{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:02:47Z","timestamp":1791201767579,"version":"4.2.0"},"reference-count":24,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":277,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anemia"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Iron deficiency anemia is primarily evaluated using hematological and iron\u2010related parameters; however, these markers may not fully reflect the systemic metabolic consequences of impaired oxygen delivery and altered iron availability. This study aimed to characterize serum metabolomic alterations associated with iron deficiency anemia using an untargeted LC\u2010HRMS approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Serum samples from 47 individuals with iron deficiency anemia and 50 healthy controls were analyzed by LC\u2010HRMS in positive and negative ionization modes. Data processing and metabolite annotation were performed using MassCube and MZmine workflows. Multivariate and univariate analyses, covariate\u2010adjusted models, metabolite set enrichment analysis, correlations with hematologic\/iron indices, and internally cross\u2010validated exploratory ROC analyses were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PCA showed partial separation between iron deficiency anemia and control groups, while OPLS\u2010DA demonstrated clearer group discrimination. Differential metabolites indicated prominent alterations in amino acid, central carbon, nitrogen\u2010related, and redox\u2010associated pathways. The principal amino\u2010acid\/nitrogen\u2010related differences remained significant after adjustment for age, sex, albumin, and total protein. In the full cohort, several discriminatory metabolites correlated with hemoglobin, ferritin, and transferrin saturation, although these correlations did not remain FDR\u2010significant within the IDA group alone. Repeated stratified 5\u2010fold cross\u2010validation yielded a mean AUC of 0.964 for the three\u2010metabolite model comprising isoleucine, isonicotinic acid, and phenylalanine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Untargeted serum metabolomics revealed a distinct metabolic signature in iron deficiency anemia, mainly involving amino acid remodeling, central carbon metabolism, nitrogen balance, and redox\u2010associated pathways. These findings provide a basis for future targeted and externally validated metabolomics studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/anem\/6256940","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:39:29Z","timestamp":1791200369000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum Metabolomic Signatures of Iron Deficiency Anemia: An Untargeted LC\u2010HRMS\u2010Based Case\u2013Control Study"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4810-6771","authenticated-orcid":false,"given":"Metin","family":"Demirel","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry Faculty of Medicine Bezmialem Vakif University  Istanbul T\u00fcrkiye  bezmialem.edu.tr"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3201-5923","authenticated-orcid":false,"given":"Fatmanur","family":"K\u00f6kta\u015fo\u011flu","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry Faculty of Medicine Bezmialem Vakif University  Istanbul T\u00fcrkiye  bezmialem.edu.tr"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9442-4300","authenticated-orcid":false,"given":"Halime Dulun","family":"A\u011fa\u00e7","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry Faculty of Medicine Bezmialem Vakif University  Istanbul T\u00fcrkiye  bezmialem.edu.tr"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9223-1054","authenticated-orcid":false,"given":"Ay\u015fe Zehra","family":"G\u00fcl","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry Faculty of Medicine Bezmialem Vakif University  Istanbul T\u00fcrkiye  bezmialem.edu.tr"},{"name":"Department of Biochemistry Sancaktepe \u015eehit Prof.Dr. \u0130lhan Varank Training and Research Hospital  Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4573-5505","authenticated-orcid":false,"given":"Ufuk","family":"Sar\u0131kaya","sequence":"additional","affiliation":[{"name":"Vocational School of Health Services Department of Medical Services and Techniques Bezmialem Vakif University  Istanbul T\u00fcrkiye  bezmialem.edu.tr"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5470-130X","authenticated-orcid":false,"given":"Ahmet Ceyhan","family":"Goren","sequence":"additional","affiliation":[{"name":"Department of Chemistry Gebze Technical University  Kocaeli T\u00fcrkiye  gyte.edu.tr"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7902-9284","authenticated-orcid":false,"given":"Cumali","family":"Karatoprak","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Faculty of Medicine Bezmialem Vakif University  Istanbul T\u00fcrkiye  bezmialem.edu.tr"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1235-3957","authenticated-orcid":false,"given":"\u015eahabettin","family":"Selek","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry Faculty of Medicine Bezmialem Vakif University  Istanbul T\u00fcrkiye  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