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Drug Deliv Transl Res. 2019 Jun;9(3):625-630. doi: 10.1007/s13346-018-00613-y.

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

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Family Division, Maccabi Healthcare Services, Tel-Aviv, Israel.
Internal Medicine Department, Ward E, Rabin Medical Center, Beilinson Campus, Petach Tikva, Israel.
Faculty of Engineering Sciences, Ben-Gurion University of the Negev, Beersheba, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Internal Medicine A, and Davidoff Cancer Center, Institute of Hematology, Rabin Medical Center, Beilinson Campus, Petach Tikva, Israel.
The Maccabi-Kahn Institute of Research and Innovation, Tel Aviv, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
The Department of Emergency Medicine, Rabin Medical Center, Beilinson Campus, 39 Jabotinski St., 49100, Petah Tikva, Israel.


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.


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


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