Nitrous oxide and vitamin B12

Basically, B12 is a bound coenzyme of methionine synthase and has a tetrapyrrole rings with a monovalent cobalt at the center. The cobalt functions as a methyl carrier in a transmethylation reaction. Nitrous oxide converts the cobalt from the monovalent form to the bivalent form. As a result, methionine synthase activity is inhibited. Recovery is believed to require absorption of new unoxidized B12 (and synthesis of new apoenzyme).

Humans seem to be far more resistant to complications from this than rodents. I don't have the energy to go through the various published studies at this point, so I will quote from Nunn's "Clinical Aspects of the Interaction Between Nitrous Oxide and Vitamin B12" (1987), Br. J. Anaesth. 59: 3-13.

It seems likely that in man, in contrast to the rat, exposure of less than 30 minutes will not cause any measurable change in methionine synthase activity. In combination with a wealth of clinical experience, this suggests that there is no special hazard for short exposures to nitrous oxide. There is a variable response to exposures lasting between 30 minutes and 2 h. However, it now seems likely that exposures of more than 2 h are likely to cause intereference with hepatic methionine synthase activity. The paucity of human data makes it more difficult to say how long an exposure is required to cause significant intereference with DNA synthesis. It is likely that there will be considerable individual variation and results obtained in healthy patients cannot be extrapolated to the patient who is seriously ill. Nevertheless, it seems likely that, once methionine synthase activity is inhibited, it will remain so for days.
With respect to repeated exposures to nitrous, be aware that this effect can build up (Nunn gives "intervals of less than 3 days" as a cut-off). So, go easy on the "hippie crack," people!

Mandatory nitrous horror story: Layzer (in (1978) "Myeloneuropathy after prolonged exposure to nitrous oxide," Lancet 2:1227) reports a case of 15 people who had been inhaling nitrous oxide for long periods of time and developed a condition resembling subacture combined degneration of the cord, whatever that means.

From A Primer of Drug Action by Robert M. Julien:

"Occasionally, certain anesthetic agents become misused drugs. Nitrous oxide is an example. A gas of low anesthetic potency, it is incapable of inducing deep levels of anesthesia if an adequate oxygen concentration is maintained. Nitrous oxide induces a state of behavioral disinhibition, analgesia, and euphoria. One of the problems occasionally encountered when nitrous oxide is used for recreational purposes is that, unless the compound is administered with at least 20 percent oxygen, hypoxia (decreased oxygen content of the blood) can be induced. But in order to achieve high enough concentrations of nitrous oxide to get a good behavioral effect, concentrations of 50 percent or greater must be inhaled. If such concentrations are mixed with room air, inhaled oxygen concentartions drop to low levels and the hypoxia may result in irreversible brain damage."

From From Chocolate to Morphine by Andrew Weil & Winifred Rosen:

"Physicians and dentists have long considered nitrous oxide to be a safe pharmacological agent. Nevertheless, there is some evidence that excessive or prolonged use of it can damage the bone marrow and nervous system by interfering with the action of vitamin B-12. Moreover its use in nonmedical settings presents several hazards that users should keep in mind. Breathing it directly from pressurized tanks is dangerous for two reasons. First, gas flowing from such tanks is very cold -- cold enough to cuase frostbite of noses, lips and (most serious) vocal cords. Being anesthetized, a user may be unaware of such injuries until too late. Second, because nitrous oxide does not support life, it should be mixed with oxygen if it is to be breathed for more than a few minutes. At private parties, oxygen tanks are rarely supplied, and people have died of asphyxiation by breathing straight nitrous oxide through face masks. One way to avoid these dangers is to fill balloons from tanks and breathe from the balloons.

Further, nitrous oxide rapidly leads to complete loss of motor control, and anyone who breathes it while standing will soon reel about and fall down. Therefore, it is unwise to try the gas unless one is in a comfortable sitting or lying position. Serious injuries have resulted from people inhaling laughing gas while standing in front of open windows, when driving cars, or when operating machinery. Others have been badly hurt by accidentally pulling heavy tanks of nitrous oxide over onto themselves while intoxicated.

People who breathe nitrous oxide for more than a few minutes at a time may experience nausea, especially if they have just eaten. They may also feel hung over for some time after. Addiction to nitrous oxide is a real possibility. Addicts may suffer serious mood and personality changes in addition to the bone marrow and nervous system damage already mentioned.

The Sputnik Nitrous Oxide Pages.

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