{"id":"0087ad2c-a87c-585e-82c4-187e86bee317","stable_key":"548ab9d6-3a9b-5bed-879c-17d03813b636:b2-tt-plasma-sam-response","predicate":"increased_in_tt_secondary_analysis","statement":"In the 47-person TT intervention subset, riboflavin increased plasma SAM and cystathionine; no response was detected in the other measured one-carbon metabolites.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"2428212a-bbea-5bdd-997d-0dc78fb7f82a","mechanism_event_label":"B2 changed selected circulating methylation-related metabolites; the study did not show that every tissue had been short of methyl groups.","subject":{"id":"86eb1eee-a8d1-539c-8c17-0911f69b6f1b","slug":"riboflavin","display_name":"Riboflavin (vitamin B2)","entity_type_key":"small_molecule"},"object":{"id":"825f2da2-01bc-5874-a3c6-64f5ac867db5","slug":"s-adenosylmethionine","display_name":"S-Adenosyl-L-methionine","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"2428212a-bbea-5bdd-997d-0dc78fb7f82a","stable_key":"548ab9d6-3a9b-5bed-879c-17d03813b636:b2-tt-plasma-sam-response-event","event_type":"observed_intervention","label":"B2 changed selected circulating methylation-related metabolites; the study did not show that every tissue had been short of methyl groups.","description":"In the 47-person TT intervention subset, riboflavin increased plasma SAM and cystathionine; no response was detected in the other measured one-carbon metabolites.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9fc32b1a-0f08-544c-a361-1c728203b6ec","slug":"mthfr","display_name":"Methylenetetrahydrofolate reductase / MTHFR","entity_type_key":"protein"},"role":"variant_context","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"ffc7d833-38ce-5224-82e0-19c0b87b45bf","slug":"cystathionine","display_name":"Cystathionine","entity_type_key":"small_molecule"},"role":"measured_product","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"e84829b1-0607-558e-8add-aaa3af4747e7","slug":"s-adenosylhomocysteine","display_name":"S-Adenosyl-L-homocysteine","entity_type_key":"small_molecule"},"role":"measured_metabolite","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"86eb1eee-a8d1-539c-8c17-0911f69b6f1b","slug":"riboflavin","display_name":"Riboflavin (vitamin B2)","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"825f2da2-01bc-5874-a3c6-64f5ac867db5","slug":"s-adenosylmethionine","display_name":"S-Adenosyl-L-methionine","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"cross_nutrient","value_text":"B2/MTHFR connects folate-dependent remethylation with methionine-cycle biomarkers.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Archived samples from prior BP trials: 115 genotype-characterized adults; TT intervention subset 24 riboflavin and 23 placebo.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"1.6 mg/day riboflavin or placebo for 16 weeks; LC-MS/MS plasma metabolites; secondary analysis, not a new independent trial.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Secondary sample analysis of prior BP trials; plasma SAM is not tissue SAM flux, DNA methylation, epigenetic silencing or a proved mediator of BP.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Riboflavin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"riboflavin","display_name":"Riboflavin (vitamin B2)","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"B2 changed selected circulating methylation-related metabolites; the study did not show that every tissue had been short of methyl groups.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[b2-robinson2020] Impact of the MTHFR C677T polymorphism on one-carbon metabolites: Evidence from a randomised trial of riboflavin supplementation (2020). https://pubmed.ncbi.nlm.nih.gov/32330571/ DOI: 10.1016/j.biochi.2020.04.004","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Human clinical setting","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"f9484ba9-840b-5433-890c-1460bb2d7229","evidence_kind":"source_excerpt","locator":"Lines 1514-1525","start_line":1514,"end_line":1525,"excerpt":"### b2-tt-plasma-sam-response\nIn the 47-person TT intervention subset, riboflavin increased plasma SAM and cystathionine; no response was detected in the other measured one-carbon metabolites.\nCondition category: machinery_impairment\nnutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: B2 changed selected circulating methylation-related metabolites; the study did not show that every tissue had been short of methyl groups.\norganism: Homo sapiens\ntissue_or_cell_type: Human clinical setting\nexperimental_model: Archived samples from prior BP trials: 115 genotype-characterized adults; TT intervention subset 24 riboflavin and 23 placebo.\nlimitations: Secondary sample analysis of prior BP trials; plasma SAM is not tissue SAM flux, DNA methylation, epigenetic silencing or a proved mediator of BP.\nexposure: 1.6 mg/day riboflavin or placebo for 16 weeks; LC-MS/MS plasma metabolites; secondary analysis, not a new independent trial.\ncross_nutrient: B2/MTHFR connects folate-dependent remethylation with methionine-cycle biomarkers.\n[b2-robinson2020] Impact of the MTHFR C677T polymorphism on one-carbon metabolites: Evidence from a randomised trial of riboflavin supplementation (2020). https://pubmed.ncbi.nlm.nih.gov/32330571/ DOI: 10.1016/j.biochi.2020.04.004","model_system":"Archived samples from prior BP trials: 115 genotype-characterized adults; TT intervention subset 24 riboflavin and 23 placebo.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [b2-robinson2020] Impact of the MTHFR C677T polymorphism on one-carbon metabolites: Evidence from a randomised trial of riboflavin supplementation (2020). https://pubmed.ncbi.nlm.nih.gov/32330571/ DOI: 10.1016/j.biochi.2020.04.004","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"4f7c9578-82bf-5e2d-b5c4-72a79fb4f6af","stable_key":"import-548ab9d6-3a9b-5bed-879c-17d03813b636","title":"Riboflavin: mechanisms, deficiency 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":"680cb6bc8249877f2410f551807f10d390fdd719014137d7414ba3420e29228d","revision_id":"7a61e299-908d-5372-860b-99ed190f9d7a","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}