived_draft · unverified_draft
### choline-tmao-event-association The highest versus lowest TMAO quartile was associated with a three-year event hazard ratio of 2.54 (95% CI 1.96–3.28) in the angiography cohort. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: A blood marker predicted risk in this clinical cohort; that alone does not prove a dietary cause. organism: Human tissue_or_cell_type: Healthy challenge participants; 4007 angiography patients in the outcome cohort experimental_model: Human isotope challenge with antibiotics plus a separate observational cohort limitations: The challenge establishes microbiota involvement; the outcome cohort establishes association, not that avoiding choline or eggs prevents events. exposure: Two eggs plus d9-PC before/after antibiotics; three-year event follow-up evidence_span: {"source_cache": "artifacts/choline-research/23614584.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9de33f54f0fce1c470cc96c18163574d26fc5c56802e60771c75fdacc5804e0a", "start_char": 0, "end_char": 2119, "text_sha256": "9de33f54f0fce1c470cc96c18163574d26fc5c56802e60771c75fdacc5804e0a"} [choline-p23614584] Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. (2013). https://pubmed.ncbi.nlm.nih.gov/23614584/ DOI: 10.1056/nejmoa1109400
Complete structured claim and evidence
All three bitartrate-containing arms increased platelet reactivity, p<0.01.
Choline bitartrate → Human platelet reactivity by aggregometry source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/33872583.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac", "start_char": 0, "end_char": 1740, "text_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac"}
experimental_model
Five-arm randomized four-week choline-form intervention
exposure
Eggs, choline bitartrate, eggs plus bitartrate, egg whites plus bitartrate, or PC supplements
limitations
Fasting TMAO and platelet assays, not cardiovascular events. Acute post-meal tracing and four-week fasting results are not the same endpoint.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
The platelet assay also changed; clinical clotting events were not tested.
primary_references
[choline-p33872583] Dietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in Participants with Normal Renal Function: A Randomized Clinical Trial. (2021). https://pubmed.ncbi.nlm.nih.gov/33872583/ DOI: 10.1016/j.amjmed.2021.03.016
tissue_or_cell_type
82 healthy volunteers with normal renal function
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1192–1203
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five-arm randomized four-week choline-form intervention · source_derived_draft · unverified_draft
### choline-bitartrate-platelets All three bitartrate-containing arms increased platelet reactivity, p<0.01. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The platelet assay also changed; clinical clotting events were not tested. organism: Human tissue_or_cell_type: 82 healthy volunteers with normal renal function experimental_model: Five-arm randomized four-week choline-form intervention limitations: Fasting TMAO and platelet assays, not cardiovascular events. Acute post-meal tracing and four-week fasting results are not the same endpoint. exposure: Eggs, choline bitartrate, eggs plus bitartrate, egg whites plus bitartrate, or PC supplements evidence_span: {"source_cache": "artifacts/choline-research/33872583.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac", "start_char": 0, "end_char": 1740, "text_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac"} [choline-p33872583] Dietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in Participants with Normal Renal Function: A Randomized Clinical Trial. (2021). https://pubmed.ncbi.nlm.nih.gov/33872583/ DOI: 10.1016/j.amjmed.2021.03.016
Complete structured claim and evidence
Four eggs daily did not significantly raise fasting TMAO, p=0.28.
Four-egg daily regimen in the 2021 choline-form trial → Circulating trimethylamine N-oxide concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/33872583.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac", "start_char": 0, "end_char": 1740, "text_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac"}
experimental_model
Five-arm randomized four-week choline-form intervention
exposure
Eggs, choline bitartrate, eggs plus bitartrate, egg whites plus bitartrate, or PC supplements
limitations
Fasting TMAO and platelet assays, not cardiovascular events. Acute post-meal tracing and four-week fasting results are not the same endpoint.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
The food intervention did not reproduce the salt-supplement result.
primary_references
[choline-p33872583] Dietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in Participants with Normal Renal Function: A Randomized Clinical Trial. (2021). https://pubmed.ncbi.nlm.nih.gov/33872583/ DOI: 10.1016/j.amjmed.2021.03.016
tissue_or_cell_type
82 healthy volunteers with normal renal function
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1205–1216
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five-arm randomized four-week choline-form intervention · source_derived_draft · unverified_draft
### choline-eggs-tmao-null Four eggs daily did not significantly raise fasting TMAO, p=0.28. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The food intervention did not reproduce the salt-supplement result. organism: Human tissue_or_cell_type: 82 healthy volunteers with normal renal function experimental_model: Five-arm randomized four-week choline-form intervention limitations: Fasting TMAO and platelet assays, not cardiovascular events. Acute post-meal tracing and four-week fasting results are not the same endpoint. exposure: Eggs, choline bitartrate, eggs plus bitartrate, egg whites plus bitartrate, or PC supplements evidence_span: {"source_cache": "artifacts/choline-research/33872583.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac", "start_char": 0, "end_char": 1740, "text_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac"} [choline-p33872583] Dietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in Participants with Normal Renal Function: A Randomized Clinical Trial. (2021). https://pubmed.ncbi.nlm.nih.gov/33872583/ DOI: 10.1016/j.amjmed.2021.03.016
Complete structured claim and evidence
The egg-only arm did not significantly raise platelet reactivity, p=0.10.
Four-egg daily regimen in the 2021 choline-form trial → Human platelet reactivity by aggregometry source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/33872583.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac", "start_char": 0, "end_char": 1740, "text_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac"}
experimental_model
Five-arm randomized four-week choline-form intervention
exposure
Eggs, choline bitartrate, eggs plus bitartrate, egg whites plus bitartrate, or PC supplements
limitations
Fasting TMAO and platelet assays, not cardiovascular events. Acute post-meal tracing and four-week fasting results are not the same endpoint.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
Source and formulation mattered for this measured response.
primary_references
[choline-p33872583] Dietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in Participants with Normal Renal Function: A Randomized Clinical Trial. (2021). https://pubmed.ncbi.nlm.nih.gov/33872583/ DOI: 10.1016/j.amjmed.2021.03.016
tissue_or_cell_type
82 healthy volunteers with normal renal function
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1218–1229
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five-arm randomized four-week choline-form intervention · source_derived_draft · unverified_draft
### choline-eggs-platelet-null The egg-only arm did not significantly raise platelet reactivity, p=0.10. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Source and formulation mattered for this measured response. organism: Human tissue_or_cell_type: 82 healthy volunteers with normal renal function experimental_model: Five-arm randomized four-week choline-form intervention limitations: Fasting TMAO and platelet assays, not cardiovascular events. Acute post-meal tracing and four-week fasting results are not the same endpoint. exposure: Eggs, choline bitartrate, eggs plus bitartrate, egg whites plus bitartrate, or PC supplements evidence_span: {"source_cache": "artifacts/choline-research/33872583.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac", "start_char": 0, "end_char": 1740, "text_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac"} [choline-p33872583] Dietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in Participants with Normal Renal Function: A Randomized Clinical Trial. (2021). https://pubmed.ncbi.nlm.nih.gov/33872583/ DOI: 10.1016/j.amjmed.2021.03.016
Complete structured claim and evidence
PC supplements did not significantly raise platelet reactivity, p=0.79.
Study-specific phosphatidylcholine supplements → Human platelet reactivity by aggregometry source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/33872583.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac", "start_char": 0, "end_char": 1740, "text_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac"}
experimental_model
Five-arm randomized four-week choline-form intervention
exposure
Eggs, choline bitartrate, eggs plus bitartrate, egg whites plus bitartrate, or PC supplements
limitations
Fasting TMAO and platelet assays, not cardiovascular events. Acute post-meal tracing and four-week fasting results are not the same endpoint.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
The PC arm also had a null platelet result.
primary_references
[choline-p33872583] Dietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in Participants with Normal Renal Function: A Randomized Clinical Trial. (2021). https://pubmed.ncbi.nlm.nih.gov/33872583/ DOI: 10.1016/j.amjmed.2021.03.016
tissue_or_cell_type
82 healthy volunteers with normal renal function
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1244–1255
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five-arm randomized four-week choline-form intervention · source_derived_draft · unverified_draft
### choline-pc-platelets-null PC supplements did not significantly raise platelet reactivity, p=0.79. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The PC arm also had a null platelet result. organism: Human tissue_or_cell_type: 82 healthy volunteers with normal renal function experimental_model: Five-arm randomized four-week choline-form intervention limitations: Fasting TMAO and platelet assays, not cardiovascular events. Acute post-meal tracing and four-week fasting results are not the same endpoint. exposure: Eggs, choline bitartrate, eggs plus bitartrate, egg whites plus bitartrate, or PC supplements evidence_span: {"source_cache": "artifacts/choline-research/33872583.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac", "start_char": 0, "end_char": 1740, "text_sha256": "b118e4fcf38f6ecdd6a982baef3e58cf39eb2bc87e67cad9fb9b55866a96c6ac"} [choline-p33872583] Dietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in Participants with Normal Renal Function: A Randomized Clinical Trial. (2021). https://pubmed.ncbi.nlm.nih.gov/33872583/ DOI: 10.1016/j.amjmed.2021.03.016
Complete structured claim and evidence
Mean infant reaction time across the four assessment ages was faster in the 930-versus-480 mg/day maternal group.
Maternal 930-versus-480 mg/day choline controlled-feeding intervention → Infant saccade reaction time in the 2018 maternal-feeding trial source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/29217669.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d5062bfc0f04b936cad236302e998e3db8bbcd9bb6c106f6cff748e513799d01", "start_char": 0, "end_char": 1693, "text_sha256": "d5062bfc0f04b936cad236302e998e3db8bbcd9bb6c106f6cff748e513799d01"}
experimental_model
Randomized double-blind controlled maternal feeding and infant follow-up
exposure
480 versus 930 mg total choline/day in the third trimester; infant testing at 4, 7, 10 and 13 months
limitations
Small trial with a specific processing-speed endpoint. Not a general intelligence claim or proof that every pregnancy benefits equally.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
The higher-intake group showed a benefit on this particular infant processing-speed measure.
primary_references
[choline-p29217669] Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: a randomized, double-blind, controlled feeding study. (2018). https://pubmed.ncbi.nlm.nih.gov/29217669/ DOI: 10.1096/fj.201700692rr
tissue_or_cell_type
26 randomized pregnant women; 24 infants assessed
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1257–1268
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind controlled maternal feeding and infant follow-up · source_derived_draft · unverified_draft
### choline-maternal-processing Mean infant reaction time across the four assessment ages was faster in the 930-versus-480 mg/day maternal group. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The higher-intake group showed a benefit on this particular infant processing-speed measure. organism: Human tissue_or_cell_type: 26 randomized pregnant women; 24 infants assessed experimental_model: Randomized double-blind controlled maternal feeding and infant follow-up limitations: Small trial with a specific processing-speed endpoint. Not a general intelligence claim or proof that every pregnancy benefits equally. exposure: 480 versus 930 mg total choline/day in the third trimester; infant testing at 4, 7, 10 and 13 months evidence_span: {"source_cache": "artifacts/choline-research/29217669.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d5062bfc0f04b936cad236302e998e3db8bbcd9bb6c106f6cff748e513799d01", "start_char": 0, "end_char": 1693, "text_sha256": "d5062bfc0f04b936cad236302e998e3db8bbcd9bb6c106f6cff748e513799d01"} [choline-p29217669] Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: a randomized, double-blind, controlled feeding study. (2018). https://pubmed.ncbi.nlm.nih.gov/29217669/ DOI: 10.1096/fj.201700692rr
Complete structured claim and evidence
The PC supplementation and placebo groups did not differ significantly in global development at the reported infant follow-up assessments.
Study-specific phosphatidylcholine supplements → Infant global-development score in the 2012 PC supplementation trial source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/23134891.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c639fd65120036e4dcce961161222da3632034d148564db3c98bcc36a788084e", "start_char": 0, "end_char": 1592, "text_sha256": "c639fd65120036e4dcce961161222da3632034d148564db3c98bcc36a788084e"}
experimental_model
Randomized double-blind placebo-controlled maternal PC supplementation
exposure
750 mg choline/day delivered as PC, not 750 mg PC mass; weeks 18 through 90 days postpartum; background food choline about 360 mg/day
limitations
Dose identity checked in full-text intervention section. Different endpoints, timing and feeding control from the 2018 trial; a null result is not proof of no effect on every possible outcome.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
This measured outcome did not improve significantly in the trial.
primary_references
[choline-p23134891] Phosphatidylcholine supplementation in pregnant women consuming moderate-choline diets does not enhance infant cognitive function: a randomized, double-blind, placebo-controlled trial. (2012). https://pubmed.ncbi.nlm.nih.gov/23134891/ DOI: 10.3945/ajcn.112.037184
tissue_or_cell_type
140 randomized women; 99 infants in follow-up
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1270–1281
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 maternal PC supplementation · source_derived_draft · unverified_draft
### choline-maternal-global-null The PC supplementation and placebo groups did not differ significantly in global development at the reported infant follow-up assessments. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: This measured outcome did not improve significantly in the trial. organism: Human tissue_or_cell_type: 140 randomized women; 99 infants in follow-up experimental_model: Randomized double-blind placebo-controlled maternal PC supplementation limitations: Dose identity checked in full-text intervention section. Different endpoints, timing and feeding control from the 2018 trial; a null result is not proof of no effect on every possible outcome. exposure: 750 mg choline/day delivered as PC, not 750 mg PC mass; weeks 18 through 90 days postpartum; background food choline about 360 mg/day evidence_span: {"source_cache": "artifacts/choline-research/23134891.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c639fd65120036e4dcce961161222da3632034d148564db3c98bcc36a788084e", "start_char": 0, "end_char": 1592, "text_sha256": "c639fd65120036e4dcce961161222da3632034d148564db3c98bcc36a788084e"} [choline-p23134891] Phosphatidylcholine supplementation in pregnant women consuming moderate-choline diets does not enhance infant cognitive function: a randomized, double-blind, placebo-controlled trial. (2012). https://pubmed.ncbi.nlm.nih.gov/23134891/ DOI: 10.3945/ajcn.112.037184
Complete structured claim and evidence
The PC supplementation and placebo groups did not differ significantly in language development at the reported infant follow-up assessments.
Study-specific phosphatidylcholine supplements → Infant language-development score in the 2012 PC supplementation trial source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/23134891.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c639fd65120036e4dcce961161222da3632034d148564db3c98bcc36a788084e", "start_char": 0, "end_char": 1592, "text_sha256": "c639fd65120036e4dcce961161222da3632034d148564db3c98bcc36a788084e"}
experimental_model
Randomized double-blind placebo-controlled maternal PC supplementation
exposure
750 mg choline/day delivered as PC, not 750 mg PC mass; weeks 18 through 90 days postpartum; background food choline about 360 mg/day
limitations
Dose identity checked in full-text intervention section. Different endpoints, timing and feeding control from the 2018 trial; a null result is not proof of no effect on every possible outcome.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
This measured outcome did not improve significantly in the trial.
primary_references
[choline-p23134891] Phosphatidylcholine supplementation in pregnant women consuming moderate-choline diets does not enhance infant cognitive function: a randomized, double-blind, placebo-controlled trial. (2012). https://pubmed.ncbi.nlm.nih.gov/23134891/ DOI: 10.3945/ajcn.112.037184
tissue_or_cell_type
140 randomized women; 99 infants in follow-up
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1283–1294
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 maternal PC supplementation · source_derived_draft · unverified_draft
### choline-maternal-language-null The PC supplementation and placebo groups did not differ significantly in language development at the reported infant follow-up assessments. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: This measured outcome did not improve significantly in the trial. organism: Human tissue_or_cell_type: 140 randomized women; 99 infants in follow-up experimental_model: Randomized double-blind placebo-controlled maternal PC supplementation limitations: Dose identity checked in full-text intervention section. Different endpoints, timing and feeding control from the 2018 trial; a null result is not proof of no effect on every possible outcome. exposure: 750 mg choline/day delivered as PC, not 750 mg PC mass; weeks 18 through 90 days postpartum; background food choline about 360 mg/day evidence_span: {"source_cache": "artifacts/choline-research/23134891.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c639fd65120036e4dcce961161222da3632034d148564db3c98bcc36a788084e", "start_char": 0, "end_char": 1592, "text_sha256": "c639fd65120036e4dcce961161222da3632034d148564db3c98bcc36a788084e"} [choline-p23134891] Phosphatidylcholine supplementation in pregnant women consuming moderate-choline diets does not enhance infant cognitive function: a randomized, double-blind, placebo-controlled trial. (2012). https://pubmed.ncbi.nlm.nih.gov/23134891/ DOI: 10.3945/ajcn.112.037184
Complete structured claim and evidence
The PC supplementation and placebo groups did not differ significantly in short-term visuospatial memory at the reported infant follow-up assessments.
Study-specific phosphatidylcholine supplements → Infant short-term visuospatial memory in the 2012 PC supplementation trial source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/23134891.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c639fd65120036e4dcce961161222da3632034d148564db3c98bcc36a788084e", "start_char": 0, "end_char": 1592, "text_sha256": "c639fd65120036e4dcce961161222da3632034d148564db3c98bcc36a788084e"}
experimental_model
Randomized double-blind placebo-controlled maternal PC supplementation
exposure
750 mg choline/day delivered as PC, not 750 mg PC mass; weeks 18 through 90 days postpartum; background food choline about 360 mg/day
limitations
Dose identity checked in full-text intervention section. Different endpoints, timing and feeding control from the 2018 trial; a null result is not proof of no effect on every possible outcome.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
This measured outcome did not improve significantly in the trial.
primary_references
[choline-p23134891] Phosphatidylcholine supplementation in pregnant women consuming moderate-choline diets does not enhance infant cognitive function: a randomized, double-blind, placebo-controlled trial. (2012). https://pubmed.ncbi.nlm.nih.gov/23134891/ DOI: 10.3945/ajcn.112.037184
tissue_or_cell_type
140 randomized women; 99 infants in follow-up
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1296–1307
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 maternal PC supplementation · source_derived_draft · unverified_draft
### choline-maternal-short-memory-null The PC supplementation and placebo groups did not differ significantly in short-term visuospatial memory at the reported infant follow-up assessments. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: This measured outcome did not improve significantly in the trial. organism: Human tissue_or_cell_type: 140 randomized women; 99 infants in follow-up experimental_model: Randomized double-blind placebo-controlled maternal PC supplementation limitations: Dose identity checked in full-text intervention section. Different endpoints, timing and feeding control from the 2018 trial; a null result is not proof of no effect on every possible outcome. exposure: 750 mg choline/day delivered as PC, not 750 mg PC mass; weeks 18 through 90 days postpartum; background food choline about 360 mg/day evidence_span: {"source_cache": "artifacts/choline-research/23134891.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c639fd65120036e4dcce961161222da3632034d148564db3c98bcc36a788084e", "start_char": 0, "end_char": 1592, "text_sha256": "c639fd65120036e4dcce961161222da3632034d148564db3c98bcc36a788084e"} [choline-p23134891] Phosphatidylcholine supplementation in pregnant women consuming moderate-choline diets does not enhance infant cognitive function: a randomized, double-blind, placebo-controlled trial. (2012). https://pubmed.ncbi.nlm.nih.gov/23134891/ DOI: 10.3945/ajcn.112.037184
Complete structured claim and evidence
The PC supplementation and placebo groups did not differ significantly in long-term episodic memory at the reported infant follow-up assessments.
Study-specific phosphatidylcholine supplements → Infant long-term episodic memory in the 2012 PC supplementation trial source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/23134891.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c639fd65120036e4dcce961161222da3632034d148564db3c98bcc36a788084e", "start_char": 0, "end_char": 1592, "text_sha256": "c639fd65120036e4dcce961161222da3632034d148564db3c98bcc36a788084e"}
experimental_model
Randomized double-blind placebo-controlled maternal PC supplementation
exposure
750 mg choline/day delivered as PC, not 750 mg PC mass; weeks 18 through 90 days postpartum; background food choline about 360 mg/day
limitations
Dose identity checked in full-text intervention section. Different endpoints, timing and feeding control from the 2018 trial; a null result is not proof of no effect on every possible outcome.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
This measured outcome did not improve significantly in the trial.
primary_references
[choline-p23134891] Phosphatidylcholine supplementation in pregnant women consuming moderate-choline diets does not enhance infant cognitive function: a randomized, double-blind, placebo-controlled trial. (2012). https://pubmed.ncbi.nlm.nih.gov/23134891/ DOI: 10.3945/ajcn.112.037184
tissue_or_cell_type
140 randomized women; 99 infants in follow-up
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1309–1320
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 maternal PC supplementation · source_derived_draft · unverified_draft
### choline-maternal-long-memory-null The PC supplementation and placebo groups did not differ significantly in long-term episodic memory at the reported infant follow-up assessments. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: This measured outcome did not improve significantly in the trial. organism: Human tissue_or_cell_type: 140 randomized women; 99 infants in follow-up experimental_model: Randomized double-blind placebo-controlled maternal PC supplementation limitations: Dose identity checked in full-text intervention section. Different endpoints, timing and feeding control from the 2018 trial; a null result is not proof of no effect on every possible outcome. exposure: 750 mg choline/day delivered as PC, not 750 mg PC mass; weeks 18 through 90 days postpartum; background food choline about 360 mg/day evidence_span: {"source_cache": "artifacts/choline-research/23134891.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c639fd65120036e4dcce961161222da3632034d148564db3c98bcc36a788084e", "start_char": 0, "end_char": 1592, "text_sha256": "c639fd65120036e4dcce961161222da3632034d148564db3c98bcc36a788084e"} [choline-p23134891] Phosphatidylcholine supplementation in pregnant women consuming moderate-choline diets does not enhance infant cognitive function: a randomized, double-blind, placebo-controlled trial. (2012). https://pubmed.ncbi.nlm.nih.gov/23134891/ DOI: 10.3945/ajcn.112.037184
Complete structured claim and evidence
The 90-day global functional/cognitive outcome did not differ significantly with citicoline: odds ratio 0.98, 95% CI 0.83–1.15.
Citicoline treatment in the COBRIT and ICTUS trials → COBRIT global functional/cognitive outcome at 90 days source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/23168823.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "57ad3435837e866a92fad1e25c19d9a4919f522026731b48ba7df3b345664186", "start_char": 0, "end_char": 2347, "text_sha256": "57ad3435837e866a92fad1e25c19d9a4919f522026731b48ba7df3b345664186"}
experimental_model
COBRIT phase 3 randomized double-blind placebo-controlled trial
exposure
Citicoline 2000 mg/day enteral/oral for 90 days
limitations
Drug-form intervention after brain injury, not correction of documented dietary choline deficiency.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
A plausible biochemical precursor did not improve this clinical trial’s outcome.
primary_references
[choline-p23168823] Effect of citicoline on functional and cognitive status among patients with traumatic brain injury: Citicoline Brain Injury Treatment Trial (COBRIT). (2012). https://pubmed.ncbi.nlm.nih.gov/23168823/ DOI: 10.1001/jama.2012.13256
tissue_or_cell_type
1213 people with complicated mild, moderate or severe traumatic brain injury
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1322–1333
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · COBRIT phase 3 randomized double-blind placebo-controlled trial · source_derived_draft · unverified_draft
### choline-citicoline-tbi-null The 90-day global functional/cognitive outcome did not differ significantly with citicoline: odds ratio 0.98, 95% CI 0.83–1.15. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: A plausible biochemical precursor did not improve this clinical trial’s outcome. organism: Human tissue_or_cell_type: 1213 people with complicated mild, moderate or severe traumatic brain injury experimental_model: COBRIT phase 3 randomized double-blind placebo-controlled trial limitations: Drug-form intervention after brain injury, not correction of documented dietary choline deficiency. exposure: Citicoline 2000 mg/day enteral/oral for 90 days evidence_span: {"source_cache": "artifacts/choline-research/23168823.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "57ad3435837e866a92fad1e25c19d9a4919f522026731b48ba7df3b345664186", "start_char": 0, "end_char": 2347, "text_sha256": "57ad3435837e866a92fad1e25c19d9a4919f522026731b48ba7df3b345664186"} [choline-p23168823] Effect of citicoline on functional and cognitive status among patients with traumatic brain injury: Citicoline Brain Injury Treatment Trial (COBRIT). (2012). https://pubmed.ncbi.nlm.nih.gov/23168823/ DOI: 10.1001/jama.2012.13256
Complete structured claim and evidence
Global recovery was similar with citicoline and placebo: odds ratio 1.03, 95% CI 0.86–1.25, p=0.364.
Citicoline treatment in the COBRIT and ICTUS trials → ICTUS global stroke recovery at 90 days source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/choline-research/22691567.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d70010453da46567d129e81a98e9e077bc3c787880287428ddb76023202d5648", "start_char": 0, "end_char": 2066, "text_sha256": "d70010453da46567d129e81a98e9e077bc3c787880287428ddb76023202d5648"}
experimental_model
ICTUS randomized masked multicenter placebo-controlled trial
exposure
Citicoline 1000 mg every 12 hours, initially IV then oral for six weeks; 90-day recovery
limitations
Trial stopped for futility. Results apply to this clinical setting, not to nutritional essentiality or all choline forms.
nutrient_topic
Choline research collection; topical membership is not evidence of a direct dietary effect. · Choline
organism
Human
plain_language
The large stroke trial did not confirm a recovery benefit.
primary_references
[choline-p22691567] Citicoline in the treatment of acute ischaemic stroke: an international, randomised, multicentre, placebo-controlled study (ICTUS trial). (2012). https://pubmed.ncbi.nlm.nih.gov/22691567/ DOI: 10.1016/s0140-6736(12)60813-7
tissue_or_cell_type
2298 adults with moderate-to-severe acute ischemic stroke
Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 1335–1346
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · ICTUS randomized masked multicenter placebo-controlled trial · source_derived_draft · unverified_draft
### choline-citicoline-stroke-null Global recovery was similar with citicoline and placebo: odds ratio 1.03, 95% CI 0.86–1.25, p=0.364. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The large stroke trial did not confirm a recovery benefit. organism: Human tissue_or_cell_type: 2298 adults with moderate-to-severe acute ischemic stroke experimental_model: ICTUS randomized masked multicenter placebo-controlled trial limitations: Trial stopped for futility. Results apply to this clinical setting, not to nutritional essentiality or all choline forms. exposure: Citicoline 1000 mg every 12 hours, initially IV then oral for six weeks; 90-day recovery evidence_span: {"source_cache": "artifacts/choline-research/22691567.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d70010453da46567d129e81a98e9e077bc3c787880287428ddb76023202d5648", "start_char": 0, "end_char": 2066, "text_sha256": "d70010453da46567d129e81a98e9e077bc3c787880287428ddb76023202d5648"} [choline-p22691567] Citicoline in the treatment of acute ischaemic stroke: an international, randomised, multicentre, placebo-controlled study (ICTUS trial). (2012). https://pubmed.ncbi.nlm.nih.gov/22691567/ DOI: 10.1016/s0140-6736(12)60813-7
Complete structured claim and evidence
Purified human BHMT uses betaine and homocysteine in the alternative methionine-forming reaction.
Betaine-homocysteine S-methyltransferase / BHMT → L-Methionine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Betaine/choline and folate routes meet at homocysteine.
experimental_model
Recombinant human BHMT and human liver-derived BHMT.
limitations
Does not establish complete folate substitution in vivo.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Homo sapiens
plain_language
Betaine supplies another recycling route.
primary_references
[millian-1998] Human betaine-homocysteine methyltransferase is a zinc metalloenzyme (1998). https://pubmed.ncbi.nlm.nih.gov/9681996/ DOI: 10.1006/abbi.1998.0757
tissue_or_cell_type
Recombinant and liver-derived enzyme
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 610–620
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human BHMT and human liver-derived BHMT. · source_derived_draft · unverified_draft
### folate-methyl-bhmt-reaction Purified human BHMT uses betaine and homocysteine in the alternative methionine-forming reaction. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Betaine supplies another recycling route. organism: Homo sapiens tissue_or_cell_type: Recombinant and liver-derived enzyme experimental_model: Recombinant human BHMT and human liver-derived BHMT. limitations: Does not establish complete folate substitution in vivo. cross_nutrient: Betaine/choline and folate routes meet at homocysteine. [millian-1998] Human betaine-homocysteine methyltransferase is a zinc metalloenzyme (1998). https://pubmed.ncbi.nlm.nih.gov/9681996/ DOI: 10.1006/abbi.1998.0757
Complete structured claim and evidence
Chemical zinc removal inactivated human BHMT; zinc reconstitution restored its activity and metal content.
Zinc(II) ion → Betaine-homocysteine S-methyltransferase / BHMT source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Zinc supports parallel remethylation.
experimental_model
Recombinant human BHMT and human liver-derived BHMT.
limitations
Demetallation is not dietary zinc deficiency.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Homo sapiens
plain_language
The betaine route requires a zinc-containing enzyme.
primary_references
[millian-1998] Human betaine-homocysteine methyltransferase is a zinc metalloenzyme (1998). https://pubmed.ncbi.nlm.nih.gov/9681996/ DOI: 10.1006/abbi.1998.0757
tissue_or_cell_type
Purified protein
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 622–632
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human BHMT and human liver-derived BHMT. · source_derived_draft · unverified_draft
### folate-methyl-bhmt-zinc Chemical zinc removal inactivated human BHMT; zinc reconstitution restored its activity and metal content. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The betaine route requires a zinc-containing enzyme. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Recombinant human BHMT and human liver-derived BHMT. limitations: Demetallation is not dietary zinc deficiency. cross_nutrient: Zinc supports parallel remethylation. [millian-1998] Human betaine-homocysteine methyltransferase is a zinc metalloenzyme (1998). https://pubmed.ncbi.nlm.nih.gov/9681996/ DOI: 10.1006/abbi.1998.0757
Complete structured claim and evidence
Bhmt deletion raised hepatic total homocysteine sixfold and plasma total homocysteine eightfold in mice.
Bhmt gene (Mus musculus) → Homocysteine source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Loss of betaine recycling burdens shared homocysteine handling.
experimental_model
Bhmt-null mice and wild-type controls.
limitations
Complete knockout, not common human polymorphisms.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Mus musculus
plain_language
Other pathways did not fully compensate.
primary_references
[teng-2011] Deletion of betaine-homocysteine S-methyltransferase in mice perturbs choline and 1-carbon metabolism, resulting in fatty liver and hepatocellular carcinomas (2011). https://pubmed.ncbi.nlm.nih.gov/21878621/ DOI: 10.1074/jbc.m111.265348
tissue_or_cell_type
Liver and plasma
trigger_kind
machinery_impairment Imported condition classification; unverified.
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 634–644
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bhmt-null mice and wild-type controls. · source_derived_draft · unverified_draft
### folate-methyl-bhmt-ko-hcy Bhmt deletion raised hepatic total homocysteine sixfold and plasma total homocysteine eightfold in mice. Condition category: machinery_impairment nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Other pathways did not fully compensate. organism: Mus musculus tissue_or_cell_type: Liver and plasma experimental_model: Bhmt-null mice and wild-type controls. limitations: Complete knockout, not common human polymorphisms. cross_nutrient: Loss of betaine recycling burdens shared homocysteine handling. [teng-2011] Deletion of betaine-homocysteine S-methyltransferase in mice perturbs choline and 1-carbon metabolism, resulting in fatty liver and hepatocellular carcinomas (2011). https://pubmed.ncbi.nlm.nih.gov/21878621/ DOI: 10.1074/jbc.m111.265348
Complete structured claim and evidence
Bhmt-null mouse liver contained about threefold more SAH than wild type.
Bhmt gene (Mus musculus) → S-Adenosyl-L-homocysteine source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Bhmt-null mice and wild-type controls.
limitations
No direct epigenetic inference.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Mus musculus
plain_language
The spent methyl-donor pool increased.
primary_references
[teng-2011] Deletion of betaine-homocysteine S-methyltransferase in mice perturbs choline and 1-carbon metabolism, resulting in fatty liver and hepatocellular carcinomas (2011). https://pubmed.ncbi.nlm.nih.gov/21878621/ DOI: 10.1074/jbc.m111.265348
tissue_or_cell_type
Liver
trigger_kind
machinery_impairment Imported condition classification; unverified.
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 657–666
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bhmt-null mice and wild-type controls. · source_derived_draft · unverified_draft
### folate-methyl-bhmt-ko-sah Bhmt-null mouse liver contained about threefold more SAH than wild type. Condition category: machinery_impairment nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The spent methyl-donor pool increased. organism: Mus musculus tissue_or_cell_type: Liver experimental_model: Bhmt-null mice and wild-type controls. limitations: No direct epigenetic inference. [teng-2011] Deletion of betaine-homocysteine S-methyltransferase in mice perturbs choline and 1-carbon metabolism, resulting in fatty liver and hepatocellular carcinomas (2011). https://pubmed.ncbi.nlm.nih.gov/21878621/ DOI: 10.1074/jbc.m111.265348
Complete structured claim and evidence
Bhmt-null mouse liver contained 43% less SAM than wild type.
Bhmt gene (Mus musculus) → S-Adenosyl-L-methionine source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Bhmt-null mice and wild-type controls.
limitations
Concentration is not methylation flux.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Mus musculus
plain_language
The hepatic methyl-donor pool fell.
primary_references
[teng-2011] Deletion of betaine-homocysteine S-methyltransferase in mice perturbs choline and 1-carbon metabolism, resulting in fatty liver and hepatocellular carcinomas (2011). https://pubmed.ncbi.nlm.nih.gov/21878621/ DOI: 10.1074/jbc.m111.265348
tissue_or_cell_type
Liver
trigger_kind
machinery_impairment Imported condition classification; unverified.
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 646–655
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bhmt-null mice and wild-type controls. · source_derived_draft · unverified_draft
### folate-methyl-bhmt-ko-sam Bhmt-null mouse liver contained 43% less SAM than wild type. Condition category: machinery_impairment nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The hepatic methyl-donor pool fell. organism: Mus musculus tissue_or_cell_type: Liver experimental_model: Bhmt-null mice and wild-type controls. limitations: Concentration is not methylation flux. [teng-2011] Deletion of betaine-homocysteine S-methyltransferase in mice perturbs choline and 1-carbon metabolism, resulting in fatty liver and hepatocellular carcinomas (2011). https://pubmed.ncbi.nlm.nih.gov/21878621/ DOI: 10.1074/jbc.m111.265348
Complete structured claim and evidence
Feeding 20 mg folate/kg diet did not ameliorate elevated plasma homocysteine in Bhmt-null mice.
Folic acid → Homocysteine source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Folate/betaine compensation has limits.
experimental_model
Bhmt-null and wild-type mice; four-week folate feeding.
exposure
0, 2 or 20 mg folate/kg diet
limitations
Mouse four-week experiment, not a human treatment rule.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Mus musculus
plain_language
Extra folate did not restore this missing route.
primary_references
[teng-2012] Homocysteinemia in mice with genetic betaine homocysteine S-methyltransferase deficiency is independent of dietary folate intake (2012). https://pubmed.ncbi.nlm.nih.gov/23014492/ DOI: 10.3945/jn.112.166835
tissue_or_cell_type
Plasma
trigger_kind
machinery_impairment Imported condition classification; unverified.
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 668–679
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bhmt-null and wild-type mice; four-week folate feeding. · source_derived_draft · unverified_draft
### folate-methyl-folate-no-hcy-rescue-bhmt Feeding 20 mg folate/kg diet did not ameliorate elevated plasma homocysteine in Bhmt-null mice. Condition category: machinery_impairment nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Extra folate did not restore this missing route. organism: Mus musculus tissue_or_cell_type: Plasma experimental_model: Bhmt-null and wild-type mice; four-week folate feeding. limitations: Mouse four-week experiment, not a human treatment rule. exposure: 0, 2 or 20 mg folate/kg diet cross_nutrient: Folate/betaine compensation has limits. [teng-2012] Homocysteinemia in mice with genetic betaine homocysteine S-methyltransferase deficiency is independent of dietary folate intake (2012). https://pubmed.ncbi.nlm.nih.gov/23014492/ DOI: 10.3945/jn.112.166835
Complete structured claim and evidence
The 20 mg folate/kg diet increased hepatic SAM in Bhmt-null mice versus 0 and 2 mg/kg diets.
Folic acid → S-Adenosyl-L-methionine source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Bhmt-null and wild-type mice; four-week folate feeding.
exposure
Four-week feeding
limitations
No proof of restored DNA methylation.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Mus musculus
plain_language
SAM improved despite persistent high homocysteine.
primary_references
[teng-2012] Homocysteinemia in mice with genetic betaine homocysteine S-methyltransferase deficiency is independent of dietary folate intake (2012). https://pubmed.ncbi.nlm.nih.gov/23014492/ DOI: 10.3945/jn.112.166835
tissue_or_cell_type
Liver
trigger_kind
machinery_impairment Imported condition classification; unverified.
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 681–691
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bhmt-null and wild-type mice; four-week folate feeding. · source_derived_draft · unverified_draft
### folate-methyl-folate-sam-bhmt The 20 mg folate/kg diet increased hepatic SAM in Bhmt-null mice versus 0 and 2 mg/kg diets. Condition category: machinery_impairment nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: SAM improved despite persistent high homocysteine. organism: Mus musculus tissue_or_cell_type: Liver experimental_model: Bhmt-null and wild-type mice; four-week folate feeding. limitations: No proof of restored DNA methylation. exposure: Four-week feeding [teng-2012] Homocysteinemia in mice with genetic betaine homocysteine S-methyltransferase deficiency is independent of dietary folate intake (2012). https://pubmed.ncbi.nlm.nih.gov/23014492/ DOI: 10.3945/jn.112.166835
Complete structured claim and evidence
Reconstituted human MTR transfers methylfolate-derived methyl groups through cobalamin to homocysteine, producing methionine and THF.
Cobalamin-dependent methionine synthase / MTR → L-Methionine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Folate methyl transfer requires B12.
experimental_model
Human MTR/MTRR expressed in insect cells; purified enzymes and extracts.
limitations
Chemistry, not dietary response.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Homo sapiens
plain_language
B12-dependent MTR recycles both homocysteine and folate.
primary_references
[yamada-2006] Human methionine synthase reductase is a molecular chaperone for human methionine synthase (2006). https://pubmed.ncbi.nlm.nih.gov/16769880/ DOI: 10.1073/pnas.0603694103
tissue_or_cell_type
Purified protein
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 482–492
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human MTR/MTRR expressed in insect cells; purified enzymes and extracts. · source_derived_draft · unverified_draft
### folate-methyl-mtr-methyl-transfer Reconstituted human MTR transfers methylfolate-derived methyl groups through cobalamin to homocysteine, producing methionine and THF. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: B12-dependent MTR recycles both homocysteine and folate. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Human MTR/MTRR expressed in insect cells; purified enzymes and extracts. limitations: Chemistry, not dietary response. cross_nutrient: Folate methyl transfer requires B12. [yamada-2006] Human methionine synthase reductase is a molecular chaperone for human methionine synthase (2006). https://pubmed.ncbi.nlm.nih.gov/16769880/ DOI: 10.1073/pnas.0603694103
Complete structured claim and evidence
Combined low-folate/low-choline feeding lowered plasma choline by 28% in men and 25% in women.
Folate (vitamin B9) → Choline source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Folate and choline status are coupled.
experimental_model
Metabolic-unit depletion/repletion: 11 men, 10 women.
exposure
Men: 25 micrograms folate/238 mg choline daily; women: 56 micrograms/147 mg
limitations
No functional choline deficiency by measured transaminase/lipid endpoints.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Homo sapiens
plain_language
Folate restriction strained choline markers during low choline intake.
primary_references
[jacob-1999] Folate nutriture alters choline status of women and men fed low choline diets (1999). https://pubmed.ncbi.nlm.nih.gov/10082779/ DOI: 10.1093/jn/129.3.712
tissue_or_cell_type
Plasma
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 693–704
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Metabolic-unit depletion/repletion: 11 men, 10 women. · source_derived_draft · unverified_draft
### folate-methyl-low-folate-choline Combined low-folate/low-choline feeding lowered plasma choline by 28% in men and 25% in women. Condition category: nutrient_deficiency nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Folate restriction strained choline markers during low choline intake. organism: Homo sapiens tissue_or_cell_type: Plasma experimental_model: Metabolic-unit depletion/repletion: 11 men, 10 women. limitations: No functional choline deficiency by measured transaminase/lipid endpoints. exposure: Men: 25 micrograms folate/238 mg choline daily; women: 56 micrograms/147 mg cross_nutrient: Folate and choline status are coupled. [jacob-1999] Folate nutriture alters choline status of women and men fed low choline diets (1999). https://pubmed.ncbi.nlm.nih.gov/10082779/ DOI: 10.1093/jn/129.3.712
Complete structured claim and evidence
Men on the combined low-folate/low-choline diet showed 26% lower plasma phosphatidylcholine.
Folate (vitamin B9) → Phosphatidylcholine source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Folate/choline restriction affects circulating phospholipid.
experimental_model
Metabolic-unit depletion/repletion: 11 men, 10 women.
limitations
Male cohort; concentration does not identify biosynthetic flux.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Homo sapiens
plain_language
A choline-containing lipid also declined.
primary_references
[jacob-1999] Folate nutriture alters choline status of women and men fed low choline diets (1999). https://pubmed.ncbi.nlm.nih.gov/10082779/ DOI: 10.1093/jn/129.3.712
tissue_or_cell_type
Plasma
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 706–716
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Metabolic-unit depletion/repletion: 11 men, 10 women. · source_derived_draft · unverified_draft
### folate-methyl-low-folate-pc Men on the combined low-folate/low-choline diet showed 26% lower plasma phosphatidylcholine. Condition category: nutrient_deficiency nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: A choline-containing lipid also declined. organism: Homo sapiens tissue_or_cell_type: Plasma experimental_model: Metabolic-unit depletion/repletion: 11 men, 10 women. limitations: Male cohort; concentration does not identify biosynthetic flux. cross_nutrient: Folate/choline restriction affects circulating phospholipid. [jacob-1999] Folate nutriture alters choline status of women and men fed low choline diets (1999). https://pubmed.ncbi.nlm.nih.gov/10082779/ DOI: 10.1093/jn/129.3.712
Complete structured claim and evidence
Folate repletion returned depressed plasma choline-status measures to baseline or above in the low-choline feeding studies.
Folic acid → Choline source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Folate repletion modifies choline status.
experimental_model
Metabolic-unit depletion/repletion: 11 men, 10 women.
exposure
2-6 weeks folic-acid repletion
limitations
Not evidence folate replaces dietary choline.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Homo sapiens
plain_language
Restoring folate improved the choline markers.
primary_references
[jacob-1999] Folate nutriture alters choline status of women and men fed low choline diets (1999). https://pubmed.ncbi.nlm.nih.gov/10082779/ DOI: 10.1093/jn/129.3.712
tissue_or_cell_type
Plasma
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 718–729
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Metabolic-unit depletion/repletion: 11 men, 10 women. · source_derived_draft · unverified_draft
### folate-methyl-folate-choline-repletion Folate repletion returned depressed plasma choline-status measures to baseline or above in the low-choline feeding studies. Condition category: nutrient_deficiency nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Restoring folate improved the choline markers. organism: Homo sapiens tissue_or_cell_type: Plasma experimental_model: Metabolic-unit depletion/repletion: 11 men, 10 women. limitations: Not evidence folate replaces dietary choline. exposure: 2-6 weeks folic-acid repletion cross_nutrient: Folate repletion modifies choline status. [jacob-1999] Folate nutriture alters choline status of women and men fed low choline diets (1999). https://pubmed.ncbi.nlm.nih.gov/10082779/ DOI: 10.1093/jn/129.3.712
Complete structured claim and evidence
Nonpregnant MTHFR rs1801133 carriers had lower labeled betaine:phosphatidylcholine enrichment ratios than noncarriers (0.8 versus 0.9).
MTHFR Ala222Val protein → Choline partitioning between betaine and phosphatidylcholine source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Folate-pathway genotype relates to choline allocation.
experimental_model
Choline feeding and isotope tracing in women across reproductive states.
limitations
Genotypes not randomized; ratio is a pathway proxy.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Homo sapiens
plain_language
Relative choline allocation shifted toward phosphatidylcholine.
primary_references
[ganz-2016] Genetic impairments in folate enzymes increase dependence on dietary choline for phosphatidylcholine production at the expense of betaine synthesis (2016). https://pubmed.ncbi.nlm.nih.gov/27342765/ DOI: 10.1096/fj.201500138rr
tissue_or_cell_type
Plasma tracer metabolites
trigger_kind
machinery_impairment Imported condition classification; unverified.
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 731–741
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Choline feeding and isotope tracing in women across reproductive states. · source_derived_draft · unverified_draft
### folate-methyl-variant-choline-allocation Nonpregnant MTHFR rs1801133 carriers had lower labeled betaine:phosphatidylcholine enrichment ratios than noncarriers (0.8 versus 0.9). Condition category: machinery_impairment nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Relative choline allocation shifted toward phosphatidylcholine. organism: Homo sapiens tissue_or_cell_type: Plasma tracer metabolites experimental_model: Choline feeding and isotope tracing in women across reproductive states. limitations: Genotypes not randomized; ratio is a pathway proxy. cross_nutrient: Folate-pathway genotype relates to choline allocation. [ganz-2016] Genetic impairments in folate enzymes increase dependence on dietary choline for phosphatidylcholine production at the expense of betaine synthesis (2016). https://pubmed.ncbi.nlm.nih.gov/27342765/ DOI: 10.1096/fj.201500138rr
Complete structured claim and evidence
In nonpregnant MTHFR rs1801133 carriers receiving 930 mg choline/day, the betaine-d9:PC-d9 enrichment ratio was 0.87, matching noncarriers receiving 480 mg/day (0.87); noncarriers receiving 930 mg/day had a ratio of 1.0.
Choline → Choline partitioning between betaine and phosphatidylcholine source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Choline modifies a folate-genotype-associated phenotype.
experimental_model
Choline feeding and isotope tracing in women across reproductive states.
exposure
480 versus 930 mg/day; recommended folate intake
limitations
The matched reference is noncarriers at 480 mg/day, not noncarriers at the same 930 mg/day; subgroup result, not universal restoration or dosing advice.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Homo sapiens
plain_language
Higher intake brought carriers to the lower-intake noncarrier reference value.
primary_references
[ganz-2016] Genetic impairments in folate enzymes increase dependence on dietary choline for phosphatidylcholine production at the expense of betaine synthesis (2016). https://pubmed.ncbi.nlm.nih.gov/27342765/ DOI: 10.1096/fj.201500138rr
tissue_or_cell_type
Plasma tracer metabolites
trigger_kind
machinery_impairment Imported condition classification; unverified.
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 743–754
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Choline feeding and isotope tracing in women across reproductive states. · source_derived_draft · unverified_draft
### folate-methyl-choline-intake-variant In nonpregnant MTHFR rs1801133 carriers receiving 930 mg choline/day, the betaine-d9:PC-d9 enrichment ratio was 0.87, matching noncarriers receiving 480 mg/day (0.87); noncarriers receiving 930 mg/day had a ratio of 1.0. Condition category: machinery_impairment nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Higher intake brought carriers to the lower-intake noncarrier reference value. organism: Homo sapiens tissue_or_cell_type: Plasma tracer metabolites experimental_model: Choline feeding and isotope tracing in women across reproductive states. limitations: The matched reference is noncarriers at 480 mg/day, not noncarriers at the same 930 mg/day; subgroup result, not universal restoration or dosing advice. exposure: 480 versus 930 mg/day; recommended folate intake cross_nutrient: Choline modifies a folate-genotype-associated phenotype. [ganz-2016] Genetic impairments in folate enzymes increase dependence on dietary choline for phosphatidylcholine production at the expense of betaine synthesis (2016). https://pubmed.ncbi.nlm.nih.gov/27342765/ DOI: 10.1096/fj.201500138rr
Complete structured claim and evidence
Human CCTbeta expression increased CCT activity and cellular CDP-choline accumulation in COS-7 cells.
Human CTP:phosphocholine cytidylyltransferase beta / PCYT1B → CDP-choline source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/9593753.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6ed2c0c0ceaa7eb2efb90c66565bae51b71023f77cdd0224159fd9814e3b7d45", "start_char": 0, "end_char": 1766, "text_sha256": "6ed2c0c0ceaa7eb2efb90c66565bae51b71023f77cdd0224159fd9814e3b7d45"}
experimental_model
Human isoform cloning and COS-7 expression studies
exposure
CCTbeta transfection and catalytic assays with lipid regulators
limitations
Expression-system findings; maximum activity required lipid regulators. Do not generalize the early clone to every subsequently described splice variant.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human PCYT1B expressed in African-green-monkey-derived COS-7 cells
plain_language
A separately identified enzyme activates the phosphocholine building block.
primary_references
[phosphorus-p9593753] Cloning and characterization of a second human CTP:phosphocholine cytidylyltransferase. (1998). https://pubmed.ncbi.nlm.nih.gov/9593753/ DOI: 10.1074/jbc.273.22.14022
tissue_or_cell_type
Cytoplasm and phospholipid biosynthesis
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 698–709
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human isoform cloning and COS-7 expression studies · source_derived_draft · unverified_draft
### phosphorus-pcyt-cdp Human CCTbeta expression increased CCT activity and cellular CDP-choline accumulation in COS-7 cells. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: A separately identified enzyme activates the phosphocholine building block. organism: Human PCYT1B expressed in African-green-monkey-derived COS-7 cells tissue_or_cell_type: Cytoplasm and phospholipid biosynthesis experimental_model: Human isoform cloning and COS-7 expression studies limitations: Expression-system findings; maximum activity required lipid regulators. Do not generalize the early clone to every subsequently described splice variant. exposure: CCTbeta transfection and catalytic assays with lipid regulators evidence_span: {"source_cache": "artifacts/phosphorus-research/9593753.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6ed2c0c0ceaa7eb2efb90c66565bae51b71023f77cdd0224159fd9814e3b7d45", "start_char": 0, "end_char": 1766, "text_sha256": "6ed2c0c0ceaa7eb2efb90c66565bae51b71023f77cdd0224159fd9814e3b7d45"} [phosphorus-p9593753] Cloning and characterization of a second human CTP:phosphocholine cytidylyltransferase. (1998). https://pubmed.ncbi.nlm.nih.gov/9593753/ DOI: 10.1074/jbc.273.22.14022
Complete structured claim and evidence
Human CCTbeta expression enhanced radiolabeling of phosphatidylcholine in COS-7 cells.
Human CTP:phosphocholine cytidylyltransferase beta / PCYT1B → Phosphatidylcholine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/9593753.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6ed2c0c0ceaa7eb2efb90c66565bae51b71023f77cdd0224159fd9814e3b7d45", "start_char": 0, "end_char": 1766, "text_sha256": "6ed2c0c0ceaa7eb2efb90c66565bae51b71023f77cdd0224159fd9814e3b7d45"}
experimental_model
Human isoform cloning and COS-7 expression studies
exposure
CCTbeta transfection and catalytic assays with lipid regulators
limitations
Expression-system findings; maximum activity required lipid regulators. Do not generalize the early clone to every subsequently described splice variant.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human PCYT1B expressed in African-green-monkey-derived COS-7 cells
plain_language
The pathway feeds a phosphorus-containing membrane lipid; it is distinct from free phosphate transport.
primary_references
[phosphorus-p9593753] Cloning and characterization of a second human CTP:phosphocholine cytidylyltransferase. (1998). https://pubmed.ncbi.nlm.nih.gov/9593753/ DOI: 10.1074/jbc.273.22.14022
tissue_or_cell_type
Cytoplasm and phospholipid biosynthesis
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 711–722
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human isoform cloning and COS-7 expression studies · source_derived_draft · unverified_draft
### phosphorus-pcyt-lipid Human CCTbeta expression enhanced radiolabeling of phosphatidylcholine in COS-7 cells. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The pathway feeds a phosphorus-containing membrane lipid; it is distinct from free phosphate transport. organism: Human PCYT1B expressed in African-green-monkey-derived COS-7 cells tissue_or_cell_type: Cytoplasm and phospholipid biosynthesis experimental_model: Human isoform cloning and COS-7 expression studies limitations: Expression-system findings; maximum activity required lipid regulators. Do not generalize the early clone to every subsequently described splice variant. exposure: CCTbeta transfection and catalytic assays with lipid regulators evidence_span: {"source_cache": "artifacts/phosphorus-research/9593753.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6ed2c0c0ceaa7eb2efb90c66565bae51b71023f77cdd0224159fd9814e3b7d45", "start_char": 0, "end_char": 1766, "text_sha256": "6ed2c0c0ceaa7eb2efb90c66565bae51b71023f77cdd0224159fd9814e3b7d45"} [phosphorus-p9593753] Cloning and characterization of a second human CTP:phosphocholine cytidylyltransferase. (1998). https://pubmed.ncbi.nlm.nih.gov/9593753/ DOI: 10.1074/jbc.273.22.14022
Complete structured claim and evidence
Human PHOSPHO1 also hydrolyzes phosphocholine, producing inorganic phosphate and choline.
Phosphocholine → Inorganic phosphate (Pi; protonation depends on pH) source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified-enzyme substrate assay
limitations
This reaction uses magnesium-dependent machinery; calcium is the eventual mineral constituent, not the demonstrated phosphatase cofactor.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Homo sapiens
plain_language
A second phospholipid-headgroup metabolite can supply phosphate.
primary_references
[roberts2004] Human PHOSPHO1 exhibits high specific phosphoethanolamine and phosphocholine phosphatase activities (2004). https://pubmed.ncbi.nlm.nih.gov/15175005/ DOI: 10.1042/BJ20040511
tissue_or_cell_type
Recombinant enzyme
Calcium: mechanism-first literature curation (2026-09-17) · lines 908–917
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified-enzyme substrate assay · source_derived_draft · unverified_draft
### phospho1-phosphocholine-hydrolysis Human PHOSPHO1 also hydrolyzes phosphocholine, producing inorganic phosphate and choline. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second phospholipid-headgroup metabolite can supply phosphate. organism: Homo sapiens tissue_or_cell_type: Recombinant enzyme experimental_model: Purified-enzyme substrate assay limitations: This reaction uses magnesium-dependent machinery; calcium is the eventual mineral constituent, not the demonstrated phosphatase cofactor. [roberts2004] Human PHOSPHO1 exhibits high specific phosphoethanolamine and phosphocholine phosphatase activities (2004). https://pubmed.ncbi.nlm.nih.gov/15175005/ DOI: 10.1042/BJ20040511
Complete structured claim and evidence
Recombinant human PHOSPHO1 showed strong Mg dependence when hydrolyzing phosphoethanolamine and phosphocholine.
Mg2+ → Phosphoethanolamine/phosphocholine phosphatase PHOSPHO1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium -> PHOSPHO1 -> phosphate production; joins the existing calcium PHOSPHO1 records.
experimental_model
Purified recombinant phosphatase assays.
limitations
Enzyme evidence does not measure the effect of oral Mg on bone; substrate Km values are not Mg deficiency thresholds.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
Magnesium helps a phosphate-releasing enzyme already connected to calcium mineralization.
primary_references
[mg-roberts2004] Human PHOSPHO1 exhibits high specific phosphoethanolamine and phosphocholine phosphatase activities (2004). https://pubmed.ncbi.nlm.nih.gov/15175005/ DOI: 10.1042/bj20040511
tissue_or_cell_type
Purified recombinant human PHOSPHO1
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1455–1465
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant phosphatase assays. · source_derived_draft · unverified_draft
### mg-phospho1-cofactor Recombinant human PHOSPHO1 showed strong Mg dependence when hydrolyzing phosphoethanolamine and phosphocholine. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium helps a phosphate-releasing enzyme already connected to calcium mineralization. organism: Homo sapiens tissue_or_cell_type: Purified recombinant human PHOSPHO1 experimental_model: Purified recombinant phosphatase assays. limitations: Enzyme evidence does not measure the effect of oral Mg on bone; substrate Km values are not Mg deficiency thresholds. cross_nutrient: Magnesium -> PHOSPHO1 -> phosphate production; joins the existing calcium PHOSPHO1 records. [mg-roberts2004] Human PHOSPHO1 exhibits high specific phosphoethanolamine and phosphocholine phosphatase activities (2004). https://pubmed.ncbi.nlm.nih.gov/15175005/ DOI: 10.1042/bj20040511
Complete structured claim and evidence
The potassium-induced increment in glucose-derived carbon-14 acetylcholine was 75% lower in deficient rat brain slices.
Thiamine (vitamin B1) → Brain acetylcholine synthesis source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Links thiamine-dependent carbon metabolism with synthesis of a choline-containing transmitter; no choline repletion outcome was tested.
evidence_location
Abstract
evidence_span
declined by 50 and 75%, respectively
experimental_model
Symptomatic pyrithiamine-induced thiamine-deficient rats; brain slices assayed with uniformly carbon-14-labeled glucose at rest and during potassium stimulation; seven-day thiamine reversal arm.
exposure
Pyrithiamine-induced deficiency followed by potassium stimulation of rat brain slices
limitations
This tracer experiment did not test choline deficiency or choline supplementation; synthesis labeling is not transmitter release.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Rattus norvegicus
plain_language
Thiamine disruption limited stimulated production of the choline-containing transmitter from glucose-derived carbon.
primary_references
[gibson-1984-brain-flux] Correlation of enzymatic, metabolic, and behavioral deficits in thiamin deficiency and its reversal (1984). https://pubmed.ncbi.nlm.nih.gov/6149477/ DOI: 10.1007/BF00965667
tissue_or_cell_type
Brain slices
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1112–1125
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Symptomatic pyrithiamine-induced thiamine-deficient rats; brain slices assayed with uniformly carbon-14-labeled glucose at rest and during potassium stimulation; seven-day thiamine reversal arm. · source_derived_draft · unverified_draft
### thiamine-def-stimulated-acetylcholine-synthesis The potassium-induced increment in glucose-derived carbon-14 acetylcholine was 75% lower in deficient rat brain slices. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Thiamine disruption limited stimulated production of the choline-containing transmitter from glucose-derived carbon. organism: Rattus norvegicus tissue_or_cell_type: Brain slices experimental_model: Symptomatic pyrithiamine-induced thiamine-deficient rats; brain slices assayed with uniformly carbon-14-labeled glucose at rest and during potassium stimulation; seven-day thiamine reversal arm. limitations: This tracer experiment did not test choline deficiency or choline supplementation; synthesis labeling is not transmitter release. evidence_location: Abstract evidence_span: declined by 50 and 75%, respectively cross_nutrient: Links thiamine-dependent carbon metabolism with synthesis of a choline-containing transmitter; no choline repletion outcome was tested. exposure: Pyrithiamine-induced deficiency followed by potassium stimulation of rat brain slices [gibson-1984-brain-flux] Correlation of enzymatic, metabolic, and behavioral deficits in thiamin deficiency and its reversal (1984). https://pubmed.ncbi.nlm.nih.gov/6149477/ DOI: 10.1007/BF00965667
Complete structured claim and evidence
Human COASY dephospho-CoA kinase activity phosphorylated dephospho-CoA to CoA using ATP; deleting the C-terminal domain retained PPAT but removed DPCK activity.
Coenzyme A synthase / COASY → 3′-Dephospho-coenzyme A source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution
exposure
DPCK assay: 5–100 micromolar dephospho-CoA, 1 mM ATP; coupled ADP readout and direct HPLC product analysis.
limitations
Recombinant enzyme and truncation studies define two distinct COASY activities; no whole-body nutritional threshold is measured.
nutrient_topic
Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
organism
Homo sapiens
plain_language
The final COASY reaction completes CoA.
primary_references
[b5-bio-daugherty2002] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 587–598
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution · source_derived_draft · unverified_draft
### b5-bio-coasy-phosphorylation Human COASY dephospho-CoA kinase activity phosphorylated dephospho-CoA to CoA using ATP; deleting the C-terminal domain retained PPAT but removed DPCK activity. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The final COASY reaction completes CoA. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution limitations: Recombinant enzyme and truncation studies define two distinct COASY activities; no whole-body nutritional threshold is measured. exposure: DPCK assay: 5–100 micromolar dephospho-CoA, 1 mM ATP; coupled ADP readout and direct HPLC product analysis. cross_nutrient: false [b5-bio-daugherty2002] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200
Complete structured claim and evidence
Human RFK phosphorylates riboflavin to FMN using ATP, yielding ADP; this precedes FLAD1-mediated FAD synthesis.
Riboflavin kinase / RFK → Riboflavin (vitamin B2) source_derived_draftungraded
Experimental context and source evidence
evidence_location
Abstract and product-bound structure
experimental_model
Human RFK structural and catalytic mechanism study
exposure
Purified RFK with flavin and adenine nucleotide ligands.
limitations
Reaction chemistry does not imply RFK controls every tissue flavin pool to the same extent.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
RFK performs the first activation step from riboflavin to FMN.
primary_references
[transport-rfk-2003] Ligand binding-induced conformational changes in riboflavin kinase: structural basis for the ordered mechanism. (2003). https://pubmed.ncbi.nlm.nih.gov/14580199/ DOI: 10.1021/bi035450t
tissue_or_cell_type
Purified protein
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 293–304
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human RFK structural and catalytic mechanism study · source_derived_draft · unverified_draft
### transport-rfk-phosphorylation Human RFK phosphorylates riboflavin to FMN using ATP, yielding ADP; this precedes FLAD1-mediated FAD synthesis. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: RFK performs the first activation step from riboflavin to FMN. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Human RFK structural and catalytic mechanism study limitations: Reaction chemistry does not imply RFK controls every tissue flavin pool to the same extent. exposure: Purified RFK with flavin and adenine nucleotide ligands. evidence_location: Abstract and product-bound structure [transport-rfk-2003] Ligand binding-induced conformational changes in riboflavin kinase: structural basis for the ordered mechanism. (2003). https://pubmed.ncbi.nlm.nih.gov/14580199/ DOI: 10.1021/bi035450t
Complete structured claim and evidence
Human and rat liver LRAT activity transferred the sn-1 acyl group of phosphatidylcholine to CRBP-bound retinol.
Phosphatidylcholine → Retinyl ester formation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Phosphatidylcholine-dependent retinol storage links retinoid metabolism to choline-containing phospholipid availability.
evidence_location
Abstract
experimental_model
Human and rat liver microsomes supplied phosphatidylcholine and CRBP-bound retinol.
exposure
Exogenous phosphatidylcholine plus CRBP-bound retinol.
limitations
Biochemical donor requirement; dietary choline deficiency was not tested.
nutrient_topic
Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A
organism
Homo sapiens and Rattus norvegicus
outcome
Human and rat liver LRAT activity transferred the sn-1 acyl group of phosphatidylcholine to CRBP-bound retinol.
plain_language
A membrane choline phospholipid supplies the fatty-acid group used to store vitamin A.
primary_references
[va-macdonald-1988] A lecithin:retinol acyltransferase activity in human and rat liver (1988). https://pubmed.ncbi.nlm.nih.gov/3178828/ DOI: 10.1016/S0006-291X(88)80818-0
tissue_or_cell_type
Liver microsomes
Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 317–330
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human and rat liver microsomes supplied phosphatidylcholine and CRBP-bound retinol. · source_derived_draft · unverified_draft
### va-lrat-phosphatidylcholine-donor Human and rat liver LRAT activity transferred the sn-1 acyl group of phosphatidylcholine to CRBP-bound retinol. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: A membrane choline phospholipid supplies the fatty-acid group used to store vitamin A. organism: Homo sapiens and Rattus norvegicus tissue_or_cell_type: Liver microsomes experimental_model: Human and rat liver microsomes supplied phosphatidylcholine and CRBP-bound retinol. limitations: Biochemical donor requirement; dietary choline deficiency was not tested. exposure: Exogenous phosphatidylcholine plus CRBP-bound retinol. outcome: Human and rat liver LRAT activity transferred the sn-1 acyl group of phosphatidylcholine to CRBP-bound retinol. evidence_location: Abstract cross_nutrient: Phosphatidylcholine-dependent retinol storage links retinoid metabolism to choline-containing phospholipid availability. [va-macdonald-1988] A lecithin:retinol acyltransferase activity in human and rat liver (1988). https://pubmed.ncbi.nlm.nih.gov/3178828/ DOI: 10.1016/S0006-291X(88)80818-0
Complete structured claim and evidence
Vitamin E-depleted zebrafish brains contained more hydroxy-DHA-PC 38:6 than supplemented-diet controls, consistent with increased oxidation of DHA-containing phosphatidylcholine.
Alpha-tocopherol → Hydroxy-DHA-PC 38:6 source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
true
evidence_location
Primary abstract
experimental_model
Defined-diet comparison and brain lipidomics
exposure
9 months; no added E versus 500 mg RRR-alpha-tocopheryl acetate/kg.
limitations
Adult zebrafish dietary comparison; lipid abundance and oxidation product measurements do not by themselves prove causal remodeling flux or human neuroprotection.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Danio rerio
plain_language
An oxidized DHA-containing lipid accumulated in the vitamin E-depleted brains.
primary_references
[ver-choi2015] Novel function of vitamin E in regulation of zebrafish (Danio rerio) brain lysophospholipids discovered using lipidomics. (2015). https://pubmed.ncbi.nlm.nih.gov/25855633/ DOI: 10.1194/jlr.m058941
tissue_or_cell_type
Adult brain
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 746–758
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Defined-diet comparison and brain lipidomics · source_derived_draft · unverified_draft
### ver-dha-pc-oxidation Vitamin E-depleted zebrafish brains contained more hydroxy-DHA-PC 38:6 than supplemented-diet controls, consistent with increased oxidation of DHA-containing phosphatidylcholine. Condition category: nutrient_deficiency nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: An oxidized DHA-containing lipid accumulated in the vitamin E-depleted brains. organism: Danio rerio tissue_or_cell_type: Adult brain experimental_model: Defined-diet comparison and brain lipidomics limitations: Adult zebrafish dietary comparison; lipid abundance and oxidation product measurements do not by themselves prove causal remodeling flux or human neuroprotection. exposure: 9 months; no added E versus 500 mg RRR-alpha-tocopheryl acetate/kg. cross_nutrient: true evidence_location: Primary abstract [ver-choi2015] Novel function of vitamin E in regulation of zebrafish (Danio rerio) brain lysophospholipids discovered using lipidomics. (2015). https://pubmed.ncbi.nlm.nih.gov/25855633/ DOI: 10.1194/jlr.m058941
Complete structured claim and evidence
Embryos from vitamin E-depleted zebrafish parents incorporated more water-18O label into LPC 22:6 and three DHA-containing phosphatidylcholines during 48–72 hours post-fertilization than vitamin E-sufficient controls, supporting increased acyl turnover.
Alpha-tocopherol → DHA phospholipid remodeling source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
true
evidence_location
Figure 7; isotope-labeling Methods
experimental_model
Parental diet manipulation and stable-isotope lipidomics
exposure
Parents fed no added E or 500 mg RRR-alpha-tocopheryl acetate/kg for ≥80 days; embryos incubated in 40% H2(18)O from 48 to 72 hpf.
limitations
Embryos rely on maternally deposited nutrients; whole-embryo tracing does not directly measure brain delivery or prove a particular repair enzyme.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Danio rerio
plain_language
Labeled-water tracing showed faster turnover of selected DHA lipids during vitamin E depletion.
primary_references
[ver-mcdougall2016] Lipidomics and H2(18)O labeling techniques reveal increased remodeling of DHA-containing membrane phospholipids associated with abnormal locomotor responses in α-tocopherol deficient zebrafish (danio rerio) embryos. (2016). https://pubmed.ncbi.nlm.nih.gov/26774753/ DOI: 10.1016/j.redox.2016.01.004
tissue_or_cell_type
Whole embryos
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 760–772
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Parental diet manipulation and stable-isotope lipidomics · source_derived_draft · unverified_draft
### ver-dha-remodeling-flux Embryos from vitamin E-depleted zebrafish parents incorporated more water-18O label into LPC 22:6 and three DHA-containing phosphatidylcholines during 48–72 hours post-fertilization than vitamin E-sufficient controls, supporting increased acyl turnover. Condition category: nutrient_deficiency nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Labeled-water tracing showed faster turnover of selected DHA lipids during vitamin E depletion. organism: Danio rerio tissue_or_cell_type: Whole embryos experimental_model: Parental diet manipulation and stable-isotope lipidomics limitations: Embryos rely on maternally deposited nutrients; whole-embryo tracing does not directly measure brain delivery or prove a particular repair enzyme. exposure: Parents fed no added E or 500 mg RRR-alpha-tocopheryl acetate/kg for ≥80 days; embryos incubated in 40% H2(18)O from 48 to 72 hpf. cross_nutrient: true evidence_location: Figure 7; isotope-labeling Methods [ver-mcdougall2016] Lipidomics and H2(18)O labeling techniques reveal increased remodeling of DHA-containing membrane phospholipids associated with abnormal locomotor responses in α-tocopherol deficient zebrafish (danio rerio) embryos. (2016). https://pubmed.ncbi.nlm.nih.gov/26774753/ DOI: 10.1016/j.redox.2016.01.004
Complete structured claim and evidence
A CoQ variant competed with phosphatidylcholine for binding to purified STARD7.
Phosphatidylcholine → Ubiquinone source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/coq10-research/36658222.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8cd5c486ecb31ad03ea06a817eb5bc56e60abdfa8ae8d50a46502974be2898ce", "start_char": 0, "end_char": 1410, "text_sha256": "8cd5c486ecb31ad03ea06a817eb5bc56e60abdfa8ae8d50a46502974be2898ce"}
experimental_model
Protein processing, localization, transport and cell-growth experiments
exposure
PARL processing and compartment-specific STARD7 expression
limitations
Purified-protein binding with a CoQ variant; not demonstrated dietary choline competition with CoQ10 absorption.
nutrient_topic
Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system
organism
Mammalian cell models
plain_language
Choline-containing membrane lipid and a CoQ analogue shared access to a transport protein.
primary_references
[coq10-p36658222] Mitochondria regulate intracellular coenzyme Q transport and ferroptotic resistance via STARD7. (2023). https://pubmed.ncbi.nlm.nih.gov/36658222/ DOI: 10.1038/s41556-022-01071-y
tissue_or_cell_type
Mitochondria and plasma membrane
Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 502–513
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Protein processing, localization, transport and cell-growth experiments · source_derived_draft · unverified_draft
### coq10-stard7-pc A CoQ variant competed with phosphatidylcholine for binding to purified STARD7. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Choline-containing membrane lipid and a CoQ analogue shared access to a transport protein. organism: Mammalian cell models tissue_or_cell_type: Mitochondria and plasma membrane experimental_model: Protein processing, localization, transport and cell-growth experiments limitations: Purified-protein binding with a CoQ variant; not demonstrated dietary choline competition with CoQ10 absorption. exposure: PARL processing and compartment-specific STARD7 expression evidence_span: {"source_cache": "artifacts/coq10-research/36658222.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8cd5c486ecb31ad03ea06a817eb5bc56e60abdfa8ae8d50a46502974be2898ce", "start_char": 0, "end_char": 1410, "text_sha256": "8cd5c486ecb31ad03ea06a817eb5bc56e60abdfa8ae8d50a46502974be2898ce"} [coq10-p36658222] Mitochondria regulate intracellular coenzyme Q transport and ferroptotic resistance via STARD7. (2023). https://pubmed.ncbi.nlm.nih.gov/36658222/ DOI: 10.1038/s41556-022-01071-y
Complete structured claim and evidence
Berberine inhibited choline-to-TMA conversion in bacterial cultures and gut consortia, including human fecal samples.
Berberine → Microbial conversion of choline to trimethylamine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/33863898.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a81ea95bbf1d7f7f1e924998b9e02bc29d908d759dd575ffdf9c56bf4deb9b77", "start_char": 0, "end_char": 1309, "text_sha256": "a81ea95bbf1d7f7f1e924998b9e02bc29d908d759dd575ffdf9c56bf4deb9b77"}
experimental_model
Choline tracer, microbial culture, microbiome transfer and atherosclerosis models
exposure
Choline-supplemented chow and berberine; deuterated choline tracing
limitations
Human fecal culture is not a human treatment trial. Reduced TMAO in mice does not establish fewer human cardiovascular events or justify reducing essential choline intake.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
C57BL/6J and ApoE-knockout mice; bacterial cultures and human fecal consortia
plain_language
The nutrient choline has a microbial metabolic branch that berberine can influence.
primary_references
[berberine-p33863898] Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome. (2021). https://pubmed.ncbi.nlm.nih.gov/33863898/ DOI: 10.1038/s41522-021-00205-8
tissue_or_cell_type
Microbial choline metabolism
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1078–1089
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Choline tracer, microbial culture, microbiome transfer and atherosclerosis models · source_derived_draft · unverified_draft
### berberine-choline-tma Berberine inhibited choline-to-TMA conversion in bacterial cultures and gut consortia, including human fecal samples. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The nutrient choline has a microbial metabolic branch that berberine can influence. organism: C57BL/6J and ApoE-knockout mice; bacterial cultures and human fecal consortia tissue_or_cell_type: Microbial choline metabolism experimental_model: Choline tracer, microbial culture, microbiome transfer and atherosclerosis models limitations: Human fecal culture is not a human treatment trial. Reduced TMAO in mice does not establish fewer human cardiovascular events or justify reducing essential choline intake. exposure: Choline-supplemented chow and berberine; deuterated choline tracing evidence_span: {"source_cache": "artifacts/berberine-research/33863898.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a81ea95bbf1d7f7f1e924998b9e02bc29d908d759dd575ffdf9c56bf4deb9b77", "start_char": 0, "end_char": 1309, "text_sha256": "a81ea95bbf1d7f7f1e924998b9e02bc29d908d759dd575ffdf9c56bf4deb9b77"} [berberine-p33863898] Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome. (2021). https://pubmed.ncbi.nlm.nih.gov/33863898/ DOI: 10.1038/s41522-021-00205-8
Complete structured claim and evidence
Berberine lowered TMA/TMAO production in choline-fed mice; labeled-choline tracing supported altered microbial conversion.
Berberine → Circulating trimethylamine N-oxide concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/33863898.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a81ea95bbf1d7f7f1e924998b9e02bc29d908d759dd575ffdf9c56bf4deb9b77", "start_char": 0, "end_char": 1309, "text_sha256": "a81ea95bbf1d7f7f1e924998b9e02bc29d908d759dd575ffdf9c56bf4deb9b77"}
experimental_model
Choline tracer, microbial culture, microbiome transfer and atherosclerosis models
exposure
Choline-supplemented chow and berberine; deuterated choline tracing
limitations
Human fecal culture is not a human treatment trial. Reduced TMAO in mice does not establish fewer human cardiovascular events or justify reducing essential choline intake.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
C57BL/6J and ApoE-knockout mice; bacterial cultures and human fecal consortia
plain_language
A microbial change was linked to a circulating metabolite in animals.
primary_references
[berberine-p33863898] Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome. (2021). https://pubmed.ncbi.nlm.nih.gov/33863898/ DOI: 10.1038/s41522-021-00205-8
tissue_or_cell_type
Microbial choline metabolism
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1091–1102
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Choline tracer, microbial culture, microbiome transfer and atherosclerosis models · source_derived_draft · unverified_draft
### berberine-tmao-mice Berberine lowered TMA/TMAO production in choline-fed mice; labeled-choline tracing supported altered microbial conversion. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A microbial change was linked to a circulating metabolite in animals. organism: C57BL/6J and ApoE-knockout mice; bacterial cultures and human fecal consortia tissue_or_cell_type: Microbial choline metabolism experimental_model: Choline tracer, microbial culture, microbiome transfer and atherosclerosis models limitations: Human fecal culture is not a human treatment trial. Reduced TMAO in mice does not establish fewer human cardiovascular events or justify reducing essential choline intake. exposure: Choline-supplemented chow and berberine; deuterated choline tracing evidence_span: {"source_cache": "artifacts/berberine-research/33863898.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a81ea95bbf1d7f7f1e924998b9e02bc29d908d759dd575ffdf9c56bf4deb9b77", "start_char": 0, "end_char": 1309, "text_sha256": "a81ea95bbf1d7f7f1e924998b9e02bc29d908d759dd575ffdf9c56bf4deb9b77"} [berberine-p33863898] Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome. (2021). https://pubmed.ncbi.nlm.nih.gov/33863898/ DOI: 10.1038/s41522-021-00205-8
Complete structured claim and evidence
ALDH7A1 oxidizes alpha-aminoadipate semialdehyde to alpha-aminoadipate using NAD+.
alpha-Aminoadipate semialdehyde → L-alpha-Aminoadipate source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human ALDH7A1 biochemical and genetic study
limitations
Compartmental isoform distribution is not resolved by this claim.
organism
Homo sapiens
plain_language
Antiquitin clears the aldehyde intermediate.
primary_references
[luo2015] Structural Basis of Substrate Recognition by Aldehyde Dehydrogenase 7A1 (2015). https://pubmed.ncbi.nlm.nih.gov/26260980/ DOI: 10.1021/acs.biochem.5b00754
tissue_or_cell_type
Lysine-catabolizing tissues
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 104–112
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human ALDH7A1 biochemical and genetic study · source_derived_draft · unverified_draft
### aldh7a1-oxidation ALDH7A1 oxidizes alpha-aminoadipate semialdehyde to alpha-aminoadipate using NAD+. Plain language: Antiquitin clears the aldehyde intermediate. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Lysine-catabolizing tissues experimental_model: Human ALDH7A1 biochemical and genetic study limitations: Compartmental isoform distribution is not resolved by this claim. [luo2015] Structural Basis of Substrate Recognition by Aldehyde Dehydrogenase 7A1 (2015). https://pubmed.ncbi.nlm.nih.gov/26260980/ DOI: 10.1021/acs.biochem.5b00754
Complete structured claim and evidence
The antiquitin defect was linked to accumulation of alpha-AASA/P6C in the lysine degradation pathway.
Biallelic ALDH7A1 disease genotypes studied by Mills 2006 → Delta1-piperideine-6-carboxylate source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Lysine catabolism generates the metabolite that can sequester PLP.
experimental_model
Affected children, expressed human ALDH7A1 variants and metabolite chemistry
exposure
ALDH7A1-associated disease and metabolite analysis.
limitations
This is inherited pathway failure, not lysine toxicity in healthy people.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
A blocked lysine pathway builds up B6-reactive metabolites.
primary_references
[mills-2006-aldh7a1] Mutations in antiquitin in individuals with pyridoxine-dependent seizures (2006). https://doi.org/10.1038/nm1366 DOI: 10.1038/nm1366
tissue_or_cell_type
Patient biological samples and biochemical pathway analysis
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1158–1169
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Affected children, expressed human ALDH7A1 variants and metabolite chemistry · source_derived_draft · unverified_draft
### b6-neuro-aldh7a1-metabolite-accumulation The antiquitin defect was linked to accumulation of alpha-AASA/P6C in the lysine degradation pathway. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A blocked lysine pathway builds up B6-reactive metabolites. organism: Homo sapiens tissue_or_cell_type: Patient biological samples and biochemical pathway analysis experimental_model: Affected children, expressed human ALDH7A1 variants and metabolite chemistry limitations: This is inherited pathway failure, not lysine toxicity in healthy people. exposure: ALDH7A1-associated disease and metabolite analysis. cross_nutrient: Lysine catabolism generates the metabolite that can sequester PLP. [mills-2006-aldh7a1] Mutations in antiquitin in individuals with pyridoxine-dependent seizures (2006). https://doi.org/10.1038/nm1366 DOI: 10.1038/nm1366
Complete structured claim and evidence
Accumulated P6C reacts with PLP through Knoevenagel condensation, reducing cofactor availability.
Delta1-piperideine-6-carboxylate → PLP source_derived_draftungraded
Experimental context and source evidence
affected_machinery
ALDH7A1 upstream clearance
availability_state
machinery_impairment Imported condition classification; unverified.
deficiency_not_equivalent
Dietary lysine or vitamin B6 deficiency
experimental_model
Chemical mechanism associated with human ALDH7A1 disease
limitations
Secondary cofactor loss does not demonstrate primary dietary vitamin B6 or lysine deficiency.
organism
Homo sapiens
plain_language
A lysine metabolite can trap active vitamin B6.
primary_references
[mills2006] Mutations in antiquitin in individuals with pyridoxine-dependent seizures. (2006). https://pubmed.ncbi.nlm.nih.gov/16491085/ DOI: 10.1038/nm1366
tissue_or_cell_type
PDE-ALDH7A1 biochemical context
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 266–276
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chemical mechanism associated with human ALDH7A1 disease · source_derived_draft · unverified_draft
### p6c-plp-trapping Accumulated P6C reacts with PLP through Knoevenagel condensation, reducing cofactor availability. Plain language: A lysine metabolite can trap active vitamin B6. Condition category: machinery_impairment organism: Homo sapiens tissue_or_cell_type: PDE-ALDH7A1 biochemical context experimental_model: Chemical mechanism associated with human ALDH7A1 disease limitations: Secondary cofactor loss does not demonstrate primary dietary vitamin B6 or lysine deficiency. affected_machinery: ALDH7A1 upstream clearance deficiency_not_equivalent: Dietary lysine or vitamin B6 deficiency [mills2006] Mutations in antiquitin in individuals with pyridoxine-dependent seizures. (2006). https://pubmed.ncbi.nlm.nih.gov/16491085/ DOI: 10.1038/nm1366
Complete structured claim and evidence

Availability and dependencies

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

When neuronal choline uptake fails

Condition: machinery_impairment · Recessive SLC5A7 variants in the CMS study.

Normal role: CHT1 supplies choline to presynaptic terminals.

Recorded consequence: Tested missense variants nearly abolished transport; affected people had neuromuscular disease.

Scope: Human genetic disease and expression assays

When CTL1 transport is impaired but membrane PC is maintained

Condition: machinery_impairment · Biallelic SLC44A1 frameshift variants.

Normal role: CTL1 contributes to cellular choline uptake and lipid homeostasis.

Recorded consequence: Transport fell despite maintained membrane PC; organelle abnormalities responded to choline in cultured cells.

Scope: Human patient fibroblasts

When acetylcholine synthesis machinery fails

Condition: machinery_impairment · Pathogenic CHAT variants tested in the 2001 study.

Normal role: ChAT combines choline and acetyl-CoA to make acetylcholine.

Recorded consequence: The E441K enzyme had no detectable catalytic activity in the assay.

Scope: Human mutant enzyme and congenital myasthenic syndrome

SAC during combined methionine and choline shortage

Condition: nutrient_deficiency · Combined methionine/choline-deficient diet.

Normal role: Choline and methionine have distinct essential metabolic roles.

Recorded consequence: SAC altered glutathione and lipogenic endpoints without demonstrating nutrient replacement.

Scope: Seven-week mouse dietary model.

When choline cannot enter mitochondria efficiently

Condition: machinery_impairment · Experimental SLC25A48 loss.

Normal role: Mitochondrial choline entry supplies betaine and downstream metabolic routes.

Recorded consequence: Choline import and downstream labeling fall; mouse brown-fat energy handling is impaired.

Scope: Human cell and mouse experiments

When choline oxidation is impaired

Condition: machinery_impairment · Experimental mouse Chdh deletion.

Normal role: Chdh contributes to conversion of choline into betaine.

Recorded consequence: Testicular betaine fell and sperm energy and motility were impaired.

Scope: Mouse testis and sperm

When choline phosphorylation fails in muscle

Condition: machinery_impairment · Biallelic CHKB disease variants.

Normal role: CHKB contributes to phosphatidylcholine synthesis.

Recorded consequence: Affected muscle had little detectable kinase activity and reduced PC.

Scope: Human muscle biopsies

When the CDP-choline pathway loses PCYT1A function

Condition: machinery_impairment · Biallelic loss-of-function variants in two patients.

Normal role: PCYT1A supplies the activated CDP-choline intermediate for PC synthesis.

Recorded consequence: PCYT1A expression and PC synthesis fell, with a multisystem clinical phenotype.

Scope: Human congenital disease

When PEMT loses its estrogen response

Condition: machinery_impairment · The studied risk-associated PEMT haplotype.

Normal role: Estrogen can induce PEMT through regulatory DNA binding.

Recorded consequence: Binding and hormone-inducible expression are impaired.

Scope: Human primary-hepatocyte and locus experiments

When low intake and impaired endogenous synthesis coincide

Condition: nutrient_deficiency · Choline-deficient feeding in Pemt-null mice.

Normal role: Dietary choline and PEMT provide routes to membrane PC.

Recorded consequence: A reduced PC/PE ratio accompanies membrane failure; changing biliary loss alters the outcome.

Scope: Mouse liver

When low intake and impaired endogenous synthesis coincide

Condition: machinery_impairment · Choline-deficient feeding in Pemt-null mice.

Normal role: Dietary choline and PEMT provide routes to membrane PC.

Recorded consequence: A reduced PC/PE ratio accompanies membrane failure; changing biliary loss alters the outcome.

Scope: Mouse liver

When delivery of a choline-containing DHA lipid fails

Condition: machinery_impairment · Experimental Mfsd2a deletion.

Normal role: Mfsd2a transports LPC-bound DHA across the BBB.

Recorded consequence: Brain LPC uptake and DHA abundance decline.

Scope: Mouse BBB and brain

When dietary choline is inadequate

Condition: nutrient_deficiency · Controlled low-choline feeding.

Normal role: Choline supports membrane, methyl-donor and neurotransmitter pathways.

Recorded consequence: Some participants developed fatty liver or muscle damage that resolved on repletion.

Scope: Human controlled-feeding cohort

The sources

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

Berberine: metabolism, nutrient connections and drug interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Calcium: mechanism-first literature curation (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Choline: metabolism, signaling and nutrient connections (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
L-Lysine: mechanism-first literature curation (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source

Recorded disagreements

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

Open questions in this collection

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

How much do FLVCR1, FLVCR2, CTL1 and CHT1 contribute in each human tissue?Transport capacity in an expression system does not establish a universal share of physiological uptake.
Which choline form and background diet change TMAO and clinical outcomes over the long term?Fasting markers, post-meal isotope tracing, platelet assays and disease events are different endpoints.
Which maternal choline exposures reliably improve which developmental outcomes?Small controlled-feeding and larger supplementation trials differ in timing, baseline intake and tests; a universal cognitive benefit is not established.
Which biomarker best reflects tissue-specific choline sufficiency?Circulating choline, transport activity, membrane pools and organ function can diverge.
Can dietary interventions compensate for a specific inherited choline-handling defect?Cell rescue and biochemical connections do not establish clinical efficacy across transporter or enzyme variants.
Does shared ALDH7A1 substrate use create physiological competition between choline and lysine routes?Substrate overlap alone does not demonstrate competition at native concentrations or justify a B6 replacement strategy.
Which aldehyde dehydrogenase dominates betaine production in each native compartment?ALDH9A1/E3 and ALDH7A1 have experimental substrate activity; one exclusive human assignment is not justified.
What is the precise cofactor dependence of native human CHDH under physiological conditions?Do not infer a confirmed human cofactor solely from bacterial choline oxidase or a sequence motif; riboflavin links here rest on separately established flavin enzymology.

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

Evidence, AI assistance and curation standards

Choline

The mechanisms

ChAT catalyzes reversible acetylcholine synthesis from choline and acetyl-CoA.

PEMT converts PE to PC through three sequential SAM-dependent methylation reactions.

SLC25A48 loss impaired choline-derived betaine production in human-cell mitochondrial metabolism experiments.

Human choline kinase alpha1 catalyzes ATP-dependent phosphorylation of choline, producing phosphocholine and ADP in magnesium-containing conditions.

Randomized folic acid supplementation at 400 micrograms/day did not alter the response to the choline-depletion diet.

Purified recombinant human ALDH7A1 metabolized betaine aldehyde.

Human CHT1-mediated choline uptake depended on Na+ in the oocyte assay.

Mfsd2a transported DHA carried by lysophosphatidylcholine rather than unesterified DHA in the tested system.

All three bitartrate-containing arms increased fasting TMAO, p<0.0001.

PC supplements did not significantly raise fasting TMAO, p=0.27.

Human FLVCR1 facilitated concentration-driven choline transport across the plasma membrane.

Human FLVCR1 facilitated concentration-driven ethanolamine transport across the plasma membrane.

Human FLVCR2 facilitated concentration-driven choline transport across the plasma membrane.

Human FLVCR2 facilitated concentration-driven ethanolamine transport across the plasma membrane.

The in-vivo experiments identified Flvcr2 as a major route for blood-to-brain choline uptake.

Human CHT1 expression produced high-affinity choline uptake in Xenopus oocytes.

Human CHT1-mediated choline uptake depended on Cl− in the oocyte assay.

Hemicholinium-3 inhibited human CHT1-mediated uptake with a reported Ki of 1.3 nM.

CHT1 supports reutilization of choline liberated by synaptic acetylcholine hydrolysis, sustaining presynaptic acetylcholine synthesis.

Tested SLC5A7 missense variants caused a near-complete loss of CHT transport activity in cell models.

Patient fibroblasts had diminished choline transport.

Membrane phosphatidylcholine content remained unchanged in the mutant fibroblasts.

Chronic choline treatment made mutant fibroblast ultrastructure resemble healthy control cells.

Choline treatment protected the mutant fibroblasts from acute iron overload.

Bacterially expressed human ChAT E441K lacked catalytic activity in the reported kinetic experiment.

VAChT recognizes acetylcholine and packages it into vesicles for subsequent release.

The human VAChT structure captured vesamicol in its inhibitory binding site.

The pathway model identifies CHDH-mediated oxidation of choline to betaine aldehyde upstream of aldehyde-dehydrogenase-mediated betaine production.

Human-cell experiments identified SLC25A48 as necessary for efficient mitochondrial choline import.

SLC25A48 loss reduced the contribution of labeled choline to purine nucleotides in HEK293T cells.

Slc25a48-null mice had impaired brown-fat mitochondrial respiration.

Slc25a48-null brown-fat mitochondria emitted more hydrogen peroxide under the measured assay conditions.

Slc25a48-null mice had impaired cold tolerance.

An independent GeneMAP study found that SLC25A48 loss strongly impaired mitochondrial choline import.

Chdh deletion lowered testicular betaine while choline and phosphocholine increased.

Sperm ATP content was significantly reduced in Chdh-null males.

Chdh-null males produced comparable amounts of sperm but had diminished sperm motility.

Purified human E3 aldehyde dehydrogenase showed betaine-aldehyde dehydrogenase activity, with the activities co-purifying across six columns.

ALDH9/E3 betaine-aldehyde activity was highest in liver, adrenal and kidney among the tested tissues; mRNA peaked in different tissues.

Human ALDH7A1 expression attenuated apoptosis caused by high extracellular sucrose or sodium chloride in CHO cells.

Rat DMGDH catalyzes oxidative demethylation of dimethylglycine to sarcosine.

Rat DMGDH structures located THF in a domain separated from the FAD-containing active center and connected by an internal channel.

In the THF-coupled DMGDH pathway, a removed one-carbon unit is captured as 5,10-methylenetetrahydrofolate rather than released as free formaldehyde.

Choline kinase activity was undetectable in the three reported muscle samples with CHKB nonsense variants.

Phosphatidylcholine levels were reduced in those affected muscle samples.

The patient variants markedly reduced PCYT1A expression.

The PCYT1A defects markedly reduced phosphatidylcholine synthesis.

Human CHPT1 catalyzes the PC-producing final step of the Kennedy pathway with choline-headgroup substrate selectivity.

CEPT1 can catalyze PC production as well as PE production.

CEPT1 also catalyzes phosphatidylethanolamine production, unlike the human CHPT1 specificity described in the study.

SAM supplies the methyl groups for each of the three PEMT-catalyzed transfers.

Estradiol increased PEMT transcription in primary human hepatocytes in a dose-dependent manner.

The increased PEMT message was accompanied by higher protein expression and enzyme activity in the hepatocyte study.

The studied risk allele failed to bind estrogen receptor at the critical PEMT regulatory region.

The risk allele also failed to bind the pioneer factor FOXA1.

The risk-associated haplotype lost hormone-inducible PEMT expression.

Choline-deficient Pemt-null mice developed a low hepatic PC/PE ratio.

Experimental manipulation supported a causal role for the lowered PC/PE ratio in loss of hepatocyte membrane integrity.

Choline-deficient Pemt/Mdr2 double-null mice maintained a normal PC/PE ratio and escaped liver failure despite steatosis.

Pemt deletion modestly reduced hepatic VLDL secretion in Ldlr-null mice.

Mfsd2a-mediated LPC transport was sodium-dependent.

Mfsd2a-null mice had markedly reduced uptake of plasma-labeled LPC-DHA into the brain.

Mfsd2a-null mice had markedly reduced brain DHA abundance.

During deprivation, fatty liver or muscle damage developed in 77% of men, 80% of postmenopausal women and 44% of premenopausal women.

Participants who developed organ dysfunction recovered normal organ function after incremental choline repletion.

Among women, 18 of 23 PEMT rs12325817 C-allele carriers developed organ dysfunction during depletion; reported odds ratio 25, p=0.002.

The PEMT rs7946 comparison did not show an association with susceptibility in this depletion study.

The BHMT rs3733890 comparison did not show an association with susceptibility in this depletion study.

Two weeks of phosphatidylcholine supplementation reduced fasting total homocysteine by 18% relative to placebo.

After two weeks, the post-methionine-load homocysteine rise was 29% lower than with placebo.

The characterized anaerobic choline-utilization pathway uses a glycyl-radical choline TMA-lyase to cleave the choline C–N bond and generate TMA.

The enzyme comparison demonstrated FMO3-mediated oxidation of TMA to TMAO.

FMO1 also oxidized TMA in the comparison, with FMO3 showing about tenfold higher specific activity.

The challenge produced time-dependent increases in TMAO and its d9-labeled isotopologue.

Antibiotics suppressed challenge-associated TMAO, which reappeared after antibiotic withdrawal.

The highest versus lowest TMAO quartile was associated with a three-year event hazard ratio of 2.54 (95% CI 1.96–3.28) in the angiography cohort.

All three bitartrate-containing arms increased platelet reactivity, p<0.01.

Four eggs daily did not significantly raise fasting TMAO, p=0.28.