{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:28:13Z","timestamp":1760059693690,"version":"build-2065373602"},"reference-count":53,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF)","award":["NRF-2020R1I1A1A01064906"],"award-info":[{"award-number":["NRF-2020R1I1A1A01064906"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background\/Objectives: Vitamin D (VD) is metabolized in the body and plays a crucial role in regulating the antioxidant system. While exposure to heavy metals (HMs) inhibits VD activity, HMs can also be absorbed following VD stimulation. Despite differing views on the interaction between HM and VD activity, the effects of HM exposure on VD-related pathways have not been examined using metabolomics. This study aimed to investigate the impact of HM exposure on VD-related antioxidant activity under VD deficiency conditions using untargeted metabolic profiling. Methods: In this retrospective cohort study, 46 plasma samples were analyzed using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF\/MS). Metabolic profiling was performed on two groups: individuals with severe VD deficiency and low HM exposure (SVDD\u2013LHM) and those with VD deficiency and high HM exposure (VDD\u2013HHM). Results: As a compensatory response to oxidative stress induced by HMs, VD-related antioxidant pathways may be associated with elevated levels of antioxidants, including bilirubin, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). In-creases in EPA and DHA were also linked to alterations in lipid metabolism, including diacylglycerol and phosphatidylcholine levels. DHA showed an area under the curve (AUC) of 0.850 (95% CI: 0.651\u20130.990), suggesting that DHA could serve as a potential biomarker for VD activity in response to HM exposure. Conclusions: The identified metabolites and metabolic pathways suggest that HM exposure may stimulate VD-related antioxidant activity, even under VD-deficient conditions.<\/jats:p>","DOI":"10.3390\/metabo15070440","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T04:04:22Z","timestamp":1751342662000},"page":"440","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of Heavy Metals on the Antioxidant Activity of Vitamin D: A Metabolic Perspective"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4829-9494","authenticated-orcid":false,"given":"Ji Seo","family":"Park","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea"},{"name":"Department of Clinical Pharmacology and Therapeutics, Kyungpook National University Hospital, Daegu 41944, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mi-Ri","family":"Gwon","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea"},{"name":"Department of Clinical Pharmacology and Therapeutics, Kyungpook National University Hospital, Daegu 41944, Republic of Korea"},{"name":"Clinical Omics Institute, School of Medicine, Kyungpook National University, Daegu 41405, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1886-7038","authenticated-orcid":false,"given":"Jae Hwa","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea"},{"name":"Department of Clinical Pharmacology and Therapeutics, Kyungpook National University Hospital, Daegu 41944, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin Ju","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea"},{"name":"Department of Clinical Pharmacology and Therapeutics, Kyungpook National University Hospital, Daegu 41944, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hae Won","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea"},{"name":"Department of Clinical Pharmacology and Therapeutics, Kyungpook National University Hospital, Daegu 41944, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1596-9968","authenticated-orcid":false,"given":"Duk-Hee","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sook Jin","family":"Seong","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea"},{"name":"Department of Clinical Pharmacology and Therapeutics, Kyungpook National University Hospital, Daegu 41944, Republic of Korea"},{"name":"Clinical Omics Institute, School of Medicine, Kyungpook National University, Daegu 41405, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young-Ran","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea"},{"name":"Department of Clinical Pharmacology and Therapeutics, Kyungpook National University Hospital, Daegu 41944, Republic of Korea"},{"name":"Clinical Omics Institute, School of Medicine, Kyungpook National University, Daegu 41405, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.bbrc.2015.01.008","article-title":"Vitamin D cell signalling in health and disease","volume":"460","author":"Berridge","year":"2015","journal-title":"Biochem. 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