The People's Perspective on Medicine

Is Liver Cancer a Risk of Acid-Suppressing Drugs?

Proton pump inhibitors (PPIs) like Nexium and Prilosec can prevent heartburn and heal ulcers. But they do have some frightening side effects and might even promote liver cancer.
A woman holds the liver. Pain in the abdomen. Cirrhosis of the liver. Sore point highlighted in red. Closeup. Isolated.

Not again! We are sick and tired or reading about another potentially serious side effect of proton pump inhibitors (PPIs). Over the last few decades the list of very worrisome adverse reactions has grown substantially. Now, a group of researchers in Taiwan have reported a possible relationship between long-term PPI use and liver cancer (hepatocellular carcinoma abbreviated HCC). That is not welcome news.

PPIs Are Super Popular:

There was a time when people swallowed antacids when they had heartburn. Old timers would put a little baking soda (sodium bicarbonate) in a glass of water, stir and swallow. It was cheap and fast. Then along came drugs like Alka-Seltzer, Tums, Rolaids, Maalox and Mylanta. They were available over the counter and were very popular.

Then came the H2 antagonists. They suppressed acid somewhat. In their day they were very high on the doctors’ hit parade of most popular drugs. We’re talking about cimetidine (Tagamet), famotidine (Pepcid) and ranitidine (Zantac). When the patents expired on these prescription drugs, they went over the counter and lost their luster with physicians.

Enter proton pump inhibitors. Drugs like omeprazole (Prilosec) and esomeprazole (Nexium) became doctors’ favorites. It took no time at all for these acid suppressing drugs to become the go-to treatment for digestive upset. People were prescribed PPIs for acid reflux, heartburn, indigestion, stomach ulcers and just about anything else affecting the upper GI tract.

People taking nonsteroidal anti-inflammatory drugs (NSAIDs) for arthritis, strains and sprains are often told to take a PPI to protect the stomach from damage. The hope is that suppressing acid will prevent NSAID-caused lesions from turning into dangerous ulcers.

In 2015 (the most recent data we have), roughly 25 million people received a prescription for a PPI, adding up to more than 117 million prescriptions. That does not include use of over-the-counter drugs such as esomeprazole (Nexium 24HR), lansoprazole (Prevacid 24HR) and omeprazole (Prilosec OTC).

How Safe Are PPIs?

Such acid-suppressing drugs have long been considered among the safest medications in the pharmacy. That is why the FDA decided 15 years ago that Prilosec could be sold without a prescription.

Physicians are beginning to worry about over-utilization of these drugs, however (Therapeutic Advances in Gastroenterology, July 2012). There is growing evidence that long-term use of PPIs may carry some serious safety problems that weren’t anticipated when the drugs were first launched.


Stomach acid is strong, and it kills many types of bacteria. When acid is suppressed, people may develop infections. Higher rates of both pneumonia and Clostridium difficile, an intestinal infection, are linked to PPI use. In addition, these drugs can change the balance of bacteria in the digestive tract (Digestive Disease and Sciences, online, May 24, 2018).  This disruption in the ecology of the intestines may in part contribute to these infections (Gut, May, 2016).

Nutritional Deficiencies:

Other unexpected complications of prolonged use of PPIs include nutritional deficiencies. Changing the pH of the stomach may lead to lower levels of magnesium, iron, zinc, calcium and vitamin B12. As a result, users may have an increased risk of osteoporosis and fractures (Osteoporosis International, April 2013).

Kidney Disease:

Another serious adverse reaction associated with these potent acid-suppressing drugs is kidney disease. There is growing evidence that long-term use of PPIs can damage the kidneys (Nephrologie & Therapeutique, April, 2018).  Clinicians have been encouraged to monitor kidney function of patients on prolonged PPI therapy.

Heart Problems:

More controversial is the link between these acid-suppressing drugs and cardiovascular health. Researchers have reported a connection between PPIs and heart attacks (PLoS One, June 10, 2015).  Other investigators have found no such risk, however (Gastroenterology, March, 2018).

Strokes, Dementia and Liver Cancer:

People taking anti-platelet drugs to prevent blood clots (clopidogrel, prasugrel, ticlopidine) may be at increased risk of both heart attacks and strokes if they also take PPIs (Stroke, Feb. 2018). Other controversial complications include reports of dementia, Alzheimer disease and liver cancer (Alimentary Pharmacology & Therapeutics, July 2018).

Although such research is scary, it should not discourage people from taking PPIs when they are essential. But doctors are being encouraged to prescribe such drugs only when absolutely necessary. We hope that people who take OTC acid-suppressing drugs without medical supervision are equally cautious.

It’s Hard to Stop PPIs:

People who get into a PPI habit often find it hard to stop cold turkey. That’s because of something called rebound hyperacidity.

When you suppress acid formation in the stomach with PPIs, the body tries to compensate. It attempts to make acid but is thwarted by the medicine. Once the acid-suppressing drug is stopped, however, the stomach starts churning out lots of acid. This can lead to unbearable heartburn that can last days or weeks.

When symptoms return with a vengeance, many people reach for their PPI. This can lead to a vicious cycle. It’s hardly any wonder that some people remain on PPIs for years or even decades.

Liver cancer is probably a relatively low risk of long-term PPI use. And for some, the benefits of the drugs outweighs the danger. For others, though, it would be wise to discuss the pros and cons of PPIs with a physician. Liver cancer is challenging. Even a small increased risk would be worrisome.

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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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I started on Lansoprazole 15mg approx. three weeks ago. I also had been on it a few years before and then only stayed on it for four weeks. It did the job but had some minor side effects.

This time, for first few days I was ok. Then I began to feel skin and scalp was tender to touch, had dry throat then felt sick and though clearly had to have meals, I had to make myself eat. Added to that I had to go to bed twice in that week as I felt so tired and absolutely devoid of my natural liveliness and enthusiasm. After two weeks I couldn’t stand that anymore and knew that I had to stop Lansoprazole. But since they had actually eased the acid and stomach burning that I had tolerated for a long time, it concerned me that all that would return again. However I could not continue on Lansoprazole. I went to doctor. I stopped them. She was correct in saying that I had used them before, and I agreed.

She gave me a prescription for Ranitidine 150 mg. I’m certain that I have had them many years ago and and found them ineffective. I am concerned as to how long this feeling of tiredness, sickness, not being hungry, dry throat and food taste, and generally feeling ill will continue. Lansoprazole was stopped on 22nd Oct.
I will be filling out side effects via Yellow Card Scheme@

I have been on omeprazole for many years and have been concerned about it especially since reading about the side affects on the People’s Pharmacy. I went to a routine doctor’s appointment yesterday and we were reviewing my meds for refill when she said she wanted to talk to me about the omeprazole and told me the new findings and concerns (exactly as told on the People’s Pharmacy) and that she was taking me off of omeprzole and putting me on zantac. An attorney that works on cases with my attorney boss told me last week that he takes 3 omeprazoles a day so he can eat whatever he wants, especially our famous NM red and green chile. Hope I can convince him to start reading the new research and save himself future major health problems or death.

After trying unsuccessfully to get off Prilosec, I started taking it again. When I became convinced of side effect dangers, I started looking around. I FOUND SOMETHING THAT WORKS! It is called ACID EASE, by Enzymatic Therapy. It is a combination of digestive enzymes , marshmallow root extract, and slippery elm bark. As long as I take 2 with each meal, I have nearly NO acid problems. When I do sense reflux, i chew 3 papaya enzyme tabs and it goes away.
I buy ACID EASE at Whole Foods, but I am sure that it is available elsewhere.

Doctors had me on Prevacid for 14 years. PPIs bleed the calcium out of your bones. An herbalist told me he could cure my GERD in 3 months, and he did. That was 4 years ago. He put me on Lower bowel, Liver & gallbladder & Joint formula, plus slippery elm. My favorite saying now a days is “If you want to stay healthy don’t go to the doctor.” When I found that Prevacid was made in India, that was a wake up for me.

What would be the best homeopathic remedy? I take Omeprazole, 40mg daily. I would rather do a natural remedy.

Absolutely Spot on.
Stay away from doctors and surgeries. Tablets and medication, in my experience, can be far more damaging to the body than simpler or older-style remedies, unless they are life-saving or an absolutely must-have life necessity medication.
I’ve learned that the hard way.

I’ve recently build a unique app on proton pump inhibitors so you can check the data there and potentially fill the form so that we can finally see how these drugs work longterm

My daughter was put on previcid when she was 6 months old. She had kidney problems by the time she was 2 years old. She also had two bouts of pneumonia and a three month stretch of diarrhea. No one ever told me those things could be related. When she was five, I found a homeopathic doctor who was able to fix all of her stomach problems and she is now off all of her medication. She is the healthiest she’s ever been and drug free

I have to agree. It’s extremely difficult to come off of omeprazol. I’ve been on it for a number of years and have tried unsuccessfully to come off of it. After two weeks I was so miserable I had to go back on the omeprazol. It took several days to get over the reflux discomfort and i still wasn’t 100% feeling less discomfort.

I plan on trying to stop omeprazole again to ward off any chance of developing Alzheimer’s because my mother had Alzheimer’s disease. I tried Zantac but that didn’t touch my reflux symptoms. I’m going to try something different and maybe your elimination diet…

What about giving it to infants?? My granddaughter has been taking a PPI since she was an infant and now she is 3! What about them? Also, she is severely disabled with PCH2.

Great. What is elimination diet?

I was put on omeprazole for a dry cough, AFTER a 24 hour acid test showed I DID NOT have GERD. I took the maximum dose of omeprazole and ranitidine for 2 weeks with ZERO changes. I quit before I could be susceptible to rebound with no increase in symptoms.

My doc can’t explain the cough which comes after a URI and lasts longer each time then goes into spontaneous remission for months. NOTHING I have ever taken for it has helped: prescription, OTC, alternative or ccombinations of the above.

Took me two months to get off omeprazole. Just kept stretching out the time between pills. Now I use diglycerized licorice 15 min before dinner. Don’t lie down after a meal; don’t eat heavy meals; and watch the acidic foods like tomatoes.

Oh, great. Yet another drug that I use putting me in danger of cancer. S! ometimes people don’t have a choice in using this stuff. I take, actually I have to take, steroids for my illness (nothing else works for me). Steroids cause many bad side effects and besides weight gain, Cataracts, Diabetes, high blood pressure, high cholestrol, circular face (moon face), depression, anixiety, Heartburn, Nasty Indegestion (to name just a few) (I’ve have/had them ALL), I now have to worry about cancer. I give up! I wouldn’t take steroids if I didn’t HAVE to…there is nothing, NOTHING out there that stops my pain and inflammation like steroids do.

I was on a PPI for about 4 years and decided to come off it myself after reading about the possible problems associated with them. It was very hard – had very bad reflux and heartburn for about 2-3 weeks. I was able to persevere and now use Zantac for reflux control and Pepsid tablets for quicker relief. This seems to be working for me.

I have Barrett’s Esophagus. I take 40 mg of Omeprazole a day a prescribed by my doctor.

What are my options?

Indeed, PPIs are dangerous. I was prescribed Aciphex (I couldn’t tolerate Prilosec or Nexium) and remained on it for 11 years because my doctor never monitored the effects. I was naive and trusted that the Aciphex was safe. How wrong that was. That long time use caused me to suffer stage III kidney disease.

Getting off Aciphex cold turkey was tough but I went on Zantac and that did ease the heartburn incidents. I hate taking anything but at this point, but a low dosage Zantac works. My kidneys are definitely a major concern. PPIs should never be used long term!

Has anyone tried Super Papaya Enzyme Plus for heartburn/indigestion? Shouldn’t it be taken after eating food one thinks will cause heartburn? Or can it be used instead of an anti-acid aefter heartburn sets in (I’ve never tried that)? It worked for me after eating something I knew would cause heartburn. I rarely use it, and have no idea why I very rarely get heartburn anymore.

I took Prilosec when it first came out. An esophageal problem with the valve caused bloating and reflux. The drug worked wonders. I was on it for years. As a 6 gallon blood donor I was shocked to be told I had low hemoglobin. My new doctor checked me, and I had no iron reserves. He took me off Prilosec, and I went back to normal. The People’s Pharmacy had a withdrawal program I bought, and it worked.

Doc does not care about keeping me on prilosec. Been on it for years, and I want to stop. How and what else should I do if acid starts up? I do take Tums to help.

I was on PPIs for over twenty. I have been trying to get off for two years. I was suffering debilitating acid and tried everything under the sun. Five years ago I began developing an intolerance to almost all foods except some fresh vegetables and grass fed meats. This was caused by PPIs, another little known side effect. Two months ago I discovered something called Restore (purchased on Amazon). It is amazing. A miracle in a bottle. I am on my third bottle and only have to take an occasional Tums or Zantac. Please research this product and see if it is right for you.

I was on prilosec for years for GERD. I’m in my 60s with lots of dementia in my immediate family and wanted off Prilosec to reduce my dementia risk. My doctor wasn’t concerned (even though the Prilosec box says don’t stay on it for more than 2 weeks….so I changed doctors).

Now, I take apple cider vinegar capsules 2x daily, don’t lay down for at least 2 hours after i eat, keep Juicy Fruit by the bed in case i get heartburn in the night (which doesn’t happen very often). Juicy Fruit is the best thing I’ve found to get rid of the burning and also the extra saliva you make is supposed to help reduce the acid. If I break the rules and need to go bed soon after eating, I take a Tagament first.

I’m convinced there is a correlation between long term PPI use and liver cancer that should be researched further. In my mother’s case, she got diagnosed with pancreatic cancer that had spread to the liver but now I wonder if it started in the liver and spread to the pancreas. She never drank, smoked or took medication other than a PPI (for 7 years). It wasn’t until she became sick that we learned it’s not meant for long term use but should be cycled on and off (no more than 4 cycles a year). There’s a reason they give that warning but it’s never explained what the increased risks of long term use actually are. With so many people on PPIs, more research on long term effects should be done.

I have taken Protonix for quite some time. At one time my B12 was low, and I had to take shots for a month or so. Now I take a B12 supplement. My nurse practitioner didn’t seem to know that the Protonix could be causing it. I also take Meloxicam for arthritis. I’ve gone off the Protonix on my own before but was told to get back on it because of the Meloxicam. I don’t want the Meloxicam to hurt my stomach but hate to constantly take the Protonix. I do have bloodwork about twice a year and at least once a year. So, hopefully, my doctor is keeping an eye on side effects.

My cardiologist put me on Prilosec years ago. I see him every 6mos. The benefits seem to out weigh the possibility of side effects. When we tried to change from daily to three times weekly or take one when when I knew I was going to have something spicy didn’t work for me. We do monitor liver and other functions.

I was on Prilosec for years and was told by my doctor I was a lifer due to my hiatal hernia. I put myself on an elimination diet, discovered what foods were my triggers, and used your great info on how to get off PPIs. The doc was very surprised. I have been successfully off Prilosec for a few years. I recommend people try an elimination diet.

Like so many drugs, the use is way too casual and overdone in the U.S. instead of looking at other options. Felt horrible when I took PPIs, and it was so good to get off them.

Your piece is very timely. I’ve Been off and on Nexium for years. Having a chronic kidney condition. I was extremely concerned to read the report you mentioned some time ago but both my internist and my nephrologist told me the trail was incomplete, and my going back on Nexium was OK.

I have been able to stretch the length of time, taking a 40MG tab, to three days apart.

I recently successfully took myself off PPIs in favor of H2 inhibitors. Tapering off took me ~ 2 months after I had been taking PPIs for at least 20 years. Near the end of the taper program I began taking the H2 inhibitors which I continue to take at OTC strengths. I do use the occasional Tums, but otherwise have not had any problems. Hope this helps and encourages others to taper off their use also.

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