{"id":"3ae907e3-dade-5e87-b7a0-ce26293a55f0","stable_key":"a9828b14-fbd7-57bf-9e01-0d52d1b42a1f:citrulline-adma-ratio","predicate":"increased","statement":"At 3 g twice daily, the arginine/ADMA ratio rose from 186 to 278.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"32829697-63f3-5f24-bd71-5d7b457af41e","mechanism_event_label":"The substrate-to-inhibitor ratio changed; this does not mean ADMA itself was removed.","subject":{"id":"f53c7bfb-3b91-56fe-bebd-28623cfe13a0","slug":"citrulline","display_name":"L-Citrulline","entity_type_key":"small_molecule"},"object":{"id":"d4cad882-0409-52bd-94c7-28742874c4cb","slug":"plasma-arginine-adma-ratio","display_name":"Plasma arginine-to-ADMA ratio","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"32829697-63f3-5f24-bd71-5d7b457af41e","stable_key":"a9828b14-fbd7-57bf-9e01-0d52d1b42a1f:citrulline-adma-ratio-event","event_type":"biochemical_relationship","label":"The substrate-to-inhibitor ratio changed; this does not mean ADMA itself was removed.","description":"At 3 g twice daily, the arginine/ADMA ratio rose from 186 to 278.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"eeca3c9e-7749-5677-b7bd-37fe8f7c228d","slug":"arginine","display_name":"L-Arginine","entity_type_key":"small_molecule"},"role":"downstream_substrate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"6c8e2535-0002-5b29-bb3d-36cb341b85d2","slug":"asymmetric-dimethylarginine","display_name":"Asymmetric dimethylarginine / ADMA","entity_type_key":"small_molecule"},"role":"measured_inhibitor","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"6d2f509b-3a5b-5a38-b3e7-b148581edec9","slug":"cgmp","display_name":"Cyclic guanosine monophosphate","entity_type_key":"small_molecule"},"role":"downstream_marker","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"f53c7bfb-3b91-56fe-bebd-28623cfe13a0","slug":"citrulline","display_name":"L-Citrulline","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"d4cad882-0409-52bd-94c7-28742874c4cb","slug":"plasma-arginine-adma-ratio","display_name":"Plasma arginine-to-ADMA ratio","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/citrulline-research/17662090.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"32e6ddf6d263120576f0f73c7fe3dd104904f3c0ba0a1c3f69cdca5751c4fa3b\", \"start_char\": 0, \"end_char\": 1980, \"text_sha256\": \"32e6ddf6d263120576f0f73c7fe3dd104904f3c0ba0a1c3f69cdca5751c4fa3b\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Double-blind placebo-controlled crossover study","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Citrulline 0.75, 1.5 or 3 g twice daily versus arginine formulations; one-week periods","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Small short trial; NO-related urine markers do not establish a clinically meaningful vascular benefit.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Citrulline research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"citrulline","display_name":"L-Citrulline","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human, 20 healthy volunteers","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The substrate-to-inhibitor ratio changed; this does not mean ADMA itself was removed.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[citrulline-p17662090] Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. (2008). https://pubmed.ncbi.nlm.nih.gov/17662090/ DOI: 10.1111/j.1365-2125.2007.02990.x","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Plasma amino acids, urine NO markers and brachial FMD","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"42e12f65-b88f-5a49-838d-6144e940d087","evidence_kind":"source_excerpt","locator":"Lines 879-890","start_line":879,"end_line":890,"excerpt":"### citrulline-adma-ratio\nAt 3 g twice daily, the arginine/ADMA ratio rose from 186 to 278.\nCondition category: normal\nnutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The substrate-to-inhibitor ratio changed; this does not mean ADMA itself was removed.\norganism: Human, 20 healthy volunteers\ntissue_or_cell_type: Plasma amino acids, urine NO markers and brachial FMD\nexperimental_model: Double-blind placebo-controlled crossover study\nlimitations: Small short trial; NO-related urine markers do not establish a clinically meaningful vascular benefit.\nexposure: Citrulline 0.75, 1.5 or 3 g twice daily versus arginine formulations; one-week periods\nevidence_span: {\"source_cache\": \"artifacts/citrulline-research/17662090.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"32e6ddf6d263120576f0f73c7fe3dd104904f3c0ba0a1c3f69cdca5751c4fa3b\", \"start_char\": 0, \"end_char\": 1980, \"text_sha256\": \"32e6ddf6d263120576f0f73c7fe3dd104904f3c0ba0a1c3f69cdca5751c4fa3b\"}\n[citrulline-p17662090] Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. 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