Long-term use of proton pump inhibitors beyond what duration may lead to a fall in circulating vitamin B12 levels?

• A. > 1 year
• B. > 3 years
• C. > 5 years
• D. > 10 years

Answer: (B)

Long-term proton pump inhibitor use reduces gastric acidity, which is needed to release vitamin B12 from dietary protein and allow it to bind intrinsic factor for absorption in the ileum. The body's B12 stores in the liver are large but finite, and daily losses are small, so depletion occurs gradually over years. Because this depletion takes time to become evident, the point at which circulating B12 levels may begin to fall is after several years of continuous acid suppression. The commonly cited threshold for this effect is greater than three years of use, which is why that duration best fits the question. After longer periods, the risk continues to rise, but the tipping point used in practice questions is just beyond three years.