Vitamin B12 (hydroxocobalamin, cyanocobalamin): advise patients with known cobalt allergy to be vigilant for sensitivity reactions

[helvella]

A somewhat lacklustre MHRA warning:

Vitamin B12 (hydroxocobalamin, cyanocobalamin): advise patients with known cobalt allergy to be vigilant for sensitivity reactions

The medicines used to treat vitamin B12 deficiency (hydroxocobalamin, cyanocobalamin) contain cobalt. There are case reports in the literature describing cobalt sensitivity-type reactions in patients being treated for vitamin B12 deficiency.

gov.uk/drug-safety-update/v...

They refer to "The medicines used to treat vitamin B12 deficiency..." when B12 is often dismissed as just a vitamin. And, despite being formulated for the purpose, these products are indeed vitamins and not in any conventional sense "medicines".

They refer only to prescribed B12 products. Ignoring methylcobalamin, adenosylcobalamin, and oral hydroxocobalamin and the many products which combine one or more of these, sometimes with other vitamins and/or micronutrients, etc. This is despite the widespread advice for those with low dietary B12 to consider supplementation which will very often be done without reference to a doctor or other prescriber.

They ignore B12 used for fortification of foods.

They appear to ignore the possibility of adverse reactions occurring in those who do not have known cobalt sensitivity. Considering how few have been diagnosed with cobalt sensitivity, I suggest that these issues could very well have a greater incidence among those who have not been so diagnosed.

And no-one who does not know cobalamin contains cobalt should be prescribing any form of B12! This aspect should not be news to any registered prescriber. But if they are referring to cobalt other than the single atom in the centre of the cobalamin, they have completely failed to make that clear.

If they believe it right to put out this information, they should do so to a much higher standard.

Despite these criticisms, it seems right that the notice is brought to the attention of members of this forum.

[Narwhal10]

Thanks helvella,

I have had a quick scan, saved and agree, lacklustre. Unimpressed with the wording and there is no mention of pernicious anaemia. You make very valid points.

There is a report button on the MHRA site. Feel free to use it.

[helvella in reply to Narwhal10]

Intended for technical issues - but have used it anyway.

[newlandvale]

My doctor suggested my small fibre neuropathic itching was due to too much b12!Unfortunately for the nhs, skin test showed no reaction whatsoever! 🤣 carry on injecting!!

[Sleepybunny]

For anyone reading this thread who has a cobalt allergy, make sure your GP knows about it and consider asking to be referred to an allergy specialist.

I have read that it's possible to undergo a desensitisation process with some allergies. I think this would be done under the care of an allergy specialist. There are specialist allergy centres in UK.

Also found a research article about hypersensitivity to B12 on Pub Med.

Search online for "Pub Med B12 hypersensitivity".

[Bellabab in reply to Sleepybunny]

pubmed.ncbi.nlm.nih.gov/146....

[helvella in reply to Sleepybunny]

This is nice and recent. Though full paper is behind a paywall.

Vitamin B12 Hypersensitivity: A Retrospective Multicenter Study

Fatema-Zahra El Rhermoul 1 , Amina Mustafa 2 , Annette Wagner 2 , Alla Nakonechna 3 , Oyindamola Stephanie Kayode 2 , Ryszard Rutkowski 4 , Leonard Q C Siew 2 , Krzysztof Rutkowski 2

PMID: 37898177 DOI: 10.1016/j.jaip.2023.10.037

Abstract

Background: Vitamin B12 (Vit B12) deficiency affects approximately 20% of those above the age of 60 years in the United Kingdom and United States. If untreated, it leads to detrimental health outcomes.

Objective: To investigate a cohort of patients with Vit B12 hypersensitivity (VB12H) referred to 3 UK allergy centers and design a pathway for the investigation of VB12H.

Methods: A total of 29 patients seen between 2014 and 2022 underwent skin prick testing (1 mg/mL) with cyanocobalamin (CC) and hydroxycobalamin (HC) and intradermal testing (0.1 and 0.01 mg/mL). Patients with negative skin tests underwent a Vit B12 drug provocation test (DPT) with either the index or the alternative drug.

Results: Of 29 patients, 18 (62%) presented with immediate VB12H. Eight experienced anaphylaxis (4 to HC and 4 to CC) and had positive skin tests to the index drug. One patient reacted to oral and 7 patients to injectable Vit B12. Seven patients sensitized to one form of Vit B12-tolerated DPT with an alternative Vit B12. One patient with immediate VB12H reacted to polyethylene glycol (PEG) in oral cobalamin. Of 29 patients, 8 presented with delayed hypersensitivity reaction; 4 patients tolerated the intramuscular index formulation, whereas 2 patients tolerated the per oral formulation. One patient presented with symptoms consistent with symmetrical drug-related intertriginous and flexural exanthema. Three patients were referred because of cobalt allergy.

Conclusion: Confirmed VB12H is rare. We propose a comprehensive evaluation protocol that includes Vit B12 skin tests and considers PEG allergy in patients presenting with VB12H.

Keywords: Cobalt allergy; Cyanocobalamin; Desensitization; Excipient; Hydroxycobalamin; PEG; SDRIFE; Skin testing; Vit B(12) allergy.

pubmed.ncbi.nlm.nih.gov/378...

[bookish]

Sorry for late response, just found the post. Are you by any chance aware whether oral supplementation/high dose/sublingual/skin patches would elicit a cobalt response in those who are allergic? Thanks

[helvella in reply to bookish]

No - but I can see arguments in both directions.

If you inject 1 milligram of B12 each month, then your body will receive the cobalt impurities associated with that alone.

If you swallow 1 milligram of B12 each day, then your body will receive the cobalt impurities associated with around 30 milligrams of B12.

Clearly we need to know more. Like the extent to which the cobalt impurities are taken into our bodies. Perhaps oral cobalt impurities more or less pass straight through without actually getting into our blood? Or maybe we can get rid of the cobalt impurities associated with one injected dose more readily than far more taken orally?

And relative dosing - I have simply assumed one injection a month versus one tablet every day for the sake of illustrating what I am saying.

[bookish in reply to helvella]

Thank you. I found the human bits of this interesting ncbi.nlm.nih.gov/books/NBK5... . It states that a B12 dose does not increase retention of inorganic cobalt, which seems to be removed via the usual routes - kidneys, liver, bile and lymph function - although women absorb more than men from the GI tract as low iron will increase cobalt absorption.

I've been taking oral and sublingual in three forms (plus patches) and three vitamers for some time, with dose in the region of 8000mcg daily for the last 18 months. I'd hope that I'd have shown some signs if the cobalt was a problem. The only thing I noticed relatively recently was itching skin with hydroxo sublinguals, after my usual ones changed shape. I contacted the supplier who said that the ingredients were exactly the same but was concerned at my using hydroxo long term as they said it could, in some, build up effectively unmetabolised and that could be affecting the skin. Because I react to other things I can't be certain that I wasn't having this issue all along, but I am not aware of it wth methyl or adenosyl. It could of course still be a gluten-in-production issue, not cobalt or hydroxo per se. But if hydroxo is not optimal for all, why is it the only NHS option? Best wishes

[helvella in reply to bookish]

Hydroxocobalamin might have looked the best at the time the decision was made.

And it certainly seems to be needed for some who cannot take cyanocobalamin (e.g. the very rare cases of Leber's).

But medicine is chock full of such things. And they are very difficult to get changed - especially from outside.

[OldmanD]

Very interesting. . . . . Got under the radar that one did. . . . .