Vitamin B 12 Deficiency Associated with Histamine 2 -Receptor Antagonists and a Proton-Pump Inhibitor

Abstract

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French

OBJECTIVE:

To report a case of vitamin B₁₂ deficiency associated with long-term use (∼4½ y) of histamine₂ (H₂)-receptor antagonists and a proton-pump inhibitor (PPI) in a patient with gastroesophageal reflux.

CASE SUMMARY:

A 78-year-old nonvegetarian white woman with symptomatic gastroesophageal reflux (GER) was started on cimetidine 300 mg 4 × daily in February 1990 and took various other antisecretory medications over the course of the next 4½ years. She had a normal serum vitamin B₁₂ concentration of 413 pg/mL in August 1992. In June 1994, her serum vitamin B₁₂ concentration was found to be in the low normal range at 256 pg/mL. Biochemical markers of vitamin B₁₂–dependent enzyme activity were measured at that time, and methylmalonic acid (MMA) and homocysteine (HCYS) were elevated at 757 nmol/L and 27.3 μmol/L, respectively. Serum folate was within the normal range at 4.9 ng/mL, and serum creatinine was slightly elevated at 1.4 mg/dL. MMA and HCYS concentrations decreased dramatically with oral replacement of vitamin B₁₂ 1000 μg/d, which confirmed vitamin B₁₂ deficiency. Oral replacement also demonstrated that the woman was able to adequately absorb nonprotein—bound vitamin B₁₂ from the gastrointestinal tract, suggesting that her deficiency was a result of food—cobalamin malabsorption. The accumulation of MMA and HCYS was not a consequence of renal dysfunction, since both metabolites dramatically decreased with vitamin B₁₂ replacement.

DISCUSSION:

Malabsorption of dietary protein-bound vitamin B₁₂ has been demonstrated with the use of H₂-receptor antagonists and PPIs. One previous case report of vitamin B₁₂ deficiency resulting from long-term use of omeprazole has been published. The malabsorption of dietary vitamin B₁₂ is thought to be a result of its impaired release from food protein, which requires gastric acid and pepsin as the initial step in the absorption process.

CONCLUSIONS:

The use of H₂-receptor antagonists and/or PPIs may impair the absorption of protein-bound dietary vitamin B₁₂ and could contribute to the development of vitamin B₁₂ deficiency with prolonged use. Patients taking these medications for extended periods of time, particularly >4 years, should be monitored for vitamin B₁₂ status.

Keywords

proton-pump inhibitor

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