vitamin B12 deficiency with acid suppressive therapy

Although gastric acid is required to cleave vitamin B12 from ingested dietary proteins, and the same parietal cells that produce acid also produce intrinsic factor, studies have been mixed as to whether acid suppressive therapy leads to low vitamin B-12 levels. a large community-based case-controlled study was done by Kaiser Permanente North California comparing 26,000 patients with an incident diagnosis of vitamin B12 deficiency with 185,000 without (see PPI and B12 deficiency jama 2013 in dropbox, or doi:10.1001/jama.2013.280490).  Results:

--Vitamin B12 deficiency was more commonly diagnosed in patients with at least a 2 year supply of PPIs compared to nonusers (OR, 1.65).
--among people taking PPIs for at least 2 years, those on a higher dose (greater than 1.5 pills per day) had a higher OR of 1.95, as compared to those who were on lower doses of less than 0.75 pills per day, with OR of 1.63, and a statistically significant trend.
--a similar trend was found with people on H2 blockers, though there was no increased risk in those taking less than 0.75 pills per day.  The odds ratios were also significantly less than with PPIs.
--In addition, there was an increasing trend of vitamin B12 deficiency with longer duration of use of PPIs, but no trend with H2 blockers
--The strength of the association between PPI use and B12 deficiency decreased with discontinuation of the PPI
--The association between PPIs and B12 deficiency was strongest among those who were younger, especially those younger than 30 years of age.  The association was also stronger for women than men.  No differences by race/ethnicity.  No difference if diagnosis of GERD or not.

so, although the study was not a randomized controlled trial, it has the benefit of being very large, did find that the likelihood of B12 deficiency increased with higher potency of acid suppression (PPI>H2 blocker) and higher doses of the PPI, more likely with longer duration of taking the PPI, decreased on stopping PPI,  and was more profound than with other conditions known to be associated with B12 deficiency such as thyroid disease.  There there also is a reasonably plausible mechanism. This again reinforces that PPI's are very strong drugs and should be used only when necessary -- prior studies have shown that it is pretty uncommon for patients initially put on PPIs to be "stepped-down" to less aggressive therapies (H2 blockers or calcium tablets), reinforcing the "step-up" approach of starting with less potent and increasing potency as clinically needed (though i also do find that even in this case, over time some patients can be down-titrated)

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