What are the long-term problems associated with taking omeprazole (Proton Pump Inhibitor)?

From the Guidelines

Long-term use of omeprazole can lead to several potential health problems, including vitamin and mineral deficiencies, kidney problems, and an increased risk of certain infections, and therefore, regular monitoring by a healthcare provider is recommended, and the lowest effective dose should be used for the shortest duration necessary to control symptoms. The potential health problems associated with long-term omeprazole use include:

• Vitamin and mineral deficiencies, particularly vitamin B12, magnesium, calcium, and iron, due to reduced stomach acid necessary for proper absorption of these nutrients, which can lead to anemia, neurological issues, or osteoporosis with increased fracture risk 1.
• Kidney problems, including chronic kidney disease and acute interstitial nephritis, as well as an increased risk of certain infections, such as Clostridium difficile infections and pneumonia, due to reduced stomach acid allowing more bacteria to survive 1.
• Hypergastrinemia (elevated gastrin levels), which can lead to rebound acid hypersecretion when stopping the medication, making it difficult to discontinue use, and potential interactions with other medications, particularly clopidogrel, which may reduce its effectiveness 1. Some studies suggest a possible link to dementia, though this connection remains controversial, and the use of proton pump inhibitors, such as omeprazole, should be carefully considered and monitored by a healthcare provider, especially in patients with a history of severe erosive esophagitis or GERD-related complications 1. It is essential to weigh the benefits and harms of long-term omeprazole use and consider alternative treatments, such as diet or topical steroid therapy, if side effects occur or if the medication is no longer necessary, and maintenance proton pump inhibitor therapy can be considered as a long-term treatment in patients with eosinophilic esophagitis who are in clinical and histological remission 1.

From the FDA Drug Label

Omeprazole delayed-release capsules can cause serious side effects, including: • Vitamin B-12 deficiency. Omeprazole delayed-release capsules reduce the amount of acid in your stomach. Stomach acid is needed to absorb vitamin B-12 properly. Talk with your doctor about the possibility of vitamin B-12 deficiency if you have been on omeprazole delayed-release capsules for a long time (more than 3 years). • Low magnesium levels in your body. This problem can be serious Low magnesium can happen in some people who take a PPI medicine for at least 3 months. If low magnesium levels happen, it is usually after a year of treatment. • Stomach growths (fundic gland polyps) People who take PPI medicines for a long time have an increased risk of developing a certain type of stomach growths called fundic gland polyps, especially after taking PPI medicines for more than 1 year • Bone fractures. People who take multiple daily doses of PPI medicines for a long period of time (a year or longer) may have an increased risk of fractures of the hip, wrist, or spine. • Certain types of lupus erythematosus. Lupus erythematosus is an autoimmune disorder (the body’s immune cells attack other cells or organs in the body) Some people who take proton PPI medicines, including omeprazole delayed-release capsules, may develop certain types of lupus erythematosus or have worsening of the lupus they already have.

The long-term problems associated with taking omeprazole include:

• Vitamin B-12 deficiency: Long-term use of omeprazole can lead to vitamin B-12 deficiency, as stomach acid is needed to absorb vitamin B-12 properly.
• Low magnesium levels: Taking omeprazole for at least 3 months can cause low magnesium levels, which can be serious and usually occurs after a year of treatment.
• Stomach growths (fundic gland polyps): Long-term use of PPI medicines, including omeprazole, increases the risk of developing stomach growths called fundic gland polyps, especially after taking PPI medicines for more than 1 year.
• Bone fractures: Taking multiple daily doses of PPI medicines, including omeprazole, for a long period of time (a year or longer) may increase the risk of fractures of the hip, wrist, or spine.
• Certain types of lupus erythematosus: Omeprazole may cause certain types of lupus erythematosus or worsen existing lupus. 2

From the Research

Long-term Problems Associated with Omeprazole

• Omeprazole, a proton pump inhibitor (PPI), has been linked to several long-term problems, including:
  • Osteoporotic fracture risk, particularly in the hip, spine, and wrist 3
  • Bone mineral density loss, with studies suggesting a significant reduction in bone density after long-term PPI use 4, 5
  • Increased risk of enteric, respiratory, and urinary tract infections due to hypochlorhydria 6
  • Potential risk of congenital malformations in pregnant patients 6
  • Hypergastrinemia, which may lead to gastric polyps, gastric carcinoids, and gastric cancer 6
• However, not all studies have found a significant association between omeprazole use and bone mineral density loss, with one study suggesting that esomeprazole, but not omeprazole, is independently associated with significant reduction of BMD 5
• The long-term use of PPIs, including omeprazole, may also lead to vitamin and mineral deficiencies, such as vitamin B12 and C, and iron, calcium, and magnesium deficiencies 6
• Clinicians and patients should be cautious about these potential adverse effects and consider alternative treatments or lifestyle modifications to minimize the risks associated with long-term PPI use 6

Specific Studies on Omeprazole

• A 2022 narrative review discussed the recent findings on the risk of osteoporotic fracture associated with PPIs, including omeprazole, and called for further research to elucidate the mechanisms associated with this bone fragility 3
• A 2013 prospective study found that treatment with PPIs, including omeprazole, resulted in a significant reduction in bone density, with a mean reduction in total vertebra T score of 0.23 ± 0.42 units (p < 0.01) 4
• A 2001 study found that adding a bedtime H2-blocker to a proton pump inhibitor b.d. regimen, including omeprazole, enhanced nocturnal gastric pH control and decreased nocturnal gastric acid breakthrough 7
• A 2021 review discussed the comprehensive information regarding the adverse effects induced by long-term use of PPIs, including omeprazole, and their possible relations, and recommended that PPIs should be avoided for long-term use mainly in older adults unless there is a proper indication 6