{"id":"676d68b6-cd4f-54ba-908e-9a9be4ddc59a","stable_key":"f812c44f-d0fd-5f01-ba2c-748c0794fcfb:coumarin-arm-positive","predicate":"reduces_in_trial","statement":"The 1993 trial reported arm edema declining from 46% to 26% above normal during active treatment (P<0.001).","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"3372402a-4f6d-5e3d-873a-0b5245c388e6","mechanism_event_label":"This small trial reported less arm swelling.","subject":{"id":"9fd9b93a-fdfd-5e09-92d3-0495bff41391","slug":"coumarin","display_name":"Coumarin","entity_type_key":"small_molecule"},"object":{"id":"55cf296b-c154-5004-b067-6846d5c97cd0","slug":"human-lymphedema-arm-volume","display_name":"Arm volume in human lymphedema","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"3372402a-4f6d-5e3d-873a-0b5245c388e6","stable_key":"f812c44f-d0fd-5f01-ba2c-748c0794fcfb:coumarin-arm-positive-event","event_type":"observed_intervention","label":"This small trial reported less arm swelling.","description":"The 1993 trial reported arm edema declining from 46% to 26% above normal during active treatment (P<0.001).","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9fd9b93a-fdfd-5e09-92d3-0495bff41391","slug":"coumarin","display_name":"Coumarin","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"55cf296b-c154-5004-b067-6846d5c97cd0","slug":"human-lymphedema-arm-volume","display_name":"Arm volume in human lymphedema","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/coumarin-research/8377779.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"d4b9a301f1334d388b1469a12453ee1af75bcb87f52277dbfac03bcdb045c9ad\", \"start_char\": 0, \"end_char\": 1907, \"text_sha256\": \"d4b9a301f1334d388b1469a12453ee1af75bcb87f52277dbfac03bcdb045c9ad\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Randomized double-blind placebo-controlled crossover trial","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Coumarin 400 mg/day and placebo, six months each","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Small older mixed-population trial; positive arm finding was not reproduced in the larger subsequent study.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Coumarin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"coumarin","display_name":"Coumarin","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"This small trial reported less arm swelling.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[coumarin-p8377779] Treatment of lymphedema of the arms and legs with 5,6-benzo-[alpha]-pyrone. (1993). https://pubmed.ncbi.nlm.nih.gov/8377779/ DOI: 10.1056/nejm199310143291604","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"31 postmastectomy arm and 21 other-cause leg lymphedema patients","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"ae3c4853-4639-5fb9-b0a0-eb08e97886dc","evidence_kind":"source_excerpt","locator":"Lines 735-746","start_line":735,"end_line":746,"excerpt":"### coumarin-arm-positive\nThe 1993 trial reported arm edema declining from 46% to 26% above normal during active treatment (P<0.001).\nCondition category: normal\nnutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: This small trial reported less arm swelling.\norganism: Human\ntissue_or_cell_type: 31 postmastectomy arm and 21 other-cause leg lymphedema patients\nexperimental_model: Randomized double-blind placebo-controlled crossover trial\nlimitations: Small older mixed-population trial; positive arm finding was not reproduced in the larger subsequent study.\nexposure: Coumarin 400 mg/day and placebo, six months each\nevidence_span: {\"source_cache\": \"artifacts/coumarin-research/8377779.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"d4b9a301f1334d388b1469a12453ee1af75bcb87f52277dbfac03bcdb045c9ad\", \"start_char\": 0, \"end_char\": 1907, \"text_sha256\": \"d4b9a301f1334d388b1469a12453ee1af75bcb87f52277dbfac03bcdb045c9ad\"}\n[coumarin-p8377779] Treatment of lymphedema of the arms and legs with 5,6-benzo-[alpha]-pyrone. (1993). https://pubmed.ncbi.nlm.nih.gov/8377779/ DOI: 10.1056/nejm199310143291604","model_system":"Randomized double-blind placebo-controlled crossover trial","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [coumarin-p8377779] Treatment of lymphedema of the arms and legs with 5,6-benzo-[alpha]-pyrone. (1993). https://pubmed.ncbi.nlm.nih.gov/8377779/ DOI: 10.1056/nejm199310143291604","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"30e0bbf1-757c-5baf-9102-e81bdd4382f0","stable_key":"import-f812c44f-d0fd-5f01-ba2c-748c0794fcfb","title":"Coumarin: metabolism, signaling and nutrient connections (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":"069009019d00c903f4dc54e3793d189f4a61fb17b4803dbe73e73a677dfd0910","revision_id":"6596e0b7-7c3e-523a-a79a-aefb725d7d4c","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[{"id":"f06d6d16-f600-5707-a7f9-81e561472def","title":"Coumarin lymphedema benefit was not reproduced in a larger trial","kind":"qualification","status":"open","why":"The 1993 crossover trial reported reduced postmastectomy arm edema; the 1999 replication in 140 women found no benefit despite the same total daily coumarin dose and six-month periods. This is an efficacy disagreement between primary studies, not an author correction.","resolution":"Unresolved discrepancy. Trial population, baseline edema, measurement methods, period/carryover effects and study conduct are candidates for investigation, not demonstrated explanations. Keep both findings and the later liver-toxicity signal visible; animal proteolysis evidence does not establish clinical efficacy.","created_at":"2026-09-18 03:19:16","record_type":"conflict","display_label":"Recorded conflict","record_url":"/conflicts/f06d6d16-f600-5707-a7f9-81e561472def","sides":[{"conflict_id":"f06d6d16-f600-5707-a7f9-81e561472def","ordinal":0,"label":"This small trial reported less arm swelling.","revision_id":"6596e0b7-7c3e-523a-a79a-aefb725d7d4c","start_line":735,"end_line":746,"quote":"### coumarin-arm-positive\nThe 1993 trial reported arm edema declining from 46% to 26% above normal during active treatment (P<0.001).\nCondition category: normal\nnutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: This small trial reported less arm swelling.\norganism: Human\ntissue_or_cell_type: 31 postmastectomy arm and 21 other-cause leg lymphedema patients\nexperimental_model: Randomized double-blind placebo-controlled crossover trial\nlimitations: Small older mixed-population trial; positive arm finding was not reproduced in the larger subsequent study.\nexposure: Coumarin 400 mg/day and placebo, six months each\nevidence_span: {\"source_cache\": \"artifacts/coumarin-research/8377779.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"d4b9a301f1334d388b1469a12453ee1af75bcb87f52277dbfac03bcdb045c9ad\", \"start_char\": 0, \"end_char\": 1907, \"text_sha256\": \"d4b9a301f1334d388b1469a12453ee1af75bcb87f52277dbfac03bcdb045c9ad\"}\n[coumarin-p8377779] Treatment of lymphedema of the arms and legs with 5,6-benzo-[alpha]-pyrone. (1993). https://pubmed.ncbi.nlm.nih.gov/8377779/ DOI: 10.1056/nejm199310143291604","source_key":"import-f812c44f-d0fd-5f01-ba2c-748c0794fcfb","source_title":"Coumarin: metabolism, signaling and nutrient connections (2026-09-17)","claim_ids":["676d68b6-cd4f-54ba-908e-9a9be4ddc59a"]},{"conflict_id":"f06d6d16-f600-5707-a7f9-81e561472def","ordinal":1,"label":"The larger trial found no arm-volume benefit.","revision_id":"6596e0b7-7c3e-523a-a79a-aefb725d7d4c","start_line":761,"end_line":772,"quote":"### coumarin-arm-null\nAt six months arm volume changed by +58 mL on coumarin versus +21 mL on placebo (P=0.80).\nCondition category: normal\nnutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The larger trial found no arm-volume benefit.\norganism: Human\ntissue_or_cell_type: 140 women with chronic arm lymphedema after breast cancer treatment\nexperimental_model: Randomized placebo-controlled crossover replication trial\nlimitations: Specific disease population and pharmacological exposure; liver-test incidence cannot be extrapolated to food doses.\nexposure: Coumarin 200 mg twice daily versus placebo, six months each\nevidence_span: {\"source_cache\": \"artifacts/coumarin-research/9929524.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"6d6d4760bdd321dda87f82927c5dfcc7120ed963c101d799473ed53ff4c7764b\", \"start_char\": 0, \"end_char\": 1579, \"text_sha256\": \"6d6d4760bdd321dda87f82927c5dfcc7120ed963c101d799473ed53ff4c7764b\"}\n[coumarin-p9929524] Lack of effect of coumarin in women with lymphedema after treatment for breast cancer. (1999). https://pubmed.ncbi.nlm.nih.gov/9929524/ DOI: 10.1056/nejm199902043400503","source_key":"import-f812c44f-d0fd-5f01-ba2c-748c0794fcfb","source_title":"Coumarin: metabolism, signaling and nutrient connections (2026-09-17)","claim_ids":["6c5ccd0a-7581-58e8-8199-e0b8cf009f2b"]}]}],"corrections":[],"research":null}