Risks of Vitamin B12 Deficiency with Long-Term PPI Therapy

Mechanism and Risk Factors

PPIs reduce gastric acid production, which impairs vitamin B12 absorption by limiting the release of vitamin B12 from food proteins and reducing its absorption in the intestine, according to the Annual Review of Nutrition 1, 2
Genetic variations in CYP2C19 may alter the effects of PPIs on vitamin B12 status, contributing to individual differences in susceptibility, as reported in the Annual Review of Nutrition 1

Some cross-sectional studies in older adults have found no significant differences in mean serum B12 levels between PPI users and non-users, despite an inverse correlation between duration of use and B12 levels, as noted in the Annual Review of Nutrition 1, 2
Randomized controlled trials comparing PPIs to antireflux surgery found no significant differences in serum vitamin B12 levels after 5 years of follow-up, according to the Annual Review of Nutrition 3, 4
The inconsistency in findings may be due to variable definitions of B12 deficiency, as discussed in the Annual Review of Nutrition 3

The FDA includes precautionary notices regarding the risk of vitamin B12 deficiency with long-term PPI use, as stated in the Annual Review of Nutrition 4
Patients taking B12-containing multivitamins may still develop deficiency with long-term PPI use, as supplementation may not fully prevent PPI-induced malabsorption, according to the Annual Review of Nutrition 1

B12 deficiency can lead to serious neurological complications if left untreated, including peripheral neuropathy and cognitive impairment, as reported in Clinical Nutrition 5
The American Gastroenterological Association does not currently recommend routine screening for B12 deficiency in all PPI users, but individual risk assessment is warranted, as stated in the Annual Review of Nutrition 4
Consider B12 supplementation in high-risk patients on long-term PPI therapy, particularly those with additional risk factors, according to the Annual Review of Nutrition 4