Proton pump inhibitor use and its effect on vitamin B12 and homocysteine levels among men and women: A large cross-sectional study

Am J Med Sci. 2022 Dec;364(6):746-751. doi: 10.1016/j.amjms.2022.07.006. Epub 2022 Jul 24.

Abstract

Background: Previous studies have demonstrated an association between proton pump inhibitors (PPI) use and vitamin B12 deficiency. However, data regarding PPI use and elevated serum homocysteine level, an important marker of vitamin B12 deficiency, are scant.

Methods: Data were collected from medical records of subjects examined at a screening center in Israel. Cross sectional analysis was conducted on 25,953 subjects. Levels of vitamin B12 and homocysteine were compared between subjects who consumed PPI medications and those who did not.

Results: The mean age of the study population was 45 years and 33% were females. Subjects who received PPI medications had a minor higher vitamin B12 levels (320 pmol/L vs 300 pmol/L, p=0.024). Levels of vitamin B12 remained higher in females receiving PPI medications after performing a stratified analysis according to subjects' gender. Homocysteine levels were higher in subjects receiving PPI medications as compared to those who did not (12.0 μmol/L vs 11.6 0 μmol/L, p<0.001). Levels remained higher in female subjects after performing a stratified analysis according to subjects' sex. There was no statistically significant difference in the prevalence of vitamin B12 deficiency (according to two cutoffs: vitamin B12≤200 or ≤140 pmol/L) as well as the prevalence of hyperhomocysteinemia (defined as homocysteine >15.0 μmol/L) between the two groups.

Conclusions: According to our study, no association was found between PPI medication use and vitamin B12 deficiency or hyperhomocysteinemia. Patients receiving PPI medications had slightly higher levels of vitamin B12 and homocysteine, however these differences were too small to have any clinical relevance.

Keywords: Homocysteine; Hyperhomocysteinemia; PPI, Proton pump inhibitor; Vitamin B12.

MeSH terms

  • Cross-Sectional Studies
  • Female
  • Folic Acid
  • Homocysteine
  • Humans
  • Hyperhomocysteinemia* / chemically induced
  • Hyperhomocysteinemia* / epidemiology
  • Male
  • Middle Aged
  • Proton Pump Inhibitors / adverse effects
  • Vitamin B 12
  • Vitamin B 12 Deficiency* / chemically induced
  • Vitamin B 12 Deficiency* / epidemiology

Substances

  • Vitamin B 12
  • Proton Pump Inhibitors
  • Homocysteine
  • Folic Acid