Can a heartburn drug cause cognitive problems?

Matthew Solan

Executive Editor, Harvard Men's Health Watch

ARCHIVED CONTENT: As a service to our readers, Harvard Health Publishing provides access to our library of archived content. Please note the date each article was posted or last reviewed. No content on this site, regardless of date, should ever be used as a substitute for direct medical advice from your doctor or other qualified clinician. 

A new study has shed light on one of the long-term effects of proton pump inhibitors (PPIs). These drugs are commonly used to treat gastroesophageal reflux disease (GERD), heartburn, and peptic ulcers. PPIs (omeprazole, lansoprazole, esomeprazole, pantoprazole, and others) help reduce the amount of stomach acid made by glands in the lining of the stomach.

Research published online on February 15 in JAMA Neurology showed that there may be an association between chronic use of PPIs and an increased risk of dementia. Experts compared prescription PPI intake and diagnosis of dementia among approximately 74,000 adults ages 75 and older. In the study, chronic PPI use was defined as at least one prescription every three months in an 18-month window. The most common PPIs in use were omeprazole (Prilosec), pantoprazole (Protonix), and esomeprazole (Nexium). All participants were free of dementia at the study’s beginning. Yet, after the eight-year follow-up, chronic PPI users had a 44% increased risk of dementia compared with those who did not take any medication. Men were at a slightly higher risk than women. Occasional users of PPIs had a much lower risk.

Putting the results in perspective

The researchers were quick to stress that this study only provided a statistical association between PPI use and risk of dementia, and that taking PPIs does not automatically mean you will get dementia. However, the study continues the ongoing discussion about the impact of long-term medication use, according to Dr. Houman Javedan, clinical director of inpatient geriatrics at Harvard-affiliated Brigham and Women’s Hospital. “Older adults take more medications as they age, and often continue them long after they are still necessary,” he says. “They either get used to taking it, and do not think to ask their doctor if they should stop, or they are afraid of what might happen if they do.”

Many older adults also take multiple drugs at one time, a situation known as polypharmacy. In fact, an estimated 44% of men and 57% of women older than age 65 take five or more medications; 12% of both men and women in this age group take 10 or more. “How different drugs interact with each other, and what the consequences of long-term use are, continues to be explored by scientists, as the researchers tried to do in this case with PPIs,” says Dr. Javedan.

It is not clear how PPIs might make a person more vulnerable to dementia. Evidence suggests parts of the drug may cross the blood–brain barrier, which becomes more porous as a person ages, and interact with brain enzymes. In initial animal studies, PPIs were shown to increase levels of beta amyloid in the brains of mice, and higher amounts of this protein have been linked to dementia and Alzheimer’s disease. Other research has shown a possible connection between chronic PPI use and vitamin B12 deficiencies, as well as an increased risk of osteoporosis. “There still may be other mechanisms at work that are unknown,” says Dr. Javedan. “But this study raises the question whether chronic PPI usage is safe, especially among the older population.”

What you should do if you take PPIs

If you currently take PPIs every day, or have for more than 18 months, you should consult with your doctor about whether to continue at your current dosage, Dr. Javedan suggests. “You only may need it when you have symptoms and not endlessly.”

Related Information: The Sensitive Gut


  1. Graham

    For those who want to try something different or even augment what they’re already taking. I second the two posts that suggested on the one hand probiotics – hugely helpful to my acid reflux- and the post about Baking Soda. My brother tried all the pills for horrible heartburn. Nothing did much. Someone suggested baking soda mixed in water. He tried it. It was instant relief. He said it was like a fire being smothered.

    I myself sometimes take Pepcid but omeprezole made me slightly dizzy when I tried it. People laugh at that but I tried it twice many months apart and I got the same effect. Didn’t like that. Don’t use it now.

  2. Melissa

    I was diagnosed with acid reflux, and activity induced reflux (from strenuous exercise) about 2 years ago. The reflux had gotten so bad it caused bronchitis, voice loss, and I was misdiagnosed initially with asthma. I was prescribed a PPI daily for three months, reduced to every other day, then as needed. At the same time, I also eliminated problem foods such as alcohol, coffee, and chocolate. On my doctor’s advice, I try to avoid eating 2-3 hours before lying down to sleep. I stop drinking an hour before sleep. I drink water with added Bragg Organic Apple Cider Vinegar. I stopped eating the last three bites on my plate when I was already full. I also began following the diet in Fast Tract Digestion Heartburn by Nathan Robillard (no sweeteners, no simple carbs, lots of charts and meal plans make it pretty easy). After about 6 weeks of following all these directions (seems like a lot) I started feeling better. The serious issues have all resolved and now it just feels like regular heartburn occasionally. Now I only take a PPI as needed. I use Gaviscon or Tums first. I have been able to add many things back into my diet on a limited basis, or as a treat. But when I start to have problems I know it’s because I’m not eating well or overindulging in too many areas. This might seem too restrictive for some, but I am committed to relying on the medication as little as possible. And I’m really glad I made that decision after reading this. I hope some of the things I’ve tried can help others. Good luck!

  3. Melissa Byler

    I have Barrett’s Esophagus and a serious case of chronic gastritis. My gastroenterologist prescribed Nexium for the GERD/gastritis and yearly endoscopies to monitor the Barrett’s. I’ll need to take PPIs for the rest of my life. I’ve been taking them for the last two years — I’m 49 now and God willing figure I’ve still got a lot of life left to live. But now I’m frightened about the recent findings over the long term effects of PPI’s. But I need these meds for some measure of relief after eating. And while I take the Nexium and have made some changes to my diet, I still suffer from GERD. I’ve learned that eating smaller meals more frequently helps though I’m shrinking in size (weight). Based on this article, the choices aren’t great — either I take PPIs to improve my quality of life and accept the risk of dementia, or I don’t take PPIs and live a miserable existance which will probably make me go crazy anyways. HELP!!

  4. Theresa Berrien

    I am strongly trying to get off of PPI’s , but water gives me heartburn, my gastro intestinal system has been a wreck since I have gone off PPI’s. I am taking a Natural supplement Lily of the Desert and Gaviscon Zantac. I was on these fro 20 + years ans am worried I have word finding problems on occasions and sometimes words come out wrong. I always thought it was from taking Ambien. Which can’t be much better. Anyway is this reversible I pray!!! once you get off of them.

  5. Brenda

    I have alternated between Prilosec and Pepcid for several years for GERD. I also have diabetes in my family, and my glucose numbers were going up. When my doctor finally said pre-diabetes, I took it seriously and began eating like I should. I also went off the above mentioned meds as soon as I heard the Alzheimer’s statistics for them. This occurred almost simultaneously. Just the eating less food, particularly sweets and carbohydrates, has almost completely solved my GERD problem. I take a rare tums if needed, but drinking water helps if I think it is coming on. I haven’t had any issues sleeping. I’ll do anything to save my brain.

  6. Rod

    How sure are we that this alternative products will not do worst than PPI? Someone who make this alternative product shoud present study like they did that prove no increase in dementia. Dementia is part of aging and is genetics. I probably prefer to have dementia on my 80’s rather than suffering with GERD symptoms my whole life. I am not sure if some people understand how difficult severe hertburn symptom is. My got feeling is that these alternative product will do different kind of long term side effect as well. I will prefer to have quality life at my prime, continue with mh PPI and ni regrets what will happen after 75 yo. Live healthy, eat helthy and enjoy life. These will make us better not avoiding a medication that brings lide back. All the best!

  7. Maria Jasmine Freeman

    “A drug without side effects has no effect”, so we we were taught in medical school. As such, it’s crucial that a drug be used only when necessary and when its benefit outweighs its risks. Moreover, long term experience with a medication is more likely to unveil its side effects; PPIs are one example, and a few side effects are reported. Vitamin B12 deficiency is one, but also some association with kidney dysfunction and heart trouble; there also comes dementia. Even at the early beginning there were reports of an effect on increasing stomach cancer risk by effect on Gastrin hormone level. We should not forget also, that these drugs can predispose to intestinal infection by suppressing our acid defense barrier. Unfortunately they r used often unnecessarily with no medical indication.
    Since human disease is the outcome of interaction between genes and the environment, it is imperative that our environment- drugs included- be as safe as possible. Who knows how a certain chemical molecule can interact with a human body genes to unleash an otherwise reined abnormality, frontotemporal dementia no exception.
    Dr Hana Fayyad( Maria Jasmine Freeman)

  8. H.

    I have seen the report that PPIs prevent Vitamin B12 uptake and that is responsible for the dementia symptoms.
    Is it possible to diminish this new side effect (dementia) by taking extra Vit. B12 or B complex while taking a PPI /day? Thanks.

    • Robert Foulds

      Not in my wife’s experience – we tried a regime of 3 injections per week for a month, then 2 per week for a month, then 1 per week per month and then 1 per month. But it had no effect I’m sorry to say.

  9. Robert Foulds

    Primary Progressive Aphasia – Fronto-temporal dementia

    During November 2011, my wife, aged 60, was prescribed an intense course of PPIs, in relation to a Hiatus Hernia and associated Oesophagitis, and a lesser daily dose was prescribed thereafter.

    Starting in January 2012, I discerned minor enunciation issues within my wife’s conversation, for instance she would say “pants” when she meant to say plants, “Buxted” rather than Buxton or “athroom” rather than bathroom. At first Sue was unaware of her speech errors, but she eventually realised what was happening and over ensuing months we both became more disturbed by the emerging problem.

    These speech errors continued and became more pronounced through the remainder of 2012, and during the early part of 2013, Sue became very anxious, and attributed her condition to the onset of Alzheimer’s Disease, a long held dread of hers because that was responsible for her mother’s painfully slow demise several years previously.

    It was about this time that I wondered if there was a link to her PPI medication and she therefore stopped taking it.

    We saw our GP a few times during 2013 and then arranged to see a consultant at Sheffield Teaching Hospitals and his immediate diagnosis was that it was Primary Progressive Aphasia, a form of fronto-temporal dementia. I had thought that also, from the research I had done, but I really didn’t want to believe it.

    Sue was then sent for a scan in October 2013 and eventually we saw another neurologist in Feb 2014, who pointed out that there was some brain atrophy and concurred with the initial diagnosis. I mentioned my PPI suspicion and was advised that it was just a coincidence.

    In Feb 2014, due to her condition, Sue had to give up her work.

    Now, March 2016, Sue cannot speak, other than to say yes or no, and those terms are often wrongly attributed. Her word choice is now very limited indeed and her writing has deteriorated to just scribbling a word that is sufficient for me to glean the gist of her intentions.

    In addition to the above, Sue is presenting profound physical limitations, which is directly attributable to her condition, whereby she has a change to her gait, walks very slowly and not very far, lacks agility, has a hand tremor and her dexterity is considerably reduced.

    Other research I have undertaken has also described a link between PPIs and Vit B12 deficiency – we tried an intense replacement therapy course, but it did not prove helpful. But then, if the damage has been done, it cannot be undone!

    As I witness my wife’s inexorable decline, I continue to harbour strong suspicions about PPIs.

  10. George Dimitriadis

    George Dimitriadis Dr. M.D.

    I am 85 years old and I take the last 20 years half pill of Pariet (Rabeprazole sodium 20 mgr),that means 10 mgr per dose, per day, and I don’ t have any problem with dementia for the present time.

  11. Bembire Venkatesh

    iam using pentoprozole 40 mg once in a day from 13 years is thare any alternatives

  12. Agusta Goodman

    Prilosec gave me double, or extra heart beat to the point of being hospitalized with that horrid discomfort. They said it wasn’t deadly, but put me in hospital because it was every other beat. Nobody could figure out why I was doing this. Finally, I remembered the Prilosec. Since it was the only med I was on, I discontinued it. Voila! No more problem.
    Two years later, I had bad GERD again and was put on Prilosec. Almost a day later the heart PVCs began again! With vengeance. And, as before, the problem quit as soon as I discontinued Prilosec. I also had this reaction to another one, but not to Zantac. Is that also cause for alarm with possible dementia?
    I MUST know because dementia scares me most of all. I’m almost eighty.

  13. Aliya Mallick

    Hello all,
    My mother, 50yrs old, has GERD for 25years now and initally was on Ranitidine and now on PPIs for >20yrs. She has also had H.pylori twice during this period. She also developed Ankylosing Spondylitis in the cervical vertebrae and recently was told she has Radiculopathies at multiple levels in the lumbo-sacral vertebraes. Could this study be in any way related to my mothers condition?

  14. Laura Cortes

    I have been taking a combination of Prilosec, Nexium, Protonics, and others for the past 20 years for my acid indigestion. If I don’t my reflux is absolutely unbearable. What kind of damage have they done to me?

    • Ewald

      There’s one simple treatment for heartburn and reflux, easily dispensed as needed (quantity) with immediate effect and no side effects whatsoever : baking soda. Dissolved in (luke warm) water. I did away with Nexium forever.

  15. Alex P

    This article says that Dr. Javedan said elderly people continue taking the medicines for a longer time than what is needed due to getting used to them or being afraid of stopping. So he blames the patient. In some cases that may be true, but I think it is common for doctors to prescribe for indefinite periods of time PPIs and other medicines that are not safe to take continuously. It is easy to blame patients, but doctors play a part in this.

  16. John

    By the age of 80, about 50% of the population will have dementia. An increase in risk of 44% means that, instead of have a 50% chance of dementia, you would have a 72% chance. However, if it is the case that dose determines risk, we need more study to see whether there are safe doses of PPI.

  17. Judy G.

    Gosh, I hate to read this. Doctors have said its ok to stay on PPI’s because people need them. I wish they could get their info right. I switched to Tums, but will find out more on what I can take.

    • Diane B.

      About a year ago, I finished a long course of Prilosec for severe GERD/reflux (per my gastroenterologist’s instruction and advice). After finishing the long Prilosec treatment, I wanted to try a natural, safe supplement instead of staying on Prilosec to help with my acid reflux. I found some good reviews online by people who suffer from acid reflux. The product is called Enzymatic Therapy DGL Ultra Chewable Tablets. It is advertised as: “DGL ULTRA extra-strength deglycyrrhizinated licorice stimulates and accelerates the natural protective factors in the digestive tract which helps relieve occasional stomach discomfort immediately. In DGL ULTRA, the glycyrrhizin compound-associated with high blood pressure-has been removed. The potent 10:1 extract makes this product ultra-concentrated, which means it provides immediate benefits and maximum absorption.” I chew one of these tablets 20 minutes before lunch and another tablet 20 minutes before eating dinner. This coats your throat and does help prevent getting acid reflux. I no longer take Prilosec and my gastroenterologist said since it is deglycyrrizinated licorice, it will not affect blood pressure in a negative way. This product (along with Gaviscon before bedtime) has helped me. The 10:1 ratio is best because you only need 1 tablet as opposed to 2 before each meal. I recommend this!

    • Desmond FitzGerald

      Me too. I stopped taking protonix after many years, and now just pop a Tums or two when needed. Seems to work fine. And don’t forget the old faithful: a glass of water, preferably warm. One of the comments above suggests baking soda disolved in water. Worth a try.

  18. Robyn Kingsfield

    I took Nexium and Rabeprazol for 24 years and quit cold turkey….now I have to use TUMS several times a day, for heartburn.
    Are TUMS safe?

    • Carolyn S.

      Unfortunately Tums and Rolaids contain aluminum and autopsies have shown that people with Alzheimers have higher levels of aluminum in the brain. We get aluminum in anti-perspirants, canned drinks, any medication or cosmetic containing aluminum lake, and canned goods. There are probably other sources too. I have had acid reflux for over 20 years and taking a prescription like Protronix usually works for me. Pepcid twice a day does not work for me. When I have indigestion, I chew a few Tums occasionally. The FDA allows many things in products that aren’t allowed in Europe. All we can do is avoid consuming the things we can. I feel better taking the prescription and hope for the best!

      • Java Joe

        Not correct. Tums has always been calcium carbonate with no aluminum compounds in it. Rolaids used to contain an aluminum compound many years ago, but now is also entirely calcium carbonate.

  19. Hannah

    What about Aciphex long use bid for 8 years? I started with this drug after the Prilosec and Pepcid were no longer effective. I too have Gerd, hiatal hernia and painful esophageal spasms. The Aciphex has worked really well, but I have been cut back to As Needed basis. I watch my diet carefully, exercise and found that for me a glass of plain Hot water can relieve some of the irritation that happens. We don’t always know what we ate or had to drink that sets us off, but just an FYI, I try my hot water and sit and relax…most of the time I can get relief and find I do not need the meds.

  20. Nancy Lange

    I was diagnosed with GERD some 15 or so years ago and the gastroenterologist put me on Prilosec (when it was a prescription med,not OTC). I began taking it and immediately the symptoms (a choking sensation where i suddenly couldn’t swallow until i “talked” myself into “relaxing”), plus a hideous, beyond-10 level pain that struck in the upper digestive tract area that couldn’t be eased by anything) were eliminated entirely! It was a miracle. The only time these symptoms return is when i try to “wean” myself of Prilosec or forget to take for one or two days. I eventually go back to Prilosec and am immediately rewarded by no pain, no problems. It doesn’t seem to matter what or when i eat or drink (i don’t drink alcoholic beverages, but do drink a cup of coffee everyday). Likewise, i don’t smoke or otherwise live a particularly unhealthy life. I am overweight, however. I say all this as i’ve worried for some time about taking Prilosec for the (apparent) rest of my life … and now you’ve discussed a possible relationship between this drug and cognitive problems. AKKKKKKK!!!! Can you suggest alternatives???

    thank you so much, Nancy Lange, Auburn, CA

    • skabak

      Let me start by saying I’m not an M.D., but my own gastroenterologist suggested using Zantac 150 or better yet a generic version, which you can get at Costco. Additiionally, I follow the suggestions of Andrew Well, who received his medical degree from Harvard, and he’ recommended taking DGL and one of his associate doctors proposed taking d-limonene. These products can be obtained on the web or at your local health store. You can get more detail if you go to Dr. Weil’s website where you can learn more about these PPI alternatives. In any event, check with you own doctor about this new research as well as any of Dr. Weil’s recommendations.

      • Richard R. Thornton, MD.

        What is the DGL written out completely? What is d-limone . Are these naturally occurring substances/

        What is Dr. Well or Weil which ever is correct—what is his specialty?

  21. BarbL

    I had side effects for both Nexium and Prilosec. I think my body knew best.

  22. Carol Rowe

    Have been taking Nexium for years, have also had an increase in Creatine levels. Will consult my doctor.

  23. Warren Gerig

    I have been on Nexium for several years because of a hiatal hernia. On advise of my Doctor I cut back to three times a week. Now none. However I have my Gerd back. What can I do about my Gerd and should I get my hiatal hernia fixed?

    Believe I have lost some of my cognitive ability. Will the cognitive ability come back now that I have stopped taking Nexium?

  24. Susan Jackson

    What about something like Pepcid which is not a PPI. I had bariatric surgery 7 years ago and suffer constantly from acid reflux. I have been taking Prilosec 2x a day since then . I now have kidney disease-creatin levels of 1.8- and wonder if that is related as well . I’ve recently changed to Pepcid 2x a day and hope that is a safer alternative.

    • Gary Tasaka

      I believe Pepcid is considered an H2 blocker which is not a PPI. I have been taking omeprazol for years and now in the process of weaning myself off of it ( taking omeprazol every other day for a month) and switching to Pepcid.

  25. Terence G Klingele MD

    On PPI bid for more than a month, take B 12 1000 mcg/day and check for macrocytes.

Commenting has been closed for this post.