{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T05:39:08Z","timestamp":1779169148146,"version":"3.51.4"},"reference-count":20,"publisher":"Walter de Gruyter GmbH","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Recreational nitrous oxide (N\n                    <jats:sub>2<\/jats:sub>\n                    O) use has emerged as a growing public health concern, with increasing reports of neurological, psychiatric, and thrombotic complications. This position paper from the EFLM Committee on Biological Markers of Nitrous Oxide Abuse highlights the urgent need for clinical and laboratory awareness, alongside coordinated action from healthcare systems and the scientific community. Short-term recommendations focus on early clinical recognition, prompt biological testing, and structured patient management. Key clinical symptoms include unexplained sensory disturbances, gait instability, bladder and bowel complaints, sexual dysfunction, mood disorders, and thromboembolic events in young individuals. Plasma homocysteine (HCY) and plasma methylmalonic acid (MMA) are central to the diagnostic approach, with HCY serving as a sensitive marker of recent exposure and MMA indicating clinical severity. Vitamin B12 and folate measurements are also essential, though B12 levels may be falsely reassuring (often in the low-normal range). Given the rapid normalization of biomarkers, testing should be performed on admission, and vitamin B12 supplementation should begin without delay, with caution regarding biomarker kinetics and possible self-supplementation by patients. In addition, this paper outlines long-term goals, including the harmonization of biomarker assays, creation of international patient registries, and development of interdisciplinary expert networks. Notably, the international network PROTOSIDE (\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.protoside.com\/\">www.protoside.com<\/jats:ext-link>\n                    ) plays a key role in facilitating case discussion, expert collaboration, and dissemination of best practices in the management of N\n                    <jats:sub>2<\/jats:sub>\n                    O-related complications. A continuous bibliographic watch and support for translational research are necessary to improve biomarker discovery and understanding of the underlying mechanisms of toxicity. By combining immediate clinical action with long-term scientific and policy development, this document lays the foundation for an international strategy to address the silent but expanding epidemic of nitrous oxide misuse.\n                  <\/jats:p>","DOI":"10.1515\/cclm-2025-1060","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T06:12:41Z","timestamp":1764137561000},"page":"813-820","source":"Crossref","is-referenced-by-count":1,"title":["Addressing the silent epidemic of recreational nitrous oxide use: a position, call to action and recommendations by the European Federation of Clinical Chemistry and Laboratory Medicine Committee on Biological Markers of Nitrous Oxide Abuse"],"prefix":"10.1515","volume":"64","author":[{"given":"Guillaume","family":"Grzych","sequence":"first","affiliation":[{"name":"Biochemistry Department, Center of Biology Pathology and Genetic , Lille University Hospital , Lille , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graham R.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Diagnostic Endocrinology , Mater Misericordiae University Hospital , Dublin , Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Medine","family":"Alpdemir","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry , University of Health Sciences, Ankara Training and Research Hospital , Ankara , T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emeline","family":"Gernez","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Center of Biology Pathology and Genetic , Lille University Hospital , Lille , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kurt","family":"Anseeuw","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine , Ziekenhuisnetwerk Antwerpen (ZNA) , Antwerp , Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne-Lise","family":"Bjorke-Monsen","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Biochemistry , Innlandet Hospital Trust , Lillehammer , Norway"},{"name":"Laboratory of Medical Biochemistry , F\u00f8rde Hospital Trust , F\u00f8rde , Norway"},{"name":"Department of Medical Biochemistry and Pharmacology , Haukeland University Hospital , Bergen , Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen","family":"Croes","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine , AZ Groeninge , Kortrijk , Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9444-9540","authenticated-orcid":false,"given":"Joe M.","family":"El-Khoury","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine , Yale School of Medicine , New Haven , CT , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jasmin","family":"Hamzic","sequence":"additional","affiliation":[{"name":"Emergency Department , University Hospital Centre Zagreb , Zagreb , Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alastair J.","family":"Noyce","sequence":"additional","affiliation":[{"name":"Centre for Preventive Neurology , Wolfson Institute of Population Health, Queen Mary University of London , London , UK"},{"name":"Department of Neurology , The Royal London Hospital, Barts Health NHS Trust , London , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanja","family":"Stankovic","sequence":"additional","affiliation":[{"name":"Center for Medical Biochemistry , University Clinical Center of Serbia , Belgrade , Serbia"},{"name":"Faculty of Medical Sciences University of Kragujevac , Kragujevac , Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Rolland","sequence":"additional","affiliation":[{"name":"Service Universitaire d\u2019Addictologie de Lyon (SUAL), Hospices Civils de Lyon, H\u00f4pital Le Vinatier , Lyon , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorgen","family":"Bramness","sequence":"additional","affiliation":[{"name":"UiT The Arctic University of Norway, Institute of Clinical Medicine , Troms\u00f8 , Norway"},{"name":"Section for Clinical Addiction Research, Oslo University Hospital , Oslo , Norway"},{"name":"Norwegian National Advisory Unit on Concurrent Substance Abuse and Mental Health Disorders, Innlandet Hospital Trust , Brumunddal , Norway"},{"name":"Department of Drugs and Tobacco , Norwegian Institute of Public Health , Oslo , 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