Work

Efficacy of sublingual and oral vitamin B12 versus intramuscular administration: insights from a systematic review and meta-analysis

Year: 2025

Type: review

Study designs: Systematic Review, Meta-Analysis

Abstract: Background: Vitamin B12 deficiency is a widespread condition, particularly among elderly individuals, patients with malabsorption syndromes, and those following plant-based diets. This systematic review and meta-analysis aimed to evaluate and compare the effectiveness of sublingual and oral vitamin B12 administration in comparison with intramuscular (IM) injections, both for improving serum cobalamin and reducing homocysteine levels. Methods: A comprehensive search was conducted across PubMed, Scopus, and Embase up to July 2024. Eligible studies included randomised controlled trials, cohort, and case-control studies assessing B12 supplementation efficacy via oral, sublingual, or IM administration routes. Meta-analyses were performed using random-effects models. Subgroup analyses evaluated four key factors: administration route efficacy, daily dosage, age group and clinical conditions that may affect vitamin B12 metabolism (e.g., underlying pathology). Sixteen studies were included in the quantitative synthesis, comprising a total of 6,098 participants. Results: > 80% in most comparisons), and Egger's test indicated potential publication bias. Given the high heterogeneity, further studies are needed to confirm the results. Conclusion: Sublingual and oral B12 supplementation appear to be as effective as intramuscular (IM) injections in improving cobalamin status and reducing homocysteine levels. Given their non-invasive nature, accessibility, and cost-effectiveness of sublingual formulations, they may represent a promising approach for long-term B12 management, particularly in patients with impaired absorption or in resource-limited settings. Further high-quality RCTs are warranted to refine dosing strategies and confirm long-term outcomes. Systematic Review Registration: CRD42024554513.

Source: Frontiers in Pharmacology

DOI: 10.3389/fphar.2025.1602976