Intramuscular injections (IMI) of B12 are the typical way to treat B12 deficiency. The injections can be painful and expensive. Norberg (1) (1999, Sweden) points out that investigations in the 1950s and 60s showed that oral B12 is absorbed by an alternative pathway not dependent on intrinsic factor or an intact ileum. Approximately 1% of an oral dose in the range of 200-2,000 µg/day was absorbed by the alternative pathway in those investigations. Based on this research, oral treatment, rather than IMI, has been in use for the majority of B12 deficiency cases in Sweden since the early 1970s.
In a literature review encouraging the use of oral B12 therapy over injections for patients with pernicious anemia, Lederle (2) (1991, USA) reported that Swedish investigators recommend 2,000 µg of oral B12 twice a day or injections to replenish B12 stores. After initial therapy, doses of 1,000 µg/day appear to be enough.
Kuzminski et al. (3). (1998, USA) studied 33 newly diagnosed B12-deficient patients (almost all had malabsorption) who received cyanocobalamin as either 1 mg intramuscularly on days 1, 3, 7, 10, 14, 21, 30, 60, and 90; or 2,000 µg orally on a daily basis for 120 days (4 months). See Table 1.
|Table 1. B12 Oral Administration Vs. Injection (Kuzminski et al.)|
|Serum B12 (pg/ml)||Serum MMA (µmol/l)||HCY (µmol/l)|
|After 4 months|
|Oral 2,000 µg/day||1,005a||.169b||10.6|
|a,b – Statistically significant difference between groups with same letters|
Kuzminski et al. conclude that 2,000 µg/day of oral cyanocobalamin was as effective as 1,000 µg injected intramuscularly each month, and might be superior.
Delpre & Stark (4) (1999, Israel) studied patients with B12 deficiency to see if B12 can be absorbed sublingually by dissolving a tablet under the tongue. The theory behind sublingual is that the mucous membranes under the tongue are efficient at absorbing certain molecules, particularly if combined with something fat-soluble such as a cyclodextrin. 5 patients had pernicious anemia, 7 were vegetarians, and 2 had Crohn’s disease (which can prevent the absorption of B12 in the ileum). The patients held two 1,000 µg B12 tablets (equaling 2,000 µg/day), made by Solgar, under their tongues for 30 minutes until completely dissolved. This was done for 7 to 12 days. Average serum B12 levels went from 127.9 ± 42.6 to 515.7 ± 235. All patients’ serum B12 normalized. There were no side effects and all patients preferred this to injections. Unfortunately, Delpre & Stark did not include a control group who chewed the B12 tablets, so there is no way to know if taking the tablets sublingually was more effective than chewing and swallowing them. On the basis of Kuzminski et al. above, chewing seems to be as effective if done for 3 months.
The large doses mentioned in this section are for people with B12 malabsorption (or vegans who have neglected their B12 intake for a few months). People without malabsorption problems or current B12 deficiency do not need such large doses.
1. Norberg B. Turn of tide for oral vitamin B12 treatment. J Intern Med. 1999 Sep;246(3):237-8.
2. Lederle FA. Oral cobalamin for pernicious anemia. Medicine’s best kept secret? JAMA. 1991 Jan 2;265(1):94-5.
3. Kuzminski AM, Del Giacco EJ, Allen RH, Stabler SP, Lindenbaum J. Effective treatment of cobalamin deficiency with oral cobalamin. Blood. 1998 Aug 15;92(4):1191-8.
4. Delpre G, Stark P, Niv Y. Sublingual therapy for cobalamin deficiency as an alternative to oral and parenteral cobalamin supplementation. Lancet. 1999 Aug 28;354(9180):740-1.
Bensky MJ, Ayalon-Dangur I, Ayalon-Dangur R, Naamany E, Gafter-Gvili A, Koren G, Shiber S. Comparison of sublingual vs. intramuscular administration of vitamin B12 for the treatment of patients with vitamin B12 deficiency. Drug Deliv Transl Res. 2019 Jun;9(3):625-630. Based on low, but relatively normal, serum B12 levels, these participants probably didn’t have pernicious anemia. There was also no evidence presented as to whether they took the B12 sublingually as distinct from swallowing.