Intranasal treatment of vitamin B12 deficiency in children

  • G. Frederiek Estourgie-van BurkEmail author
  • P. Hugo M. van der Kuy
  • Tim G. de Meij
  • Marc A. Benninga
  • C. M. Frank Kneepkens
Short Communication


Vitamin B12 deficiency is traditionally treated with intramuscular injections of cobalamin, which are stressful events for children. In adults, studies have shown adequate absorption of intranasally administered vitamin B12. To date, data concerning efficacy of intranasal administration of vitamin B12 in children are lacking. We report on ten cases of children with vitamin B12 deficiency who were successfully treated with intranasal administration of a spray containing hydroxocobalamin. The mean baseline vitamin B12 concentration increased from 126.3 pmol/l (SD 55.4) to 1914.7 pmol/l (SD 1509.7). No side effects were reported.

Conclusion: In children, intranasal application of vitamin B12 seems a safe and effective alternative to intramuscular injections, leading to higher compliance and less burden to patients.

What is Known:

• Children with vitamin B12deficiency are traditionally treated with intramuscular cobalamin injections, which are costly and painful.

• Studies in adults showed that intranasal application of hydroxocobalamin leads to normalisation of vitamin B12levels.

What is New:

• The intranasal application of vitamin B12resulted in a substantial increase of the mean baseline vitamin B12levels without any side effect.

• These data encourage a systematic evaluation of intranasal treatment of vitamin B12deficiency in order to define safety, optimal dosage and administration frequency.


Cobalamin deficiency Hydroxocobalamin Nasal spray Paediatric 



Methylmalonic acid


Authors’ contributions

All authors contributed to the study conception and design. Acquisition of the data was performed by FE, TdM, MB and FK. FE, HvdK and FK were involved in data interpretation. The first draft of the manuscript was written by FE. FE and FK wrote the manuscript. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

Informed consent was obtained from all participants.


  1. 1.
    Bensky MJ, Ayalon-Dangur I, Ayalon-Dangur R, Naamany E, Gafter-Gvili A, Koren G, Shiber S (2019) Comparison of sublingual vs. intramuscular administration of vitamin B12 for the treatment of patients with vitamin B12 deficiency. Drug Deliv Transl Res 9:625–630. CrossRefPubMedGoogle Scholar
  2. 2.
    Benson J, Phillips C, Kay M, Webber MT, Ratcliff AJ, Correa-Velez I, Lorimer MF (2013) Low vitamin B12 levels among newly-arrived refugees from Bhutan, Iran and Afghanistan: a multicentre Australian study. PLoS One 8:e57998. CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Blom HJ, van Rooij A, Hogeveen M (2007) A simple high-throughput method for the determination of plasma methylmalonic acid by liquid chromatography-tandem mass spectrometry. Clin Chem Lab Med 45:645–650. CrossRefPubMedGoogle Scholar
  4. 4.
    Cuevas-Nasu L, Mundo-Rosas V, Shamah-Levy T, Méndez-Gómez Humaran I, Avila-Arcos MA, Rebollar-Campos Mdel R, Villalpando S (2012) Prevalence of folate and vitamin B12 deficiency in Mexican children aged 1 to 6 years in a population-based survey. Salud Publica Mex 54:116–124CrossRefGoogle Scholar
  5. 5.
    Miller JL, Capino AC, Thomas A, Couloures K, Johnson PN (2018) Sedation and analgesia using medications delivered via the extravascular route in children undergoing laceration repair. J Pediatr Pharmacol Ther 23:72–83. CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Pawlak R, Lester SE, Babatunde T (2014) The prevalence of cobalamin deficiency among vegetarians assessed by serum vitamin B12: a review of literature. Eur J Clin Nutr 68:541–548. CrossRefPubMedGoogle Scholar
  7. 7.
    Slot WB, Merkus FW, Van Deventer SJ, Tytgat GN (1997) Normalization of plasma vitamin B12 concentration by intranasal hydroxocobalamin in vitamin B12-deficient patients. Gastroenterology 113:430–433. CrossRefPubMedGoogle Scholar
  8. 8.
    Stabler SP (2013) Clinical practice. Vitamin B12 deficiency. N Engl J Med 368:149–160. CrossRefPubMedGoogle Scholar
  9. 9.
    Tillemans MP, Donders EM, Verweij SL, Van der Hoeven RT, Kalisvaart KJ (2014) Effect of administration route on the pharmacokinetics of cobalamin in elderly patients: a randomized controlled trial. Curr Ther Res Clin Exp 76:21–25. CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    U.S. National Library of Medicine. TOXNET Toxicology Data Network. Hydroxocobalamin. Accessed 26 Oct 2019
  11. 11.
    Wang H, Li L, Qin LL, Song Y, Vidal-Alaball J, Liu TH (2018) Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database Syst Rev 3:CD004655. CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of PaediatricsSt. Antonius HospitalNieuwegeinThe Netherlands
  2. 2.Department of Clinical PharmacyErasmus Medical CentreRotterdamThe Netherlands
  3. 3.Department of Paediatric Gastroenterology and NutritionAmsterdam University Medical Centres, Location VU Medical CentreAmsterdamThe Netherlands
  4. 4.Department of Paediatric Gastroenterology and NutritionAmsterdam University Medical Centres, Location Academic Medical Centre/Emma Children’s HospitalAmsterdamThe Netherlands

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