Woman with heartburn

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:

The researchers from Hong Kong wrote:

“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).”

CONCLUSION:

“…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:

Will PPIs Protect You From Esophageal Cancer?

There is also this:

Do Acid Suppressing Drugs Protect Against Cancer or Increase the Risk?

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.

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  1. Carol
    Roanoke
    Reply

    When these concerns were brought up to doctors, they said, “Stay off the internet.”

  2. Pat
    Austin Tx
    Reply

    When I read the severe side effects on my prescription receipt, I didn’t take omeprazole. It says “A very bad reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause bad health problems that may not go away, and sometimes death.” So I lost 5 pounds, changed my diet, and got more exercise. Now I’m fine. It took 2 months.

  3. Daisy
    Reply

    To Graedons Thanks for all the great info!

  4. Daisy
    Alabama
    Reply

    I took PPIs for several years between 1999 and 2003 for reflux. I asked the gastrointerologist if there was there any danger in taking them long term and he said no. Most doctors do not take side effects seriously enough so I usually do. I have since used Pepcid as needed only and it works just about as well.
    I had a scope of stomach and esophogus 6 yr ago and it was OK. Only symptoms of digestive problems are pretty frequent indigestion/reflux and constipation. (I also get colonoscopies every 5 yr. as some colon cancer in family.)
    With this new info I am wondering if I need to have any tests to see if I have undetected cancer or other problem?

    • Daisy
      Reply

      Diane, I might ask gastro how long PPI needed, and tell your concern, and if its much longer you could seek another gastro’s opinion unless you really don’t want to risk irritating the one you have. I’ve found doctors in recent years very sensitive to hearing anything that bugs them but maybe you have a stronger relationship than I do with most of mine.

  5. Chris
    IL
    Reply

    My father took Nexium regularly for years and ended up with esophageal cancer. I am convinced that Nexium caused this. He had chemo and ended up dying from the effects of the chemo.

    I believe if the doctor had stressed diet and exercise over taking Nexium this would not have occurred. Doctors are too quick to prescribe medications over nutrition and lifestyle changes.

  6. Robert L.
    Spokane Washington
    Reply

    I had bleeding ulcers about 6 years ago. The first one was at the intersection of the stomach and little intestine. The Doctor treated it and stopped the bleeding. The second one was on the wall of my stomach and the Doctor treated it. He diagnosed my problem saying you have H pylori but a followup test could not find any problem and would not attempt to treat it. While traveling in Portugal the bleeding started again We went to a clinic in Evoura Portugal. The head of the clinic examined me and determined that I had H pylori in my stomach. This Doctor recently cured 100 patients using an antibacterial medicine. I received the same treatment and was cured. A second problem I have is Barrett’s esophagus treated with pantoprozal for at least 7 years with no side effects.

  7. Robert L.
    Spokane Washington
    Reply

    I had bleeding ulcers about 6 years ago. The first one was at the intersection of the stomach and little intestine. The Doctor treated it and stopped the bleeding. The second one was on the wall of my stomach and the Doctor treated it. He diagnosed my problem saying you have H pylori but a followup test could not find any problem and would not attempt to treat it. While traveling in Portugal the bleeding started again We went to a clinic in Evoura Portugal. The head of the clinic examined me and determined that I had H pylori in my stomach. This Doctor recently cured 100 patients using an antibacterial medicine. I received the same treatment and was cured. A second problem I have is Barrett’s esophagus treated with pantoprozal for at least 7 years with no side effects.

  8. Julia
    Brick NJ
    Reply

    This information was so informative things explained so a ordinary patient would understand thank you

  9. Gayle
    Dallas
    Reply

    I believe the FDA made a very dangerous and careless decision to allow acid-suppressing drugs (PPIs) over the counter. These drugs need to be prescribed and monitored by a physician.

    I have been on Nexium for many years with no problems. I am under the care of a Gastroenterologist. The medication is very effective in controlling my GERD; however, the generic Nexium does not help me at all.

    My insurance refuses to pay for any acid-suppressing medications stating “there are many choices over the counter.”. I take 40 MG Nexium but over the counter Nexium is 20 MG. I contacted my insurance company to advise them I take 40 mg Nexium, not 20 MG which is not available OTC. They advised the 40 MG would not be covered. I asked my insurance company “So are you saying I need to take two 20 MG Nexium for the proper dosage my doctor prescribed? Are you now prescribing increased dosages to customers because I thought it was illegal for an insurance company to prescribe medication?” Their response “There are many choices OTC”.

    As a consumer, I don’t know one Nexium from the other on the drugstore shelf as there are several choices and they are all 20 MG.

    How many people are self diagnosing themselves with the need for acid-suppressing (PPIs) without medical supervision? When did it become legal for insurance companies to basically start prescribing increased dosages of medication? The FDA needs to take these medications back to being prescription only.

  10. David
    Reply

    Wide spread use of PPI’s started with the loss of patent protection for the H2’s. Prior to that time a pretty good case could be made for using PPI’s secondarily. When promotion of H2’s stopped because of their generic status, the PPI’s stepped right in the door. Once again the rule of unintended consequences.

  11. Diane
    Chapel Hill
    Reply

    I am in the hospital recovering from the removal of a stromal tumor in the stomach. My Gastro has had me on PPIs for the last two months but my Internist isn’t happy with the decision. What does the patient in the middle do?

  12. Bonnie
    Reply

    It’s like–you take the PPI to reduce gastric reflux and prevent esophageal cancer and now we learn that taking the drug over a 3 year term can cause stomach cancer, pancreatic cancer, etc.
    What is a person to do?

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