Can omeprazole cause neuropathy? Exploring the vitamin B12 link

October 12, 2025 •

3 min read

Over 42,000 adverse event reports analyzed by researchers found an over eight-fold increase in neuropathy reports in patients taking proton pump inhibitors (PPIs) compared to those on H2 blockers. While not a direct cause, chronic use of omeprazole can lead to vitamin B12 deficiency, which is a well-established cause of neuropathy. This article explores the link between long-term omeprazole use and potential nerve damage.

Quick Summary

Long-term omeprazole use is associated with an increased risk of vitamin B12 deficiency, which can result in peripheral neuropathy. The risk is tied to duration and dosage, necessitating careful monitoring.

Key Points

Indirect Link: Omeprazole does not directly cause neuropathy, but its long-term use can lead to vitamin B12 deficiency, a known cause of nerve damage.
Chronic Use Risk: The risk of developing neuropathy increases with the duration and dosage of omeprazole therapy.
Mechanism: Omeprazole reduces stomach acid, which is necessary for the proper absorption of dietary vitamin B12.
Reversibility: Neuropathy caused by B12 deficiency is often reversible with supplementation and discontinuation of the PPI, particularly if caught early.
Symptoms: Signs of this neuropathy include numbness, tingling, muscle weakness, and balance issues, primarily in the hands and feet.
Monitoring is Key: Patients on long-term omeprazole should have their vitamin B12 levels monitored regularly by a healthcare provider.
Alternatives Exist: Other medications and lifestyle changes can manage acid reflux, especially for individuals at higher risk of nutrient deficiencies.

The Mechanism: Omeprazole and Vitamin B12 Deficiency

The connection between long-term omeprazole use and neuropathy is primarily due to its impact on vitamin B12 absorption. Vitamin B12 is crucial for healthy nerve function.

Stomach acid is necessary to release vitamin B12 from food proteins, allowing it to bind with intrinsic factor for absorption. Omeprazole reduces stomach acid by blocking proton pumps. This reduced acidity hinders B12 release from food, potentially leading to a deficiency over time.

Symptoms and Risk Factors

Neuropathy from vitamin B12 deficiency typically presents as peripheral neuropathy. Symptoms can include:

Numbness and tingling in the hands and feet.
Muscle weakness.
Difficulty with balance.
Cognitive issues in severe cases.

Risk factors for developing neuropathy while on omeprazole include:

Using the medication for two years or longer.
Taking higher doses.
Advanced age.
Pre-existing conditions like diabetes.

Evidence from Studies and Adverse Event Reports

A 2019 analysis of the FDA's Adverse Event Reporting System (FAERS) compared PPI and H2-receptor blocker use. This analysis found an over eight-fold increase in neuropathy reports among PPI users compared to those on H2-receptor blockers. The study suggested B12 deficiency as a possible cause for the observed neuropathies. A case study demonstrated that neuropathy linked to PPI-induced B12 deficiency can be reversible with discontinuation of the PPI and B12 supplementation.

Management and Prevention

To manage the risk of neuropathy in patients on long-term omeprazole:

Monitor vitamin B12 levels with blood tests.
Provide B12 supplementation if a deficiency is found.
Periodically assess the need for continued PPI therapy and consider lower doses or discontinuation if possible.
Explore alternative treatments for acid reflux, especially for those at higher risk.

Comparison Table: Omeprazole vs. Alternatives


Feature	Omeprazole (PPI)	H2-Receptor Blockers (e.g., Famotidine)	Antacids (e.g., Tums, Maalox)
Mechanism	Irreversible blockage of stomach proton pumps.	Reversible blockage of histamine H2 receptors, reducing acid production.	Directly neutralizes existing stomach acid.
Long-Term Neuropathy Risk	Associated with increased risk due to potential B12 deficiency.	Significantly lower risk of neurological adverse events, including neuropathy.	No known link to neuropathy via B12 deficiency.
Onset of Action	Slower onset (days) as it works on acid pumps.	Faster onset (hours) for acid suppression.	Immediate relief for symptomatic heartburn.
Duration of Effect	Long-lasting, providing 24-hour control of acid.	Shorter duration compared to PPIs.	Short-lived, requiring repeated dosing.
Best For	Chronic, severe GERD, healing ulcers.	Moderately frequent heartburn, short-term use.	Occasional, immediate heartburn relief.

Conclusion

Long-term omeprazole use is associated with an increased risk of neuropathy due to its potential to cause vitamin B12 deficiency. This risk is heightened with prolonged use and higher doses. Early detection of B12 deficiency and supplementation can often reverse the neuropathy. It is crucial for healthcare providers and patients to regularly review the need for long-term omeprazole, monitor for symptoms of deficiency, and consider alternative treatments.

Frequently Asked Questions

Omeprazole works by reducing stomach acid. Stomach acid is essential for releasing vitamin B12 from dietary protein so it can be absorbed. By reducing acid, omeprazole hinders this process over time, leading to a B12 deficiency and potentially neuropathy.

The risk is highest for individuals on high doses of omeprazole or those who take it for an extended period, typically two years or longer. Older adults and people with other risk factors for B12 deficiency are also more vulnerable.

The earliest signs often include a tingling or 'pins and needles' sensation in the hands and feet, which can progress to numbness and muscle weakness if the deficiency is not addressed.

Yes, in many cases, neuropathy caused by vitamin B12 deficiency is reversible. Stopping the PPI and beginning B12 supplementation can allow the nerves to recover, especially when the condition is detected early.

You should not stop taking omeprazole without consulting a healthcare provider. Discuss your symptoms with your doctor, who can perform tests to confirm a B12 deficiency and determine the best course of action, which may include supplementation or changing medications.

Alternatives include H2-receptor blockers (like famotidine), antacids, and lifestyle modifications such as diet changes. The appropriate alternative depends on the severity and frequency of symptoms.

Prevention strategies include using the lowest effective dose for the shortest time necessary, monitoring B12 levels during long-term therapy, and supplementing with B12 if a deficiency is identified.