The consequences of vitamin B12 (B12) deficiency most commonly include neurologic (CNS and peripheral nervous system) and hematologic (megaloblastic anemia). Because the progression of symptoms and signs related to B12 deficiency can be subtle, yet extremely burdensome to patients, clinicians must maintain a high level of vigilance for circumstances in which B12 deficiency can predictably occur, such as alcoholism and malnutrition.

Use of proton pump inhibitors (PPIs) and histamine-type 2-receptor antagonists (H2RA) is widespread in the United States. In 2012, more than 150 million prescriptions were written for PPIs alone. These numbers underestimate use since OTC versions of PPIs are also available.

Absorption of B12 requires that it first be cleaved from its food protein source on entering the GI tract. Gastric acid is required to release B12 from food. Since PPIs and H2RAs reduce gastric acidity, it should come as no surprise that they might be associated with greater risk for B12 deficiency.

A case-control study using the population of the Kaiser Permanente Northern California Healthcare system provided the opportunity to compare PPI/H2RA use among persons confirmed to have B12 deficiency (n = 25,956) vs controls (n = 184,199).

Receiving a PPI prescription for ≥ 2 years was associated with a 65% increased odds ratio of B12 deficiency. Similarly, receipt of H2RA treatment for that same interval was associated with a 25% increased risk.

The benefits of PPI and H2RA treatment are often substantial. That B12 deficiency is more likely to occur when using long-term GERD treatments should not discourage their use, but rather, increase clinician vigilance for the possibility of B12 insufficiency, especially when potentially appropriate symptoms or signs appear.