Proton Pump Inhibitors (PPIs) are among the most popular drugs in the pharmacy. Physicians prescribe them to 15 million people every year for ulcers, acid reflux, heartburn and Barrett’s esophagus. They believe that powerful acid-suppressing drugs like esomeprazole (Nexium), lansoprazole (Prevacid) and omeprazole (Prilosec) protect the digestive tract from cancer. But a new study suggests that people taking PPIs after being treated for a stomach infection called Helicobacter pylori are at higher, not lower, risk of stomach cancer (Gut, online, October 31, 2017).
Helicobacter Pylori, the Bug from Hell:
The gastroenterology community was slow to recognize that a spiral-shaped germ called Helicobacter pylori caused stomach ulcers and cancer. Dr. Barry Marshall was awarded the Nobel Prize in Physiology or Medicine for his discovery that Helicobacter pylori infection caused stomach ulcers.
The medical establishment was convinced that acid was the culprit behind ulcers. Spicy food and stress were thought to increase acid production and trigger ulcer formation. Antacids were the treatment of choice. The mantra was “no acid, no ulcer.” The loudest shouters pooh poohed Dr. Marshall’s research. Eventually, though, he and a colleague were able to prove that Helicobacter pylori was the real problem.
This is a nasty bacterium. It burrows into the tight junction between stomach mucosal cells where it makes an enzyme (protease) that destroys the mucus protecting our stomach lining. This can cause inflammation, irritation, indigestion, gastritis and ulceration. Untreated, it can lead to stomach cancer.
Eradicating Hel Is No Easy Matter:
Doctors often shorten Helicobacter pylori to H. pylori. We call it Hel. Getting rid of this bacterial infection in the stomach is challenging. Doctors use triple or even quadruple therapy with a variety of drugs. The American College of Gastroenterology recommends first-line treatment with the antibiotics clarithromycin, amoxicillin and metronidazole plus a proton pump inhibitor (American Journal of Gastroenterology, online, Jan. 10, 2017).
There are problems with this approach. First, it doesn’t always work to eradicate Hel. Second, even when antibiotics work to kill off this germ, the PPIs that are included in the regimen may cause more harm than good if taken for long periods of time. That’s the conclusion of a brand new study from Hong Kong.
Acid-Suppressing Drugs and Stomach Cancer:
The new research compared people taking PPIs long term to those taking other acid reducing drugs, such as cimetidine, famotidine or ranitidine. These histamine-2 receptor antagonists (H2RAs) are known respectively as Tagamet, Pepcid and Zantac. Such drugs also block acid formation, but not as strongly as PPIs.
The scientists found that even after H. pylori was successfully treated, long term users of PPIs were more than twice as likely to get stomach cancer. People who took PPIs daily for more than three years were eight times more likely to develop gastric cancer than people who never took these drugs. People who took H2RAs had no increased risk of stomach cancer.
In Their Own Words:
“In this population-based study that addressed the risk of gastric cancer development in H. pylori-infected individuals after receiving eradication treatment, we found that long-term use of PPIs increased the risk of gastric cancer development. Our results showed that even after apparent successful H. pylori eradication therapy, those who used long-term PPIs had a 2.4 fold increase in the risk of gastric cancer development than non-users. This increase in risk was not observed among H2RA users…Patients who took PPIs daily for more than 3 years were at the highest risk (HR [hazard ratio] 8.34).”
“…Physicians should therefore exercise caution when prescribing long-term PPIs to those patients even after successful eradication of H. pylori.”
Why Do We Think This Research Is Important:
What makes this research concerning to us is what we pharmacologists call the dose response curve. It’s a fairly simple concept. If we see a greater effect from a higher dose we feel more confident that it is cause and effect.
Here is an example. One baby aspirin might cause a little stomach upset for highly sensitive people. Two full-strength 325 mg tablets are likely to cause a bit more stomach upset in average folks. A handful of aspirin tablets all at once can trigger significant gastritis, ulcers and even a serious toxic reaction in most people.
In the case of PPIs, the people who took acid-suppressing drugs daily for more than three years were substantially more likely to develop stomach cancer than those who “only” took the drugs for a year. And weaker acid suppressors like H2RAs apparently posed no increased risk.
How Can Acid-Suppressing Drugs Be Linked to Cancer?
The Hong Kong researchers noted that:
“A recent meta-analysis showed that the risk of gastric cancer is increased by 43% among PPI users” (Clinical Gastroenterology and Hepatology, Dec. 2016).
They go on to point out that:
“…PPIs stimulate the production of gastrin, which is a potent growth factor, and hypergastrinemia has been shown to induce hyperplasia of enterochromaffin-like cells.”
Okay, that is doctorspeak. In other words, big words and medical mumbo-jumbo. To help you better understand what might be going on, here is what we wrote in our book, Best Choices from The People’s Pharmacy. It was published over a decade ago.
“The really big elephant in the room with the PPIs is a fear of cancer. For years there has been a quiet controversy brewing regarding a possible relationship between acid suppression and the risk of cancer. In 1985 we wrote:
‘Scientists fear that if bacteria set up housekeeping in your stomach, they can go to work converting nitrate to nitrite. . . . Nitrate is a chemical which can come from food, water, or even saliva; by itself it probably does little harm. But if nitrate is turned into nitrite by bacteria, all hell can break lose, because the end product can be something very bad indeed–nitrosamines. Nitrosamines are among the most potent cancer-causing chemicals known to man.’
“Over the last several decades there has been an alarming increase in what was once a rare kind of esophageal cancer. Adenocarcinoma of the esophagus has turned into an epidemic. Gastroenterologists are mystified about the causes of this deadly condition. Some have told us that it’s brought on by the American diet. Others blame it on reflux and insist that PPIs can solve the problem by reducing acid exposure to delicate tissues. Has reflux really increased that much in the last couple of decades, and if so, why?
“A provocative editorial in the American Journal of Gastroenterology entitled ‘Acid Suppression and Adenocarcinoma of the Esophagus: Cause or Cure?’ lays out the confusion and the contradictions (American Journal of Gastroenterology, Oct. 2004). Thomas Schell, MD, points out that “decreasing acid reflux by the use of PPIs might help to slow or halt this deadly progression.” But he also reminds his colleagues that lack of acid in the stomach (achlorhydria) “is a known risk factor for adenocarcinoma of the stomach.” Dr. Schell notes that nitrosamines formed by bacteria in the stomach ‘would also expose the esophagus to these carcinogens.’
“There are three other disconcerting problems linked to long-term use of PPIs. When the stomach ceases to produce acid, it senses that something has gone terribly awry and it tries desperately to get acid-producing cells working again. It does this by making a compound called gastrin, which aids in digestion and also triggers the production of stomach acid. When acid levels do not rise, gastrin production continues indefinitely, often at very high levels.
“Imagine that the float device in your toilet was stuck in the “on” position. The water would keep running forever, which is what happens with gastrin in your stomach. There is no acid “float” to turn off the gastrin supply.
“Too much gastrin is not a good thing. In fact, there is increasing concern that gastrin may stimulate abnormal cell growth throughout the digestive tract, increasing the risk of cancers of the stomach, pancreas, and colon, as well as the esophagus.”
What About Acid-Suppressing Drugs and the Esophagus?
Most gastroenterologists believe that PPIs are absolutely essential in preventing pre-cancerous changes in the esophagus (Barrett’s esophagus) from turning into esophageal cancer. They may well be right. But there are some confusing and conflicting data. You may find our prior article on this topic of interest:
There is also this:
The People’s Pharmacy Perspective on Acid-Suppressing Drugs:
PPIs are very helpful for curing stomach ulcers. A strong acid environment can wreak havoc on a lesion in the wall of the stomach that has been triggered by pain relievers like aspirin, ibuprofen or naproxen. With luck, the ulcer should heal within a few weeks.
Long-term use of PPIs for garden-variety heartburn worries us. It’s not just the cancer controversy. PPIs have been associated with a number of serious side effects including heart attacks, strokes, kidney damage, dementia, weakened bones, fractures and infections. We agree with the Hong Kong investigators who urge their colleagues to exercise caution in prescribing PPIs long term.
Of course no one should ever stop taking any medication without careful consultation with the prescriber. Stopping PPIs suddenly can lead to rebound hyperacidity. That can cause unbearable heartburn symptoms that may last for weeks or even months.
Some people may need to take PPIs for a long time or even indefinitely. There are some medical conditions that require strong acid-suppressing drugs.
Our goal in issuing this health alert is to make people aware of the complex nature of acid-suppressing drugs. Balancing benefits against risks requires good communication between prescriber and patient. The latest research should prompt just such a conversation.