{"id":"c117d9c6-a4d8-5219-a58c-7ae6410a64e9","stable_key":"5d8e27d8-6a74-5560-827f-3f90908bbc34:ala-sydney2-tss","predicate":"reduces_short_term","statement":"In SYDNEY 2, TSS fell by 4.9, 4.5 and 4.7 points in the 600-, 1200- and 1800-mg groups versus 2.9 with placebo over five weeks.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"59be9eeb-0641-5892-ad64-c4c78a357c83","mechanism_event_label":"This short trial found greater symptom-score improvement with ALA.","subject":{"id":"ab091982-3acb-5a87-80fb-85dfe292c1e0","slug":"lipoic-acid","display_name":"Lipoic acid","entity_type_key":"small_molecule"},"object":{"id":"62a921c6-c975-5b84-9384-87dd9649091e","slug":"diabetic-neuropathy-tss","display_name":"Diabetic polyneuropathy Total Symptom Score / TSS","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"59be9eeb-0641-5892-ad64-c4c78a357c83","stable_key":"5d8e27d8-6a74-5560-827f-3f90908bbc34:ala-sydney2-tss-event","event_type":"observed_intervention","label":"This short trial found greater symptom-score improvement with ALA.","description":"In SYDNEY 2, TSS fell by 4.9, 4.5 and 4.7 points in the 600-, 1200- and 1800-mg groups versus 2.9 with placebo over five weeks.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"ab091982-3acb-5a87-80fb-85dfe292c1e0","slug":"lipoic-acid","display_name":"Lipoic acid","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"62a921c6-c975-5b84-9384-87dd9649091e","slug":"diabetic-neuropathy-tss","display_name":"Diabetic polyneuropathy Total Symptom Score / TSS","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/ala-research/17065669.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"3a54016cad3453fec96e99aa5906435793d7baaddaf5254d5ce335aac5bb4519\", \"start_char\": 0, \"end_char\": 1756, \"text_sha256\": \"3a54016cad3453fec96e99aa5906435793d7baaddaf5254d5ce335aac5bb4519\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"SYDNEY 2 randomized double-blind placebo-controlled trial","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Oral ALA 600, 1200 or 1800 mg/day for five weeks","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Short-term symptom endpoint; no proof of nerve regeneration, lifelong benefit or correction of a nutritional deficiency.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"lipoic-acid","display_name":"Lipoic acid","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"This short trial found greater symptom-score improvement with ALA.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ala-p17065669] Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. (2006). https://pubmed.ncbi.nlm.nih.gov/17065669/ DOI: 10.2337/dc06-1216","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"181 participants with diabetic distal symmetric polyneuropathy","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"d9b669a7-668b-556e-b90b-80e9fbc1f9d2","evidence_kind":"source_excerpt","locator":"Lines 1118-1129","start_line":1118,"end_line":1129,"excerpt":"### ala-sydney2-tss\nIn SYDNEY 2, TSS fell by 4.9, 4.5 and 4.7 points in the 600-, 1200- and 1800-mg groups versus 2.9 with placebo over five weeks.\nCondition category: normal\nnutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: This short trial found greater symptom-score improvement with ALA.\norganism: Human\ntissue_or_cell_type: 181 participants with diabetic distal symmetric polyneuropathy\nexperimental_model: SYDNEY 2 randomized double-blind placebo-controlled trial\nlimitations: Short-term symptom endpoint; no proof of nerve regeneration, lifelong benefit or correction of a nutritional deficiency.\nexposure: Oral ALA 600, 1200 or 1800 mg/day for five weeks\nevidence_span: {\"source_cache\": \"artifacts/ala-research/17065669.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"3a54016cad3453fec96e99aa5906435793d7baaddaf5254d5ce335aac5bb4519\", \"start_char\": 0, \"end_char\": 1756, \"text_sha256\": \"3a54016cad3453fec96e99aa5906435793d7baaddaf5254d5ce335aac5bb4519\"}\n[ala-p17065669] Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. (2006). https://pubmed.ncbi.nlm.nih.gov/17065669/ DOI: 10.2337/dc06-1216","model_system":"SYDNEY 2 randomized double-blind placebo-controlled trial","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [ala-p17065669] Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. (2006). https://pubmed.ncbi.nlm.nih.gov/17065669/ DOI: 10.2337/dc06-1216","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"d8afa8c2-ced9-5b28-90ca-2ac120ec7202","stable_key":"import-5d8e27d8-6a74-5560-827f-3f90908bbc34","title":"Alpha-lipoic acid: cofactor assembly, redox signaling 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":"611da198ab85a272eb26b64ee330ef6d1a762853a8481f3191c4acfca9f3cf3d","revision_id":"618b4ce6-3157-5222-8325-408064be5ea5","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[{"id":"37ef0a7a-afef-50bd-8d5c-a6d28cc675f2","title":"Diabetic neuropathy: short-term symptom benefit versus a longer negative symptom endpoint","kind":"contradiction","status":"open","why":"SYDNEY 2 reported greater TSS improvement with oral ALA over five weeks; ALADIN III did not show a significant final TSS advantage at seven months. These are divergent clinical findings about symptomatic benefit, not a reversed chemical label. Route, duration, trial population, placebo response and analysis differ; their causal contribution is not established.","resolution":"Preserve both findings with their endpoints and regimens. A short-term benefit cannot be assumed to persist, and the longer null result does not erase the short-term trial. Mechanistic explanations remain proposals until tested.","created_at":"2026-09-17 18:17:49","record_type":"conflict","display_label":"Recorded conflict","record_url":"/conflicts/37ef0a7a-afef-50bd-8d5c-a6d28cc675f2","sides":[{"conflict_id":"37ef0a7a-afef-50bd-8d5c-a6d28cc675f2","ordinal":0,"label":"This short trial found greater symptom-score improvement with ALA.","revision_id":"618b4ce6-3157-5222-8325-408064be5ea5","start_line":1118,"end_line":1129,"quote":"### ala-sydney2-tss\nIn SYDNEY 2, TSS fell by 4.9, 4.5 and 4.7 points in the 600-, 1200- and 1800-mg groups versus 2.9 with placebo over five weeks.\nCondition category: normal\nnutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: This short trial found greater symptom-score improvement with ALA.\norganism: Human\ntissue_or_cell_type: 181 participants with diabetic distal symmetric polyneuropathy\nexperimental_model: SYDNEY 2 randomized double-blind placebo-controlled trial\nlimitations: Short-term symptom endpoint; no proof of nerve regeneration, lifelong benefit or correction of a nutritional deficiency.\nexposure: Oral ALA 600, 1200 or 1800 mg/day for five weeks\nevidence_span: {\"source_cache\": \"artifacts/ala-research/17065669.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"3a54016cad3453fec96e99aa5906435793d7baaddaf5254d5ce335aac5bb4519\", \"start_char\": 0, \"end_char\": 1756, \"text_sha256\": \"3a54016cad3453fec96e99aa5906435793d7baaddaf5254d5ce335aac5bb4519\"}\n[ala-p17065669] Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. (2006). https://pubmed.ncbi.nlm.nih.gov/17065669/ DOI: 10.2337/dc06-1216","source_key":"import-5d8e27d8-6a74-5560-827f-3f90908bbc34","source_title":"Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17)","claim_ids":["c117d9c6-a4d8-5219-a58c-7ae6410a64e9"]},{"conflict_id":"37ef0a7a-afef-50bd-8d5c-a6d28cc675f2","ordinal":1,"label":"The result depended partly on which symptom analysis and time point were examined.","revision_id":"618b4ce6-3157-5222-8325-408064be5ea5","start_line":1144,"end_line":1155,"quote":"### ala-aladin3-final-tss-null\nALADIN III found no significant between-group TSS change at day 19 or after seven months, although an early daily-score area-under-curve analysis favored ALA.\nCondition category: normal\nnutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The result depended partly on which symptom analysis and time point were examined.\norganism: Human\ntissue_or_cell_type: 509 people with type 2 diabetes and symptomatic polyneuropathy\nexperimental_model: ALADIN III multicenter randomized placebo-controlled trial\nlimitations: Different route, duration and design from SYDNEY 2; preserve daily-score AUC and final-visit findings separately.\nexposure: Three weeks intravenous treatment followed by six months oral ALA 600 mg three times daily or comparator sequences\nevidence_span: {\"source_cache\": \"artifacts/ala-research/10480774.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"d28f04985ace61dd6036ea4d08d84e59c47ba587cea6438b7851e036abc1c673\", \"start_char\": 0, \"end_char\": 2880, \"text_sha256\": \"d28f04985ace61dd6036ea4d08d84e59c47ba587cea6438b7851e036abc1c673\"}\n[ala-p10480774] Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III Study). ALADIN III Study Group. Alpha-Lipoic Acid in Diabetic Neuropathy. (1999). https://pubmed.ncbi.nlm.nih.gov/10480774/ DOI: 10.2337/diacare.22.8.1296","source_key":"import-5d8e27d8-6a74-5560-827f-3f90908bbc34","source_title":"Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17)","claim_ids":["35f135bb-c8e0-5571-a42b-1ca6e8dafaaa"]}]}],"corrections":[],"research":null}