Comparative efficacy of vitamin B12 supplementation routes in adults with replacement indication: a systematic review
Abstract
Vitamin B12 deficiency is common and often requires long-term supplementation to prevent serious complications, yet the comparative efficacy of the oral, sublingual, and intramuscular routes remains uncertain. This systematic review evaluated the efficacy of different vitamin B12 supplementation routes in adults with an indication for replacement. PubMed, Embase, and Cochrane CENTRAL were searched without language or date restrictions, from inception to July 18, 2025, updated July 13, 2026, following PRISMA 2020 reporting. Eligible studies were randomized trials and observational cohorts comparing oral, sublingual, or intramuscular vitamin B12 supplementation in adults with an indication for replacement; pediatric and non-comparative studies were excluded. Risk of bias was assessed with RoB 2.0 (trials) and ROBINS-I (cohorts). The primary outcome was serum vitamin B12 or clinical response. This systematic review was registered with PROSPERO, number CRD420251126832. 13 studies met the inclusion criteria: 7 randomized controlled trials, 3 observational cohorts, 2 conference abstracts, and 1 research letter Included studies were conducted across 10 countries spanning Asia, Europe, North and South America, and Oceania, in both single-center and multicenter settings. Comparisons of oral vs. intramuscular supplementation were most frequent (8 studies), several suggesting comparable or superior biochemical responses with oral administration. Sublingual supplementation was…
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Evidence Hub reads this as a systematic review, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid.
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