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
Year: 2025
Type: article
Abstract: Recreational nitrous oxide (N 2 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 ( www.protoside.com ) plays a key role in facilitating case discussion, expert collaboration, and dissemination of best practices in the management of N 2 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.
Institutions: Université de Lille, Centre Hospitalier Universitaire de Lille, Mater Misericordiae University Hospital, Ankara Eğitim ve Araştırma Hastanesi, Ziekenhuisnetwerk Antwerpen Stuivenberg, Innlandet Hospital Trust, Haukeland University Hospital, Helse Førde, AZ Groeninge, Yale University, University Hospital Centre Zagreb, Queen Mary University of London, Barts Health NHS Trust, Royal London Hospital, University of Kragujevac, Univerzitetski Klinički Centar Srbije, Hospices Civils de Lyon, Centre Hospitalier Le Vinatier, Oslo University Hospital, Norwegian Institute of Public Health, UiT The Arctic University of Norway, Universitair Ziekenhuis Leuven, KU Leuven, University of Liège, Centre Hospitalier Universitaire de Liège
Language: English
Subfield: Toxicology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4416716762