There are 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 Reader Wants to know: Will PPIs Protect Against Cancer?
Q. I’ve been taking omeprazole (Prilosec) for more than 30 years. During an upper GI scoping back then, the doctor diagnosed the beginning of Barrett’s esophagus. He prescribed omeprazole.
I take it daily. However, with all the problems PPIs can cause, I am not certain that this drug is the wisest choice for my health going forward. Is weaning off the drug even an option, given the Barrett’s esophagus diagnosis?
A. Your question is more complex than it might seem. Gastroenterologists generally recommend regular endoscopy every few years to monitor cellular changes that can occur with Barrett’s esophagus (BE). There are new cell-collection devices that can also screen for problems. The guidelines for managing BE call for long-term treatment with proton pump inhibitors (PPIs) like omeprazole.
There is some controversy, however. A systematic review and meta-analysis of nine studies concluded that PPIs may not protect BE patients against esophageal cancer (PLoS One, Jan. 10, 2017).
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.
More recent reviews involving additional studies concluded that PPIs do reduce the risk of abnormal cellular growth and cancer in BE patients (Expert Review of Clinical Pharmacology, Jan. 2022).
To make this even more complicated, large studies published in the journals Gut (Jan. 2022) and Oncology Letters (Jan. 2024) concluded that the use of proton pump inhibitors is associated with an increased risk of gastric and esophageal cancers.
A study of lifestyle interventions found that alcohol and smoking raise the risk for BE, while vitamin C, folic acid, aspirin and fiber reduce it (Cancer Medicine, Aug. 2021). https://pubmed.ncbi.nlm.nih.gov/34128354/
To prepare yourself for meeting with your physician to discuss these complicated issues, you may find our eGuide to Overcoming Digestive Disorders helpful. It is located under the Health eGuides tab at www.PeoplesPharmacy.com.
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:
