Evidence map›Paper›PMID 41487531›Full record

SynthesisFrontiers in pharmacology2025

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

Marta Mazur, Artnora Ndokaj, Claudia Salerno, Jessica Vallone, Roman Ardan, Sabina Bietolini, Florence Carrouel, Aleksandra Wilk, Rachel Sarig, Livia Ottolenghi and 1 more

Abstract readSystematic Review
In one paragraph

Synthesis in Frontiers in pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Marta MazurBeSSA Department - Interdisciplinary Department of Well-being, Health and Environmental Sustainability, Sapienza University of Rome, Rieti, Italy.
Artnora NdokajDepartment of Oral and Maxillofacial Sciences, Sapienza University of Rome, Rome, Italy.
Claudia SalernoDepartment of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
Jessica ValloneDepartment of Oral and Maxillofacial Sciences, Sapienza University of Rome, Rome, Italy.
Roman ArdanDepartment of Economic Sciences, Koszalin University of Technology, Koszalin, Poland.
Sabina BietoliniDepartment of Humanities, Motor Sciences and Education, Niccolò Cusano University (UNICUSANO), Rome, Italy.
Florence CarrouelHealth Systemic Process Laboratory (P2S), UR4129, University Claude Bernard Lyon 1, University of Lyon, Lyon, France.
Aleksandra WilkDepartment of Histology and Embryology, Pomeranian Medical University, Szczecin, Poland.
Rachel SarigDepartment of Oral Biology, The Goldschleger School of Dental Medicine, Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
Livia OttolenghiDepartment of Oral and Maxillofacial Sciences, Sapienza University of Rome, Rome, Italy.
Denis BourgeoisHealth Systemic Process Laboratory (P2S), UR4129, University Claude Bernard Lyon 1, University of Lyon, Lyon, France.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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: Vitamin B12 supplementation was associated with a significant increase in serum cobalamin levels across all routes of administration (pooled mean difference = +402.6 pg/mL; 95% CI: 293.6 to 511.5; p < 0.001). Homocysteine levels were also significantly reduced across all groups (pooled mean difference = -4.83 μmol/L; 95% CI: -6.55 to -3.11; p < 0.001). No statistically significant differences were observed between oral, sublingual, and intramuscular (IM) routes of administration (p = 0.270 for cobalamin levels and p = 0.485 for homocysteine levels), nor between randomised controlled trials and observational studies (p = 0.268 for cobalamin levels). No dose-response effect was observed (p = 0.485), suggesting that absorption efficiency rather than dosage may be the determining factor. Subgroup analyses by age and clinical conditions (e.g., gastrectomy, unspecified deficiency) revealed comparable efficacy across populations. However, heterogeneity was substantial (I 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.

Indexed as

bioavailabilitycobalaminefficacymeta-analysistherapeutic approachesvitamin B12

Identifiers

PMID41487531
PMCPMC12757266

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.