For more than 20 years now, medications known as Proton Pump Inhibitors have been used to treat a number of gastric, specifically acid-related, conditions. In various cases, proton pump inhibitors (PPI) have supplanted other form of medication for acid reflux.

According to a review of PPI use in the US in 2009, approximately 21 million American adults used prescription PPIs. In cost terms, this number came up to $13 billion when over-the-counter (OTC) medications are included with prescriptions. Although these medications were developed to heal stomach ulcers, most people use proton pump inhibitors regularly to control and manage frequently occurring acid reflux symptoms. In fact, many of those adults have been taking these drugs for years.

While PPIs have proven to be effective at reducing or eliminating GERD symptoms for many, they come with some limitations and side effects of their own. Some of the adverse effects of proton pump inhibitor medications can have serious long-term implications.

Even the FDA and CMS have recognized that proton pump inhibitor medication can have adverse effects. According to a guideline published by the CMS, prescription proton pump inhibitors should only be used for four to eight weeks, depending on the severity of the condition. OTC use for heartburn symptoms is limited to 14 days.

Regardless of this caution and medical advice, multitudes of people still proceed to use or rather overuse PPIs. Unfortunately, too often doctors prescribe proton pump inhibitors even when there is no medical reason for the medication:

Some studies have examined the appropriateness of PPI prescriptions. In one study of older patients in Italy, 30% were taking a PPI with no clear indication, although a further 11% of this cohort possessed a recognized indication and were not on treatment (that is, PPIs were underprescribed). A study of 124,133 first-time adult users from Denmark found that only one third met criteria for potential long-term use. In the same catchment population, only 4% of pre-existing long-term users (defined as more than 60 daily doses over a six-month period) had a diagnosis that merited long-term management.

What is a Proton Pump Inhibitor?

Proton pump inhibitors are a type of medication that is commonly used to control symptoms of conditions like GERD, peptic ulcers, and other gastric conditions. As their name indicates, PPIs inhibit or limit the proton pumps or proton/potassium pumps or parietal cells in the stomach.

Parietal cells are epithelial cells located in the membrane of the stomach and they produce stomach acid, also known as proton pump stimulation. However, by using PPIs, one can inhibit proton pump stimulation and stop or reduce the production of stomach acid, leading to a reduction of acid reflux symptoms.

Some examples of proton pump inhibitors include Prilosec (omeprazole), Prevacid (lansoprazole), Protonix (pantoprazole), and various others. The majority of them have similar mechanisms of actions and rate of effectiveness.

However, these PPIs trigger some side effects in the body that can potentially harm various organs in the body.

Reasons to Avoid Using a Proton Pump Inhibitor

Impaired Nutrient Absorption

Proton pump inhibitor users have been shown to have a higher risk of vitamin and nutrient deficiency. According to a study, PPI usage is linked to a deficiency of vitamin B12, vitamin C, calcium, iron, and magnesium.

This is most likely related to the unbalanced inhibition of stomach acid production. Stomach acid is crucial for the absorption of various vitamins, minerals, and macro- and micronutrients. Achlorhydria or a lack of stomach acid can impair absorption.

Increased Risk of Gut Infections

The acidic nature of stomach acid or HCL, under normal circumstances, is crucial for destroying bacteria and other microbes in the stomach. When a person consumes PPIs, the environment or pH of the stomach becomes basic or alkaline. This means that the microbes that would normally be killed by acidity can now pass through the digestive system unscathed.

According to a 2016 study focused on acid-suppression medication and bacterial gastroenteritis, the use of PPI had a 3.71 times increased risk of Campylobacter infection and increased the risk of Clostridium difficile 1.7 times. The study was conducted for both community and hospital samples and produced similar results.

Medical researchers also believe that proton pump inhibitors are linked with SIBO (small intestinal bacterial overgrowth). Their study showed that patients that used PPIs have a  1.71 times increased risk of developing SIBO.  The Mayo Clinic developed this video to highlight how proton pump inhibitors decrease diversity in gut microbiome and increase risks for complications

Malabsorption of Calcium

There is a reason why the FDA issued a warning in 2011 that cautioned proton pump inhibitor users to limit their use. The warning stated that people should not use over-the-counter PPIs for no longer than two weeks at a time for up to three rounds a year.

The main reason for this warning was an association found between PPI use and malabsorption of calcium. A 2015 population-based study showed a significant association between PPI use and fractures in young adults.

Additionally, PPIs affect bone health in other than just calcium deficiency. For instance, osteoclasts, which are bone cells responsible for calcium resorption, are directly affected by PPIs. This is because these cells also possess proton pumps that can get affected by a proton pump inhibitor.

Increased Cardiovascular Risk

A 2015 study focused on PPI usage and risk of myocardial infarction showed that people on proton pump inhibitor medication have a higher risk of suffering a heart attack than those that use other kinds of antacids.

Another study in 2016 observed that the exposure of esomeprazole (a PPI) caused rapid aging in endothelial cells while also lowering their ability to split. Along with that, PPIs are also linked to causing a reduction in nitric oxide production. Nitric oxide occurs naturally in our body to promote the dilation of blood vessels to facilitate blood flow. PPIs may reduce its production, increasing the risk of a cardiac episode.

Exacerbation of Liver Disease

The use of proton pump inhibitors is usually high among patients that have chronic liver disease. Various studies report high PPI use in 32% of people with non-alcoholic fatty liver disease or NAFLD and 67%-72% of people with cirrhosis.

A recent study found proton pump inhibitors promote the growth of Enterococcus bacteria in mice. This is important because this very bacterium is responsible for exacerbating alcohol-induced liver disease, NAFLD, and non-alcoholic steatohepatitis. In fact, a study found that even two-week-long use of PPIs was sufficient to increase Enterococcus bacteria.

Increased Risk of Renal Disease

Several studies conducted over time have shown proton pump inhibitors have an impact on kidneys. A study published in 2016 compared patients that used some kind of proton pump inhibitor to patients that used an H2 blocker.

The results showed that patients on PPIs were 28% more at risk for developing chronic kidney disease. But that’s not all, as the results also showed that PPI users were 96% more at risk of developing end-stage renal disease.

Even though the mechanism of action is not clear, the results are enough to warn one to be cautious while using PPIs, especially for long periods of time.

Risk of PPI Withdrawal-Induced Rebound Reflux

There is a chance that when you use PPIs, your body might experience rebound reflux. This is likely triggered when your body experiences a lack of stomach acid and produces an increased amount of Gastrin to compensate and regain balance in the stomach. This can be extremely painful and most adults will return to their use of proton pump inhibitors immediately to avoid the pain.

We highly recommend that you discuss reducing your PPI use with your doctor before you begin because our physician will have some strategies to assist you with this withdrawal. In addition, RefluxMD’s medical directors have developed a step-down program you might consider, but again, be certain to work closely with your physician.

Are proton pump inhibitors right for you?

With the above reasons to avoid PPIs concluded, we would like to say that these are only some of the main ones. Scientists have conducted hundreds of studies that have shown adverse effects and health risks associated with the overuse of PPIs. The ones we have mentioned are the most common ones.

If these side effects of PPIs have convinced you to avoid using them, you can consider taking alternative medications, remedies, and making lifestyle changes to improve your symptoms. However, always consult your physician before discontinuing or initiating the use of proton pump inhibitors.

Medical resources used for this article

Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population, by Dr. Nigam H. Shah MD, Dr. Paea LePendu MD, et al., PLOS peer-reviewed medical research, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0124653

Proton Pump Inhibitors: U.S. Food and Drug Administration-Approved Indications and Dosages for Use in Adults, US Food and Drug Administration, Center for Medicare and Medicaid Services, https://www.cms.gov/Medicare-Medicaid-Coordination/Fraud-Prevention/Medicaid-Integrity-Education/Pharmacy-Education-Materials/Downloads/ppi-adult-dosingchart.pdf

Time to halt the overprescribing of proton pump inhibitors, Dr. Daniel Marks MB BS BSc (Hons) Ph.D. MRCP, Pharmaceutical Journal of the Royal Pharmaceutical Society, https://www.pharmaceutical-journal.com/daniel-j-b-marks/1516.bio

Association of Long-Term Proton Pump Inhibitor Therapy with Bone Fractures and Effects on Absorption of Calcium, Vitamin B₁₂, Iron, and Magnesium, by Dr. Robert T. Jensen MD, Published in Current Gastroenterology Reports, https://link.springer.com/article/10.1007%2Fs11894-010-0141-0

Acid‐suppression medications and bacterial gastroenteritis: a population‐based cohort study, by Dr. Li Wei MD, Dr. Lasantha Ratnayake MD, et al, British Pharmaceutical Society, https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bcp.13205

Use of proton pump inhibitors is associated with fractures in young adults: a population-based study, by Dr. D. E. Freedberg MD, Dr. K. Haynes MD, et al, research published in Osteoporosis International, https://link.springer.com/article/10.1007%2Fs00198-015-3168-0

Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population, by Dr. Nigam H. Shah MD, Dr. Paea LePendu MD, et al, PLOS ONE online peer-reviewed journal, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0124653

Gastric acid suppression promotes alcoholic liver disease by inducing overgrowth of intestinal Enterococcus, by Dr. Cristina Llorente MD, Dr. Peter Jepsen MD, et al., Nature Communications, https://www.nature.com/articles/s41467-017-00796-x

Popular medications linked to higher risk of kidney failure, by Jen Christensen, a producer/editor with CNN’s Health, Medical & Wellness Unit based upon medical research published in the Journal of the American Society of Nephrology, CNN, https://edition.cnn.com/2016/04/14/health/proton-pump-inhibitors-kidney-failure/?no-st=1553737887

The effect of omeprazole on ultrastructural changes in gastric parietal cells, by Dr. Hiroyuki Karasawa MD, Dr. Norio Tani MD, Dr.Takeshi Miwa MD, medical research published in Gastroenterologia Japonica, https://link.springer.com/article/10.1007%2FBF02918848