Low or deficient vitamin B12 status is a leading cause of megaloblastic anemia, where impaired DNA synthesis disrupts red blood cell division and produces large, fragile megaloblasts instead of healthy cells. Clinically, vitamin B12–deficiency anemia is relatively common, with some population studies suggesting that up to 10–15% of older adults have biochemical B12 deficiency and a subset of these develop overt megaloblastic changes and anemia. In addition to fatigue and pallor from reduced oxygen‑carrying capacity, patients may show macrocytosis on CBC, elevated methylmalonic acid and homocysteine, and, if unrecognized, can progress to severe anemia that coexists with potentially irreversible neurologic complications This medication is commonly used for Stomach Acid.
Habeb B, Khair S, Reid A (July 14, 2025) Unmasking Pernicious Anemia: A Reversible Cause of Pancytopenia Due to Severe Vitamin B12 Deficiency. Cureus 17(7): e87911. Lee YP, Loh CH, Hwang MJ, Lin CP. Vitamin B12 deficiency and anemia in 140 Taiwanese female lacto-vegetarians. J Formos Med Assoc. 2021 Nov;120(11):2003-2009. Ankar A, Kumar A. Vitamin B12 Deficiency. 2024 Sep 10. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan–. PMID: 28722952. Wong CW. Vitamin B12 deficiency in the elderly: is it worth screening? Hong Kong Med J. 2015 Apr;21(2):155-64.
Some side effects may be linked to nutrient depletion caused by this medication.
Long-term use of PPIs might raise the risk of calcium deficiency and weaken bones. A potential mechanism for this is chronic hypergastrinemia, a condition where the stomach produces excess gastrin due to PPI use. This can lead to parathyroid hyperplasia, where the parathyroid glands overproduce a hormone that pulls calcium from bones. Additionally, PPIs significantly reduce stomach acid production, which can hinder calcium absorption from food in the intestines. Individuals taking PPIs, especially individuals at higher risk of bone issues or those on long-term PPI therapy, should consider calcium supplementation to help protect against deficiency.
Research suggests that long-term use of medications that reduce stomach acid, like H2 blockers and PPIs, may be linked to vitamin B12 deficiency. Stomach acid plays a role in releasing vitamin B12 from food, and reduced acid levels caused by these medications could hinder proper B12 absorption. Some studies find an increased risk of B12 deficiency, particularly in older adults or those using these medications for extended periods. Individuals taking H2 blockers or PPIs long-term should consider vitamin B12 supplementation.
There is evidence that proton pump inhibitors (PPIs) might decrease vitamin C levels in the body. A study showed that even a short course of omeprazole, a common PPI, reduced vitamin C levels in healthy volunteers, regardless of their dietary intake. This suggests that PPIs may reduce the bioavailability of vitamin C, meaning the body has a harder time absorbing and using it. Vitamin C plays a crucial role in immune function and antioxidant defenses and therefore individuals using PPI therapy should consider supplementation with vitamin C to protect against a deficiency.
Studies find that proton pump inhibitors (PPIs) may increase your risk of magnesium deficiency. A large study involving over 100,000 participants found a significant association between PPI use and lower magnesium levels (hypomagnesemia). PPIs work by reducing stomach acid production, which can also play a role in magnesium absorption. Individuals taking PPIs, particularly long-term use, should consider magnesium supplementation to help protect against deficiency.