{"id":"04b5c3dd-43ce-5704-b915-5a1051beb4f4","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:fol-repletion-endpoint-difference","predicate":"repletion_homocysteine_response_depended_on_intake","statement":"During repletion, elevated homocysteine decreased with total folate intake 516 but not 286 micrograms/day, while the DNA methylation readout improved across 286–516 micrograms/day.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"99e14e76-102c-53f1-a03a-9715a60a6ec0","mechanism_event_label":"Different folate-related measurements did not recover identically.","subject":{"id":"d322bfef-5135-599f-82e6-0aa58748dc8b","slug":"folic-acid","display_name":"Folic acid","entity_type_key":"small_molecule"},"object":{"id":"5b635b42-bc0d-5c54-aa94-9cf76cd0ed47","slug":"homocysteine","display_name":"Homocysteine","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"99e14e76-102c-53f1-a03a-9715a60a6ec0","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:fol-repletion-endpoint-difference-event","event_type":"observed_intervention","label":"Different folate-related measurements did not recover identically.","description":"During repletion, elevated homocysteine decreased with total folate intake 516 but not 286 micrograms/day, while the DNA methylation readout improved across 286–516 micrograms/day.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"83814e45-eef9-508d-9d1a-0281ffd2c46c","slug":"lymphocyte-genomic-dna-methylation","display_name":"Lymphocyte genomic DNA methylation","entity_type_key":"cellular_process"},"role":"distinct_endpoint","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"d322bfef-5135-599f-82e6-0aa58748dc8b","slug":"folic-acid","display_name":"Folic acid","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"5b635b42-bc0d-5c54-aa94-9cf76cd0ed47","slug":"homocysteine","display_name":"Homocysteine","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"experimental_model","value_text":"Eight healthy postmenopausal women aged 49–63 in a metabolic unit, sequential depletion/repletion.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Five weeks 56 micrograms/day folate, four weeks 111, then three weeks 286–516 using folic acid added to a low-folate diet.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Historical experimental intakes in eight participants do not establish a universal requirement or treatment regimen.","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":"Different folate-related measurements did not recover identically.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[fol-jacob1998] Moderate folate depletion increases plasma homocysteine and decreases lymphocyte DNA methylation in postmenopausal women (1998). https://pubmed.ncbi.nlm.nih.gov/9649607/ DOI: 10.1093/jn/128.7.1204","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Human blood or whole-person clinical endpoints","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"b68ceedb-1bbe-5e79-9c03-1b24da2a605a","evidence_kind":"source_excerpt","locator":"Lines 1433-1443","start_line":1433,"end_line":1443,"excerpt":"### fol-repletion-endpoint-difference\nDuring repletion, elevated homocysteine decreased with total folate intake 516 but not 286 micrograms/day, while the DNA methylation readout improved across 286–516 micrograms/day.\nCondition category: nutrient_deficiency\nnutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Different folate-related measurements did not recover identically.\norganism: Homo sapiens\ntissue_or_cell_type: Human blood or whole-person clinical endpoints\nexperimental_model: Eight healthy postmenopausal women aged 49–63 in a metabolic unit, sequential depletion/repletion.\nlimitations: Historical experimental intakes in eight participants do not establish a universal requirement or treatment regimen.\nexposure: Five weeks 56 micrograms/day folate, four weeks 111, then three weeks 286–516 using folic acid added to a low-folate diet.\n[fol-jacob1998] Moderate folate depletion increases plasma homocysteine and decreases lymphocyte DNA methylation in postmenopausal women (1998). https://pubmed.ncbi.nlm.nih.gov/9649607/ DOI: 10.1093/jn/128.7.1204","model_system":"Eight healthy postmenopausal women aged 49–63 in a metabolic unit, sequential depletion/repletion.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [fol-jacob1998] Moderate folate depletion increases plasma homocysteine and decreases lymphocyte DNA methylation in postmenopausal women (1998). https://pubmed.ncbi.nlm.nih.gov/9649607/ DOI: 10.1093/jn/128.7.1204","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}