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

BackgroundProton 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.MethodsElectronic 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.ResultsTwenty-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; I-2 = 54%). Overall risk of PPI use among vitamin B12 deficient individuals was higher than those without deficiency (OR 1.49, 1.20-1.85; I-2 = 68%). Most studies found no difference between serum vitamin B12 levels among PPI users compared to non-users.ConclusionAlthough 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.RegistrationThis study was not registered on PROSPERO

Automated summary

This systematic review examines the impact of proton pump inhibitors (PPI) on the absorption of vitamin B12 and finds that PPI use may increase the risk of vitamin B12 deficiency. Although some studies suggest a slightly higher risk of vitamin B12 deficiency in PPI users, the pooled analysis results are not clear enough, and better-designed prospective studies are needed to further clarify this issue.