Table 8. Randomized Controlled Trials Comparing Oral Vitamin B12 to Intramuscular Vitamin B12 in Patients with Vitamin B12 Deficiency.

Author, Year	Number of Patients	Population	Cut-off for B12 Deficiency	Interventions	Primary Outcome	Intent-to-Treat Analysis	Outcomes
Castelli et al, 2011 (71)	50 (48 completed the study, both drop-outs from the oral group)	Vitamin B12-deficient patients ≥60 years or ≥18 years with GI abnormalities or receiving a restricted diet	< 258 pmol/L	Oral (n = 22): 1,000 μg taken daily for 90 days IM (n = 26): 1,000 μg given on days 1, 3, 7, 10, 14, 21, 30, 60, and 90	Proportion of patients in each treatment arm with normalized vitamin B12 levels (≥ 258 pmol/L)	Yes	All patients had vitamin B12 levels > 258 pmol/L on days 61 and 91
Bolaman et al, 2003a (69)	70 (10 dropped out after < 10 days of treatment)	Patients with megaloblastic anemia (including 11 patients with suspected pernicious anemia) ≥16 years	< 118 pmol/L	Oral (n = 26): 1,000 μg taken daily for 10 days, then weekly for 4 weeks, then monthly IM (n = 34): 1,000 μg given daily for 10 days, then weekly for 4 weeks, then monthly	Hemoglobin level and signs or symptoms of anemia	No; drop-outs excluded from analysis	Significant improvement in hemoglobin levels in both groups from baseline to 90 days, approaching normal value (P < .01)
Kuzminski et al, 1998a (68)	38 (5 excluded from analysis because of folate deficiency, not B12 deficiency)	Vitamin B12 deficient (including 7 with confirmed pernicious anemia)	< 118 pmol/L	Oral (n = 18): 2,000 μg daily for 120 days IM (n = 15): 1,000 μg given on days 1, 3, 7, 10, 14, 21, 30, 60, and 90	Not specified	No; 5 patients with folate deficiency excluded from analysis	The mean vitamin B12 level in both the oral and intramuscular group was > 240 pmol/L

Abbreviations: GI, gastrointestinal; IM, intramuscular.

^aThese randomized controlled trials were included in the Cochrane systematic review by Vidal-Alaball et al, 2005. (67)