Unhappy Liver

Have you ever met people who have a hard time admitting they might have made a mistake? Such individuals defend their decisions and actions no matter what the consequences. It feels to us as if the Food and Drug Administration is a lot like that. The agency has a hard time reversing course. Once the FDA declares a class of drugs safe for over-the-counter use, it seemingly hates to admit there’s a problem. Such appears to be the case with serious PPI side effects.

New PPI Side Effects:

Proton Pump Inhibitors (PPIs) are among the most popular drugs in the drug store. You may not recognize generic names like dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole and rabeprazole. The brand names, however, are almost household words: Aciphex, Dexilant, Nexium, Prevacid, Prilosec and Protonix. Millions of people swallow such pills every day.

PPIs and Liver Disease:

A study utilizing a mouse model suggests that these powerful acid-suppressing drugs may increase liver inflammation and liver disease (Nature Communications, Oct. 10, 2017). This may be a particular problem for people who drink a lot of alcohol.

PPIs are very effective at blocking stomach acid secretion. As a result, the balance of microbes in the intestines changes, and that can affect liver health. With reduced stomach acid, bacteria in the Enterococcus genus flourish. They can migrate to the liver and cause inflammation and damage.

The researchers analyzed stool samples from human subjects. These were alcoholics who were at risk for liver damage. The individuals who were taking proton pump inhibitors had higher levels of Enterococcus in their stool samples. They also seemed to be more vulnerable to alcohol-induced liver disease.

Learn to Love Your Liver:

Americans pretty much take their livers for granted…until something goes wrong. The French, on the other hand, love their livers. They are quite concerned about maintaining healthy livers, even though they do drink a lot of wine.

Without a healthy liver you are in very big trouble. Sadly, liver disease is increasing at an alarming rate. Obesity plays a big role. Fatty liver disease is a serious problem that results from the obesity epidemic. Alcohol abuse leads to cirrhosis of the liver. It too is a killer.

The idea that changing the bacterial balance in the gut with PPIs might affect the liver worries us. The lead author of the research is Bernd Schnabl, MD. He told the University of California San Diego Health Communications Department:

“Our stomachs produce gastric acid to kill ingested microbes, and taking a medication to suppress gastric acid secretion can change the composition of the gut microbiome. Since we found previously that the gut microbiome — the communities of bacteria and other microbes living there — can influence liver disease risk, we wondered what effect gastric acid suppression might have on the progression of chronic liver disease. We found that the absence of gastric acid promotes growth of Enterococcus bacteria in the intestines and translocation to the liver, where they exacerbate inflammation and worsen chronic liver disease.”

“Our findings indicate that the recent rise in use of gastric acid-suppressing medications might have contributed to the increased incidence of chronic liver disease. Although obesity and alcohol use predispose a person to acid reflux requiring antacid medication, many patients with chronic liver disease take gastric acid suppressive medications without appropriate indication. We believe clinicians should consider withholding medications that suppress gastric acid unless there is a strong medical indication.”

Other PPI Side Effects:

Changing the Gut Microbiome:

Dr. Schnabl is not the only researcher to discover that PPI side effects include changing the bacterial balance in the intestinal tract. Dutch investigators reported the following (Gut, May, 2016) :

“The differences between PPI users and non-users observed in this study are consistently associated with changes towards a less healthy gut microbiome. These differences are in line with known changes that predispose to C. difficile infections and can potentially explain the increased risk of enteric infections in PPI users. On a population level, the effects of PPI are more prominent than the effects of antibiotics or other commonly used drugs.”

Learn more about the disrupted microbiome at this link:

“Do Heartburn Drugs Disturb Bacterial Balance in the GI Tract?”

Kidney Disease:

All this bad news comes on top of prior research suggesting that proton pump inhibitors may increase the risk for kidney disease. Here is an article on this topic:

“Can PPI Heartburn Drugs Harm Kidneys Without Early Symptoms?”

More PPI Side Effects:

As if kidney and liver disease were not enough, here is a list of other potential PPI complications:

Scary PPI Side Effects:

• Infections (pneumonia, Clostridium difficile, aka C. diff)

• Heart attacks and vascular calcification

• Dementia, Alzheimer’s disease

• Malabsorption of nutrients (calcium, magnesium, zinc, vitamin B12)

• Weakened bones, osteopenia, osteoporosis, fractures

• Blood disorder (thrombocytopenia, anemia, iron deficiency)

PPI Side Effects and Early Death:

As scary as the PPI side effects listed above may be, the ultimate adverse reaction is death. An epidemiological study published in BMJ (July 4, 2017) was titled:

“Risk of Death Among Users of Proton Pump Inhibitors:

A Longitudinal Observational Cohort Study of United States Veterans.”

The investigators conclude:

“This study provides insights into the excess risk of death associated with PPI use. In a large primary cohort of new users of acid suppression therapy followed for a median of 5.71 years, we show a significant association between PPI use and risk of all-cause mortality. Risk was increased among those with no documented medical indications for PPI use and with prolonged duration of use…

“PPI are widely used by millions of people for indications and durations that were never tested or approved; they are available over the counter (without prescription) in several countries and generally perceived as safe class of therapeutics. They are often overprescribed, rarely deprescribed and frequently started inappropriately during a hospital stay, and their use extended for long-term duration without appropriate medical indication.

“…we consistently found a significant association between PPI use and increased risk of death. The consistency of study findings in our report and the growing body of evidence in the literature showing a host of adverse events associated with PPI use are compelling, and because of the high prevalence of PPI use, it may have public health implications. Exercising pharmacovigilance and limiting PPI use to instances and durations where it is medically indicated may be warranted.”

The investigators who carried out the liver studies also recommend that clinicians reserve PPI-type drugs for people who absolutely must suppress stomach acid.
[Nature Communications, Oct. 10, 2017]


Despite all the worrisome PPI side effects described above, never stop a PPI without medical supervision. And never stop a PPI suddenly. Rebound hyperacidity can be horrific. You can learn about horrible heartburn from PPI withdrawal at this link.

Where’s the FDA?

Imagine the FDA’s outrage if a dietary supplement or herb were linked to heart attacks, strokes, kidney or liver disease. There almost assuredly would be immediate regulatory action. Go back and read the list of PPI side effects. These are not trivial complications. Some are life threatening. And yet the FDA seems uninterested in alerting the public to such adverse reactions. Remember, PPIs are 1) readily available in pharmacies, supermarkets, gas stations, quickie marts and other convenience stores and 2) it is not easy to stop PPIs after you have taken them for several weeks.

Do you think the FDA should do anything about the growing list of serious PPI side effects? We would love to get your feedback in the comment section below.

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  1. Marla
    Dallas, TX

    My 91-year-old mother has severe acid reflux and was diagnosed with GERD and Barrett’s esophagus syndrome. She has been taking a spectrum of PPI medications for over 30 years. A life-long athlete and avid tennis player, she played tennis up until two weeks after her 90th birthday when she suddenly suffered a compression fracture from “severe” osteoporosis that had never been diagnosed. Her decline over the past year has been heartbreaking. I blame the PPIs.

  2. Darlene

    I’ll stop barely short of calling the FDA – IDIOTS – because I find so many things they do shocking! We the American public are there guinea pigs for testing drugs!!!!!

    I took 4 months of weaning myself off at least 10 years of use of PPI’s ironically I’ve had higher than normal liver enzymes in that 10 year period. After my first year off them I finally had NORMAL liver enzymes on my annual physical! Now I know why!

  3. Parrish

    This is just more evidence of how much influence pharmaceutical companies and medical device manufacturers wield at the FDA. In reality, these are civil servants ill-equipped to deal with the powerful lobbyists these corporations employ.

  4. Barbara B.

    So you make your choice: Unbearable stomach and esophageal pain (I had ulcerations to the point of not being able to swallow bread) and food, acid and bile coming up into your mouth and nearly choking you or causing you to vomit or you take a PPI. I have been on Nexium for several years now and have had NO side effects ever! I believe (and my doctor believes) that Nexium healed the ulcerations. You ‘pay your nickel and you take your ride’ – you choose the danger of PPI’s or you face the danger of cancerous lesions. I’m certain I would have been in much more serious gastric trouble without PPIs. Not ALL medicine is bad. I remember a time when the ‘authorities’ said that coffee would ‘kill’ you. Take your pick.

  5. Ann

    I had problems swallowing and began to lose my voice/ got very hoarse if i sang even 2 songs.(& I love to sing!) so I was referred to an ENT who did a scope and told me everything was normal– must be acid reflux and put me on a PPI.

    Well, I was an RN by training so I read the box and the warnings scared me (it said “don’t take long term “, and here he is telling me to basically stay on it the rest of my life!)

    Long story short, an Endocrinologist finally caught my toxic multinodular goiter when I began to have cardiac symptoms and the needle biopsy came back questionable. Fortunately the post surgery analysis was not cancer– but I wonder when it would have “switched” over if I had not had the surgery (and been VERY persistent that we had not addressed the underlying problem).

  6. barbara

    I had a worker’s comp knee injury and the clinic handed out advil/motrin every visit to take 600 mg 3x per day. they also handled out the ppi to take for stomach upset. I told them I did not need that as I did not have upset. but they insisted on giving it to me even after I told them I would not take it. I threw it away. thank God. I had enough problems with over prescribed advil. I still have knee pain but I am now taking “exercise” and knee rubs. the side effects of some of these medications are too scary.

  7. Michael

    I have been using PPI for at least 15 years. Tried to stop once and ended up on the floor thinking the pain was so bad I might be having a heart attack. I take 20 MG’s at night. I was trying everything everybody said and just couldn’t stand it. Went back and all is well.

  8. MARY

    I have been taking prilosec and then the generic for well over 20 years. This has stopped all stomach problems. I tried a different medicine that was not supposed to cause any problems, however the cost of the prescription was high and the over the counter did nothing, so I am back on the generic prilosec. If any one has a solution that will enable me to stop the generic and change to a medicine that works, please let me know.

  9. Hank

    Interesting. My mother, now 97 was taking a lot of Tums, Prilosec, etc for upset stomach. Then she went through a period of dizzy spells and falling.

    Now she takes dried ginger whenever she feels dizzy. It has been years since she felt the need to take Tums, Prilosec, etc.

  10. GiGi
    Spartanburg SC

    With a very active case of Crohn’s (22 years) and added diagnosis of Ulcerative Colitis (1 year), I have lots of “gastric issues”. My gastroenterologist has tried to work with getting me off PPI’s but I have ended up in the ER due to epigastric pain so bad I thought I was having a heart attack. But, all the talk of the harm of PPI’s scare me. I take 40 mg. of Nexium twice a day – morning and at night. I feel like I have no choice but to take something. I don’t drink or smoke and I can’t eat acidic foods anyway. So what choice do long-term users with these issues have?
    Love your site and columns. Read them every week and have used many of your home remedies for my husband.

  11. Janene

    I was on Nexium for 15 years with the blessing of 4 doctors including 2 gastroenterologists. About a year ago it was suggested that I take Ranitidine also as my acid reflux was starting to return even with the Nexium.

    I found this concerning but the final straw happened when I ate a quesadilla made with fresh roasted green chile. I immediately had cramping and stomach pain and ended up on the floor pale and sweating and feeling intensely ill. My stomach and digestive track were highly inflamed. I weaned off the drugs and have been on a very slow journey back to health. My worst problem now is leaky gut and a systemic Candida Albicans infection which has altered my life. I can have no sugar or alcohol among other foods and have to take a ton of supplements. My DOM says my liver is still not functioning fully and I still have digestive issues.

  12. BBBob

    I believe this is another case of drug manufacturers being allowed to advertise and sell drugs which have not been sufficiently tested by the FDA or third party testing. I first read cautionary warnings of these drugs more than a year ago, yet, the responsible agencies seem to have done nothing to put out a general warning or insist that manufacturers include warnings on labels or to doctors who are only too happy to prescribe them. Having patients tell doctors what drugs they want is the wrong way around; it should be doctors who recommend or prescribe drugs without pressure from misinformed patients who believe everything they see advertised, and drug makers anxious to make huge profits by “selling” to patients instead of doctors. Freedom of speech is one thing; freedom to deliberately misinform the public with the risk of serious health side-effects is another matter.

  13. Paulis

    These drugs are prescribed very casually, with little thought given to their toxicity. People trust their doctors, perhaps too much. I know. My father was on omeprazole for years. Also statins.

    We watched his creatinine levels go up and his kidneys fail. He died of kidney failure, an unknown disease in our family. He had no other lifestyle issues or previous illnesses that might had caused it. No connection was ever made by any doctor to his medications. But I make that connection and I wonder where were the studies and oversight that could prevent all this suffering?

  14. Ed

    Several months ago, my doc explained the side effects of PPI’s and told me I should get off the Nexium that I had been taking for over a year, and switch to Ranitidine. However, she didn’t warn me about the problems with suddenly stopping the PPI. These, as outlined in the article, were fierce. I got the guide offered here which helped a lot but it still was not a fun process. As I write this, there is a Walgreen ad for esomeprazole right next to the box.

    • Ellen

      Prescribed drugs to reduce bone loss eventually led to gerd…. which led to rx for Nexium. Then I learned that Nexium causes bone loss…..what’s wrong with this picture?!?

      Against my doctors advice, I gradually weened myself off both drugs. I have learned better solutions for strengthening bones.

      However, following breast cancer surgery, my oncologist’s first recommendation was a cancer preventive rx that causes bone loss. And his response to my concern was that I could take a proton pump rx! After my vehement objection, he prescribed Tamoxifen which is a tried and true drug that causes neither of the other two problems.

      You have to be your own health advocate these days. Thank goodness for The People’s Pharmacy!!!

  15. Lombard

    My father used generic Prilosec for many years on advice from the gastroenterologist. No doctor ever questioned whether he should remain on it or recommend shorter courses of treatment. He was put on it because he complained of heartburn.

    Of course he would get terrible heartburn when he stopped taking it so he couldn’t stop using it without some help. He had “unexplained” kidney disease [no other risk factors] and as a consequence very low hemoglobin.

    A bunch of other complications followed which shortened his life span. A PPI may be of use in certain situations but it was designed to be used for a few weeks at a time and then discontinued for a reason.

  16. Mary

    I have Barrett;s Syndrome and have been advised by my physician to take omeprazole every morning. I do not drink alcohol. I take melatonin with the omeprazole since I read on your site that it mitigates some of the side effects. My doctor says, take your chances by taking it or end up with esophageal cancer. What would you advise? It’s difficult to believe anyone these days.

    • Joe Graedon

      Mary, Your doctor is the person you need to trust. You also need to ask your physician for data so you can evaluate how helpful PPIs are in preventing esophageal cancer. If they were 100% effective it would not be a question. Of course you would need to take a PPI.

      There is some controversy about 1) how often Barrett’s Esophagus turns into cancer and 2) how effective PPIs are in preventing that very serious complication. Your doctor should be willing and able to provide you data so you can make a shared and informed decision going forward. There clearly are instances where a PPI is totally appropriate.

  17. Ann

    I have used PPIs for several years until I read your article about kidney involvement. I have a small cyst on my kidney that is being monitored. I stopped using PPIs and the cyst shrunk. My stomach problems became worse however so I did away with eating animal products and my stomach issues went away. We are victims of big Ag and theFDAs regulations. We need to listen to our bodies and take as few medications as possible. Diet is the primary healing agent. Thanks for your very helpful information. Ann

  18. Mandy

    I took PPI’s for several years and always had pressure and pain in the upper half of my digestive system (and lots of BIG burping). I told my gastro doc and he just nodded. After reading articles on People’s Pharmacy last year, I gradually took myself off all the stomach medicine I had been taking. Voila! The pressure and pain disappeared!

    I saw my doctor again about 6 months later and told him the happy news. He said “a lot of people have that problem with PPI’s”. Shocked, I said, “Why didn’t you tell me?” He said he thought I needed to be on the medicine. Let me just say that my gastro symptoms are nearly gone WITHOUT the medicine. I take an excellent probiotic and I think that helps.

  19. Carmen

    Not sure if this is related however my mother who had a lumpectomy due to early detection of breast cancer passed because it matasized. While in hospital, the doctors put her on many medications including PPI. She stayed on this drug for 16 years. I feel this drug compromised her liver causing her early detection to spread to stage four cancer. When she passed , her liver was extremely enlarged.

  20. Sally

    Joan B. — I was on Prilosec for six years and no doctor ever checked to see if I still needed it. Eventually, it destroyed my gallbladder and I had to have the gallbladder removed. Haven’t seen this side effect mentioned, but the gastroenterologists know about it.

  21. Susan

    this article should alert everyone who uses these medications! I had no idea of the degree of harm although when I’ve used PPIs I could tell something would go seriously wrong with my gut so I switched to baking soda and a low carb high fat moderate protein diet and now currently have very little if any reflux. Gut health, in my opinion, is key to overall health. I have learned so much from your articles and radio show. Thank you and keep us informed!!!

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