{"doi":"10.1021/acs.est.5c01597","title":"Metabolic Signature of Arsenic Exposure and Metabolism: The Folic Acid and Creatine Trial","abstract":"Arsenic exposure remains a leading public health concern. Folic acid (FA) supplementation enhances one-carbon metabolism (OCM), thus promoting arsenic methylation and facilitating urinary arsenic elimination. Here, we investigate the metabolic profiles linked to arsenic exposure and metabolism based on a FA clinical trial. Arsenic exposure was assessed by the concentrations of blood arsenic (bAs) species: arsenite [InAs III ], arsenate [InAs V ], monomethyl- [MMA], and dimethyl- [DMA] arsenicals. Arsenic metabolism was assessed by the relative distribution (%) of these arsenicals in urine. Nontargeted metabolomic profiling was analyzed by LC-HRMS. OCM-related metabolites were analyzed by HPLC/MS/MS. Metabolomic profiling identified 8 unique metabolites and 812 metabolomic features (FDR < 0.05) associated with bAs (predominantly As V ), and 66 metabolites and 285 metabolomic features with %uAs (predominantly %uInAs). Metabolic pathways enriched for bAs and %uAs were similar, highlighting phenylalanine, tyrosine, and tryptophan biosynthesis. A FA-induced %uInAs change was associated with four metabolites, three of which share links to acetyl-CoA metabolism. Of 11 measured OCM metabolites, cystathionine was positively associated with all bAs species. Methionine, S-adenosylmethionine, S-adenosylhomocysteine, cysteine, choline, betaine, and dimethylglycine were associated with increased As methylation profiles in urine (FDR < 0.05). Collectively, these findings may aid in the discovery of mechanisms underlying arsenic-induced health outcomes and potential targeted interventions. This trial was registered with clinicaltrials.gov: NCT01050556","journal":"Environmental Science & Technology","year":2025,"id":515163,"datarank":0.3003757991343688,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.008489276776071756,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.008489276776071756,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":6,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9535,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT01050556"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":352865,"name":"Haotian Wu","orcid":"0000-0002-6271-0249","position":1,"is_corresponding":false},{"id":347736,"name":"Jeff Goldsmith","orcid":"0000-0002-6150-8997","position":2,"is_corresponding":false},{"id":340277,"name":"Ronald A. Glabonjat","orcid":"0000-0003-3104-1940","position":3,"is_corresponding":false},{"id":425438,"name":"Vesna Ilievski","orcid":null,"position":4,"is_corresponding":false},{"id":702947,"name":"Olgica Balac","orcid":null,"position":5,"is_corresponding":false},{"id":548550,"name":"Vesna Slavkovich","orcid":"0000-0002-5155-2847","position":6,"is_corresponding":false},{"id":923720,"name":"Brismar Pinto‐Pacheco","orcid":"0000-0002-0111-5825","position":7,"is_corresponding":false},{"id":49809,"name":"Xiangping Lin","orcid":"0000-0001-6045-4459","position":8,"is_corresponding":false},{"id":373570,"name":"Faruque Parvez","orcid":"0000-0002-5079-3825","position":9,"is_corresponding":false},{"id":1379391,"name":"Gabriela L. Jackson","orcid":null,"position":10,"is_corresponding":false},{"id":654984,"name":"Abu Bakkar Siddique","orcid":"0000-0002-1484-0823","position":11,"is_corresponding":false},{"id":693861,"name":"Mohammad Nasir Uddin","orcid":"0000-0003-0223-9763","position":12,"is_corresponding":false},{"id":373572,"name":"Tariqul Islam","orcid":"0000-0003-1623-5210","position":13,"is_corresponding":false},{"id":463378,"name":"Irene Martínez-Morata","orcid":"0000-0003-3165-4931","position":14,"is_corresponding":false},{"id":864024,"name":"Ana Navas-Acien","orcid":null,"position":15,"is_corresponding":false},{"id":231480,"name":"Megan M. Niedzwiecki","orcid":"0000-0001-6647-141X","position":16,"is_corresponding":false},{"id":1273683,"name":"Marianthi-Anna Kioumourtzoglou","orcid":null,"position":17,"is_corresponding":false},{"id":108967,"name":"Brandon L. Pierce","orcid":"0000-0002-7829-952X","position":18,"is_corresponding":false},{"id":425143,"name":"Joseph H. Graziano","orcid":null,"position":19,"is_corresponding":false},{"id":505039,"name":"Teodoro Bottiglieri","orcid":"0000-0002-4199-7551","position":20,"is_corresponding":false},{"id":231481,"name":"Douglas I. Walker","orcid":"0000-0003-2912-398X","position":21,"is_corresponding":false},{"id":606805,"name":"Mary V. Gamble","orcid":"0000-0003-4169-1162","position":22,"is_corresponding":false},{"id":1378709,"name":"Wending Li","orcid":"0000-0001-5405-8708","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T02:48:34.431522Z","pmid":"40668877","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}