The People's Perspective on Medicine

Why Popular Heartburn Drugs PPIs Are Linked to Premature Deaths

Acid-suppressing drugs called proton pump inhibitors (PPIs) are go-to drugs for heartburn. Should you be concerned that PPIs are linked to premature deaths?
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Millions of people take proton pump inhibitors (PPIs) to suppress the secretion of stomach acid. At last count, doctors wrote over 100 million prescriptions for drugs like dexlansoprazole (Dexilent), esomeprazole (Nexium), lansoprazole (Prevacid), omeprazole (Prilosec), pantoprazole (Protonix) and rabeprazole (Aciphex). Such drugs have been mainstays for treating heartburn, GERD (gastroesophageal reflux disease) and ulcers. Initially, doctors thought these drugs had minimal side effects. The FDA considered PPIs so safe that it approved drugs like Prilosec, Prevacid and Nexium for over-the-counter sale. But researchers continue ask whether PPIs are linked to premature deaths from a range of conditions.

Alert | PPIs Are Linked to Premature Deaths

Red warning flags have been flying over PPIs for years.

Researchers in St. Louis introduced their latest study in BMJ (May 30, 2019) this way:

“Proton pump inhibitors (PPIs) are widely used either as prescription or over-the-counter drugs. Several studies suggest that taking PPIs is associated with a number of serious adverse events including cardiovascular disease, acute kidney injury, chronic kidney disease, dementia, pneumonia, gastric cancer, Clostridium difficile infections, and osteoporotic fractures. Some of these adverse events are associated with an increased risk of death.”

These were investigators at the Veterans Affairs St. Louis Health Care System and the Washington University School of Medicine in St. Louis. They examined the health records of more than 150,000 patients taking PPIs and over 50,000 men taking histamine 2 (H2) blockers (such as cimetidine, famotidine or ranitidine). Many of these were older men, with records that extended at least 10 years. The study raises even more red flags about the dangers of prolonged use of proton pump inhibitors.

What They Found:

The St. Louis study found that patients who started taking a PPI like omeprazole were 17% more likely to die during the following decade than those taking a different type of heartburn medicine such as a histamine 2 blocker like ranitidine. The excess deaths were mostly due to cardiovascular causes, cancers, kidney disease and infections.

The researchers in their own words:

“We examined the causes of death associated with new use of PPIs in a longitudinal observational cohort of US veterans. Overall, there were 45.20 attributable deaths per 1000 PPI users; 38.65% were related to circulatory system diseases, 28.63% to neoplasms [cancers], 13.83% to genitourinary system diseases [chronic kidney disease], and 9.29% to infectious and parasitic diseases.”

Some of their observations and conclusions:

“PPIs are often used without indication and for much longer than needed.”

“Over-the-counter use of PPIs should only be for a brief duration of time (generally not to exceed 14 days).”

“The evidence from all available studies suggests that long term PPI use is associated with serious adverse events, including an increased risk of all cause mortality, and our results specifically suggest an increased mortality due to cardiovascular disease, chronic kidney disease, and upper gastrointestinal cancer. Because of the high prevalence of PPI use, the findings have public health implications and underscore the important message that PPIs should be used only when medically indicated and for the minimum duration necessary.”

Why PPIs Are Linked to Premature Deaths:

Researchers are closing in on the mechanisms that could be causing cardiovascular complications and kidney damage. Oxidative stress is one possibility. It involves the formation of free radical compounds that can be destructive to biological systems.

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Another proposed mechanism is damage to the lining of blood vessels (endothelial senescence). Other enzyme systems may also be negatively impacted by PPIs. Finally, reducing acid production in the stomach may lead to “microbiome perturbation.” In other words, the ecological balance of the bacteria in our digestive tracts could be disrupted with negative consequences.

How Long Have we Known That PPIs Are Linked to Premature Deaths?

You will be astonished to learn that there have been warning flags around PPIs for decades. Here is an intriguing message we received from a pharmacist with a long memory:

A Pharmacist Remembers a Link Between Omeprazole and Cancer:

Many patients find it hard to believe that PPIs could be associated with cancer. They are often told that such drugs can prevent cancer. You may find our perspective on this of interest:

Do Acid-Suppressing Drugs Cause Cancer?

 

What About PPIs and Kidney Damage?

Not surprisingly, this is a controversial issue. We have been writing about it for some time. Gastroenterologists are not happy to read about this connection. Here is a link you may find of interest:

PPIs and Kidney Damage | Nephrologist Spanks GI Doc

Take an extra minute to read some of the comments.

When PPIs Are Necessary!

We recognize that there are situations where PPIs are medically essential. They can help cure stomach ulcers. People who suffer from a condition called Zollinger-Ellison syndrome make way too much acid in their stomachs. Tumors in the digestive tract (gastrinomas) make excessive amounts of gastrin which turbo-charges the acid-making process. PPIs are appropriate in such situations.

Stopping PPIs Is NOT So Easy:

Most people can take antacids on an “as needed” basis. If you go to the ballpark and eat pizza, hot dogs with sauerkraut and top it off with a beer or two, you just might experience heartburn. Taking Tums or Rolaids to calm indigestion is not a big deal. Neither is a drug like Pepcid AC, Tagamet or Zantac.

People who take omeprazole or lansoprazole for several weeks may discover something called rebound hyperacidity. The heartburn that results can be challenging.

Larry in Raleigh, NC rarely had heartburn until pantoprazole:

“Even a short period on PPIs can set you up for withdrawal symptoms. I was prescribed pantoprazole for 30 days following a gastro-endoscopic ultrasound as part of a CPVA (heart procedure). I rarely had heartburn before, but I had it for a month after ending the pantoprazole. The bacterial imbalance persisted for a couple of months but has resolved.

“If this happens again, I’ll taper off, maybe spreading the last week’s supply over two weeks on alternate days.”

Another Larry, this time in Illinois, phased off PPIs very gradually:

“Getting off of Prilosec was a nightmare. I was on Prevacid before going on Prilosec OTC. I have been on a PPI for nearly 20 years.

“It took 3 days before the rebound happened the first time I tried quitting cold turkey. I tried quitting cold turkey several times but the burn typically would return every 2 to 3 days.

“I bought a good quality pill cutter at Amazon. Cutting the pill in half caused some reflux issues so I increased it where I was taking 3/4 of the tablet. I did that for 2 weeks before going to half a pill for 2 weeks. I was taking 1/4 of a pill a day for 2 weeks. Then I started taking it every other day for 2 weeks.

“I still had minor problems where sometimes I felt acid in the back of my throat or a mild stinging sensation in my stomach. I took Tagamet for about 2 weeks before weaning myself off of that gradually.

“It was then I started taking a bunch of other things: DGL Licorice, a strong probiotic formula. That along with a low carb diet put an end to the PPIs. It has been about two months and I have not had any real problems. I just avoid the foods I know trigger reflux even on my low carb diet.

Getting Off PPIs CAN be Challenging:

 

Share your own PPI story below in the comment section. Are you concerned about the recent research showing that PPIs are linked to premature deaths? Have you been able to get off a PPI without problems? How did you do it? 

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.” .
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Although some heartburn drugs are available without a prescription, at high doses they increase the risk for stroke. What are the alternatives?

Show 1078: How to Have Good Digestion Without Heartburn Drugs (Archive)
Citations
  • Xie, Y., et al, "Estimates of all cause mortality and cause specific mortality associated with proton pump inhibitors among US veterans: cohort study," BMJ, May 30, 2019, doi: https://doi.org/10.1136/bmj.l1580
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I have used a PPI, esomeprazole (Nexium), 40mg daily for 20+ years. Two months ago I started the Keto Diet and read that some people were able to stop taking their PPI medication. I had tried before to get off of the PPI medication; was armed with Tums and other antacids but could not manage the acid rebound. While on the Keto Diet I quit using the PPI medication cold turkey with no side effects. I have used one Tums during the last two months after eating a lot of crushed peppers on top of spaghetti.

I lost 15 pounds in two months on the Keto Diet but the very best part is, I eliminated one daily medication from my life. I am so thrilled to be off of one daily medication. The feeling is incredible. I appreciate reading your newsletters and your readers’ comments and hope that others will also be able to stop their PPI medications successfully.

Why is everyone looking at the the PPIs as the cause of these maladies? Perhaps it could be something that is causing people to need the PPIs that is also to blame for some if not all of the health problems. Maybe some food additive or chemical residue from farm chemicals?

Thank you for the information. I began taking aciphex over 20 years ago for GERD. It has been the only medication that worked. As a result of taking this medication for so many years, I have to have an egd every year. In the past 3 years they have removed close to 200 polyps. With many more still there. They cannot remove them all as I would bleed out. Now I’ve been diagnosed with Mast Cell Activation and take aciphex, 2 ranitidine and cromolyn daily. I’m very concerned and don’t know where to turn. I want off the aciphex, as they have thought it has caused the polyps. But then they tell me to keep taking it. Any suggestions?? Thank you

Arlene, my brother is right there with you. The GP and GI doc have nothing else to offer. Can’t someone come up with an answer?

A few years ago the research studies indicated that PPIs caused bone density problems. I was concerned and talked with my gastro Dr. He said “Oh — they’re junk studies.” So, another study or other research studies out of St. Louis say that PPIs caused deaths. Did the people conducting the study also study people NOT taking PPIs in same age brackets and report fewer deaths? Did they take into consideration family medical histories? So many other factors can play a part in the outcome of these studies. Perhaps that is why my gastro Dr. (ex-professor at a medical university) said these were junk studies.

Julia,

If there were only one or two studies linking PPIs to serious health problems we might agree with your gastro doctor. There are now quite a few…as we document in all the links in the various articles we offer. It is quite easy for an “expert” to dismiss studies as “junk science” that disagree with his or her premise. Has your gastro doctor actually read all the studies? the BMJ is a peer reviewed journal comparable to JAMA or New England Journal of Medicine. We seriously doubt that the reviewers would have accepted a publication that was not controlled for issues you are concerned about.

My sister in law used Omeprazole for over 20 years, and now at age 69 she has terminal brain cancer. Is there a connection? My own experience with acid reflux has been to change my diet somewhat and stop eating 2-3 hours before bedtime. This has helped, but now I am doing intermittent fasting and this has virtually stopped my reflux. But as we age, our stomach acid levels decrease so why would we want to decrease them even more with PPIs? Acid reflux is the result of low acid, not high acid, as our system does not detect enough acid to close the valve in the esophagus. Did you ever get acid reflux in your teens or 20’s when you had much more acid than 20-40 years later? I bet not.

Medicine has this one all backwards, as they have tricked millions into taking PPIs to solve a problem that doesn’t exist. If I have problems with acid, I will take some lemon juice and water or baking soda and water. Absolutely no PPIs or even Tums for me, and after my doctor did the throat scan 4 years ago (age 65) looking for cancer in my esophagus, he said I would be on PPIs for the rest of my life. Is it any wonder that doctors don’t know any other cures except using drugs, drugs and more drugs?

“Other enzyme systems may also be negatively impacted by PPIs”

Would you expand on this? I don’t know much about “enzyme systems”, or would you write us an article about enzyme systems or how to gain weight safely?

Thank you.

My wife and brother had digestive issues that lingered for months. Her son suggested that she start drinking Kombucha tea. Since her and my brother started drinking the tea their digestive system has been working fine. I did some research on Kombucha tea, and it is a probiotic that does wonders. It has been shown to attack and kill H-pylori. In my opinion, most “heartburn” is caused by a relaxed esophageal sphincter caused by processed foods, not excess acid.

I was on a PPI for a years. One of those things that a doctor prescribed and then kept continuing to prescribe because it wasn’t giving me trouble. When I read about the problems it could cause I decided on my own to taper off the drug very slowly. I don’t remember exactly how slowly, but slowly. I have been off the ppi for a couple of years. I was drinking a little cider vinegar in water before my evening meal, but don’t even do that anymore. Occasionally when I’ve eaten something that causes heartburn, I use Zantac and/or Gaviscon at bedtime. I am so glad I was able to discontinue use of the PPIs.

I have worked as a Family Doc and herbalist since 1982. One of my favorite challenging efforts is to help patients wean off PPI with a natural protocol that works if followed. All these years I have seen reports from GI docs year after year finding chronic gastritis on the scope and prescribing higher doses of PPI or the new one with no healing.

I trained with herbalists and naturopaths to learn about the power of vagus nerve stimulation with bitters on the tongue to empty the stomach and herbs to help gastric healing like DGL, marshmallow root and aloe after removing all indigestible foods like grains, and animal products and salty processed foods.

The PPIs were approved for 2 weeks use to heal gastric ulcers. Plant based unprocessed diet without aspirin, NSAIDs and drugs that shut down digestion works best for prevention gastritis. Most people over 50 have reduced stomach acid so have delay in digestion. Everyone gets rebound.

On upper endoscopy, my GI specialist identified hiatal hernia and Barrett’s Esophagus about 15 years ago. I have taken PPI almost daily during this time (now omeprazol). I never experienced acid reflux symptoms during my entire life, and still do not, so I was surprised at that diagnosis. He follows up with endoscopy every three years, and the condition remains unchanged.
So, there seems to be a dilemma here — controlling the acid splash into the esophagus while simultaneously reducing the PPI. What have other persons done in this situation?

Sometime in the past I was diagnosed with a Hiatal Hernia. It bothered me once, then went away. More recently had a similar problem, and the doctor prescribe pantaprazole, a powerful PPI. I refused. You see, I had been reading up on that medication for sometime. The physician was upset because I did not take her advice. I have never liked PPIs and will never take them.

I’ve been told by my doc that it is medically necessary for me take protonix for my Barrett’s esophagus which could lead to cancer. I feel like I’m between a rock and a hard place. Anyone else going thru this?

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