Association between Acid-Lowering Agents, Metformin, and Vitamin B12 among Boston-Area Puerto Ricans

J Nutr. 2023 Aug;153(8):2380-2388. doi: 10.1016/j.tjnut.2023.05.031. Epub 2023 Jun 9.

Abstract

Background: Vitamin B12 involves several physiological functions, and malabsorption is reported with medication use.

Objectives: Studies have reported an inverse association between the use of metformin or acid-lowering agents (ALAs), such as proton pump inhibitors, histamine 2 receptor antagonists, and blood vitamin B12 concentration, because of malabsorption. The concomitant use of these medications is underreported. We sought to examine these associations in a cohort of Boston-area Puerto Rican adults.

Methods: This analysis was conducted within the Boston Puerto Rican Health Study (BPRHS), an ongoing longitudinal cohort that enrolled 1499 Puerto Rican adults aged 45-75 y at baseline. Our study comprised 1428, 1155, and 782 participants at baseline, wave2 (2.2 y from baseline), and wave3 (6.2 y from baseline), respectively. Covariate-adjusted linear and logistic regression was used to examine the association between baseline medication use and vitamin B12 concentration or deficiency (vitamin B12 <148 pmol/L or methylmalonic acid >271 nmol/L), and long-term medication use (continuous use for ∼6.2 y) and wave3 vitamin B12 concentration and deficiency. Sensitivity analyses were done to examine these associations in vitamin B12 supplement users.

Results: At baseline, we observed an association between metformin use (β = -0.069; P = 0.03) and concomitant ALA and metformin use (β = -0.112; P = 0.02) and vitamin B12 concentration, but not a deficiency. We did not observe associations between ALA, proton pump inhibitors, or histamine 2 receptor antagonists, individually, with vitamin B12 concentration or deficiency.

Conclusions: These results suggest an inverse relationship between metformin, concomitant ALA, metformin use, and serum vitamin B12 concentration.

Keywords: acid-lowering agents (ALA); histamine 2 receptor antagonists (H2RA); metformin; proton pump inhibitors (PPI); vitamin B12.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Diabetes Mellitus, Type 2*
  • Histamine
  • Histamine H2 Antagonists / adverse effects
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Metformin* / therapeutic use
  • Proton Pump Inhibitors / adverse effects
  • Vitamin B 12
  • Vitamin B 12 Deficiency*

Substances

  • Metformin
  • Vitamin B 12
  • Proton Pump Inhibitors
  • Histamine
  • Histamine H2 Antagonists
  • Hypoglycemic Agents