{"id":"50501807-cdf1-5668-8dae-80a4d1429ed1","stable_key":"8b3cf083-ea9c-54f5-b42b-bf1fef5b2978:metformin-b12-homocysteine","predicate":"modulates","statement":"Patients with vitamin B-12 deficiency at study end had a mean homocysteine of 23.7 micromol/l, compared with 18.1 in those with low B-12 and 14.9 in those with normal B-12.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"87675f24-a00c-50a1-9243-eb6242c01dd0","mechanism_event_label":"The lower the vitamin, the higher this metabolite climbed.","subject":{"id":"8390898f-7915-5c30-8ada-c416a386f5f3","slug":"serum-cobalamin-concentration","display_name":"Serum cobalamin concentration","entity_type_key":"cellular_process"},"object":{"id":"7b9438d1-45ad-58a2-8b0c-260a9841612d","slug":"human-fasting-homocysteine","display_name":"Human fasting plasma total homocysteine concentration","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"87675f24-a00c-50a1-9243-eb6242c01dd0","stable_key":"8b3cf083-ea9c-54f5-b42b-bf1fef5b2978:metformin-b12-homocysteine-event","event_type":"observed_intervention","label":"The lower the vitamin, the higher this metabolite climbed.","description":"Patients with vitamin B-12 deficiency at study end had a mean homocysteine of 23.7 micromol/l, compared with 18.1 in those with low B-12 and 14.9 in those with normal B-12.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"5b635b42-bc0d-5c54-aa94-9cf76cd0ed47","slug":"homocysteine","display_name":"Homocysteine","entity_type_key":"small_molecule"},"role":"rising_marker","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"519971b1-5aef-5ad7-8022-840144855cd0","slug":"metformin","display_name":"Metformin","entity_type_key":"drug"},"role":"upstream_actor","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"8390898f-7915-5c30-8ada-c416a386f5f3","slug":"serum-cobalamin-concentration","display_name":"Serum cobalamin concentration","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"7b9438d1-45ad-58a2-8b0c-260a9841612d","slug":"human-fasting-homocysteine","display_name":"Human fasting plasma total homocysteine concentration","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"biomarker_context","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/metformin-research/20488910.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"6c9e09d44fe1103e6927321e925e69e31c38d1a688fd2ac18ea96927098de922\", \"start_char\": 0, \"end_char\": 2518, \"text_sha256\": \"6c9e09d44fe1103e6927321e925e69e31c38d1a688fd2ac18ea96927098de922\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Multicentre randomised placebo-controlled trial, 390 people with type 2 diabetes on insulin","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"850 mg metformin three times daily for 4.3 years versus placebo","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The strongest available human causal evidence for the B12 effect. It measured concentrations and deficiency incidence, not clinical deficiency syndromes.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake.","comparator":null,"unit":null,"notes":"","entity":{"slug":"metformin","display_name":"Metformin","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The lower the vitamin, the higher this metabolite climbed.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[metformin-p20488910] 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":"Whole body","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":"ef5880a0-a250-5342-83cf-3bf3fee9cbcf","evidence_kind":"source_excerpt","locator":"Lines 1074-1085","start_line":1074,"end_line":1085,"excerpt":"### metformin-b12-homocysteine\nPatients with vitamin B-12 deficiency at study end had a mean homocysteine of 23.7 micromol/l, compared with 18.1 in those with low B-12 and 14.9 in those with normal B-12.\nCondition category: biomarker_context\nnutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake.\nplain_language: The lower the vitamin, the higher this metabolite climbed.\norganism: Human\ntissue_or_cell_type: Whole body\nexperimental_model: Multicentre randomised placebo-controlled trial, 390 people with type 2 diabetes on insulin\nlimitations: The strongest available human causal evidence for the B12 effect. It measured concentrations and deficiency incidence, not clinical deficiency syndromes.\nexposure: 850 mg metformin three times daily for 4.3 years versus placebo\nevidence_span: {\"source_cache\": \"artifacts/metformin-research/20488910.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"6c9e09d44fe1103e6927321e925e69e31c38d1a688fd2ac18ea96927098de922\", \"start_char\": 0, \"end_char\": 2518, \"text_sha256\": \"6c9e09d44fe1103e6927321e925e69e31c38d1a688fd2ac18ea96927098de922\"}\n[metformin-p20488910] Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. 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