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Long-Term PPI Use: Side Effects, Risks & When to Stop

By Dr. Vikas Singla in Gastroenterology, Hepatology & Endoscopy

Dec 30 , 2025 | 2 min read

Proton pump inhibitors (PPIs) are among the most commonly used and misused medications in routine clinical practice. A frequently overlooked problem is self-medication and prolonged, unsupervised use of PPIs for nonspecific symptoms such as bloating, gas, or abdominal discomfort.

While PPIs are highly effective in suppressing gastric acid secretion, they do not address the underlying causes of bloating, which are more often related to dietary factors, altered gut motility, or functional gastrointestinal disorders. Using PPIs for these symptoms offers minimal benefit and exposes patients to avoidable long-term risks. This underscores the importance of proper medical evaluation rather than empirical or self-prescribed therapy.

Micronutrient and Electrolyte Deficiencies

One of the well-documented complications of chronic PPI use is micronutrient deficiency. Prolonged acid suppression interferes with normal gastrointestinal absorption and has been associated with:

Hypomagnesemia
Iron-deficiency anaemia
Vitamin B12 deficiency
Hypocalcemia
Hypokalemia

Reduced gastric acidity impairs the absorption of non-heme iron and may increase hepcidin levels, thereby increasing the risk of iron-deficiency anaemia in a dose- and duration-dependent manner. Vitamin B12 deficiency occurs due to impaired release of B12 from dietary proteins, a process that requires gastric acid. Large population-based studies have demonstrated clinically significant electrolyte disturbances in long-term PPI users.

In everyday practice, we frequently encounter patients presenting to the OPD with unexplained iron-deficiency anaemia, who show improvement after discontinuation or dose reduction of unnecessary PPI therapy.

Gastrointestinal and Bone-Related Effects

Chronic acid suppression has also been linked to the development of fundic gland polyps. Although these polyps are usually benign, they are clearly associated with long-term PPI use and often regress after stopping the medication.

In addition, prolonged hypochlorhydria and compensatory hypergastrinemia impair calcium absorption. This results in a modest but clinically relevant increase in fracture risk, particularly involving the hip and spine, especially in elderly patients or those with other risk factors for osteoporosis.

Increased Risk of Infections

Sustained PPI use has been associated with a higher risk of infections, most notably:

Clostridioides difficile infection
Community-acquired pneumonia

Reduced gastric acidity alters gut microbiota and weakens the stomach’s natural barrier against ingested pathogens, increasing susceptibility to both gastrointestinal and respiratory infections.

Alternatives for Patients Requiring Long-Term Acid Suppression

In patients with truly refractory gastro-oesophageal reflux disease (GERD) who continue to require long-term PPIs despite optimal medical therapy, surgical or endoscopic interventions may be considered.

Anti-reflux surgery and newer endoscopic therapies can provide durable symptom control and significantly reduce dependence on lifelong medication in carefully selected patients.

Proven Indications for Long-Term PPI Therapy

Long-term PPI use should be reserved for patients with clear, evidence-based indications, including:

Severe erosive GERD (Los Angeles grade C or D)
Barrett’s oesophagus
Secondary prevention of recurrent peptic ulcer bleeding
Gastroprotection in high-risk patients on long-term NSAIDs or antiplatelet therapy
Zollinger–Ellison syndrome
PPI-responsive eosinophilic esophagitis

Conclusion

PPIs are highly effective and life-saving when used appropriately, but they are not benign medications. Unnecessary long-term use, particularly for symptoms like bloating and gas, should be avoided. Regular review of indications, doses, and durations is essential to minimise harm while maximising benefit.

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