ReviewAdvances in nutrition (Bethesda, Md.)2018
Proton Pump Inhibitors, H2-Receptor Antagonists, Metformin, and Vitamin B-12 Deficiency: Clinical Implications.
Review in Advances in nutrition (Bethesda, Md.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 2 of them syntheses that pooled it.
What it found
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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.
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.
Who cites it
67 citing papers in PubMed, 2 syntheses or guidelines pooled it, 141 citations in OpenAlex.
- Vitamin B12 Deficiency in Sickle Cell Disease: Method-Driven Estimates and Systematic Diagnostic Misclassification.European journal of haematology · 2026Pooled it
- Pooled it
- Vitamins and Chronic Wounds: How Altered Pharmacokinetics and Comorbidities Contribute to Vitamin Deficiencies.Basic & clinical pharmacology & toxicology · 2026Review
- Article
- Associations between Biomarkers of Vitamin BThe Journal of nutrition · 2026Article
- Delusional parasitosis with shared psychotic features secondary to vitamin B12 deficiency and mild cognitive impairment: a case report.BMC psychiatry · 2026Article
- The acute presentation of nitrous oxide-induced vitamin B-12 deficiency in a postoperative lumbar discectomy patient: illustrative case.Journal of neurosurgery. Case lessons · 2026Article
- Association of Long-Term Proton Pump Inhibitor Use With Nutrient Deficiencies: A Retrospective Cross-Sectional Study.Cureus · 2026Article
- Balancing therapeutic benefits and hidden risks of proton pump inhibitors in pediatric practice: a narrative review and update.Clinical and experimental pediatrics · 2026Article
- The association between medication use and vitamin BBMC geriatrics · 2026Article
- Vitamin B12 and Reproductive Health: Clinical Insights, Emerging Mechanistic Understanding, and Nutritional Aspects.Molecular reproduction and development · 2026Review
- Prevalence of Vitamin B12 Deficiency Among Patients With Type 2 Diabetes Mellitus on Long-Term Metformin Therapy.Cureus · 2026Article
- Association of low vitamin BEuropean child & adolescent psychiatry · 2025Article
- Curcumin as a promising therapeutic agent for diabetic neuropathy: from molecular mechanisms to functional recovery.Diabetology & metabolic syndrome · 2025Review
- Vitamin B12 Deficiency in Patients With Diabetic Peripheral Neuropathy: A Hospital-Based Cross-Sectional Study.Cureus · 2025Article
- Assessment of Patient Knowledge and Potential Screening Gaps in Vitamin B12 Deficiency.Cureus · 2025Article
- Concomitant use of metformin and proton pump inhibitors increases vitamin B12 deficiency risk in type 2 diabetes.Journal of diabetes investigation · 2025Article
- A multicenter retrospective study evaluating the effect of proton pump inhibitors on adjuvant tegafur-uracil/leucovorin efficacy for stage II-III colorectal cancer.Scientific reports · 2025Article
- Prevalence, associated factors, and impact of vitamin B12 deficiency in older medical inpatients.European geriatric medicine · 2025Article
- The clinical utility and cost-effectiveness of routine vitamin BThe South African journal of psychiatry : SAJP : the journal of the Society of Psychiatrists of South Africa · 2025Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is clear evidence that proton-pump inhibitors (PPIs), H2-receptor antagonists (H2RAs), and metformin can reduce serum vitamin B-12 concentrations by inhibiting the absorption of the vitamin. However, it is unclear if the effects of these drugs on serum vitamin B-12 are associated with increased risk of biochemical or functional deficiency (as is indicated by elevated blood concentrations of homocysteine and methylmalonic acid) or clinical deficiency (including megaloblastic anemia and neurologic disorders such as peripheral neuropathy and cognitive dysfunction). This review provides an overview of vitamin B-12 absorption and biochemistry and the mechanisms by which PPIs, H2RAs, and metformin affect these functions. It also summarizes the literature relating the use of these drugs to the risk of vitamin B-12 deficiency. Also discussed is that strategies for assessing vitamin B-12 status and diagnosing vitamin B-12 deficiency have evolved in recent years beyond solely measuring serum total vitamin B-12. Multiple analyte testing, a strategy in which ≥2 of 4 biomarkers of vitamin B-12 status-serum total vitamin B-12, holotranscobalamin, homocysteine, and methylmalonic acid-are measured, increases sensitivity and specificity for diagnosing vitamin B-12 deficiency. It is concluded that randomized controlled trials are now needed that use the strategy of multiple analyte testing to determine if PPIs, H2RAs, and metformin do indeed increase the risk of vitamin B-12 deficiency. Until these studies are conducted, a reasonable recommendation for physicians and their patients who are taking these drugs is to monitor vitamin B-12 status and to provide vitamin B-12 supplements if altered blood biomarkers or clinical signs consistent with low or deficient vitamin B-12 status develop.
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Registered trials
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.