{"id":"f01b1a20-b259-548b-8610-7338af79e0a6","stable_key":"d8050016-13c9-5391-9d61-63de73590053:zeaxanthin-dose-normalized","predicate":"shows_subproportional_response_in","statement":"Dose-normalized bioavailability was 40% lower at 10 mg than at 1 mg.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"fe776cba-9982-553b-96f7-9059ad123979","mechanism_event_label":"Ten times the dose did not give ten times the normalized response.","subject":{"id":"0a60c685-7502-5ece-9da2-2c1a2e3bcdf1","slug":"zeaxanthin","display_name":"Dietary (3R,3-prime-R)-zeaxanthin","entity_type_key":"small_molecule"},"object":{"id":"3ab59416-de8e-53f9-86ff-6b811b886534","slug":"human-plasma-zeaxanthin","display_name":"Human plasma zeaxanthin concentration","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"fe776cba-9982-553b-96f7-9059ad123979","stable_key":"d8050016-13c9-5391-9d61-63de73590053:zeaxanthin-dose-normalized-event","event_type":"observed_intervention","label":"Ten times the dose did not give ten times the normalized response.","description":"Dose-normalized bioavailability was 40% lower at 10 mg than at 1 mg.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"250ebafa-b862-5908-bf50-0be7d63494f7","slug":"3-prime-dehydro-lutein","display_name":"3-prime-Dehydrolutein","entity_type_key":"small_molecule"},"role":"measured_metabolite","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"0a60c685-7502-5ece-9da2-2c1a2e3bcdf1","slug":"zeaxanthin","display_name":"Dietary (3R,3-prime-R)-zeaxanthin","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"3ab59416-de8e-53f9-86ff-6b811b886534","slug":"human-plasma-zeaxanthin","display_name":"Human plasma zeaxanthin concentration","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/zeaxanthin-research/14985215.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"dfc182ac3b22c31acf68cf01ed05f57cfb325798513d570a4071e8c19fd39c88\", \"start_char\": 0, \"end_char\": 1830, \"text_sha256\": \"dfc182ac3b22c31acf68cf01ed05f57cfb325798513d570a4071e8c19fd39c88\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Repeated-dose plasma kinetic study","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"1 or 10 mg synthetic zeaxanthin daily for 42 days; follow-up to day 76","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Plasma kinetics do not define retinal adequacy or a dose recommendation; metabolite origin is inferred from time courses.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"zeaxanthin","display_name":"Dietary (3R,3-prime-R)-zeaxanthin","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"20 healthy volunteers","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Ten times the dose did not give ten times the normalized response.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[zeaxanthin-p14985215] Plasma kinetics of zeaxanthin and 3'-dehydro-lutein after multiple oral doses of synthetic zeaxanthin. (2004). https://pubmed.ncbi.nlm.nih.gov/14985215/ DOI: 10.1093/ajcn/79.3.410","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Plasma","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"98c8ee69-67a1-5c28-8572-f78481527a91","evidence_kind":"source_excerpt","locator":"Lines 860-871","start_line":860,"end_line":871,"excerpt":"### zeaxanthin-dose-normalized\nDose-normalized bioavailability was 40% lower at 10 mg than at 1 mg.\nCondition category: normal\nnutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Ten times the dose did not give ten times the normalized response.\norganism: 20 healthy volunteers\ntissue_or_cell_type: Plasma\nexperimental_model: Repeated-dose plasma kinetic study\nlimitations: Plasma kinetics do not define retinal adequacy or a dose recommendation; metabolite origin is inferred from time courses.\nexposure: 1 or 10 mg synthetic zeaxanthin daily for 42 days; follow-up to day 76\nevidence_span: {\"source_cache\": \"artifacts/zeaxanthin-research/14985215.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"dfc182ac3b22c31acf68cf01ed05f57cfb325798513d570a4071e8c19fd39c88\", \"start_char\": 0, \"end_char\": 1830, \"text_sha256\": \"dfc182ac3b22c31acf68cf01ed05f57cfb325798513d570a4071e8c19fd39c88\"}\n[zeaxanthin-p14985215] Plasma kinetics of zeaxanthin and 3'-dehydro-lutein after multiple oral doses of synthetic zeaxanthin. 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