The People's Perspective on Medicine

Heartburn Drugs and Esophageal Cancer?

A new study does not show that taking PPIs reduces the likelihood of esophageal cancer in people with Barrett's esophagus.

Q. I have been using Nexium for years and have been told I’ll need it forever because I have Barrett’s esophagus.

I know that Nexium can interfere with the absorption of important minerals and I have already had one hip fracture. I do not want to get esophageal cancer, but I worry about the long-term effects of Nexium.

A. Barrett’s esophagus is a condition in which the cells lining the lower portion of the food tube become abnormal. This disorder moderately increases the risk for esophageal cancer, which is why your doctor prescribed an acid-suppressing drug. Esophageal cancer is hard to treat and has long been considered one of the deadliest of cancers.

For decades, doctors have believed that acid was the culprit behind the abnormal cellular changes of Barrett’s and the eventual conversion of those cells into cancer. The assumption has been-no acid, no damage. In addition to curing ulcers and preventing heartburn, drugs like esomeprazole (Nexium), lansoprazole (Prevacid), omeprazole (Prilosec), pantoprazole (Protonix) or rabeprazole (Aciphex) were supposed to keep Barrett’s esophagus from developing into cancer.

Contradictory Research

Danish investigators did a nationwide case-control study matching nearly 10,000 patients with Barrett’s esophagus to healthy subjects (Alimentary Pharmacology and Therapeutics, May, 2014). Proton pump inhibitors (PPIs) such as the “zole” drugs mentioned above did not provide any cancer protection. In their own words, here is what these investigators found:

“In this population-based study among patients with Barrett’s oesophagus, we were not able to prove a preventive effect from proton pump inhibitors, instead we found an increased risk of oesophageal adenocarcinoma and high-grade dysplasia [pre-cancerous abnormal cells] related to long-term PPI therapy.”

What? Read that again slowly. Not only did these powerful acid-suppressing drugs not protect against esophageal cancer, they were actually linked to a very dangerous kind of cancer called adenocarcinoma of the esophagus.

A Medical Mystery: The Change in Esophageal Cancer!

Over the last forty years there has been a dramatic shift in the nature of esophageal cancer. This is unheard of in cancer epidemiology. The underlying pathology of cancer does not change radically in a short period of time unless there is some underlying environmental exposure. As humans, we do not “evolve” or change our biology so quickly.

Several decades ago squamous cell carcinoma was responsible for 90 percent of all cases of esophageal cancer. Squamous cells are the cells that normally line the esophagus, so it is not surprising that they would be the ones that would go bad in esophageal cancer.

In recent years, however, adenocarcinoma has become the dominant form of esophageal cancer, representing roughly 80 percent of all cases. This more aggressive and dangerous kind of cancer originates in gland cells that are not normally found in the esophagus.

We have asked many gastroenterologists why there has been such an increase in esophageal cancer over the last 30 years and why there has been such a sudden and dangerous shift in the pathology of esophageal cancer. The answers usually range from obesity and smoking to alcohol abuse and the drinking of hot beverages. Sorry, we aren’t buying.

Could PPIs be Contributing to Esophageal Cancer?

This is heresy. Remember, acid suppressing drugs have been used for the last few decades presumably to prevent esophageal cancer. Is it possible that they have actually been contributing to this problem? Of course, we cannot answer that definitively based on just one study. There are other reports that have found no association between PPIs and adenocarcinoma of the esophagus.

Here’s the key issue, so please pay attention. Remember that gastroenterologists have focused on acid as the culprit behind Barrett’s esophagus and esophageal cancer. What if there were other players in this drama? The Danish authors point out:

“there is more to reflux than just acid.”

We have been writing about other stomach contents for years. Bile, produced by the liver but sometimes found in the stomach, can cause inflammation, cell proliferation and cell mutations. The Danes suggest that

“PPI use may facilitate the formation of carcinogenic bile acids, explaining some of our findings.”

They also go on to note that another key player in stomach juice is gastrin. This compound stimulates formation of stomach acid and promotes muscular contractions. The Danish scientists point out that gastrin levels skyrocket when people take PPI-type drugs. Gastrin stimulates cell growth that may contribute to cancer formation. They suggest that,

“This may increase the risk of gastrointestinal tumours.”

No one should ever stop taking PPIs without a thoughtful conversation with the prescribing physician. This provocative Danish research needs to be replicated before any conclusions can be made. But the questions that are raised should not be shoved under the rug either!

Fractures and PPIs

Your concerns about fracture are justified, since Nexium and similar drugs are among those associated with a higher risk of osteoporosis (Therapeutic Advances in Musculoskeletal Disease, Oct. 2014). To date, there have been 34 studies involving nearly two million participants. Analysis of this research suggests “overall there is an association between PPI therapy and risk of fracture” (Current Treatment Options in Gastroenterology, Dec. 2014).

Again, do NOT stop Nexium, but discuss these complicated issues with your doctor. There are other ways to reduce your risk of developing esophageal cancer. Learn more about some surprising findings regarding aspirin and Barrett’s esophagus at this link.

Would you like to read more about PPIs and cancer, PPI addiction and other ways to deal with indigestion? We have written about these topics in much greater depth in our book, Best Choices from The People’s Pharmacy.

Share your own experience with PPIs (positive or negative) below. Have they worked to control Barrett’s esophagus? Have cells returned to normal? We want to hear from you. Have you had trouble stopping PPIs? Let us know how you managed to discontinue such medications. Others can benefit from your story.

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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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After having surgery for Hyperparathyroidism in February, I found my GERD had regressed a bit and was not too concerned about it. After about a month, I still had a little heartburn one to 3 times per week, but then started having a little trouble swallowing and had to wait for food to finish going down. Not fun! I had a scope done in July and they found GERD and Barrett’s Esophagus. Started a PPI at Gastro doc’s suggestion. Stomach hurt right away, sleep started to be effected and then my hips really started hurting (like they had before the parathryoid surgery). I do have osteoporosis in my hips already due to my wacky parathyroid glands, so that hip pain really concerned me. Let GI doc know and he wanted to switch me to a different PPI. Talked with my primary care doc and we decided together to do a trial of ranitidine and I am researching some other natural remedies that will hopefully get to the root of the problem. I think I may have low stomach acid (one of my sisters does) and I am working on more dietary changes and losing weight. Hopefully all of these will help! I do not like the idea of eliminating all of the acid in my stomach, it does not make sense! It’s there for a reason.

Meta analysis (combined results of many, many studies), conducted the same year showed 71% decrease in adenocarcinoma risk in those with barretts esophagus who were treated with a PPI. In addition, the reduction in risk was found to be dose-dependent (meaning: take more of the drug, have less risk).

I wouldn’t make treatment recommendations for my patients based on the warning found on this website when the overwhelming body of research indicates that these drugs are cancer-preventative!

We have just published this paper with our hypothesis on how PPIs might not only promote dysplasia and adenocarcinoma of the esophagus, but also Barrett’s esophagus (metaplasia) itself. Overall, bile salts + PPI = culprit.

Alsalahi O and Dobrian AD (2015) Proton pump inhibitors: the culprit for Barrett’s esophagus? Front. Oncol. 4:373. doi: 10.3389/fonc.2014.00373

I have researched many online publications regarding PPIs and the like i.e. prilosec nexium etc and while each individuals circumstances both physiological and psychological are different these drugs are not getting to the real reasons people are suffering from GERD, Heartburn, Gastritis, etc. Be it under production of stomach acid not over or bacterial overgrowth due to over prescribed anti-biotics or just an undetermined bacterial overgrowth, what is clear is these drugs have many, some very negative severe life and health altering effects. To say “side-effects” just seems like way too little emphasis being placed on the real harm they are really doing. Remember the MD’s oath? “1st do no harm”! The solution is not to continue this never ending lifetime of taking them, as a side I read that the length of time a person should be on PPIs is only a few months not forever, but to actually find/determine what’s really causing the problem and address it with protocols and healing therapies the get to the root of the problem not just trying to cover them up with quick fixes that many times don’t do much or as has been posted by the Danes in their research, actually make for worse health situations. I guess what I’m really saying is we need Holistic health care for everyone! Our docs need to get with it and embrace a whole body mind approach to healing! I hope and pray they are listening to people like the Graedon’s ! Thank you :o)

I was taking Nexium twice daily for years, then began reading about the damages it could cause, so I began taking it once daily; then eventually once every other day. Still had no reflux problems. I recently tripped and landed on my knees on concrete. Hurt terribly and bad bruises. Nothing broken, though but now have bursitis in one knee… very painful.

About ten years ago due to some sense of reflux and light belching I was placed on PPIs and used different ones over a period of several years. They made me feel horrible. My bowel movements were terrible and I felt lousy. Fit, but slender, I also lost weight to such an extant that friends and co-workers remarked on my appearance and expressed concern.

Finally, thanks to a wise ENT doctor and a couple all-clear endoscopies, I stopped the PPIs completely and immediately my bowel problems went away and I gained weight back and felt like myself again. I think that the drug companies pushed these medicines and the medical community bought into them as a panacea but I always questioned something that made me feel so unhealthy. Lifestyle changes such as dietary changes are a better approach and I’m glad my ENT questioned these medicines.

I’m an RN and have heard from a number of patients that when they cut out bread and most starches, their reflux stopped. Not evidence but an interesting anecdote.

I was on Nexium for 9 years. It did help my reflux disease but now I have a stomach full of polyps. I have yearly endoscopies to collect a few polyps for biopsy. So far no cancer. I now take Pepsid AC as needed when my heartburn is severe. I will never take a PPI again. I also try to keep troublesome foods out of my diet.

Several years ago I was prescribed Nexium for acid reflux by our family doctor. I took it daily for about a year, and it mostly stopped the acid reflux, but I never felt confident that it was good in the long run to stop a natural secretion in the gut, which is what Nexium does.

Finally my niece (a nurse) told me she was gluten intolerant and recommended that I be tested for it too, since it can be genetic. Instead of getting a test I just stopped the Nexium and also stopped eating bread or other wheat products for a few days, and not only felt better but did not have “acid reflux.”

When I went back to eating bread, my symptoms (painful indigestion) started again. So I quit wheat products again, this time permanently, and indigestion never returned. I find I can eat limited amounts of spelt bread (made from the old original form of wheat that has less gluten) so I can have my piece of toast for breakfast — it’s delicious toasted! And an occasional tomato sandwich in the summer, which is a southerner’s soul food. But otherwise I stay away from bread, cakes, crackers, cookies, wheat cereal and the like, which do nothing but on weight anyway!

What about Ranitidine? I’m taking 150Mg twicea day

I’m wondering if drugs like Zantac or Pepcid have the same dangers as the stronger PPIs. I was on Prilosec briefly but couldn’t handle the side effects so I have used Zantac ever since because I just can’t find a natural remedy that works for me. Is using Zantac a concern for cancer?

I’m not a doctor but NYU docs on their show “Dr. Radio” flat out said that PPIs cause esophageal cancer and that one should investigate H2 Blockers as a substitute, as they do not have that history. Zantac is an H2 Blocker and Nexium and Prilosec is a PPI. Just for what it’s worth.

I’m surprised you didn’t mention radio-frequency ablation. It cures Barrett’s. I was diagnosed before it became available and found it online when it was still experimental. It took two treatments, but now I’ve been free of Barrett’s for 5 years. And RFA is now a standard treatment. IIRC, the results of testing showed that 85% of treated patients were still free of Barrett’s after 5 years. For more info see:

My spouse was diagnosed with BE with HGD 15 years ago. He had a Nissan, did not work. From 2014-2015 he had RFA. Seemingly worked. He had been free of BE from 2015-2017. Last week, after 8 months from his last clear Endo, the BE was back, possibly cancer at this point. He has consistently taken Nexium since it came out. He is on a double dose of 40mg a day. I am wondering if this is a link to why standard treatments that are so successful on others have not been with his case. Very frustrating.

PPI’s can reduce our utilization of various nutrients such as B12.
So can metformin.

Dr. Hyla Cass has a book called Supplement Your Prescription that lists various drugs and the vitamins & minerals they inhibit.

I highly recommend checking it out if you are on ANY prescription drug.

Hi – regarding the fractures and ppi use, I read that the increased incidence of fractures was found only amongst post-menopausal women.
Thanks for your show & forums.

I had surgery in 2004 called a fun spoliation which basically cuts out the damage in the esophagus and stomach and reconnects them both. When I had the surgery there was a criteria that had to be met such as diet changes did not help, medication and double dose medication did not help. The surgery was only done on 1 in a 100 people then. It was a tough surgery but results were good. Never had to take another antacid in 10 years. My surgery was done in West Chester medical hospital which is a teaching hospital in New York.

There may be another mechanism… Anti secretory drugs i.e., those that lower acid production in the stomach (proton pump inhibitors and histamine blockers) may encourage the growth of bacteria there… these bacteria encourage the production of nitrates and nitrites from food and certain drugs. Nitrites can form nitrosamines and nitrosamides, which are carcinogens. It has been known that other older anti-secretory effects to control ulcers e.g., nerve cutting, also are associated with increased gastric cancer perhaps due to the same mechanism.

Using Vitamins C and E frequently could help, as these help to neutralize nitrites and nitrates…

what about PPI’s & B12 deficiencies

Magnesium deficiencies are one of the major concerns for people taking these drugs. I have noticed that the drug companies are now adding magnesium to them. I have been on these for 20 years, Barretts was the concern. There is no road to leaving these drugs, the reflux is unbearable. We need stomach acid for good health, never start these drugs for any reason, especially for simple indigestion!

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