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 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.  

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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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