{"id":"91bdd6dc-a90d-5cef-bbcf-405f7b1a9e08","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:fol-b12-interaction-mma","predicate":"positively_associated_in_low_b12_stratum","statement":"In low-serum-B12 strata, circulating methylmalonic acid increased as folate increased above approximately 20 nmol/L; the relationship ran oppositely in B12-replete strata.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"ac1a5e26-a7fd-53ca-bd69-acb87e9b156b","mechanism_event_label":"More circulating folate did not guarantee a better B12-related marker.","subject":{"id":"69fa9bd2-2d5e-5468-b810-496ee7effcfc","slug":"serum-folate-concentration","display_name":"Serum folate concentration","entity_type_key":"cellular_process"},"object":{"id":"a2fda496-9308-54c5-b478-bc0b0c175570","slug":"methylmalonic-acid","display_name":"Methylmalonic acid","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"ac1a5e26-a7fd-53ca-bd69-acb87e9b156b","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:fol-b12-interaction-mma-event","event_type":"observed_intervention","label":"More circulating folate did not guarantee a better B12-related marker.","description":"In low-serum-B12 strata, circulating methylmalonic acid increased as folate increased above approximately 20 nmol/L; the relationship ran oppositely in B12-replete strata.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"b6d9b937-895d-5e0a-8cc5-0454a0b7d373","slug":"vitamin-b12","display_name":"Vitamin B12 (cobalamins)","entity_type_key":"chemical_species"},"role":"status_modifier","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"69fa9bd2-2d5e-5468-b810-496ee7effcfc","slug":"serum-folate-concentration","display_name":"Serum folate concentration","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"a2fda496-9308-54c5-b478-bc0b0c175570","slug":"methylmalonic-acid","display_name":"Methylmalonic acid","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"biomarker_context","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"cross_nutrient","value_text":"The measured interaction concerns B12 status and total folate, not all folate formulations equally.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Cross-sectional adult NHANES III 1991–1994 (4940) and NHANES 1999–2002 (5473) analyses, exclusions for several confounders.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Measured serum folate, B12, total homocysteine and MMA; stratification at serum B12 148 pmol/L; no randomized folate exposure.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"No direct enzyme-flux measurement or causal proof of folate toxicity. Survey subsets and B12 definitions differ from the older-adult cognition analysis.","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":"More circulating folate did not guarantee a better B12-related marker.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[fol-selhub2007] In vitamin B12 deficiency, higher serum folate is associated with increased total homocysteine and methylmalonic acid concentrations (2007). https://pubmed.ncbi.nlm.nih.gov/18056804/ DOI: 10.1073/pnas.0709487104","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":"biomarker_context","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"1d42eb06-102b-5c2a-880a-090b0ba04158","evidence_kind":"source_excerpt","locator":"Lines 1580-1591","start_line":1580,"end_line":1591,"excerpt":"### fol-b12-interaction-mma\nIn low-serum-B12 strata, circulating methylmalonic acid increased as folate increased above approximately 20 nmol/L; the relationship ran oppositely in B12-replete strata.\nCondition category: biomarker_context\nnutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: More circulating folate did not guarantee a better B12-related marker.\norganism: Homo sapiens\ntissue_or_cell_type: Human blood or whole-person clinical endpoints\nexperimental_model: Cross-sectional adult NHANES III 1991–1994 (4940) and NHANES 1999–2002 (5473) analyses, exclusions for several confounders.\nlimitations: No direct enzyme-flux measurement or causal proof of folate toxicity. Survey subsets and B12 definitions differ from the older-adult cognition analysis.\nexposure: Measured serum folate, B12, total homocysteine and MMA; stratification at serum B12 148 pmol/L; no randomized folate exposure.\ncross_nutrient: The measured interaction concerns B12 status and total folate, not all folate formulations equally.\n[fol-selhub2007] In vitamin B12 deficiency, higher serum folate is associated with increased total homocysteine and methylmalonic acid concentrations (2007). https://pubmed.ncbi.nlm.nih.gov/18056804/ DOI: 10.1073/pnas.0709487104","model_system":"Cross-sectional adult NHANES III 1991–1994 (4940) and NHANES 1999–2002 (5473) analyses, exclusions for several confounders.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [fol-selhub2007] In vitamin B12 deficiency, higher serum folate is associated with increased total homocysteine and methylmalonic acid concentrations (2007). https://pubmed.ncbi.nlm.nih.gov/18056804/ DOI: 10.1073/pnas.0709487104","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}