Gastric acid inhibitors linked to vitamin B12 deficiency

The use of gastric acid inhibitors for 2 or more years is strongly associated with symptomatic vitamin B12 deficiency, according to a report.

This association with proton pump inhibitors (PPls) and histamine H2 receptor antagonists (H2RA) was stronger than that for other conditions known to be associated with vitamin B12 deficiency, such as thyroid disease, diabetes and atrophic gastritis, said the division of research, Kaiser Permanente, Oakland, California.

These findings do not recommend against acid suppression for persons with clear indications for treatment, but clinicians should exercise appropriate vigilance when prescribing these medications and use the lowest possible effective dose.

Previous studies of the relationship between these drugs and vitamin B12 deficiency have produced conflicting results, and there haven’t been any large population-based studies to date.

They examined by performing a case-control study within a large, community-based population that was ethnically diverse and had equal access to health care.

The case subjects were adults within the Kaiser Northern California health care system who had a new diagnosis of vitamin B12 deficiency between 1997 and 2011. Any individuals who had conditions known to cause vitamin B12 deficiency directly were excluded from the study.

Control subjects for each case subject were up to 10 adults who did not have vitamin B12 deficiency and who were matched for sex, area of residence, race/ ethnicity, year of birth, and membership duration.

Only people who had taken PPIs or H2RAs for 2 years or more were included. This yielded 25,965 cases and 184,199 matched controls for the analysis.

In the primary analyses, a new diagnosis of vitamin B12 deficiency was more common in PPI users than in nonusers, with an odds ratio of 1.65. It also was more common among H2RA users than in nonusers, with an odds ratio of 1.25.

Using a higher mean daily dose of proton pump inhibitors (1.5 or more PPI pills per day) was more strongly associated with vitamin B12 deficiency, with an odds ratio of 1.95, than was a lower mean daily dose (less than 0.75 PPI pills per day), which had an odds ratio of 1.63. These same patterns were seen with higher vs. lower H2RA doses.

Similarly, vitamin B12 deficiency was more strongly associated with longer duration of PPI use than with shorter durations. However, no such trend was noted with the duration of H2RA use.

The strength of the association between vitamin B12 deficiency and PPI use diminished after the medication was discontinued.

The link was strongest among current users (odds ratio, 1.80), weaker among patients whose most recent use was 2-3 years previously, and weakest among those who’s most recent use was 3 or more years previously.

The association between vitamin B12 deficiency and the use of acid inhibitors was strongest among patients younger than 30 years of age and diminished with increasing age. It also was stronger among women than among men.

The strength of the association, however, did not differ across racial/ ethnic categories, or between patients who had a diagnosis of gastroesophageal reflux disease and those who did not, investigators noted.

The strength of the association also did not change over time, it was similar between cases diagnosed in 1997-2003, before proton pump inhibitors were made available as over-the-counter medications, as among cases diagnosed afterward, they pointed out.

At a minimum, the use of these medications identifies a population of higher risk of B12 deficiency, independent of additional risk factors.