Vitamin B₁₂ supplementation futile for preventing demyelination in ongoing nitrous oxide misuse

To the Editor: Recreational misuse of nitrous oxide remains a significant public health problem,1 sustained in part by the ready availability online of gas‐containing canisters intended for use in the catering industry. Known as “nangs” or “whippits” and usually purchased in bulk, each canister contains 8 g of nitrous oxide. When inhaled, this gives a seconds‐long “high”, which is typically prolonged by using several “nangs” in a single session. Some individuals can consume hundreds each day.

Prolonged exposure to nitrous oxide leads to the oxidisation of vitamin B₁₂, rendering it unusable in key enzymatic reactions necessary for normal myelin synthesis.2 Over time, this leads to a potentially devastating neuropsychiatric syndrome that commonly presents with ataxia.3 Notably, the culprit shortage of vitamin B₁₂ is a qualitative one and can be purely so, meaning that marked clinical deficits emerge in the presence of serum B₁₂ levels that appear normal on standard laboratory assays. Furthermore, with continued exposure to nitrous oxide, these deficits will respond poorly to vitamin B₁₂ supplementation.

In a year‐long clinical audit at Royal Prince Alfred Hospital (2017–2018), seven nitrous oxide users, all aged between 20 and 30 years, presented with ataxia that ranged from mild to severe (Box 1). Most patients also had psychiatric symptoms. Nearly every patient estimated using 100 or more canisters of nitrous oxide per day in the months before being seen. Four patients also reported engaging in B₁₂ supplementation (both oral and parenteral), aiming to circumvent the harmful sequelae of prolonged nitrous oxide misuse.

Laboratory studies showed that all seven patients had accumulated homocysteine, as is usually seen when vitamin B₁₂ is in short supply in the body.2 Individuals who reported taking supplements had serum B₁₂ levels that were either normal or in excess of normal, implicating a qualitative deficiency of metabolically useful B₁₂. Evidence of demyelination was seen on spinal cord imaging in six patients, including all those who used supplements, with the “inverted V” sign4 visible on T2‐weighted magnetic resonance imaging sequences (Box 2). Despite treatment according to best practice guidelines, all patients left hospital with persistent symptoms, and most were unable to walk or to attend to their bodily needs without the assistance of family members (modified Rankin score, 4). Sadly, one of the least affected individuals re‐presented to hospital with worsened symptoms because of continued nitrous oxide misuse.

At every opportunity nitrous oxide users should be reminded of the futility of B₁₂ supplementation, as one of many reasons why they should choose to avoid this profoundly destructive drug.

Box 2 – T2‐weighted magnetic resonance imaging sequence showing “inverted V” sign, indicating the presence of dorsal column demyelination

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