{"id":"0d3fee42-f851-5235-a6a5-0ff7815ae5ed","stable_key":"e0ea2d6a-7429-5e9f-b774-41e5e3288da3:e-clin-phs-hemorrhagic-stroke","predicate":"increases_observed","statement":"PHS II found increased hemorrhagic-stroke incidence with vitamin E assignment (HR 1.74, 95% CI 1.04–2.91).","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"7f361c79-ae2f-5488-86ef-1224203bf621","mechanism_event_label":"A bleeding-related stroke outcome increased in this trial.","subject":{"id":"1e078aed-0416-5fe7-8b8b-36bc2ca8ab7a","slug":"all-rac-alpha-tocopherol","display_name":"All-rac-alpha-tocopherol","entity_type_key":"small_molecule"},"object":{"id":"6805a826-7470-5209-8bf5-f3ae6db14821","slug":"hemorrhagic-stroke-incidence","display_name":"Hemorrhagic stroke incidence","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"7f361c79-ae2f-5488-86ef-1224203bf621","stable_key":"e0ea2d6a-7429-5e9f-b774-41e5e3288da3:e-clin-phs-hemorrhagic-stroke-event","event_type":"observed_intervention","label":"A bleeding-related stroke outcome increased in this trial.","description":"PHS II found increased hemorrhagic-stroke incidence with vitamin E assignment (HR 1.74, 95% CI 1.04–2.91).","status":"provisional","compartment":null,"participants":[{"entity":{"id":"1e078aed-0416-5fe7-8b8b-36bc2ca8ab7a","slug":"all-rac-alpha-tocopherol","display_name":"All-rac-alpha-tocopherol","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"6805a826-7470-5209-8bf5-f3ae6db14821","slug":"hemorrhagic-stroke-incidence","display_name":"Hemorrhagic stroke incidence","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Physicians Health Study II randomized factorial trial; 14641 male US physicians aged at least 50","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Synthetic alpha-tocopherol 400 IU on alternate days, with factorial vitamin C 500 mg/day; mean follow-up 8 years.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Mostly primary prevention in male physicians; historical regimen is not nutritional repletion. Primary Methods specify synthetic alpha-tocopherol; no unverified ester identity is attached. The clinical endpoint does not prove that altered vitamin K metabolism caused these events.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin E research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-e","display_name":"Vitamin E","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A bleeding-related stroke outcome increased in this trial.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[e-clin-phs2008] Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial. (2008). https://pubmed.ncbi.nlm.nih.gov/18997197/ DOI: 10.1001/jama.2008.600","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Cardiovascular clinical events","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"54dfd1dd-fa57-5890-8504-151caea175d0","evidence_kind":"source_excerpt","locator":"Lines 1362-1373","start_line":1362,"end_line":1373,"excerpt":"### e-clin-phs-hemorrhagic-stroke\nPHS II found increased hemorrhagic-stroke incidence with vitamin E assignment (HR 1.74, 95% CI 1.04–2.91).\nCondition category: normal\nnutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A bleeding-related stroke outcome increased in this trial.\norganism: Homo sapiens\ntissue_or_cell_type: Cardiovascular clinical events\nexperimental_model: Physicians Health Study II randomized factorial trial; 14641 male US physicians aged at least 50\nlimitations: Mostly primary prevention in male physicians; historical regimen is not nutritional repletion. Primary Methods specify synthetic alpha-tocopherol; no unverified ester identity is attached. The clinical endpoint does not prove that altered vitamin K metabolism caused these events.\nexposure: Synthetic alpha-tocopherol 400 IU on alternate days, with factorial vitamin C 500 mg/day; mean follow-up 8 years.\ncross_nutrient: false\n[e-clin-phs2008] Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial. (2008). https://pubmed.ncbi.nlm.nih.gov/18997197/ DOI: 10.1001/jama.2008.600","model_system":"Physicians Health Study II randomized factorial trial; 14641 male US physicians aged at least 50","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [e-clin-phs2008] Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial. (2008). https://pubmed.ncbi.nlm.nih.gov/18997197/ DOI: 10.1001/jama.2008.600","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"3ac41dba-4727-5116-a556-ac3bbb0dc41c","stable_key":"import-e0ea2d6a-7429-5e9f-b774-41e5e3288da3","title":"Vitamin E: transport, membrane protection 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":"a90b6565e092c6a2da07f74cf758792c2cf63b40746260c8ff12bd64322c36f4","revision_id":"956793d1-23e4-5397-9291-25c1732a8e02","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}