Why nitrous oxide can cause vitamin B12 deficiency

In November 2023, the UK government made nitrous oxide a Class C controlled substance, citing growing concern about the harm it was causing to young people. Despite that reclassification, the Crime Survey for England and Wales found that 3.3% of adults aged 16 to 24 still used nitrous oxide in the year ending March 2024. Many of those people will likely have thought that it was just harmless fun. But regular nitrous oxide use can cause enormous invisible damage to your nervous system, driven by its effect on vitamin B12.

What nitrous oxide does in the body

Nitrous oxide, often called laughing gas, is usually inhaled recreationally from balloons filled from small metal canisters. A single balloon produces euphoria, dissociation, light-headedness, and a floaty sensation for about a minute. How short those effects last is part of why nitrous oxide may not seem very serious. Users often use several balloons in a session, but may only take nitrous oxide on the weekends or at parties.

Each time you use nitrous oxide, it may not feel like a big deal. But the cumulative damage can be very serious. This is because each time you use nitrous oxide, it affects vitamin B12, and those effects can lead to lasting harm.

Why vitamin B12 is so important

Most of the harm from nitrous oxide doesn’t come from the gas itself, but from what nitrous oxide does to vitamin B12. B12 is also known as cobalamin, and it is essential to two critical processes in the body.

The first is DNA synthesis. B12 helps an enzyme that cells need in order to copy their DNA, and without enough active B12, cells cannot divide and replicate properly.

The second is myelin maintenance. Myelin is the protective sheath around nerve fibres that allows electrical signals to travel efficiently along them. Making and maintaining myelin depends on a series of reactions that require functioning B12. When B12 activity is disrupted, myelin begins to degrade. The nerves it protects are then gradually exposed, so they can’t function properly.

How nitrous oxide disrupts vitamin B12

Vitamin B12 contains a cobalt atom at its centre. Nitrous oxide oxidises this cobalt atom, converting B12 from its active form into an inactive one. This process is irreversible, so the B12 molecule cannot be restored to function once oxidation has occurred.

This inactivation directly disables an enzyme called methionine synthase. The enzyme requires active B12 to work and cannot function without it. When methionine synthase is inhibited, two things go wrong simultaneously.

First, homocysteine, a compound the enzyme normally converts into methionine, begins to accumulate in the blood. Second, another breakdown product called methylmalonic acid starts to build up. Both homocysteine and methylmalonic acid are harmful at elevated levels, and their build-up drives the neurological damage that nitrous oxide causes.

This is why nitrous oxide can be dangerous even if you get enough B12 through your diet or supplements. Nitrous oxide does not necessarily deplete your body’s store of B12, but stops it from doing the jobs it’s supposed to do.

Why standard blood tests can miss the effects

That last point is one of the most important things to understand about nitrous oxide toxicity, even for doctors who may not have encountered nitrous oxide B12 deficiency before.

The standard test for B12 deficiency measures the total amount of B12 in your bloodstream. In nitrous oxide toxicity, this figure can appear normal because the inactive, oxidised B12 is still present in the blood. Your body and standard blood tests cannot reliably distinguish functionally active B12 from inactivated B12.

The more sensitive markers for functional B12 deficiency are methylmalonic acid and homocysteine. As explained above, when methionine synthase is disabled, both of these build up. Elevated methylmalonic acid in particular is a reliable indicator that B12 is not functioning properly, even when levels on a standard test appear normal. That is why anyone experiencing neurological symptoms after using nitrous oxide should have these markers checked.

It is also worth noting that nitrous oxide is undetectable on standard drug screens. This means that unless you tell your doctor you’ve been using it, they may not consider that nitrous oxide is the cause of your symptoms. This can delay timely diagnosis and treatment, which can allow symptoms to get worse.

Warning signs to look out for

The early symptoms of nitrous oxide-induced B12 disruption are easy to dismiss or attribute to some other cause. Tingling or numbness in the hands or feet that feels like pins and needles is typically the first sign. Fatigue and weakness follow, along with difficulty with balance and coordination as the damage progresses.

Because the damage builds up gradually and the connection to nitrous oxide use is not widely known, many people never seek medical help or only go to a doctor when their symptoms have become more serious. By that stage, the neurological damage may be more difficult to reverse.

In more advanced cases, you may experience weakness in your limbs, an unsteady gait, difficulty with fine motor tasks, and, in severe cases, urinary incontinence and spasticity (muscle tightness, twitches, and spasms). These symptoms show there has been damage to parts of the spinal cord, a condition known as subacute combined degeneration.

Subacute combined degeneration

Subacute combined degeneration of the spinal cord is one of the most serious consequences of nitrous oxide-induced B12 dysfunction. It involves the gradual breakdown of the protective coating on nerves in the spinal cord, particularly the parts responsible for spatial awareness, sensory experiences, muscle coordination, and balance.

Case reports have documented this condition occurring in young people following recreational nitrous oxide use. One case describes a 28-year-old woman who developed weakness in both legs, pins and needles, and difficulty walking after using the equivalent of one large canister per week for ten months. Another describes a 19-year-old man with profound B12 deficiency and spinal cord lesions visible on MRI following recreational use. In both cases, vitamin B12 replacement led to improvement. However, full recovery does not happen in all cases.

The important thing to understand is that subacute combined degeneration can occur with what many people would probably think is occasional or moderate use. You don’t need to use nitrous oxide every day. All it takes is enough cumulative exposure to inactivate sufficient B12 that myelin maintenance breaks down.

Who is most at risk of serious harm

Anyone who uses nitrous oxide regularly is at risk, but some groups face substantially greater danger.

People with pre-existing low or borderline B12 levels, including some vegans, vegetarians, older adults, and those with certain gastrointestinal conditions, have less functional reserve to draw on. Nitrous oxide exposure that a person with normal B12 might tolerate without immediate symptoms can lead to more rapid deterioration in someone whose B12 was already marginal.

People who take nitrous oxide in high quantities in a single session are also at elevated risk. The oxidation of B12 by nitrous oxide depends on how much you use, so a session involving many balloons over a few hours can leave a significant proportion of your circulating B12 inactive.

How often you use nitrous oxide matters, too. Your body can replenish some B12 activity between episodes, but with regular use, the cumulative deficit just continues to grow. If you use nitrous oxide every week, you don’t give your system enough time to recover, so your functional B12 levels get lower and lower.

How to get help

Nitrous oxide is now classified as Class C in the UK, and the neurological harms associated with its regular use are well established. If you or someone you know has been using nitrous oxide regularly and has begun to experience tingling, weakness, or problems with balance and coordination, these symptoms require immediate medical attention. You need to tell your doctor exactly what you have been using. A standard B12 blood test is not sufficient. Methylmalonic acid and homocysteine should also be measured.

If nitrous oxide use has become difficult to stop, Oasis Bradford offers confidential assessment, treatment, and support for nitrous oxide addiction. Please reach out to us today so we can explain every option that is available to you.