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Am Fam Physician. 2022;105(6):663-664

Author disclosure: No relevant financial relationships.

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. 

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Clinical Inquiries provides answers to questions submitted by practicing family physicians to the Family Physicians Inquiries Network (FPIN). Members of the network select questions based on their relevance to family medicine. Answers are drawn from an approved set of evidence-based resources and undergo peer review. The strength of recommendations and the level of evidence for individual studies are rated using criteria developed by the Evidence-Based Medicine Working Group (

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