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

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 similar to 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 (beta = -0.069; P = 0.03) and concomitant ALA and metformin use (beta = -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.