Vitamin B12 is widely-used as a supplement for patients with ileal malabsorption and those with pernicious anemia.
Rare. Deaths reported.
Risk factors
Intravenous administration.
Clinical manifestations
(occurring within weeks or months, but sometimes after several years of treatment)
General: anaphylactic shock
Cutaneous: generalized urticaria, angioedema, eczematous rash, pruritus,
Respiratory: bronchospasm.
Recurrence of allergic reactions to vitamin B12 may occur after ingestion of Marmite (yeast derived extract containing at least 15 µg of cyanocobalamin/100 g).
Diagnostic methods
Cutaneous testing: usually negative but:
  • skin-prick tests: positive with pure hydroxocobalamin
  • intradermal skin-tests: positive at 1/100 to 1/10 dilution in one patient.

No specific IgE found

Specific histamine-release: positive in one patient.
The vitamin itself, the preservatives (benzyl alcohol) or some contaminants may be involved. Contact dermatitis has been reported, due to the cobalt ring contained in this vitamin.
Possible IgE-mediated hypersensitivity (positive cutaneous tests, specific histamine release).
Cross-sensitivity between hydroxocobalamin and cyanocobalamin has been described but is not always found.
In patients with hydroxocobalamin allergy; if cutaneous testing shows negative results; cyanocobalamin can be used in increasing intramuscular doses (0.1mg; 0.5mg; 1 mg).
Adjunction of corticosteroids or antihistamines may be useful.
Desensitization in patients allergic to both hydroxocobalamin and cyanocobalamin may be performed.
For example with cyanocobalamin: 0.1 ml (1/100 = 10 µg/ml) to 0.5 ml pure (500 µg)
Oral route may be an alternative, but reactions have been reported and therapeutic efficacy is lower.


  1. Tordjman R, Genereau T, Guinnepain M.T, Weyer A, Lortholary O, Royer I, Casassus P, Guillevin L, "Reintroduction of vitamin B12 in 2 patients with prior B12-induced anaphylaxis", Eur. J. Haematol., 1998; 60 (4): 269-70
  2. Branco-Ferreira M, Clode M.H, Pereira-Barbosa M.A, Palma-Carlos A.G, "Anaphylactic reaction to hydroxycobalamin", Allergy., 1997; 52 (1): 118-9
  3. Denis R, Amin S, Cummins D, "Sensitivity reaction to parenteral vitamin B12: recurrence of symptoms after Marmite ingestion", Clin. Lab. Haematol., 1996; 18 (2): 129-31
  4. de Blay F, Sager M.F, Hirth C, Alt M, Chamouard P, Baumann R, Pauli G, "IgE-mediated reaction to hydroxocobalamin injection in a patient with pernicious anaemia", Lancet, 1992; 339: 1535-6

As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.