The People's Perspective on Medicine

Will PPIs Protect You from Esophageal Cancer?

Many people take PPIs like omeprazole for heartburn. Others have been diagnosed with Barrett's esophagus. Will PPIs block conversion to esophageal cancer?
Mature 50s Asian man stomachache,  pressing on stomach with painful expression, sitting on sofa at home, medicines on table.

There are new guidelines from the American Gastroenterological Association (Gastroenterology, March, 2017). They inform physicians that best practices require prescribing proton pump inhibitors (PPIs) to patients with Barrett’s esophagus for long periods of time. The goal of the treatment is to prevent this condition from turning into esophageal cancer. How good is the evidence?

GERD and Barrett’s Esophagus:

Heartburn that persists is both uncomfortable and worrisome. That’s because GERD (gastroesophageal reflux disease) can occasionally lead to abnormal cellular growth at the bottom of the esophagus. This is called Barrett’s esophagus.

Doctors worry about Barrett’s because it is a risk factor for esophageal cancer. They used to think that people with Barrett’s esophagus were 40 times more susceptible to this dangerous malignancy.

Research has shown, however, that this outcome is a lot less common than most health professionals think. About one person in 860 with Barrett’s will develop esophageal cancer every year (New England Journal of Medicine, Oct. 13, 2011).

That does not mean patients with this condition should ignore it. Far from it! When esophageal cancer occurs it is an extremely serious condition. Anything that could prevent Barrett’s from progressing to cancer would be beneficial.

PPIs vs. Esophageal Cancer:

Most physicians prescribe a proton pump inhibitor (PPI) for patients with Barrett’s esophagus. Guidelines from the American College of Gastroenterology recommend aggressive treatment with a PPI such as esomeprazole (Nexium), lansoprazole (Prevacid) or omeprazole (Prilosec).

The American Gastroenterological Association in its “AGA CLINICAL PRACTICE UPDATE: EXPERT REVIEWS” published in Gastroenterology, March, 2017, state:

“For patients with symptomatic GERD and Barrett’s, PPI therapy is highly effective for symptom relief and may potentially offer a chemopreventive effect, particularly since symptomatic reflux is a known risk factor for esophageal adenocarcinoma (EAC). In patients with Barrett’s esophagus who have no symptoms of GERD, PPIs are prescribed primarily to reduce the risk of progression to EAC.”

The experts for the AGA go on to state that:

“Epidemiologic studies generally support this practice, but there is currently no randomized data directly demonstrating that PPIs prevent progression of Barrett’s to EAC.”

A Different Perspective:

A study in PLOS One (Jan. 10, 2017) found a disappointing lack of evidence that these drugs prevent cancer of the esophagus. The article was titled:

“Proton Pump Inhibitors Do Not Reduce the Risk of Esophageal Adenocarcinoma in Patients with Barrett’s Esophagus: A Systematic Review and Meta-Analysis”

The Conclusions:

“In summary, no definitive protective effects against the development of EAC [esophageal adenocardinoma] and/or HGD [high-grade dysplasia] were seen for patients with BE [Barrett’s esophagus] with long-term PPI usage. Until and unless results of future studies can confirm such an association, PPI usage should be restricted to symptom control according to current guidelines. These findings indicate that for an unselected group of patients with BE, chemoprevention by use of PPIs to reduce progression should not be considered directly as routine care.”

These conclusions will surely be controversial, especially among gastroenterologists. PPIs have been the mainstay of reflux treatment for decades. They are perceived as highly effective and super safe.

PPI Side Effect Controversy:

In recent years, however, long-term side effects have come to light. They include kidney disease, pneumonia, intestinal infections, vitamin and mineral deficiencies, hip fractures and dementia.

Whenever we write about such complications, it makes some people nervous.

One reader complained:

“Every time I see an article about PPIs, it makes me sick! I have to be on Nexium because my acid reflux is awful. It caused a cough whenever I tried to eat. I wish you wouldn’t carp on the side effects so often. I’m sure everyone has gotten the message.”

Another reader wrote:

“I have Barrett’s esophagus and have been taking Dexilant [dexlansoprazole] for about five years now. I consider this a miracle drug. I had horrific heartburn and the Dexilant saved me.

“I went five years with no reflux whatsoever. But now I’m forgetting things. I don’t know if it’s just because I have so much on my mind, or if it’s from the medicine.

“My GI doctor warned me about dementia, but he said the risk of Barrett’s esophagus turning into esophageal cancer was of more concern than the possibility of dementia.”

Gastroenterologists Downplay Side Effects:

In its recent “Clinical Practice Update” the AGA experts state that:

“Despite the long list of potential adverse effects associated with PPI therapy, the quality of evidence underlying these associations is consistently low to very low. In addition, the magnitudes of absolute risk increase for individual patients are modest, particularly at once daily dosing.”

In other words, if there is a risk it is low.

That said, there is a growing recognition that PPIs have often been prescribed casually. That is why the AGA experts conclude:

“When PPIs are inappropriately prescribed, modest risks become important because there is no potential benefit.”

They go on to note that there are not specific recommendations to counteract PPI adverse effects.

What To Do?

No one should EVER stop taking a PPI without medical supervision. Rebound hyperacidity can make life miserable. Some people experience severe symptoms of heartburn for weeks or even months.

When people are seeking routine remedies for standard heartburn there are lots of options. Here is a video with a few of our favorites:

To learn more about heartburn and a variety of ways to ease symptoms, you may wish to review our Guide to Digestive Disorders. Anyone who would like a copy, please send $3 in check or money order with a long (no. 10) stamped (70 cents), self-addressed envelope:

  • Graedons’ People’s Pharmacy, No. G-3,
  • P. O. Box 52027, Durham
  • NC 27717-2027

It can also be downloaded for $2 from the website:

Rate this article
4.9- 17 ratings
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.” .
Digestive Disorders

Download this guide to getting off heartburn medicine. Preventing ulcers. Effective treatments for constipation and diarrhea. Foods and drugs that cause gas.

Digestive Disorders
Join over 150,000 Subscribers at The People's Pharmacy

We're empowering you to make wise decisions about your own health, by providing you with essential health information about both medical and alternative treatment options.

Showing 19 comments
Add your comment

Sadly, I was put on Aciphex (a PPI for acid reflux ) and remained on it for 11 years until I learned that a serious side affect of kidney damage is very real. I chose to stop taking the Aciphex and took Zantac 150 mg. to help with the withdrawals. I have been off Aciphex now for over 3 years and still taking Zantac 75 mg. but at least my kidneys are not being damaged any further. I now live with stage 3 kidney failure as a result of Aciphex. It’s a terrible price to pay for my Gastroenterologist not being pro-active in my care.

I have been on PPI for about 5 years I have Barrett’s esophagus and would like to get off of PPI but not sure what to do I have talked to my Doctor and she keeps telling me that having Barretts and taking PPI out weights the side effects of PPI. Not sure what to do keep taking PPI and going crazy about reading all the new side effects of PPI or having Barrett’s esophagus problems.

I believe constipation and side effects of medications are leading causes of acid reflux. If we address these causes we can reduce or eliminate acid reflux. Food sensitivity is another major cause. Get tested for food intolerances!

I take PPI because of bariatric surgery, which necessitates reduction in acid production in the stomach. If I do not take the drug, it triggers reflux discomfort and nausea. As a result of the side effects discussed for PPIs, particularly bone related ones for a person in my seventies, I decided to see if it is possible to decrease the amount of PPI I take. I have successfully reduced the dosage to every third day, while using DGL Licorice. With this combination I take DGL every day and the PPI every third or fourth day without any discomfort.

My husband has Barretts and has been on PPI’s for years. He was having trouble with food backing up and throwing up as he also has no motility in his esophagus. Doc injected Botox into his esophagus and it has been a miracle for him. Weaned himself off Prilosec and doing great. Thus may last for a month or years, but his has been over a year, so far and he would do it again if he has to.

I had pretty severe GERD and was prescribed a PPI. Because of the possibility of long-term side effects, I tapered off the PPI and began taking a papaya enzyme tablet each night. I have had little to no problems with reflux on this regimen.

When people discuss the side effects of PPIs and possibly discontinuing one, why does no one ever mention surgery to tighten the valve which prevents the stomach contents from getting into the esophagus? It’s a surgery which can be done laparoscopically, and I have met a few people who have been very happy with the result. ???

About seven years ago, I was diagnosed with silent reflux by an ENT doctor who gave me a script for PPIs and sent me on my way. Soon after, my gastroenterologist performed an upper endoscopy and lab results showed Barrett’s esophagus. My esophagus was pink and healthy looking, not typical of someone with Barrett’s.

Mind you, I never had heartburn and an overnight ph monitoring showed no reflux. My gastro doc still wanted me to take PPIs. But I refused, as my research back then found that PPIs were never shown to stop the progression of Barrett’s to adenocarcinoma. Plus I was well aware about a number of bad side effects and risk factors (more risks keep popping up!).

I was put on a monitoring program with a series of upper endoscopies over three year’s time. The last endoscopy showed no evidence of Barrett’s and monitoring was stopped! I’m so glad I had refused to take the PPIs, explaining to my gastroenterologist my well-researched reasons why. The icing on the cake is reading about this study published in PLOS One confirming my beliefs. Thank-you People’s Pharmacy!

Botox injection worked for my husband.

Fifteen years ago, I was diagnosed with Barrett’s & two of the highest ranked Gastroenterology clinics in the U.S. — PP nearest neighbors — agreed my risk was very high of developing esophageal cancer and that I required a fundoplasty. Having just lost my health insurance I felt stymied & afraid of the consequences of not proceeding with this expensive surgical procedure paid out of pocket.

At that point, I had been on protonix for a year & decided after much research to stop using this immune system numbing drug. I did not move to OTC PPI’s but instead was elated to find red licorice extract used to treat Barrett’s in many European nations with great success & a very low cost.

Having another esophageal exam four years later showed no Barrett’s and no symptoms of acid reflux. The presiding Gastroenterologists insisted that I take protonix again. I laughed & walked out of his office. When do we stop pretending that we are protected by our medical clinicians and/or the oversight of government agencies. Medicine is a business. It is not a public service.

Why don’t you include baking soda in your recommendations for heartburn? I find it to give me the fastest relief and no side affects. Doesn’t happen every day, but when it hits me at night, I don’t want to suffer any length of time.

Regarding Peoples Pharmacy reporting side effects of PPI, I am ever grateful. I was prescribed the Rx after having an A/V malformation repaired in my stomach. I also have renal failure. As I had quit smoking I thought my symptoms of increased confusion and swollen legs were caused by that. I stopped the Prilosec and notified my Dr. He agreed… So kudus to the People’s Pharmacy.

Is there any evidence that PPIs protects one from esophageal cancer in folks who have reflux but don’t have Barrett’s?

Rather than treat with drugs, how about a midden fundalplication, a laparoscopic procedure to prevent acid from harming the esophagus? I had mine in 1996 and best thing I ever did.

My daughter had serious GERD and Barrett’s esophagus. Had bad reactions from prescription drugs. She now uses aloe vera juice and other natural supplements. A year after starting this her doctor was amazed and delighted at her improvement.

Please do not stop reporting side effects of PPIs. It was because of your reporting on a small study from Italy that I learned what was causing a horrible scaly patchy rash all over my husband’s body that was driving him crazy, and that his doctors, including a dermatologist, could not diagnose. It was a rare side effect of omeprazole.

The rash disappeared in two weeks after he stopped taking it. Further, I started looking into other side effects and found that his muscle weakness and mental confusion were also related to the med. Just days before I read your article he had said he didn’t see the point of living if he had to live like this always. I have not seen the study reported anywhere else and I am eternally grateful to you.

Is there a difference between GERD and mild heartburn? I take a calcium carbonate antacid about 5 or 6 times a week, usually at bedtime. Once when I mentioned that at the doctor’s office, the nurse practitioner entered GERD on my chart and tried to push a prescription. I don’t think it’s severe enough to warrant a powerful drug, but she was concerned about esophogeal cancer. Years later I asked the doctor to take GERD off my chart, but I think it has been added again. I don’t think it’s severe enough to have a diagnosis on my chart. What’s the clinical definition of GERD?

I was diagnosed with GERD about thirty years ago and was prescribed Protonix initially, later Nexium and finally Prilosec. This dance of medications was based on availability of samples and cost of medication. Eventually I was on Prilosec daily, every day. I developed Barrets Esophagus anyway. I also developed a condition called Schatzki’s Ring. Not doing very well. I began before anyone really knew about the side effects.

I was on PPIs, sometimes as many as two a day, for decades. About ten years ago I decided that the side effects were worth considering stopping the medication all together and I cut back from daily, to every other day, then four/three times a week to none. My GI guy was against it but he couldn’t have me come in every day to force a pill down my throat. I have been PPI free for five or six years at this point.

I had no rebound effect and my GERD has disappeared. I do take Papaya Enzyme tablets (pretty cheap, pretty natural) but not even every day and mostly because i like the taste. I read here on the Peep’sFarmacy that it is is helpful with digestion.
I may be luckier than most but I doubt it.

My gastroenterologist cured my acid reflux with cytotec. What do you know about how this drug works? After a bad experience with Nexium, I took cytotec for 4 weeks and was cured. He also told me not take papaya enzyme pills more frequently than twice a week, because they ‘digested’ the lining of the esophagus if used too oftenP

* Be nice, and don't over share. View comment policy^