{"id":"736e210a-b6f9-503b-a8e5-50304baf73c7","stable_key":"e0ea2d6a-7429-5e9f-b774-41e5e3288da3:e-clin-vitamin-k-pivka","predicate":"increases","statement":"High-dose RRR-alpha-tocopherol increased PIVKA-II in both 12-week adult trials: mean values rose from 1.7 to 11.9 ng/mL and from 1.8 to 5.3 ng/mL.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"004ae0e9-6d21-55a9-afa4-48be5e2f87bc","mechanism_event_label":"High-dose vitamin E altered a vitamin K-dependent clotting-protein marker.","subject":{"id":"ae6048a7-d112-5d3a-8e7c-ad5a152642f9","slug":"rrr-alpha-tocopherol","display_name":"RRR-alpha-tocopherol","entity_type_key":"small_molecule"},"object":{"id":"5e5c0ed6-7bed-5839-bbb5-67b0fe2ea730","slug":"undercarboxylated-prothrombin","display_name":"Undercarboxylated prothrombin / PIVKA-II","entity_type_key":"protein_state"},"evidence_count":1,"mechanism_event":{"id":"004ae0e9-6d21-55a9-afa4-48be5e2f87bc","stable_key":"e0ea2d6a-7429-5e9f-b774-41e5e3288da3:e-clin-vitamin-k-pivka-event","event_type":"observed_intervention","label":"High-dose vitamin E altered a vitamin K-dependent clotting-protein marker.","description":"High-dose RRR-alpha-tocopherol increased PIVKA-II in both 12-week adult trials: mean values rose from 1.7 to 11.9 ng/mL and from 1.8 to 5.3 ng/mL.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"4a379566-6578-58ce-bd09-cc3af14f00f6","slug":"vitamin-k","display_name":"Vitamin K","entity_type_key":"chemical_species"},"role":"interacting_nutrient","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"ae6048a7-d112-5d3a-8e7c-ad5a152642f9","slug":"rrr-alpha-tocopherol","display_name":"RRR-alpha-tocopherol","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"5e5c0ed6-7bed-5839-bbb5-67b0fe2ea730","slug":"undercarboxylated-prothrombin","display_name":"Undercarboxylated prothrombin / PIVKA-II","entity_type_key":"protein_state"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"true","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Two independent 12-week randomized trials; 38 adults with rheumatoid arthritis and 32 healthy men","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"RRR-alpha-tocopherol 1000 IU/day; participants were not receiving oral anticoagulant therapy.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Biochemical marker study, not a bleeding-events trial. The study does not identify CYP4F2 activation, direct GGCX inhibition or clinical vitamin K deficiency as the causal route.","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":"High-dose vitamin E altered a vitamin K-dependent clotting-protein marker.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[e-clin-booth2004] Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. (2004). https://pubmed.ncbi.nlm.nih.gov/15213041/ DOI: 10.1093/ajcn/80.1.143","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Circulation and vitamin K-dependent carboxylation","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"6fd7c2cc-c515-5c4b-ae9f-b93b25a45ebf","evidence_kind":"source_excerpt","locator":"Lines 1258-1269","start_line":1258,"end_line":1269,"excerpt":"### e-clin-vitamin-k-pivka\nHigh-dose RRR-alpha-tocopherol increased PIVKA-II in both 12-week adult trials: mean values rose from 1.7 to 11.9 ng/mL and from 1.8 to 5.3 ng/mL.\nCondition category: normal\nnutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: High-dose vitamin E altered a vitamin K-dependent clotting-protein marker.\norganism: Homo sapiens\ntissue_or_cell_type: Circulation and vitamin K-dependent carboxylation\nexperimental_model: Two independent 12-week randomized trials; 38 adults with rheumatoid arthritis and 32 healthy men\nlimitations: Biochemical marker study, not a bleeding-events trial. The study does not identify CYP4F2 activation, direct GGCX inhibition or clinical vitamin K deficiency as the causal route.\nexposure: RRR-alpha-tocopherol 1000 IU/day; participants were not receiving oral anticoagulant therapy.\ncross_nutrient: true\n[e-clin-booth2004] Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. (2004). https://pubmed.ncbi.nlm.nih.gov/15213041/ DOI: 10.1093/ajcn/80.1.143","model_system":"Two independent 12-week randomized trials; 38 adults with rheumatoid arthritis and 32 healthy men","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [e-clin-booth2004] Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. (2004). https://pubmed.ncbi.nlm.nih.gov/15213041/ DOI: 10.1093/ajcn/80.1.143","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}