Drug Delivery and Translational Research

, Volume 9, Issue 3, pp 625–630 | Cite as

Comparison of sublingual vs. intramuscular administration of vitamin B12 for the treatment of patients with vitamin B12 deficiency

  • Merav Jacobson Bensky
  • Irit Ayalon-Dangur
  • Roi Ayalon-Dangur
  • Eviatar Naamany
  • Anat Gafter-Gvili
  • Gideon Koren
  • Shachaf ShiberEmail author
Original Article


There are several methods to treat vitamin B12 deficiency (VB12d): intramuscular (IM), oral, sublingual (SL), and intranasal vitamin B12 (VB12) preparations. Large studies comparing the efficacy of SL vs. IM supplements are lacking. The aim of the present study was to compare the efficacy of SL versus the standard IM administration of VB12 in restoring B12 levels. This was a retrospective analysis of data from the computerized pharmacy records of Maccabi Health Service (MHS). Data were recorded for all patients older than 18 years of age who were prescribed VB12 during January 2014–December 2017. The main outcome was the change in levels of serum vitamin B12 (sVB12) after treatment. Overall, there were 4281 patients treated with VB12 supplements. Of them, 830 (19.3%) patients were treated with VB12 IM injections and 3451 (80.7%) with SL tablets. The mean ± SD difference between sVB12 levels before and after administration of VB12 supplements was significantly higher in the SL group vs. IM injection group (252 ± 223 vs. 218 ± 184 ng/L, p < 0.001). SL VB12 significantly increased the odds ratio (OR) for an increase of sVB12 levels, compared to the IM group, OR 1.85, CI 95% 1.5–2.3, p < 0.001. This is the largest study that documents therapy with SL preparations of VB12 sufficient and even superior to the IM route. The SL overcomes the challenges of IM injections and should be the first line option for patients with VB12d.


Vitamin B12 Intramuscular (IM) Oral Sublingual (SL) Efficacy 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Controlled Release Society 2019

Authors and Affiliations

  1. 1.Family DivisionMaccabi Healthcare ServicesTel-AvivIsrael
  2. 2.Internal Medicine Department, Ward ERabin Medical CenterPetach TikvaIsrael
  3. 3.Faculty of Engineering SciencesBen-Gurion University of the NegevBeershebaIsrael
  4. 4.Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael
  5. 5.Internal Medicine A, and Davidoff Cancer Center, Institute of HematologyRabin Medical CenterPetach TikvaIsrael
  6. 6.The Maccabi-Kahn Institute of Research and InnovationTel AvivIsrael
  7. 7.The Department of Emergency MedicineRabin Medical CenterPetah TikvaIsrael

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