Proton Pump Inhibitor (PPI) Alternatives

Proton pump inhibitor alternatives are medications and nondrug remedies that treat conditions such as acid reflux and heartburn. Non-PPI options include histamine blockers, antacids, probiotics and lifestyle changes.

There are three classes of medicines that treat symptoms such as heartburn. These include the PPIs esomeprazole (Nexium), omeprazole (Prilosec), pantoprazole (Protonix) and lansoprazole (Prevacid). The others are antacids such as Maalox, Mylanta and Tums, plus H2 (histamine) receptor antagonists such as famotidine (Pepcid) and cimetidine (Tagamet).

A 2022 study reviewed research comparing several PPIs.

Other PPI alternatives that can provide relief are natural and nonmedical options such as herbal and home remedies. In some cases, surgery is an option.

While proton pump inhibitors (PPIs) are powerful drugs that treat heartburn, gastroesophageal reflux disease (GERD) and stomach ulcers, studies and PPI lawsuits link their long-term use with serious side effects, including serious electrolyte disturbances, osteoporosis-related fractures, intestinal infections and poor vitamin absorption. PPIs also can interact with other drugs, leading more people to inquire about alternatives.

Antacids work well as an alternative to PPIs, neutralizing stomach acids to relieve occasional heartburn and other symptoms of GERD and acid indigestion. Over-the-counter antacids only treat some symptoms and not the underlying causes of GERD. They may provide quick relief of minor symptoms.

Zantac (ranitidine) was a popular heartburn medication until the U.S. Food and Drug Administration requested its manufacturers withdraw it from the U.S. market in April 2020. Sanofi has since introduced a new formula, OTC Zantac 360, made with famotidine.

Antacids are among the safest drugs for acid reflux and side effects are rare. Depending on the antacid’s ingredients, side effects may include diarrhea, constipation, calcium loss and kidney stones.

Various nonmedical and natural PPI alternatives may treat acid reflux. Naturopathic treatments can be appealing because of a reduced risk of adverse side effects.

The effectiveness of these nonmedical and natural remedies will vary from person to person. Patients taking PPIs should speak with their doctor before stopping them. They should also talk to their doctor before switching to a PPI alternative.

PPIs & Lifestyle Modifications

Lifestyle intervention may play a role in the nonmedical treatment of GERD. Research indicates that smoking tobacco contributes to GERD, leading physicians to often recommend that people with GERD quit smoking.

Regular physical activity and diet changes may be beneficial for those with acid reflux as well. There are some indications that avoiding eating large meals, not eating before bedtime, not reclining or leaning (recumbence) after meals and elevating your head and chest in bed may also help.

Another lifestyle change that could potentially prevent or improve acid reflux symptoms is eliminating high-acid foods and beverages believed to trigger heartburn and reflux episodes. These include alcohol, garlic, black pepper, spicy foods, raw onions, citrus fruits, coffee, chocolate and carbonated drinks.

Histamine blockers, also called H2 blockers or H2 antagonists, are a class of drugs that block the actions of the compound histamine at histamine receptors. When effective, they can reduce stomach acid production. Although H2 blockers have largely been surpassed by PPIs, they can still be effective in the treatment of GERD symptoms and complications.

Consumers can get H2 blockers through a prescription or over the counter.

H2 blockers work because they’re competitive antagonists of histamine at the histamine receptors of parietal cells, which secret stomach acid. H2 blockers suppress the secretion of acid by the cells, reducing overall gastric acid.

H2 blockers enjoy a few advantages over antacids: They’re more effective against acid reflux symptoms, they have a longer duration of action, and they can be taken before meals to prevent heartburn.

Most people tolerate H2 blockers, which are considered safer than PPIs. But they also have potential side effects, which include nausea, upset stomach, diarrhea, constipation, headache and tiredness. These are also the most common proton pump inhibitors side effects.

Cytoprotective drugs coat the lining of the stomach and small intestine. The coating prevents stomach acids from damaging the stomach lining.

Sucralfate and misoprostol require a prescription, while products such as Pepto-Bismol are available over the counter.

Sucralfate and misoprostol require a prescription. Pepto-Bismol is available over the counter.

When taken during pregnancy, misoprostol may cause miscarriage. Sucralfate is safer for pregnant women with GERD. Research hasn’t shown the drug to cause any adverse effects to the mother or the fetus.

Doctors have a small group of antibiotics at their disposal as PPI alternatives for treating stomach ulcers. These antibiotics work because they kill off the Helicobacter pylori (H. pylori) bacterium that frequently colonizes the lining of the stomach.

H. pylori infection irritates the stomach lining, allowing gastric acid to erode the lining around the infection. Ulcers form because of the weakening stomach lining.

Another PPI alternative for H. pylori infections is bismuth subsalicylate (Pepto-Bismol or Kaopectate).

Prior to PPIs, physicians prescribed H2 blockers and other acid reducers in combination with antibiotics to treat stomach ulcers. They now prefer PPIs as a first course of treatment.

When medical management of GERD isn’t effective and symptoms persist despite these therapies, doctors may recommend surgical options. Surgery may also be considered because of PPI side effects or a personal preference to not take medication any longer.

Although surgical intervention can be a safe and effective PPI alternative, side effects and complications may occur. Your surgeon will discuss these complications before you undergo any procedure.

Rare complications of anti-reflux surgery include difficulty belching, a bloating sensation and difficulty swallowing immediately after surgery.

GERD is among the most common digestive diseases for which people seek medical care. Persistent GERD symptoms necessitate a visit to the doctor because they can cause serious complications and damage.

PPIs and PPI alternatives can control GERD and associated symptoms. But PPI alternatives do not have the same efficacy for everyone who has GERD symptoms. Results also vary from person to person.

Consult your doctor if your GERD symptoms do not improve or if they get worse after using PPI alternatives.