{"id":"c553c11d-3f21-57a3-b6af-4f5bc5adb077","stable_key":"e0ea2d6a-7429-5e9f-b774-41e5e3288da3:e-clin-tonic-alt","predicate":"does_not_significantly_improve","statement":"TONIC did not meet its primary sustained-ALT endpoint with vitamin E: 15/58 children (26%) responded versus 10/58 (17%) with placebo (P=0.26).","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"bf46ff65-1493-56bb-b475-84ac4d2cf6fe","mechanism_event_label":"The pediatric trial did not achieve its primary liver-enzyme outcome.","subject":{"id":"ae6048a7-d112-5d3a-8e7c-ad5a152642f9","slug":"rrr-alpha-tocopherol","display_name":"RRR-alpha-tocopherol","entity_type_key":"small_molecule"},"object":{"id":"19b51365-7654-589c-b391-2a0aabb01ab8","slug":"sustained-alt-reduction","display_name":"Sustained alanine aminotransferase reduction","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"bf46ff65-1493-56bb-b475-84ac4d2cf6fe","stable_key":"e0ea2d6a-7429-5e9f-b774-41e5e3288da3:e-clin-tonic-alt-event","event_type":"observed_intervention","label":"The pediatric trial did not achieve its primary liver-enzyme outcome.","description":"TONIC did not meet its primary sustained-ALT endpoint with vitamin E: 15/58 children (26%) responded versus 10/58 (17%) with placebo (P=0.26).","status":"provisional","compartment":null,"participants":[{"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":0,"notes":""},{"entity":{"id":"19b51365-7654-589c-b391-2a0aabb01ab8","slug":"sustained-alt-reduction","display_name":"Sustained alanine aminotransferase reduction","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":"TONIC randomized double-blind trial; 173 children aged 8–17 with biopsy-confirmed NAFLD","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"RRR-alpha-tocopherol 400 IU twice daily for 96 weeks; E and placebo groups n=58 each.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Primary sustained-ALT endpoint and secondary histology must remain distinct. Not evidence for every child, every liver condition or long-term clinical outcome.","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":"The pediatric trial did not achieve its primary liver-enzyme outcome.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[e-clin-tonic2011] Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. (2011). https://pubmed.ncbi.nlm.nih.gov/21521847/ DOI: 10.1001/jama.2011.520","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Liver enzymes and biopsy","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"8157118a-50bc-5fad-a1f4-b0c9b68bbc04","evidence_kind":"source_excerpt","locator":"Lines 1427-1438","start_line":1427,"end_line":1438,"excerpt":"### e-clin-tonic-alt\nTONIC did not meet its primary sustained-ALT endpoint with vitamin E: 15/58 children (26%) responded versus 10/58 (17%) with placebo (P=0.26).\nCondition category: normal\nnutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The pediatric trial did not achieve its primary liver-enzyme outcome.\norganism: Homo sapiens\ntissue_or_cell_type: Liver enzymes and biopsy\nexperimental_model: TONIC randomized double-blind trial; 173 children aged 8–17 with biopsy-confirmed NAFLD\nlimitations: Primary sustained-ALT endpoint and secondary histology must remain distinct. Not evidence for every child, every liver condition or long-term clinical outcome.\nexposure: RRR-alpha-tocopherol 400 IU twice daily for 96 weeks; E and placebo groups n=58 each.\ncross_nutrient: false\n[e-clin-tonic2011] Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. (2011). https://pubmed.ncbi.nlm.nih.gov/21521847/ DOI: 10.1001/jama.2011.520","model_system":"TONIC randomized double-blind trial; 173 children aged 8–17 with biopsy-confirmed NAFLD","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [e-clin-tonic2011] Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. (2011). https://pubmed.ncbi.nlm.nih.gov/21521847/ DOI: 10.1001/jama.2011.520","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}