{"id":"ee55795d-12e9-5237-949a-54df0adce3d9","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-metformin-homocysteine-boundary","predicate":"did_not_significantly_raise_overall_homocysteine","statement":"The overall metformin-versus-placebo homocysteine change was +5% (95% CI -1% to 11%; P=0.091), although participants with low end-study B12 had higher homocysteine.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"ec1421c7-fdfb-519c-939a-e6f2bf3975cc","mechanism_event_label":"A B12 effect did not make the overall homocysteine trial result statistically significant.","subject":{"id":"519971b1-5aef-5ad7-8022-840144855cd0","slug":"metformin","display_name":"Metformin","entity_type_key":"drug"},"object":{"id":"5b635b42-bc0d-5c54-aa94-9cf76cd0ed47","slug":"homocysteine","display_name":"Homocysteine","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"ec1421c7-fdfb-519c-939a-e6f2bf3975cc","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-metformin-homocysteine-boundary-event","event_type":"observed_intervention","label":"A B12 effect did not make the overall homocysteine trial result statistically significant.","description":"The overall metformin-versus-placebo homocysteine change was +5% (95% CI -1% to 11%; P=0.091), although participants with low end-study B12 had higher homocysteine.","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_stratifier","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e176a266-711e-5469-89da-3fb2d3f244ad","slug":"folate","display_name":"Folate (vitamin B9)","entity_type_key":"chemical_species"},"role":"additional_measured_nutrient","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"519971b1-5aef-5ad7-8022-840144855cd0","slug":"metformin","display_name":"Metformin","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"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":3,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"Preserves the B12/folate/homocysteine measurements without a universal depletion cascade.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Multicenter randomized placebo-controlled trial: 390 insulin-treated patients with type 2 diabetes.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Metformin 850 mg three times daily versus placebo for 4.3 years; historical experimental exposure.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"End-study B12 strata are not randomized mediators. The folate decrease lost significance after adjustment for BMI and smoking.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-b12","display_name":"Vitamin B12 (cobalamins)","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A B12 effect did not make the overall homocysteine trial result statistically significant.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[b12-dejager2010] Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial (2010). https://pubmed.ncbi.nlm.nih.gov/20488910/ DOI: 10.1136/bmj.c2181","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Human blood or whole-person endpoints","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"ea7ed394-c4f1-52be-8a38-b0aae69ac250","evidence_kind":"source_excerpt","locator":"Lines 1636-1647","start_line":1636,"end_line":1647,"excerpt":"### b12-metformin-homocysteine-boundary\nThe overall metformin-versus-placebo homocysteine change was +5% (95% CI -1% to 11%; P=0.091), although participants with low end-study B12 had higher homocysteine.\nCondition category: normal\nnutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A B12 effect did not make the overall homocysteine trial result statistically significant.\norganism: Homo sapiens\ntissue_or_cell_type: Human blood or whole-person endpoints\nexperimental_model: Multicenter randomized placebo-controlled trial: 390 insulin-treated patients with type 2 diabetes.\nlimitations: End-study B12 strata are not randomized mediators. The folate decrease lost significance after adjustment for BMI and smoking.\nexposure: Metformin 850 mg three times daily versus placebo for 4.3 years; historical experimental exposure.\ncross_nutrient: Preserves the B12/folate/homocysteine measurements without a universal depletion cascade.\n[b12-dejager2010] Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial (2010). https://pubmed.ncbi.nlm.nih.gov/20488910/ DOI: 10.1136/bmj.c2181","model_system":"Multicenter randomized placebo-controlled trial: 390 insulin-treated patients with type 2 diabetes.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [b12-dejager2010] Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial (2010). https://pubmed.ncbi.nlm.nih.gov/20488910/ DOI: 10.1136/bmj.c2181","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"73145023-2982-5848-aff2-8d8875d6b9c5","stable_key":"import-7fc92b9e-9cbf-556e-8719-6b5244625250","title":"Vitamin B12: 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":"ad5b3a51d36e856aa7fdfd1cc23f690b094689bad87d28e1a621a54675a01c92","revision_id":"118bd616-0c13-549f-bfeb-bc439715b89c","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}