COMPARATIVE EFFICACY OF ORAL, SUBLINGUAL, AND INTRAMUSCULAR VITAMIN B12 SUPPLEMENTATION: A SYSTEMATIC REVIEW AND META-ANALYSIS

Aim: vitamin B12 deficiency is common and can lead to hematological and neurological complications. Although intramuscular (IM) injection is the standard treatment, oral and sublingual routes are gaining interest due to better tolerability and patient preference. This systematic review and meta-analysis assessed the efficacy of oral and sublingual B12 supplementation compared to IM administration in increasing serum cobalamin levels. Methods: following PRISMA guidelines, a literature search was performed in PubMed, Scopus, and Web of Science for studies from January 2010 to February 2024. Eligible studies included RCTs and observational designs evaluating serum B12 changes after oral, sublingual, or IM administration. Out of 368 records, 17 met inclusion criteria; 12 were included in the meta-analysis. Results: pooled results showed no significant difference between non-invasive and IM routes in raising serum B12 (mean difference: -12.6 pmol/L; 95% CI: -28.4 to 3.2; p = 0.11). Clinical outcomes were similar across routes. Adherence and patient satisfaction were higher with oral and sublingual options. Heterogeneity was moderate (I² = 43%). Conclusions: oral and sublingual vitamin B12 supplementation demonstrate comparable efficacy to intramuscular injection in restoring serum cobalamin levels, particularly in individuals with mild to moderate deficiency. These findings support the consideration of non-invasive delivery routes in clinical practice, especially in patients where compliance or procedural burden is a concern. Further well-designed, long-term trials are warranted to confirm these findings and to explore outcomes across different clinical subpopulations.