{"id":"bd81e59f-6844-564d-9fbf-84163eeb5d29","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:folate-methyl-choline-intake-variant","predicate":"modifies","statement":"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.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"adee02d3-664f-51cf-857a-453396ea714e","mechanism_event_label":"Higher intake brought carriers to the lower-intake noncarrier reference value.","subject":{"id":"8e1d19fd-ad66-575d-81c4-9122f78915e5","slug":"choline","display_name":"Choline","entity_type_key":"small_molecule"},"object":{"id":"1a59b158-bf30-56cb-9c64-3f7a3dea3e35","slug":"choline-betaine-partition","display_name":"Choline partitioning between betaine and phosphatidylcholine","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"adee02d3-664f-51cf-857a-453396ea714e","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:folate-methyl-choline-intake-variant-event","event_type":"biochemical_relationship","label":"Higher intake brought carriers to the lower-intake noncarrier reference value.","description":"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.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"8e1d19fd-ad66-575d-81c4-9122f78915e5","slug":"choline","display_name":"Choline","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"1a59b158-bf30-56cb-9c64-3f7a3dea3e35","slug":"choline-betaine-partition","display_name":"Choline partitioning between betaine and phosphatidylcholine","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"cross_nutrient","value_text":"Choline modifies a folate-genotype-associated phenotype.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Choline feeding and isotope tracing in women across reproductive states.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"480 versus 930 mg/day; recommended folate intake","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"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.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"folate","display_name":"Folate (vitamin B9)","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Higher intake brought carriers to the lower-intake noncarrier reference value.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[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","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Plasma tracer metabolites","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"5d044652-dee1-5175-a3c8-eb0a9a500f01","evidence_kind":"source_excerpt","locator":"Lines 743-754","start_line":743,"end_line":754,"excerpt":"### folate-methyl-choline-intake-variant\nIn 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.\nCondition category: machinery_impairment\nnutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Higher intake brought carriers to the lower-intake noncarrier reference value.\norganism: Homo sapiens\ntissue_or_cell_type: Plasma tracer metabolites\nexperimental_model: Choline feeding and isotope tracing in women across reproductive states.\nlimitations: 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.\nexposure: 480 versus 930 mg/day; recommended folate intake\ncross_nutrient: Choline modifies a folate-genotype-associated phenotype.\n[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","model_system":"Choline feeding and isotope tracing in women across reproductive states.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study 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","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"f4ce1a62-9582-5f7a-84f5-a23d0e1bfc68","stable_key":"import-ec174d5a-4903-5745-8646-df0e9d4265e8","title":"Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"e564d43989ece1006c95cd0748e9af6fe369074599a2eebba0a99ebff864b0dd","revision_id":"76674a33-b2a1-5e41-b71b-44399038ff7c","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}