Clinical Question

How effective is oral vitamin B₁₂ supplementation compared with intramuscular supplementation in patients with vitamin B₁₂ deficiency?

Evidence-Based Answer

For normalizing serum vitamin B₁₂ levels, oral and intramuscular vitamin B₁₂ supplementation are equivalent after one to four months. (Strength of Recommendation [SOR]: C, disease-oriented evidence, systematic review of two randomized controlled trials [RCTs], and two additional RCTs.) For increasing vitamin B₁₂ levels, oral supplementation at 2,000 mcg per day is more effective than intramuscular supplementation at 1,000 mcg per day; however, 1,000 mcg per day orally is equivalent to 1,000 mcg per day intramuscularly. (SOR: C, disease-oriented evidence, RCTs.) Oral vitamin B₁₂ is also effective at maintaining normalization of vitamin B₁₂ levels. (SOR: C, disease-oriented evidence, one case series.)

Evidence Summary

A 2018 Cochrane review examined three parallel RCTs from Turkey, the United States, and India of patients with vitamin B₁₂ deficiency.¹ The trials compared oral vitamin B₁₂ with intramuscular cyanocobalamin supplementation. Two studies compared 1,000 mcg per day of oral vitamin B₁₂ with intramuscular vitamin B₁₂ and found no differences. The third trial compared 2,000 mcg per day of oral vitamin B₁₂ with intramuscular vitamin B₁₂ and found oral vitamin B₁₂ to be more effective at raising blood levels (mean difference of 680 pg mer mL [501.70 pmol per L]; 95% confidence interval, 392.7 to 967.3). [corrected] Patients 39 to 72 years of age (44% women; N = 153) who had serum vitamin B₁₂ levels less than 200 pg per mL (147.56 pmol per L) were included. Evaluated outcomes were vitamin B₁₂ levels (two RCTs) and normalization of vitamin B₁₂ levels (two RCTs). Study limitations included poor quality of randomization and blinding protocols.