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Pernicious Anaemia Society
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Other oxides of nitrogen and related compounds

Having had numerous comments about nitrous oxide and B12 - is it now time to ask about the impact of the other oxides? Nitric oxide (NO), Nitrogen dioxide (NO2) and compounds such as glyceryl trinitrate which release nitric oxide.

Do any of these affect levels of available B12 significantly - like nitrous oxide?

Had a wander round PubMed and started to see all sorts of tantalising glimpses - mostly the interesting information being behind paywalls, or understanding walls (where my understanding cannot get over them).

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This is an interesting subject. As s person with lifelong sinus problems I tend to mouth breath a lot. That is known to effect nitric oxide levels. I wonder if that could have any effect on b12?


I also have sinus problems, had 2 ops. on them recently. Can you elaborate on mouth breathing and "That is known to effect nitric oxide levels."

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I believe sinus breathing adds nitric oxide to the air and it's supposed to kill pathogens.

Mouth breathers don't get the benefit of that.

Sadly my understanding is at a schoolboy level too.

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Nitric oxide is an important chemical in the body. It acts as a signalling molecule in many systems. Indeed, Viagra works via controlling NO. It is Not converted to nitrous oxide (N2O).

Nitrogen dioxide (NO2) is a brown corrosive gas with a choking, acrid smell (I know, I've smelt a leak in our lab).

So neither should effect B12


Not being a chemist, I have had my eyes turned by paragraphs such as the ones below:

Due to defect in one carbon transfer by NO: Nitric oxide (NO) is produced by most cell types and regulates a diverse array of biological functions29–31. NO is known to react with heme proteins, porphyrins, and cobalamins to form nitrosyl-metal complexes32–36. NO has been reported to inhibit methionine synthase activity in vitro37–39, and it might be expected to bind to the cobalt in cobalamin because, first, NO binds tightly to the iron in heme40; second, ferrous heme and cbl(III) are isoelectronic; and third, in both heme and cobalamin, the metal ion is coordinated to four in-plane nitrogen atoms of a tetrapyrrole ring and has two out-of-plane ligands41. NO has a remarkably high affinity for ferrous heme with a binding constant on the order of 1012 to 1014 M-¹, and NO also binds to ferric heme42. Iron and cobalt are transition metals adjacent in the periodic table, and the porphyrin ring of heme and the corrin ring of cobalamin are both substituted tetrapyrrole rings43. Thus, it is not surprising that NO binds to the cobalt in cobalamin, and it is observed that NO reacts with all three valency states of cobalamin44.


Although now recognized to be an important reactive nitrogen species in biological systems that modifies the structures of proteins, DNA and lipids, there are few studies on the reactivity of NO2, including the reactions between NO2 and transition metal complexes. We report kinetic studies on the reactions of NO2 with two forms of vitamin B12 - cob(II)alamin and nitrocobalamin. UV-visible spectroscopy and HPLC analysis of the product solution show that NO2 cleanly oxidizes the metal center of cob(II)alamin to form nitrocobalamin, with a second-order rate constant of (3.5±0.3)×10(8)M(-1)s(-1) (pH7.0 and 9.0, room temperature, I=0.20M). The stoichiometry of the reaction is 1:1. No reaction is detected by UV-visible spectroscopy and HPLC analysis of the product solution when nitrocobalamin is exposed to up to 2.0molequiv. NO2.


I struggle to know whether I am suffering a schoolboy howler level of misunderstanding, the paper was poorly written, or there might be something in it. :-)


Yes, it's no surprise that NO will bind to B12 in vitro. The questions that need to be asked are: does it bind in vivo and is the binding irreversible. As everybody has NO in their bodies I'd be very surprised if the body didn't have some mechanism, if one were needed, to prevent it causing problems.

NO2 exposure in humans will be minimal. I'd be much more worried about it dissolving in the fluid of the lungs to produce nitric acid.


The issue around nitrous oxide is more to do with the fact that it is used as an anaesthetic and is also appearing as a recreational drug - so exposures that aren't related to normal environmental levels.

As fbirder says - the fact that NO will combine with B12 but is already present in the body anyway means that there must be mechanisms within the body that stop this being a problem. That doesn't rule out the possibility of problems in some individuals due to genetic variants where things get out of balance but if that is the case then the lack of an identified problems would point to it being extremely rare.


It was actually the thought of people prescribed glyceryl trinitrate for heart issues that made me question. Not at all sure how much of an effect it would have.

think that is going to be a bit more complex than looking at the nitrogen and oxygen compounds. From what I can work out it needs specific compounds to release the nitric oxide that then reacts - think at the cell level - that result in blood cells dilating. Definitely not a bio-chemist but it does sound to me as if this is happening in such a way that any significant interaction with B12 is unlikely ... unless overdosing which wouldn't be recommended anyway.

Anyone who has any sort of heart condition or suffers from angina should always get professional medical advice before considering B12 supplementation anyway - as there are other potential complications.


This year old post has just been reported for offensive language. No idea why because I can't see any.

As the post is a year old, going to turn off replying.

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