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As an organic compound soluble in water, thiamin is essential for carbohydrate metabolism in plants and animals, and in its active form\u2014as part of the thiamin pyrophosphate coenzyme\u2014performs these functions. Thereby, thiamin represents an essential vitamin to human health and is involved in several pathways that regulate several pathophysiological mechanisms. Cardiovascular disease is significantly impacted by thiamine imbalance and its supplementation offers substantial improvements to the associated conditions. In this comprehensive review, we aimed to examine the dual role of thiamine deficiency and accumulation, focusing on an analysis of the causes of thiamine deficiency. We detailed the effects of thiamine deficiency on metabolism and on cardiovascular risk and heart failure, explaining the molecular mechanisms involved in metabolic dysfunction, and highlighting the role of B1 vitamin supplementation in diabetes mellitus management and atherosclerosis development and progression. Indeed, B1 supplementation counteracts oxidative stress and inflammation, significantly ameliorating glycemic and lipemic profiles. Additionally, we reported the beneficial effects of thiamine in counteracting cardiotoxicity induced by cancer therapy. Although preclinical data strongly support the benefits of thiamine, clinical trial findings are in contrast and contradictory, hampered by limitations such as small sample sizes and inadequate follow-up. Further research is needed to investigate thiamine\u2019s potential benefits, overcoming current study limitations and evaluating its use as a supplemental therapy alongside standard treatments in different high-cardiovascular-risk conditions.<\/jats:p>","DOI":"10.3390\/ijms26073090","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T04:11:40Z","timestamp":1743135100000},"page":"3090","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Pivotal Role of Thiamine Supplementation in Counteracting Cardiometabolic Dysfunctions Associated with Thiamine Deficiency"],"prefix":"10.3390","volume":"26","author":[{"given":"Giovanna","family":"Ritorto","sequence":"first","affiliation":[{"name":"Pharmacology Laboratory, Institute of Research for Food Safety and Health IRC-FSH, Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Ussia","sequence":"additional","affiliation":[{"name":"Pharmacology Laboratory, Institute of Research for Food Safety and Health IRC-FSH, Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7106-5595","authenticated-orcid":false,"given":"Rocco","family":"Mollace","sequence":"additional","affiliation":[{"name":"Pharmacology Laboratory, Institute of Research for Food Safety and Health IRC-FSH, Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"},{"name":"Department of Experimental Medicine, University \u201cTor Vergata\u201d of Rome, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7736-2207","authenticated-orcid":false,"given":"Maria","family":"Serra","sequence":"additional","affiliation":[{"name":"Pharmacology Laboratory, Institute of Research for Food Safety and Health IRC-FSH, Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2940-3482","authenticated-orcid":false,"given":"Annamaria","family":"Tavernese","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University Campus Bio-Medico of Rome, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4199-207X","authenticated-orcid":false,"given":"Ernesto","family":"Palma","sequence":"additional","affiliation":[{"name":"Veterinary Pharmacology Laboratory, Institute of Research for Food Safety and Health IRC-FSH, Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1047-4467","authenticated-orcid":false,"given":"Carolina","family":"Muscoli","sequence":"additional","affiliation":[{"name":"Pharmacology Laboratory, Institute of Research for Food Safety and Health IRC-FSH, Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0392-7173","authenticated-orcid":false,"given":"Vincenzo","family":"Mollace","sequence":"additional","affiliation":[{"name":"Pharmacology Laboratory, Institute of Research for Food Safety and Health IRC-FSH, Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"},{"name":"Renato Dulbecco Institute, Lamezia Terme, 88046 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2345-6751","authenticated-orcid":false,"given":"Roberta","family":"Macr\u00ec","sequence":"additional","affiliation":[{"name":"Pharmacology Laboratory, Institute of Research for Food Safety and Health IRC-FSH, Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1002\/ncp.10234","article-title":"Role of Thiamin in Health and Disease","volume":"34","author":"Polegato","year":"2019","journal-title":"Nutr. 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