Drug-Induced Vitamin B12 Deficiency: Current Evidence, Diagnostic Challenges, and Therapeutic Strategies
- 1Medicina Interna, Hospital Universitario 12 de Octubre, 28041 Madrid, Madrid, Spain
- 2Departamento Médico, ITF Research Pharma SLU, 28108 Alcobendas, Madrid, Spain
Abstract
Background/Objectives: Drug-associated vitamin B12 deficiency has emerged as a significant concern in clinical nutrition, as long-term use of metformin and proton pump inhibitors (PPIs) is common and may compromise cobalamin status through different physiological mechanisms. This narrative review summarizes mechanisms, risk profiles, diagnostic pitfalls, monitoring strategies and treatment options for vitamin B12 deficiency associated with chronic medication use. Methods: A narrative literature review was conducted by searching major biomedical databases and screening reference lists to identify relevant clinical studies, meta-analyses, narrative and systematic reviews, and clinical practice guidelines on vitamin B12 physiology, drug–nutrient interactions, biomarkers of cobalamin status, and supplementation strategies. Results: Metformin is consistently associated with lower serum vitamin B12 concentrations, particularly with high doses and prolonged exposure; PPIs may reduce the release of food-bound cobalamin through gastric acid suppression. Combined use may increase risk in older adults and in patients with restrictive diets, malabsorption or neurological symptoms. Serum vitamin B12 alone has limited diagnostic accuracy in borderline ranges; methylmalonic acid and homocysteine may help identify functional deficiency. High-dose oral vitamin B12 is effective in most clinical scenarios and may reduce healthcare burden compared with intramuscular therapy. Conclusions: A proactive, risk-based approach to monitoring and treatment may prevent hematological and neurological complications while preserving essential therapies such as metformin.
Related
- Current Evidence on Gene-Based and Epigenetic Therapeutic, Diagnostic, and Prognostic Strategies in Epithelial-Derived Carcinomas: A Scoping Review
- The Role of Neutrophil Extracellular Traps (NETosis) in Systemic Lupus Erythematosus: Molecular Mechanisms, Pathogenic Roles, Diagnostic Biomarkers, and Emerging Therapeutic Strategies
- Stem Cell-Derived Extracellular Vesicles in Bladder Cancer: Diagnostic Potential and Therapeutic Challenges.
- Research progress of extracellular vesicles in PMOS: molecular mechanisms, diagnostic value, and therapeutic strategies
- P015 Long-standing isolated alkaline phosphatase elevation attributed to vitamin D deficiency revealing extensive polyostotic Paget’s disease of bone: a diagnostic challenge and therapeutic dilemma
BibTeX
@article{segovia2026druginduced,
title = {{Drug-Induced Vitamin B12 Deficiency: Current Evidence, Diagnostic Challenges, and Therapeutic Strategies}},
author = {Ramón Costa Segovia and Lara Molines Guillem},
journal = {Metabolites},
year = {2026},
month = oct,
doi = {10.3390/metabo16110822},
url = {https://www.mdpi.com/2218-1989/16/11/822},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Drug-Induced Vitamin B12 Deficiency: Current Evidence, Diagnostic Challenges, and Therapeutic Strategies
AU - Ramón Costa Segovia
AU - Lara Molines Guillem
PY - 2026
DA - 2026/10/28
JO - Metabolites
DO - 10.3390/metabo16110822
UR - https://www.mdpi.com/2218-1989/16/11/822
AB - Background/Objectives: Drug-associated vitamin B12 deficiency has emerged as a significant concern in clinical nutrition, as long-term use of metformin and proton pump inhibitors (PPIs) is common and may compromise cobalamin status through different physiological mechanisms. This narrative review summarizes mechanisms, risk profiles, diagnostic pitfalls, monitoring strategies and treatment options for vitamin B12 deficiency associated with chronic medication use. Methods: A narrative literature review was conducted by searching major biomedical databases and screening reference lists to identify relevant clinical studies, meta-analyses, narrative and systematic reviews, and clinical practice guidelines on vitamin B12 physiology, drug–nutrient interactions, biomarkers of cobalamin status, and supplementation strategies. Results: Metformin is consistently associated with lower serum vitamin B12 concentrations, particularly with high doses and prolonged exposure; PPIs may reduce the release of food-bound cobalamin through gastric acid suppression. Combined use may increase risk in older adults and in patients with restrictive diets, malabsorption or neurological symptoms. Serum vitamin B12 alone has limited diagnostic accuracy in borderline ranges; methylmalonic acid and homocysteine may help identify functional deficiency. High-dose oral vitamin B12 is effective in most clinical scenarios and may reduce healthcare burden compared with intramuscular therapy. Conclusions: A proactive, risk-based approach to monitoring and treatment may prevent hematological and neurological complications while preserving essential therapies such as metformin.
SN - 2218-1989
ER -