Can Proton Pump Inhibitors (PPIs) decrease vitamin B12 absorption?

Proton Pump Inhibitors and Vitamin B12 Absorption

Yes, PPIs do decrease vitamin B12 absorption, particularly with long-term use (>2 years) and higher doses (>1.5 pills/day), and this effect is dose-dependent. 1

Mechanism of PPI-Induced B12 Malabsorption

• PPIs reduce gastric acid secretion, which is essential for:
  • Converting dietary vitamin B12 from its protein-bound form to free B12
  • Creating the acidic environment necessary for optimal B12 absorption 1, 2

Evidence for B12 Malabsorption with PPIs

The relationship between PPI use and vitamin B12 status has been established through multiple observational studies:

• A large nested case-control study from Kaiser Permanente Northern California found that higher PPI doses (>1.5 pills/day) had a stronger association with vitamin B12 deficiency (OR: 1.95; 95% CI: 1.77,2.15) compared to lower doses (<0.75 pills/day) (OR: 1.63; 95% CI: 1.48,1.78) in patients receiving ≥2-year supply of PPIs 1

• The FDA drug label for omeprazole explicitly states: "Daily treatment with any acid-suppressing medications over a long period of time (e.g., longer than 3 years) may lead to malabsorption of cyanocobalamin (vitamin B-12) caused by hypo- or achlorhydria" 2

• A study by Dharmarajan et al. found that while no immediate differences in B12 levels were detected between PPI users and non-users, the duration of PPI use was inversely correlated with vitamin B12 levels, even in patients taking multivitamins 1

Risk Factors for PPI-Induced B12 Deficiency

Patients at highest risk include:

• Long-term PPI users (>2-3 years) 2, 3
• Those taking higher doses (>1.5 pills/day) 1
• Older adults 4
• Patients with other risk factors for B12 deficiency 1

Important Clinical Considerations

1. Standard B12 testing may underestimate deficiency:

   • A study of long-term PPI users found that 31% of patients with normal serum B12 actually had functional B12 deficiency when additional markers (homocysteine and methylmalonic acid) were measured 3
   • B12 replacement reduced these elevated markers, confirming the diagnosis 3

2. Supplementation may not fully prevent deficiency:

   • Even patients taking multivitamins with 100% daily value of B12 showed an inverse correlation between PPI duration and B12 levels 1, 4
   • Oral B12 supplementation slowed but did not prevent the decline in B12 status during prolonged PPI use 4

Monitoring Recommendations

For patients on long-term PPI therapy:

• Monitor vitamin B12 status periodically, especially in older adults and those on high-dose or prolonged therapy 4
• Consider measuring both serum B12 and functional markers (homocysteine and methylmalonic acid) for more accurate assessment 3, 5
• Be aware that mean corpuscular volume (MCV) is not a reliable screening marker for B12 deficiency 6

Clinical Implications

The B12 deficiency associated with PPI use can lead to significant clinical consequences:

• Neurological disorders including peripheral neuropathy and cognitive dysfunction 5
• Megaloblastic anemia 5
• Elevated homocysteine levels, which may increase cardiovascular risk 3

PPIs should be used at the lowest effective dose for the shortest duration necessary, with periodic reassessment of the need for continued therapy, especially in patients at high risk for B12 deficiency.