A man with blond hair in a white shirt putting his hands over his chest, demonstrating that he is experiencing heartburn, a common symptom of GERD.

Proton Pump Inhibitors for Treating Reflux

Gastroesophageal reflux disease (GERD) is a digestive disease that occurs when the stomach’s contents return back up into the esophagus. Carrying stomach acid or bile, the contents of the stomach irritate the esophagus’ lining. Symptoms of the disease include heartburn, difficulty swallowing, excessive salivation, bloating, and chest pain. Fortunately, GERD is a treatable disease with generally manageable symptoms. One common treatment for GERD is proton pump inhibitors (PPIs).

What Are Proton Pump Inhibitors?

PPIs are a class of medications designed to block and reduce the production of stomach acid in patients with gastrointestinal disorders (namely GERD). They target the site of acid production: the parietal cells. These medications provide treatment, giving the esophagus time to heal and preventing symptoms such as heartburn.

PPIs are one of many treatment options for GERD, ulcers of the stomach, Helicobacter pylori (a bacterium found in the stomach), and a rare condition called Zollinger-Ellison syndrome.

How Do PPIs Work?

The stomach contains proton pumps that produce acid. PPIs work to diminish that acid secretion by binding to proton pumps, and then sending signals to acid-forming cells (parietal cells). These signals essentially tell the cells to stop “pumping” acid back up into the esophagus.

PPIs must be taken about 30 to 60 minutes before a meal in order to be effective.

Types of PPIs

There are various types of PPIs, available both over-the-counter (OTC) and in prescription form. All of them are structurally and chemically similar, and suggested to work equally as well. There is no research suggesting otherwise.

Types of PPIs that are available over-the-counter include:

  • Omeprazole;
  • Lansoprazole;
  • Esomeprazole;
  • Zegerid (omeprazole and sodium bicarbonate).

Lansoprazole and omeprazole are also available in prescription form, as are the following PPIs:

  • Dexlansoprazole;
  • Rabeprazole;
  • Pantoprazole.

Omeprazole and Lansoprazole have been available the longest and are highly trusted among physicians and patients alike. Other medications are relatively newer. Some are designed for specific uses. For instance, Rabeprazole and Pantoprazole are smaller, making them a convenient choice for people who have difficulty swallowing pills. Pantoprazole is also generally cheaper, making it a more affordable option for people paying for their own medications.

PPI Side Effects

The most common side effects of PPIs include headaches, diarrhea, abdominal pain, gas, and bloating — though these medications are generally well-tolerated. Long-term use of PPIs in rare cases have resulted in more adverse side effects such as bone fractures, infections, myocardial infarction, renal disease, and dementia. However, more research is needed to confirm these notions.

What Are the Benefits of Proton Pump Inhibitors?

There are significant benefits to PPIs, which explains why they are such a common treatment for acid reflux. Not only do PPIs inhibit acid secretion as they’re supposed to, but they also do not wear off even after long-term usage. Their effectiveness largely stays the same throughout a treatment plan. This could mean minimal dosage changes and less switching of medications or treatment plans.

What Are the Risks of Proton Pump Inhibitors?

PPIs are largely safe and effective medications for gastrointestinal disorders. However, long term use of PPIs may cause more adverse side effects, as previously mentioned. One adverse effect of PPIs, for instance, is thought to be pneumonia. Exacerbating that, patients diagnosed with SARS-CoV-2 are suggested to have more severe clinical outcomes if they’re currently using PPIs.

Research suggests that “PPIs disrupt the healthy human gut microbiome.” Disruptions to the gut microbiome make it easier to contract Clostridium difficile infection (CDI), an inflammation of the colon. Another research study suggests that long-term PPI use leads to less calcium absorption in the body, in turn causing “negative calcium balance, increased osteoporosis, development of secondary hyperparathyroidism, increased bone loss, and increased fractures.”


Other research studies show patients experiencing vitamin B12 deficiencies, small intestinal bacterial overgrowth, and anemia after taking PPIs.

Limitations of Proton Pump Inhibitors

Like any drug, PPIs have their limitations. For one, these medications require meal-associated dosing. This means PPIs must be taken some time (typically, a half-hour to an hour) prior to eating in order to be effective. Patients may forget to take the medication before eating or experience heartburn in the absence of eating. In either case, PPIs are not medications that work on demand.

PPIs also are most effective when taken for brief periods of time, rather than every day for a long duration of time. The FDA recommends a time period of 4 to 8 weeks. People who have self-medicated with OTC PPIs may abuse this suggested time frame, diminishing the effectiveness of the medication. On the other hand, people may need a more permanent solution to GERD or other heartburn-inducing conditions.

These limitations may force people to seek out other medications for GERD or even look into surgery. The TIF procedure is a minimally invasive option performed on patients with GERD. This procedure is performed through the mouth and inside the stomach, leaving behind no incision marks.

Surgery may ultimately be the best option for those with chronic or long-lasting symptoms of GERD. PPIs or H2 receptor blockers (another treatment option for GERD) are only temporary solutions to these symptoms. Surgery, on the other hand, seeks to restore the esophageal valve to its original state, thus eliminating symptoms at the source.