Proton Pump Inhibitors, H2-Receptor Antagonists, Metformin, and Vitamin B-12 Deficiency: Clinical Implications
Miller JW • Advances in Nutrition
Key Finding
PPIs/H2RAs: HR 1.83 (95% CI 1.36-2.46) for B12 deficiency with ≥10 months use; Metformin: mean B12 reduction of -54 pmol/L (95% CI -81 to -26)
Key Findings
- 1PPIs/H2RAs: HR 1.83 for B12 deficiency (≥10 months use)
- 2Metformin: -54 pmol/L mean B12 reduction
- 3Dose-dependent effects with metformin
- 4Multiple biomarkers recommended over routine supplementation
Original title: “Proton Pump Inhibitors, H2-Receptor Antagonists, Metformin, and Vitamin B-12 Deficiency: Clinical Implications”
Plain English Summary
Narrative review examining whether gastric acid-lowering medications (PPIs, H2RAs) and metformin reduce vitamin B12 absorption. PPIs/H2RAs show HR 1.83 for B12 deficiency with long-term use; metformin reduces serum B12 by -54 pmol/L on average.
In-Depth Analysis
Abstract
The review examines whether gastric acid-lowering medications (PPIs, H2RAs) and metformin reduce vitamin B12 absorption and increase deficiency risk.
Key Results
PPIs/H2RAs
- •Meta-analysis: HR 1.83 (95% CI 1.36-2.46) for B12 deficiency with long-term use (≥10 months)
- •Diagnostic criteria varied across studies
Metformin
- •Randomized trials: mean reduction of -54 pmol/L (95% CI -81 to -26) in serum B12
- •Dose-dependent effects observed
Functional Markers
- •Studies examining methylmalonic acid and homocysteine showed limited evidence that reduced serum B12 translates to functional deficiency
Recommendations
Monitor B12 status using multiple biomarkers rather than routine supplementation, with individualized assessment based on baseline status and clinical presentation.
Paradigm Relevance
How this study applies to different clinical perspectives:
Standard Medical
RelevantConventional clinical guidelines used by most doctors
Why it matters:
Provides evidence base for drug-nutrient interaction monitoring in standard care.
Research Consensus
RelevantCurrent scientific understanding, often ahead of guidelines
Why it matters:
Quantifies risks and provides framework for rational monitoring strategies.
Metabolic Optimization
RelevantProactive targets for optimal health, not just disease absence
Why it matters:
Supports proactive assessment in anyone on these medications, especially combination therapy.
Study Details
- Type
- Review Article
- Methodology
- Narrative review synthesizing mechanistic studies, meta-analyses of observational/case-control studies, and recent literature on multiple analyte B12 testing
Evidence Quality
Grade B - Narrative review with meta-analysis data. Source: PMC6054240
Related Biomarkers
Calculate & Evaluate on Metabolicum
Original Source
DOI (Digital Object Identifier) is a permanent link to this publication. Unlike website URLs that can change, a DOI always resolves to the correct source.
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