Nitrous oxide-induced B12 deficiency myelopathy: Perspectives on the clinical biochemistry of vitamin B12

Beginning with a case report of nitrous oxide (N2O)-induced B12 deficiency myelopathy, this article reviews the clinical biochemistry of vitamin B12, and examines the pathogenetic mechanisms by which B12 deficiency leads to neurologic damage, and how this damage is potentiated by N2O exposure. The article systematically examines the available experimental data relating to the two main coenzyme mechanisms that are usually suggested in clinical articles, particularly the deficient methylation hypothesis. The article demonstrates that neither of these mechanisms is fully consistent with the available data. The article then presents a novel mechanism based on new data from the neuroimmunology basic science literature which suggests that the pathogenesis of B12 deficiency myelopathy may not be related to its role as a coenzyme, but rather to newly discovered functions of B12 in regulating cytokines and growth factors.