[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-411380-105":59,"doc-detail-411380-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","runaway-uncoupling-in-24-dinitrophenol-poisoning-clinical-and-mitochondrial-observations-from-two-cases","Runaway uncoupling in 2,4-dinitrophenol poisoning - Clinical and mitochondrial observations from two cases","","2,4-Dinitrophenol (DNP) is a potent mitochondrial uncoupler that was marketed in the 1930s for weight reduction and later banned by the FDA after severe toxicity reports. Since the early 2000s, DNP has reemerged as an illicit “fat-burner,” producing distinctive metabolic disturbances with high fatal risk. Two Swedish cases are described: one fatal following suicidal ingestion and one non-fatal after weight-reduction use, characterized via clinical data and mitochondrial respirometry. Findings suggest a self-amplifying feedback loop leading to “runaway uncoupling” and death, emphasizing supportive glucose and hyperkalemia management, with cooling and high ventilation as possible countermeasures.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/runaway-uncoupling-in-24-dinitrophenol-poisoning-clinical-and-mitochondrial-observations-from-two-cases/411380/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/runaway-uncoupling-in-24-dinitrophenol-poisoning-clinical-and-mitochondrial-observations-from-two-cases/411380.png","ImageObject",300,407,{"name":92,"@type":93},"eBook King","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is 2,4-dinitrophenol (DNP) and why is it dangerous?","Question",{"text":112,"@type":113},"DNP is a mitochondrial uncoupler that disrupts normal coupling of ATP synthesis and oxygen consumption. It causes hypermetabolism and can progress to catastrophic ATP depletion, leading to high-risk, potentially fatal outcomes.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What distinguishes the two Swedish cases reported in the article?",{"text":117,"@type":113},"One case was fatal after suicidal ingestion, showing rapid deterioration within hours with severe metabolic and thermoregulatory complications. The other was non-fatal after weight-reduction use, showing similar toxicity features that were reversible and prolonged.",{"name":119,"@type":110,"acceptedAnswer":120},"How does the proposed “runaway uncoupling” mechanism drive progression to death?",{"text":121,"@type":113},"Excess CO₂ production from mitochondrial uncoupling leads to local acidosis that enhances mitochondrial DNP uptake. This creates a self-amplifying feedback loop that accelerates metabolic collapse.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},411380,1790814684,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":39,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":46,"preview_page_count":4},962088006270,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","Toxicology Reports 16 (2026) 102183  \nContents lists available at ScienceDirect  \nToxicology Reports  \njournal [homepage:](homepage: www.elsevier.com/locate/toxrep)[ www.elsevier.com/locate/toxrep](homepage: www.elsevier.com/locate/toxrep)  \n| Runaway uncoupling in 2,4-dinitrophenol poisoning: Clinical and mitochondrial observations from two cases\u003Cbr>Erik Lindeman a,* , Tine Sommerb, M¨arta Lefflerb, Shusuke Sekine c,d, Eskil Elm´er c,e, Fredrik Sj¨ovallb, Wilhelm Wallquistb\u003Cbr>a Swedish Poisons Information Center, Solna Strandva¨g 21, Stockholm 171 54, Sweden\u003Cbr>b Department of Intensive and Perioperative Medicine, Skåne University Hospital, Inga Marie Nilssons gata 47, Malmo¨ 214 28, Sweden c Mitochondrial Medicine, Department of Clinical Sciences Lund, Lund University, Lund, Sweden\u003Cbr>d Department of Anesthesiology, Tokyo Medical University, Japan\u003Cbr>e Clinical Neurophysiology, Medical Imaging and Physiology, Skåne University Hospital, Lund, Sweden |  |  |\n| --- | --- | --- |\n| A R T I C L E I N F O |  | A B S T R A C T |\n| Handling Editor: Prof. L.H. Lash |  | 2,4-Dinitrophenol (DNP) is a potent mitochondrial uncoupler briefly marketed in the 1930s as a weight-reducing agent before being banned by the FDA after reports of severe toxicity. Since the early 2000s, DNP has reemergedas an illicit “fat-burner”, causing characteristic metabolic disturbances with a high risk of fatal outcome. We describe two Swedish cases of DNP poisoning: one fatal after suicidal ingestion and one non-fatal after use for weight reduction. Clinical data, mitochondrial respirometry, and analysis of gas exchange and ventilatory dynamics were used to characterize the metabolic disturbances under intensive care. The fatal case progressed within hours to respiratory acidosis, hyperthermia, severe hyperkalemia, and peri-mortem rigidity consistent with catastrophic ATP depletion. The non-fatal case showed similar but reversible toxicity, with sustained yet manageable hypermetabolism lasting more than a week. Serial platelet respirometry demonstrated a marked initial increase in uncoupled respiration, followed by a progressive decline with a functional half-life of 4.9 days. Together, these cases suggest a self-amplifying feedback loop central to DNP toxicity, in which excessive CO₂ production from mitochondrial uncoupling causes local acidosis that enhances mitochondrial DNP uptake. Glucose supplementation and hyperkalemia management are essential supportive measures, whereas active cooling and high minute ventilation may blunt this self-reinforcing metabolic acceleration. Severe poisoning may result in a state of “runaway uncoupling,” a term we propose for the catastrophic progression to death observed in numerous DNP poisonings. This feedback loop illustrates the unpredictable toxicokinetics of DNP and reinforces the FDA’s early conclusion: DNP is “unfit for human consumption”. |\n| Keywords: DNP Hyperthermia\u003Cbr>Mitochondrial uncoupling Postmortem redistribution |  |  |\n\n1. Introduction  \n2,4-Dinitrophenol (DNP) was first synthesized in the 19th century and briefly used as a food dye. This application was discontinued after studies demonstrated that the compound elevated body temperature, stimulated respiration and accelerated the onset of rigor mortis in laboratory animals [1]. DNP entered large-scale industrial use in France during World War I in the manufacture of munitions. Factory workers exposed to airborne DNP-dust and through skin contact, experienced weight loss, profuse sweating and hyperthermia, with several fatalities reported [1, 2].  \nIn 1933, researchers at Stanford University reported that DNP  \ninduced weight loss by stimulating a hypermetabolic state [3]. This publication directly triggered the compound’s widespread use in the United States as an over-the-counter weight-reduction agent [4,5]. However, by the late 1930s, numerous adverse outcomes had been reported, including skin changes, neuropathy and the development of so-called “din","cbCaicyT2zQfJSYi","https://ap.wps.com/l/cbCaicyT2zQfJSYi","pdf",2675447,"English","# Introduction\n## Background of DNP toxicity and historical use\n## Mechanistic basis of DNP-induced hypermetabolism","[{\"question\":\"What is 2,4-dinitrophenol (DNP) and why is it dangerous?\",\"answer\":\"DNP is a mitochondrial uncoupler that disrupts normal coupling of ATP synthesis and oxygen consumption. It causes hypermetabolism and can progress to catastrophic ATP depletion, leading to high-risk, potentially fatal outcomes.\"},{\"question\":\"What distinguishes the two Swedish cases reported in the article?\",\"answer\":\"One case was fatal after suicidal ingestion, showing rapid deterioration within hours with severe metabolic and thermoregulatory complications. The other was non-fatal after weight-reduction use, showing similar toxicity features that were reversible and prolonged.\"},{\"question\":\"How does the proposed “runaway uncoupling” mechanism drive progression to death?\",\"answer\":\"Excess CO₂ production from mitochondrial uncoupling leads to local acidosis that enhances mitochondrial DNP uptake. This creates a self-amplifying feedback loop that accelerates metabolic collapse.\"}]","Runaway uncoupling in 2,4-dinitrophenol poisoning - Clinical and mitochondrial observations from two cases | PDF",1790588416]