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What are the long-term side effects from taking omeprazole?

The short answer:

Omeprazole is considered a well‑tolerated drug with a good safety profile. However, there is a growing body of evidence that long-term usage of omeprazole is associated with numerous serious side effects. This includes hypomagnesemia, increased risk of infection, vitamin B 12 deficiency, iron deficiency anemia, osteoporosis, and mental disorders such as delusions and confusion

Key Facts:

  • Omeprazole belongs to proton pump inhibitors which is a well‑tolerated class of drugs with a good safety profile.
  • Omeprazole is used for the treatment of symptoms related to increased gastric acid secretions.
  • The common side effects of omeprazole include nausea, vomiting, flatulence, and constipation.
  • The long-term use of omeprazole could lead to the following:
    • Hypomagnesemia
    • Increased risk of infection
    • Vitamin B12 deficiency
    • Iron deficiency anemia
    • Osteoporosis and bone fractures
    • Mental disorders such as delusions and confusion


Indications of omeprazolele

Common side effects of omeprazole

Long-term side effects of omeprazole

What are the indications of omeprazole?

Omeprazole is commonly used for the treatments of the following (Ref):

  • Heartburn
  • Treatment of gastric ulcer
  • Indicated for the short-term treatment of peptic ulcer disease in adults
  • Gastroesophageal reflux disease in pediatric and adult populations
  • For conditions prone to hypersecretion, such as Zollinger-Ellison syndrome, multiple endocrine adenomas, and systemic mastocytosis in adults
  • Used for stress ulcer prophylaxis

What are the common side effects of omeprazole?

Despite omeprazole and Proton pump inhibitors (PPIs) being considered a well‑tolerated class of drugs with a good safety profile. However, certain side effects are reported with omeprazole administration.

Common side effects of omeprazole:

  • Constipation
  • Headache
  • Nausea
  • Vomiting
  • Gas and bloating (Flatulence)
  • Stomach pain

What are the side effects of long-term use of omeprazole?

There is a growing body of evidence that has been published regarding the potential side effects of omeprazole and other PPIs associated with their long‑term use (Ref).

Taking omeprazole and other proton pump inhibitors in the long term may lead to several side effects including the following:

Decrease magnesium blood level:

Taking omeprazole for more than 3 months could decrease your magnesium blood level. Leading to the so-called hypomagnesemia.

  • A study published in 2014 showed that:
    • long term administration of omeprazole and other Proton pump inhibitors are associated with decreased magnesium blood levels (Hypomagnesaemia).
    • Omeprazole was found to inhibit the active absorption of magnesium leading to a decreased magnesium blood level.
    • The developed hypomagnesemia was found to respond to the withdrawal of omeprazole treatments.

Low magnesium blood levels could lead to the following:

  • Fatigue and weakness
  • Mental disorder as confusion
  • Loss of appetite
  • Muscles spasm
  • Tremors and muscles cramps
  • Sleeplessness
  • Hyperexcitation
  • Anxiety and depression also associated with magnesium deficiency
  • Irregular heartbeat
  • Increased risk of osteoporosis (Ref).
  • Low magnesium level is also associated with increased blood pressure (Ref).

Increased risk of infection

Studies showed a link between long-term administration of omeprazole and PPIs with increased risk of infection practically Clostridium difficile and pneumonia.

Researchers attributed this to the effect of long-term administration of omeprazole and PPIs in the reduction of gastric acidity, which may allow organisms to reach the intestine more easily.

  • A meta-analysis study published in 2012 reported that:
    • There was a 65% increase in the incidence of Clostridium difficile-associated diarrhea among patients using PPIs compared with non-users.
    • The authors recommend that the routine use of PPIs for gastric ulcer prophylaxis should be more prudent.
  • A systemic review published in 2015 reported that the uses of omeprazole and PPI are associated with a 1.5-fold increased risk of Community-Acquired Pneumonia, with the highest risk within the first 30 days after initiation of therapy.

Vitamin B12 deficiency:

Long‑term use of PPIs reduces the acidity in the stomach. This leads to a reduction in the absorption and digestion of various minerals and vitamins, such as vitamin B12.

The absorption of vitamin B12 requires gastric acid and pepsin. In the case of reduction of gastric acid secretion by long-term administration of omeprazole and other PPIs, vitamin B12 deficiency may result.

Moreover, the reduced acidity by long-term administration of omeprazole leads to overgrowth of the intestinal bacteria, hence these bacteria consume vitamin B12 through their metabolic process, consequently decreasing the absorption of vitamin B12.

  • A study showed that:
    • Patients taking proton pump inhibitors for more than 12 months were more likely to have vitamin B12 deficiency than individuals not taking proton pump inhibitors.
    • The authors also reported that treatment with cyanocobalamin for 8 weeks seemed to improve vitamin B12 blood levels.
  • Another large study examined the association between vitamin B12 deficiency and long-term uses of PPIs and H2 receptor blocking (acid-lowering agents with a different mechanism than PPI). The authors found that:
    • This study involved 659 adult patients and the follow-up continued over 6 years.
    • Results showed Vitamin B12 deficiency during prolonged PPI use in older adults, but not with prolonged H2 blocker use.
    • H2 blocker use did not influence serum B12 status.
    • Concomitant oral administration of B12 supplements was found to slow down but did not prevent the decline in B12 blood levels during prolonged PPI use.

Iron deficiency anemia

Dietary iron is mostly present in the ferric state (Fe3+) and has to be reduced into the ferrous state (Fe2+) by the gastric acid in order to become absorbable in the duodenum.

Long-term treatment with omeprazole and other PPIs decreases gastric acid secretion which is critical for iron absorption. As a result, iron absorption is decreased with long-term use of omeprazole.

Osteoporosis and bone fractures

The FDA published a document in 2011 reporting an increased risk of bone fractures in patients receiving long-term PPIs.

  • A previous study showed that:
    • Patients taking PPI had a 1.5‑fold increased risk of developing hip fractures compared with individuals not using PPIs,
    • The risk of bone fracture increased with a longer duration of PPI therapy at high doses.
    • The authors attributed this effect to reduced calcium absorption with long-term treatment with PPIs.
  • Another meta-analysis study based on 24 observational studies involving more than 2000000 patients showed that:
    • The risk of hip fractures was significantly greater in those taking high doses of PPIs compared to those who didn’t take PPIs.
    • The increased risk was also reported for both medium and low doses of PPIs.
    • The authors reported no association between increased risk of bone fractures and H2 receptor antagonist administration.

Mental disorders:

Long-term administration of omeperazole is reported to cause mental disorders.

  • A study published in 2018 reported that:
    • A 12-year-old girl suffered from psychotic symptoms, including formal thought disorder and delusional ideas after omeprazole administration.
    • These symptoms were immediately decreased and eliminated when omeprazole is replaced with ranitidine.