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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?
From the mouth of a man a fire erupts. Hot BMS

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.

PPIs Associated with Multidrug-Resistant Microorganisms:

A meta-analysis of 26 observational studies including nearly 30,000 people revealed another reason PPIs are linked to premature deaths (JAMA Internal Medicine, online, Feb. 24, 2020). The investigators found that people taking PPIs are more likely to harbor multidrug resistant gut organisms. The research identified microbes such as vancomycin-resistant enterococci, methicillin-resistant or vancomycin-resistant Staphylococcus aureus, or multidrug-resistant Pseudomonas or Acinetobacter species. These microbes could obviously cause problems for the person infected with them. In addition, however, they can contribute to the significant public health problem of drug-resistant infections. That is why, in an accompanying commentary, experts recommend that doctors consider de-prescribing PPIs whenever they can. Even better would be to avoid prescribing them at all for patients who don’t really need them. 

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.” .
Show 1078: How to Have Good Digestion Without Heartburn Drugs (Archive)
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Show 1078: How to Have Good Digestion Without Heartburn Drugs (Archive)
  • 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
  • Willems RPJ et al, "Evaluation of the association between gastric acid suppression and risk of intestinal colonization with multidrug-resistant microorganisms: A systematic review and meta-analysis." JAMA Internal Medicine, online, Feb. 24, 2020. DOI: 10.1001/jamainternmed.2020.0009
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When getting off prescription reflux meds, be careful if you switch to Tums. My dad used Tums for years for heartburn, and his heart doctor noticed calcium buildup in his heart valves. He told him no more Tums. He later had to have a pacemaker. I would be leery of taking too much calcium in Tums after this.

I’m so grateful for this information on PPIs. I was on 60mg/day of Lansoprazole for about seven years until five months ago when I weaned off and switched to Famotidine. Now I will closely monitor my kidney function. These PPIs are terrifying.

Further, I’ve been told by doctors multiple times to “eat more salt.” One even told me my serum salt levels were so low as to be on the verge of dangerously low. I sprinkled salt on everything, even granola, and it didn’t even get levels to the bottom of the normal scale. Since this was spoiling my enjoyment of eating, I put myself (with the knowledge of my PCP) on the daily recommended dose of salt tablets plus two extra. That helped get the reading almost onto the normal scale and sometimes just over the line. The process grew tedious and expensive. I wondered where all that salt was going!

I read that PPIs can interfere with electrolyte absorption though sodium and chloride were not listed. I thought “well they’re electrolytes” and I made the decision to wean off PPIs and switch to Pepcid with my PCP’s support. A blood test within three months of taking the last PPI, my sodium and chloride levels popped up right into the middle of the normal range, and with zero extra salt added to my food and no salt tablets, just a normal healthy diet.

Thank you so much for pointing out the potential electrolyte issue with PPIs!

Is a digestive enzyme a good alternative to a PPI? Any recommendations on which one/ones?

I took Nexium, or the genetic esomeprazole, for over 20 years. After reading about the bad side effects that had been found, I started a fairly lengthy process to wean myself off the drug. For the first month, I started skipping the drug every seventh day. The next month it was every sixth day, and so on until I got down to only taking the drug every other day. Then, after that month, I started skipping it two days in a row for a month. The next month I skipped three days, and so on until I finally just stopped taking it at all. Amazingly, I’ve not had any acid reflux issues at all and only rarely suffer any heartburn issues, which I treat with Pepcid.

Several years ago I had hydrocephalus, which damages your brain. Among the consequent symptoms is acid stomach because your brain gives wrong instructions to your body and causes the release of excess stomach acid. I had very bad GERD, but PPIs just caused my body to produce more acid and were horribly constipating. Read a book by a gastroenterologist on remedies for GERD (wish I could recall his name). He suggested using zinc carnosine. I used Source Naturals Gastric Soothe per bottle directions and was able to wean away from PPIs. Went to a new gastro whose PA was writing down my meds. As to zinc carnosine, he told her “That’s something to protect her stomach.” So I got it from a book, but a conventional gastro recognized its benefit.

In the St. Louis study it mentioned ranitidine as possibly safer(?). Just wanted to note that my insurance company recently sent me a 4 page “urgent recall” list of all the ranitidine lot numbers that have been pulled off OTC and prescription shelves. Is ranitidine safe again?

Sadly not, but for different reasons. Ranitidine is a compound that can degrade into a nitrosamine that could increase your risk for cancer. The study was considering risk for premature death due to “cardiovascular causes, cancers, kidney disease and infections.” So even though cancer was included, and ranitidine was less likely than a PPI like omeprazole to trigger it, it still isn’t completely off the hook.

I have been on Nexium for over 30 years. My internist says I need to stay on it because I have Barratt’s. Is there something else I could do?

I was prescribe Nexium many years ago. I took the med for about a year. When the symptoms returned, my wife had been reading about “virgin coconut oil” and its many benefits.

I take about 2 tablespoons a day of coconut oil. Heartburn and the “fire” in my stomach are no longer a problem. Issues with digestion are no longer a problem. Issues with my fading memory are no longer a problem. Constipation is no longer a problem.

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?

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