Vitamin B12 deficiency and use of proton pump inhibitors: a systematic review and meta-analysis

ABSTRACT

Background

Proton pump inhibitors (PPI) may impact the absorption of vitamin B12. We performed a systematic review to ascertain if PPI use increases risk of vitamin B12 deficiency.

Methods

Electronic databases (PubMed, Embase, Scopus) were searched on first of September 2022. We selected studies that compared the frequency of vitamin B12 deficiency in PPI users and non-users. Pooled Odds Ratio (OR) was calculated for the occurrence of vitamin B12 deficiency in PPI users compared to non-users. The risk of bias was assessed using the Newcastle Ottawa scale.

Results

Twenty-five studies were included. The pooled OR of vitamin B12 deficiency among PPI users (2852 participants) was higher than non-users (28070 participants) (OR 1.42, 95% CI: 1.16–1.73; I² = 54%). Overall risk of PPI use among vitamin B12 deficient individuals was higher than those without deficiency (OR 1.49, 1.20–1.85; I² = 68%). Most studies found no difference between serum vitamin B12 levels among PPI users compared to non-users.

Conclusion

Although the pooled OR of vitamin B12 deficiency was slightly increased in PPI users, but there was significant heterogeneity, and the pooled OR was too low to imply an association clearly. Better-designed prospective studies in long-term users may clarify the issue.

Registration

This study was not registered on PROSPERO

KEYWORDS:

• Proton pump inhibitors
• cobalamin
• vitamin B12
• malabsorption
• Pantoprazole
• Rabeprazole
• Esmoprazole
• Omeprazole

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Author contributions

Conception: AK Dutta, V Sharma. Search: V Sharma. Screening and Selection: A Choudhury, V Jearth, V Sharma. Data Extraction: A Choudhury, A Jena, V Sharma. Analysis: V Sharma. RoB: A Choudhury, A Jena. Initial Draft: A Choudhury, A Jena, V Sharma. Critical revisions and intellectual content: G Makharia, U Dutta, M Goenka, R Kochhar, V Sharma. All authors approved the final version.

Data availability statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/17474124.2023.2204229

Additional information

Funding

This paper was not funded.