‘Popping’ and ‘Whipping’ the Cobalamin: A case series on recreational substance induced functional Vitamin B12 deficiency

<title>Abstract</title> <p>Functional vitamin B12 deficiency is a recognized cause of reversible myelopathy and peripheral neuropathy. While nitrous oxide is an increasingly recognized cause of vitamin B12 inactivation, the neurological consequences of amyl nitrite ("poppers") remain poorly described. We present a case series highlighting neurological manifestations associated with recreational nitrogen-containing compounds and emphasize the importance of recognizing functional vitamin B1 deficiency in these patients. Three men (ages 31–38 years) presented with progressive neurological symptoms following recreational exposure to nitrogen containing compounds. Two patients reported nitrous oxide ("whippits") use, while one reported regular amyl nitrite use for sexual enhancement. Presenting symptoms included paresthesias, gait instability, sensory ataxia, myalgias, hyperesthesia, urinary urgency, constipation, and Lhermitte's phenomenon. Neurological examination revealed impaired vibration sense, sensory ataxia with positive Romberg sign, diffuse hyperreflexia, and Lhermitte's sign. Magnetic Resonance Imaging (MRI) brain and cervical spine were unremarkable in two patients, and nerve conduction studies (NCS) were normal where performed. Serum vitamin B12 levels ranged from 94 to 215 pg/mL, including one patient with borderline deficiency despite clinically significant neurological manifestations. All patients received intramuscular cyanocobalamin with marked clinical improvement or complete resolution of symptoms. Nitrous oxide irreversibly oxidizes the cobalt atom within cobalamin, rendering vitamin B12 metabolically inactive and disrupting methionine synthase activity, resulting in impaired myelin synthesis. Amyl nitrite appears to produce a similar functional cobalamin deficiency through nitrite mediated oxidation of cobalamin, although this mechanism is considerably less recognized in clinical practice. The resulting impairment of methylation pathways and accumulation of neurotoxic metabolites can produce myelopathy and neuropathy despite normal neuroimaging or only borderline reductions in serum vitamin B12 concentrations. Recreational exposure to nitrous oxide and amyl nitrite should be considered in patients presenting with unexplained myeloneuropathy or sensory ataxia, particularly when vitamin B12 levels are low or borderline. A detailed substance use history is essential, as early recognition and prompt parenteral vitamin B12 replacement may lead to substantial neurological recovery and prevent irreversible disability.</p>