Does omeprazole affect cholesterol levels and cardiovascular health?

October 13, 2025 •

3 min read

While long considered a benign medication, emerging studies suggest that prolonged use of the proton pump inhibitor (PPI) omeprazole may lead to metabolic changes. This raises the important question: Does omeprazole affect cholesterol and the broader cardiovascular system, potentially impacting overall heart health?

Quick Summary

Long-term omeprazole use is associated with altered lipid profiles, including elevated total cholesterol, LDL, and triglycerides, without impacting HDL levels. This effect is linked to increased cardiovascular risk through mechanisms involving nitric oxide reduction and potential drug interactions with statins.

Key Points

Long-term Use Associated with Altered Lipids: Prolonged omeprazole therapy has been linked to elevated levels of total cholesterol, LDL, and triglycerides in some studies.
No Significant Impact on HDL: Current research indicates that omeprazole typically does not significantly affect high-density lipoprotein (HDL) levels.
Potential for Cardiovascular Risk: Studies suggest that long-term PPI use, including omeprazole, may increase the risk of heart disease and adverse cardiovascular events, independent of other risk factors.
Mechanism Involves Nitric Oxide: One proposed mechanism is that PPIs may increase levels of ADMA, an inhibitor of nitric oxide, leading to vascular dysfunction.
Statin Drug Interaction: Omeprazole can negatively interact with some statins, such as atorvastatin, potentially reducing their effectiveness by affecting metabolism.
Monitoring is Key for Long-Term Users: Patients, especially those with pre-existing cardiovascular risks, should have their lipid profile monitored closely during prolonged omeprazole use.
Risk Is Higher with Chronic Use: Concerns regarding cholesterol and cardiovascular health are primarily associated with chronic, long-term omeprazole use, not short-term treatment.

Understanding Omeprazole and Cholesterol

Omeprazole is a widely used proton pump inhibitor (PPI) prescribed for conditions like GERD and peptic ulcers. However, recent research has explored its long-term safety, particularly concerning lipid metabolism and cardiovascular health. Studies provide insights into the potential relationship between omeprazole and cholesterol.

How Omeprazole May Influence Lipid Metabolism

Two potential mechanisms are being investigated regarding how omeprazole and other PPIs might affect cholesterol and cardiovascular risk: direct metabolic changes and drug interactions with heart medications.

Altered Lipid Profile: Prolonged omeprazole therapy has been linked to changes in blood lipids. A 2022 study noted that patients using omeprazole for over a year had elevated total cholesterol, low-density lipoprotein (LDL), and triglycerides compared to a control group. High-density lipoprotein (HDL) levels did not show a significant change in this study.
Impact on Nitric Oxide and Endothelial Function: A 2013 study in Circulation proposed a mechanism connecting PPIs to increased cardiovascular risk. It suggested that PPIs, including omeprazole, might increase plasma levels of asymmetrical dimethylarginine (ADMA), which inhibits nitric oxide (NO) synthase. This could lower NO levels, potentially leading to vascular dysfunction, inflammation, and thrombosis—factors that increase the risk of cardiovascular events.
Drug-Drug Interactions with Statins: A study published on medRxiv in 2024 highlighted a drug interaction between omeprazole and atorvastatin. Combining these medications was associated with increased levels of a statin lactone metabolite, which is less effective at inhibiting HMG-CoA reductase. This interaction could decrease the effectiveness of the statin, indirectly impacting cholesterol management and raising cardiovascular risk.

Clinical and Research Findings

Several studies have investigated the relationship between omeprazole and cholesterol and cardiovascular health, showing varied results.

A large prospective cohort study in 2024 using UK Biobank data linked regular PPI use to a higher risk of several cardiovascular outcomes, including coronary heart disease and heart failure. While examining PPIs as a class, this study supports broader concerns about long-term PPI use and cardiovascular health.
A systematic review and meta-analysis focusing on patients post-percutaneous coronary intervention (PCI) found discrepancies between observational studies and randomized controlled trials (RCTs). Observational data suggested a moderate rise in adverse cardiovascular events, but RCTs did not confirm this, indicating a need for more definitive research.

Long-Term vs. Short-Term Omeprazole Use

It's important to consider the duration of omeprazole use, as concerns about cholesterol and cardiovascular risk are primarily linked to prolonged therapy, typically defined as use exceeding a year.


Feature	Short-Term Omeprazole Use	Long-Term Omeprazole Use
Typical Duration	A few weeks to a few months	Greater than 12 months
Effect on Cholesterol	Generally not associated with significant lipid changes.	Associated with elevated total cholesterol, LDL, and triglycerides.
Associated Risks	Typically considered safe with mild side effects (e.g., headache, diarrhea).	Linked to altered lipid profiles, potential endothelial dysfunction, and increased cardiovascular event risk.
Cardiovascular Studies	Early studies focused on short-term gastric effects rather than lipid profiles.	Emerging studies identify cardiovascular risk and adverse lipid outcomes with prolonged use.
Metabolic Changes	No significant metabolic changes generally observed.	Associated with changes in biochemical profiles, including liver enzymes and vitamin/mineral levels.

Mitigating Potential Risks

Patients on long-term omeprazole, especially those with existing cardiovascular risk factors, should work with their healthcare provider to manage potential effects on cholesterol and heart health.

Regular Monitoring: Monitoring lipid profiles may be necessary for individuals on extended therapy.
Reviewing Medication Use: Healthcare providers should regularly assess the need for and duration of PPI treatment. For long-term use, exploring alternative medications or dose adjustments might be appropriate, particularly for high-risk patients.
Considering Alternative PPIs: Some research suggests certain PPIs, like pantoprazole, may have a lower risk of drug interactions with statins. Switching to a PPI that doesn't significantly inhibit the enzyme CYP2C19, which metabolizes certain statins and clopidogrel, could be an option.

Conclusion

While omeprazole is effective for acid-related conditions, growing evidence, particularly regarding long-term use, suggests that potential effects on cholesterol and cardiovascular health should be considered. Studies indicate possible links to altered lipid profiles, endothelial dysfunction, and negative drug interactions with statins. It is important to note that many of these findings are observational, and more extensive randomized controlled trials are needed to establish causation. Patients should not stop taking omeprazole without consulting their healthcare provider. Discussions with a doctor can help balance the treatment's benefits against potential long-term risks.

Frequently Asked Questions

Some observational studies have shown that long-term omeprazole use is associated with elevated levels of total cholesterol, LDL cholesterol, and triglycerides. However, the link is still under investigation, and causation has not been definitively proven.

While long-term omeprazole has been linked to increases in total cholesterol and LDL, studies have not found a significant impact on high-density lipoprotein (HDL) levels.

Beyond potential cholesterol effects, omeprazole may interfere with nitric oxide production, a substance crucial for vascular health. Reduced nitric oxide can contribute to vascular dysfunction, inflammation, and an increased risk of adverse cardiovascular events.

Yes, research suggests that the observed effects on lipid profiles are associated primarily with prolonged omeprazole therapy (over one year). Short-term use is not typically linked to these metabolic changes.

While generally considered safe, omeprazole can interfere with the metabolism of certain statins, such as atorvastatin, potentially reducing their effectiveness. If you are on both medications, your doctor may monitor your lipid levels more closely or consider an alternative PPI with a lower potential for interaction.

The effects on cholesterol and potential drug interactions can vary among different PPIs. Some PPIs, like pantoprazole, may have a lower risk of certain drug interactions, but more research is needed to fully understand the differences across the entire class.

Do not stop taking your medication abruptly. You should discuss your concerns with your healthcare provider, who can evaluate your individual cardiovascular risk, monitor your lipid profile, and determine if an adjustment to your treatment plan is necessary.