Long-Term Use of Popular Heartburn Drugs Increase Risk of Stomach Cancer: Review


Use for one year and three years was associated with a 1.5- and 2.4-fold increase in the risk of stomach cancer, respectively.

Proton pump inhibitors (PPIs), a popular class of heartburn drugs, are linked to stomach cancer, a recent review found.

The review indicates that prolonged use of PPIs—exceeding three months—“is significantly associated with an elevated risk of cancer,” while shorter-term usage “appears to pose a comparatively lower risk,” the authors wrote.

PPIs are potent drugs that lower stomach acidity. They work by binding irreversibly to proton pumps—proteins in the stomach that release protons, a component of stomach acid. This action prevents the secretion of protons.

PPIs are commonly prescribed to treat acid reflux, which occurs when acid in the stomach reverses up the esophagus, causing heartburn. They are also used to treat gastroesophageal reflux disease (GERD), a more chronic form of acid reflux, as well as gastric and gut ulcers.

Increased Risk of Stomach Cancer and Polyps

The authors reviewed several papers investigating the link between PPI use and cancer risk, finding a link between PPI use and stomach cancer and polyps. No other cancer links were identified.

One of the studies they cited evaluated data from about 2,400 records and found that long-term use for one year and three years was associated with a 1.5- and 2.4-fold increase in the risk of stomach cancer, respectively.
Other research that followed 3,271 patients who were given PPIs after a Helicobacter pylori infection found that long-term PPI use was associated with a twofold increase in the risk of stomach cancer.

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While a study in women found that PPI use was associated with reduced risk of breast, ovarian, and cervical cancer, the authors of the review cautioned against concurrent use of PPIs in cancer treatment, citing studies finding worse outcomes and increased mortality risk.

Why the Risk?

Several possible mechanisms may explain how PPIs could contribute to cancer development.

These drugs may disrupt gut microbiome health by increasing the pH of stomach content.

This “may potentially alter the gut microbiome, reduce the diversity and abundance of beneficial bacteria, and lead to gastrointestinal inflammation. In turn, this could promote the overgrowth of harmful bacteria that produce carcinogens and increase the risk of cancer,” the authors wrote.

PPIs may also result in hypergastrinemia. Since they increase stomach pH, the stomach may increase the production of gastrin, a type of protein in the stomach.

However, gastrin stimulates the growth and activity of certain stomach cells, and the higher the concentration of gastrin, the greater the cell activity and proliferation, increasing cancer risk.

Apart from these proposed mechanisms, PPIs also have a wide range of side effects. Increased stomach acid pH can lead to indigestion, nutritional deficiencies, bacterial overgrowth, and gut problems. It is also linked to infections with bacteria like Helicobacter pylori and Clostridium difficile.

Helicobacter pylori infections can cause painful stomach ulcers. The bacteria survive and proliferate at a pH between 3.5 and 8. A healthy stomach has a pH between 1 and 2.

Clostridium difficile infections are usually transmitted through food. However, the risk of infections can rise if stomach acid is not acidic enough to kill the bacteria.

According to the review, PPI use is also associated with an increased risk of dementia, fractures, osteoporosis, and liver and kidney diseases.

Alternatives to Proton Pump Inhibitors

People with GERD and indigestion can replace PPIs with less-potent alternatives, including antacids and H2 blockers, once their underlying physiological problems are better managed.

Dr. Scott Rollins from the Integrative Medicine Center of Western Colorado told The Epoch Times that while PPIs can be highly effective in controlling a potentially dangerous stomach ulcer in these patients, they may have cumulative adverse effects.

Compared to antacids and H2 blockers, traditionally used to alleviate heartburn, PPIs are slower to activate and last much longer.

Antacids increase the pH of stomach acid immediately upon entering the stomach and only last for around an hour. H2 blockers last several hours, but PPIs can take up to 12 hours to activate, and their effects can last for up to three days.

Patients are also often advised to take PPIs daily, and many take them for years. This can cause long-term problems, including inflammatory gut issues.

Dr. Rollins has found that many patients complaining of GERD often have unaddressed inflammatory gut problems. Once these problems are addressed by improving diet for six to 12 weeks, GERD symptoms tend to resolve or improve significantly, such that patients only need to take antacids.

He also pointed out that while heartburn is often treated by reducing stomach acid, counterintuitively, it may occur due to insufficient stomach acid, which can occur due to old age, thyroid problems, and a type of stomach autoimmune disease.

Dr. Jonathan Wright, who specializes in natural therapies, said in a YouTube video that “99 percent” of his patients who experience heartburn suffer from insufficient stomach acid rather than excess.

Between the esophagus and the stomach is a ring of muscle known as the lower sphincter. This sphincter is the opening of the stomach and is responsible for closing it to prevent undigested food and stomach acid from backflowing up the esophagus.

Heartburn occurs when the sphincter does not close properly. Acid and food return to the esophagus, causing pain and damage.

Several things can cause the sphincter to malfunction. One is that the stomach acid’s pH is not low enough. Therefore, while PPIs may reduce the symptoms, they may actually be counterproductive.

Therefore, Dr. Wright recommends that patients whose heartburn is caused by insufficient stomach acid can supplement with betadine hydrochloric acid (stomach acid) after they start a meal.

Other factors that can affect the sphincter include alcohol, caffeine, and smoking. Being overweight can also put more pressure on the stomach, leading to acid reflux.


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