{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T08:19:30Z","timestamp":1787905170759,"version":"build-2784847793"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100032753","name":"Universidad Alfonso X El Sabio","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100032753","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Toxicol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Caffeine toxicity represents a growing public health challenge due to the widespread availability of highly potent formulations. Ingestions of 3\u201310\u00a0g can be fatal, with serious toxicity occurring at plasma concentrations 15\u00a0mg\/L or greater. This review provides a framework explaining its diverse clinical consequences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A comprehensive literature search was conducted across PubMed, Scopus, and Google Scholar using AI-assisted tools, prioritizing clinical, forensic, toxicokinetic, and molecular mechanism studies while excluding chronic moderate consumption.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Caffeine toxicity is dose-dependent, progressing from adenosine receptor antagonism to phosphodiesterase inhibition, intracellular calcium release, and GABA-A antagonism. In overdose, these mechanisms interact synergistically to cause severe neurological, cardiovascular, and metabolic complications. Furthermore, the CYP1A2 metabolic system becomes saturated, prolonging the elimination half-life up to 27\u00a0h and causing a disproportionate rise in plasma concentrations. Interactions with drugs like mexiletine drastically reduce clearance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Severe poisoning stems from complex, synergistic molecular interactions. Hypokalemia serves as a promising, actionable clinical biomarker for severity assessment. When massive ingestions saturate endogenous detoxification, hemodialysis becomes essential for survival. Unregulated markets for pure caffeine require stricter regulatory interventions and intensified clinical surveillance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/ftox.2026.1933375","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T08:04:47Z","timestamp":1787904287000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Toxicology of caffeine poisoning: molecular mechanisms, toxicokinetic profiles, and clinical implications"],"prefix":"10.3389","volume":"8","author":[{"given":"Antonia","family":"Socias","sequence":"first","affiliation":[{"name":"Servicio de Medicina Intensiva, Hospital Universitario Son Ll\u00e0tzer","place":["Palma de Mallorca, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Blancas","sequence":"additional","affiliation":[{"name":"Servicio de Medicina Intensiva, Hospital Universitario del Tajo","place":["Aranjuez, Spain"]},{"name":"Universidad Alfonso X el Sabio","place":["Villanueva de la Ca\u00f1ada, Spain"]},{"name":"Fundaci\u00f3n para la Investigaci\u00f3n Biom\u00e9dica e Innovaci\u00f3n, Hospital Universitario Infanta Sof\u00eda y Hospital Universitario del Henares","place":["San Sebasti\u00e1n de los Reyes, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s40780-021-00220-z","article-title":"Pharmacokinetics of self-administered caffeine in an overdose case in a Japanese hospitalised patient","volume":"7","author":"Adachi","year":"2021","journal-title":"J. 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