Oral vs. Intramuscular Vitamin B₁₂: Efficacy, Safety Compared

An analysis of 3 randomized controlled trials (RTC) found that when compared to intramuscular (IM) vitamin B₁₂, oral vitamin B₁₂ was associated with similar outcomes in terms of efficacy and safety in the treatment of vitamin B₁₂ deficiency, although the evidence was deemed ‘low quality’. 

Researchers from Beijing University of Chinese Medicine and the Catalan Health Institute, Spain sought to investigate the effects of oral vitamin B₁₂ vs. IM vitamin B₁₂ to determine whether outcomes for vitamin B₁₂ deficient patients would differ based on the formulation. “Doctors may not be prescribing oral vitamin B₁₂ formulations because they may be unaware of this option or have concerns regarding its effectiveness,” the authors write.

They searched CENTRAL, MEDLINE, Embase, and LILACS, as well as the WHO ICTRP and ClinicalTrials.gov for randomized controlled trials that directly compared oral and IM vitamin B₁₂. The 3 trials used for analysis included 153 participants in total (74 administered oral vitamin B₁₂, 79 administered IM vitamin B₁₂). The average follow-up period was 3–4 months.  

Results from 2 trials using 1000μg/day oral vitamin B₁₂ showed no clinically relevant difference in vitamin B₁₂ levels when compared with the IM formulation. In 1 trial, a mean difference of 680pg/mL favoring oral vitamin B₁₂ was noted when 2000μg/day was used. Of the 2 trials that reported treatment related adverse events, 1 found that 2 of 30 individuals in the oral vitamin B₁₂ group left the study due to adverse events, while the other reported no adverse events in either treatment group. Additionally, oral vitamin B₁₂ demonstrated lower treatment-associated costs than IM vitamin B₁₂ in one trial (low-quality evidence due to serious imprecision). 

The authors concluded that while low-quality evidence suggests both formulations are safe and effective for normalizing vitamin B₁₂ levels, more trials should be conducted that have “better randomization and blinding procedures, recruit more participants, and provide adequate reporting.” 

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