Key Takeaways
-
Short-term use is generally safe. A 4- to 8-week course rarely causes more than a mild headache, nausea, or loose stools.
-
Most headline side effects are weaker than they sound. In a 3-year randomized trial of 17,598 people, the only clear difference with daily pantoprazole was a slightly higher chance of gut infection (1.4% vs. 1.0%).
-
Your gut takes the biggest hit. Long-term use shifts your gut bacteria, raises the odds of SIBO by about 71%, and is linked to lower vitamin B12 and magnesium and a modestly higher risk of gallstones.
-
Some people should stay on their PPI. Severe esophagitis, Barrett’s esophagus, and high bleeding risk are good reasons to continue. For mild reflux, on-demand dosing can cut PPI use roughly in half.
-
Expect a few weeks of rebound if you stop. About 40 to 50% of healthy volunteers get heartburn after stopping a PPI, so a slow taper helps.
-
Build the foundation first. Earlier dinners, diet changes, and gut support often let you use less acid suppression, with your clinician’s guidance.
✓ Reviewed by our Scientific Review Board · All claims supported by peer-reviewed research · Last updated April 2026
If you’ve taken a PPI like omeprazole (Prilosec) or pantoprazole (Protonix) long-term, you’ve probably seen alarming headlines about dementia, kidney disease, and broken bones.
However, most proton pump inhibitor side effects are uncommon, and many of the most concerning ones come from studies that can’t prove cause and effect. The more practical concerns, like gut infections, small intestinal bacterial overgrowth (SIBO), and nutrient changes, are real and manageable.
In the clinic, we often meet people who started a PPI during a rough patch of reflux and simply never stopped, a pattern seen worldwide. Below, we’ll cover which side effects matter, who should stay on their medication, and a gentle, stepwise plan to use less if that’s right for you.
What Are Proton Pump Inhibitors, and Why Are So Many People on Them?
Proton pump inhibitors (PPIs) lower stomach acid by shutting down the tiny “pumps” in your stomach lining that release it. They’re the strongest acid reducers available. Clinicians use them to treat reflux and ulcers, help clear H. pylori, and protect the stomach in people who take aspirin or NSAIDs.
| Generic name | Common brand | Available over the counter? |
|---|---|---|
Omeprazole |
Prilosec |
Yes |
Esomeprazole |
Nexium |
Yes |
Lansoprazole |
Prevacid |
Yes |
Pantoprazole |
Protonix |
No |
Rabeprazole |
Aciphex |
No |
Dexlansoprazole |
Dexilant |
No |
Medication Effects vs. Effects of Lower Stomach Acid
Proton pump inhibitor side effects come from two places:
- The medication itself. Reactions to the drug, like headache, nausea, rare allergic reactions, and interactions with other medications, usually show up early.
- Lower stomach acid over time. Stomach acid helps you digest protein, absorb vitamin B12, iron, calcium, and magnesium, and keep swallowed microbes in check. Months or years of low acid can affect your nutrient levels, your gut microbiome, and even your gallbladder.
Most long-term side effects fall into the second group, which also points to practical solutions.
Proton Pump Inhibitor Side Effects: Short-Term and Long-Term
Most proton pump inhibitor side effects are mild, and many people never notice any at all. Short-term effects like headache or nausea usually fade within a few weeks. Long-term concerns mostly involve your gut and nutrient levels, and they’re smaller and more manageable than headlines suggest.
Common Short-Term Proton Pump Inhibitor Side Effects
Most people tolerate PPIs well in the short term. Side effects tend to be mild and often fade within a few weeks 1 2. The most common are headache, nausea, stomach pain, diarrhea or constipation, gas, and bloating.
A rare but important reaction is acute interstitial nephritis, an allergic-type inflammation of the kidneys that can appear at any point during treatment 2. Contact your prescriber if you notice a new rash, fever, unusual fatigue, or a change in how much you urinate.
PPIs can also interact with other medications. By lowering acid, they can change how well some drugs are absorbed, including certain antifungals and HIV medications. Omeprazole and esomeprazole can also weaken the blood thinner clopidogrel (Plavix) 3. Ask your pharmacist to review your medication list whenever you start a PPI.
Here are a few simple ways to ease short-term PPI side effects:
- Time it right. Take your PPI 30 to 60 minutes before breakfast so it works well at a lower dose.
- Give it a week or two. Mild headaches and digestive changes often settle on their own.
- Ask about switching. If one PPI doesn’t agree with you, another type may work better.
- Track your gut. New bloating or loose stools can be an early sign of changes in your gut bacteria.
Common Long-Term Proton Pump Inhibitor Side Effects
Most long-term proton pump inhibitor side effects come from observational studies, which follow large groups of people over time. These studies spot patterns. They can’t prove the PPI caused the problem, since people on PPIs for years also tend to be older, take more medications, and have more health conditions 3 4.
A 2022 umbrella review (a study that pulls together many meta-analyses) found that 52 of 91 reported links were statistically significant. After accounting for bias, none were backed by high- or moderate-quality evidence 5. The real risks are smaller and more specific than headlines suggest.
Here are the long-term effects to know. Most trace back to two things: lower stomach acid and a shifted gut microbiome.
- Lower stomach acid and higher gastrin. Reduced acid is the goal of the medication. Over months or years, though, it can blunt protein digestion and weaken your stomach’s defense against swallowed microbes. Your body also responds by raising gastrin, a hormone that signals acid production. Gastrin rises more with daily use than with on-demand use, and it helps explain rebound heartburn when you stop 3 6.
- Gut microbiome changes. PPIs can noticeably shift your gut bacteria. A study of more than 1,800 people found PPI users had less diverse gut bacteria, along with more bacteria that normally live in the mouth 7. These shifts help explain many of the gut symptoms people notice with long-term PPI use.
- Gut infections, including C. difficile. With less stomach acid to neutralize bacteria, more of the microbes you swallow survive. In the largest randomized trial on PPI safety, gut infections were slightly more common with daily pantoprazole (1.4% vs. 1.0%) 8. Tell your clinician you take a PPI if you’re prescribed antibiotics or hospitalized, since these situations can further impact your body’s defense systems.
- Gallbladder and gallstones. In a UK study of 477,293 adults followed for about 8 years, regular PPI users had about a 22% higher risk of gallstones, even after accounting for other risk factors 9. Researchers think PPIs may slow gallbladder emptying and shift gut bacteria in ways that change how bile is processed. The extra risk is small, about 3 additional cases per 1,000 people per year. It’s worth knowing if you already have gallbladder risk factors or pain under your right ribs after fatty meals.
- SIBO. This is the side effect we see most often in the clinic. A meta-analysis of 19 studies and 7,055 people found about 71% higher odds of small intestinal bacterial overgrowth in PPI users 10. If new bloating or gas started after your PPI, see our guide to SIBO symptoms, causes, and treatment.
- Low magnesium. PPI users have about a 43% higher risk of low magnesium 11. Watch for cramps, twitching, fatigue, or palpitations. If your levels run low, a supplement like our Magnesium Citrate can help. Check with your clinician before supplementing, especially if you have kidney disease.
- Low vitamin B12 and iron. Reduced absorption can lead to fatigue, brain fog, tingling, or low iron over time 12. Routine testing isn’t recommended for everyone 4, but blood work is reasonable if you’ve used a PPI for a year or more and have symptoms.
- Fractures. Observational studies link long-term use to a modest rise in hip fracture risk 13. Strength training, enough protein, calcium, and vitamin D from food help protect your bones.
- Chronic kidney disease. Observational studies show a link 14, though the largest trial found no increase over three years 8. Routine kidney testing isn’t recommended for PPI use alone 4.
- Dementia. A 2023 meta-analysis covering more than 200,000 dementia cases found no clear link but stated that some risk can’t be ruled out 15.
- Heart disease. An observational study found a link between adverse cardiovascular events and certain PPIs taken alongside clopidogrel (a prescription anti-clotting medication) 16. A multi-year randomized controlled trial found no increase in heart attacks or strokes in people with stable heart disease who were taking PPIs and blood-thinning medication or aspirin 8.
- Stomach cancer. In one large observational study, long-term PPI use after H. pylori treatment was linked to about 2.4 times higher risk of stomach cancer 17.
Proton Pump Inhibitor Side Effects at a Glance
| Possible side effect | When it shows up | How strong is the evidence? | Practical next step |
|---|---|---|---|
Headache or dizziness |
Short term |
Give it a week or two; ask about switching PPIs |
|
Nausea or stomach pain |
Short term |
Take it 30 to 60 minutes before breakfast |
|
Diarrhea, constipation, gas, or bloating |
Short term |
Track your gut; lasting changes may signal bacterial shifts |
|
Drug interactions |
Any time |
Well documented 3 |
Have your pharmacist review your medication list |
Allergic kidney inflammation (acute interstitial nephritis) |
Any time, but rare |
Well documented 2 |
Report a new rash, fever, fatigue, or urine changes right away |
Lower stomach acid and higher gastrin |
Long term |
Use the lowest effective dose; taper slowly |
|
Gut microbiome changes and SIBO |
Long term |
Watch for new bloating; support your gut |
|
Gut infections, including C. difficile |
Long term |
Consistent, seen in a large randomized trial 8 |
Extra care with antibiotics, travel, and hospital stays |
Gallstones and gallbladder inflammation |
Long term |
Mention right-sided pain after fatty meals to your clinician |
|
Low magnesium |
Long term |
Fairly consistent 11 |
Ask about testing if you have cramps or fatigue |
Low B12 and iron |
Long term |
Moderate 12 |
Ask about testing if you’re tired, foggy, or tingly |
Fractures |
Long term |
Strength training, protein, vitamin D, and calcium |
What the Research Shows
The largest PPI safety trial offers real reassurance. In a randomized trial, 17,598 adults with stable heart or artery disease took pantoprazole 40 mg or a placebo daily for about three years. Researchers tracked pneumonia, fractures, kidney disease, dementia, heart problems, and cancer. The only clear difference was a small rise in gut infections (1.4% vs. 1.0%) [8]
Gastroenterology. 2019 Sep; 157(3) 682-691.e2
Who Should Stay on a PPI, and Who Can Consider Tapering?
The most useful question to ask is simple: Do I still need my PPI? The American Gastroenterological Association (AGA) recommends that people with uncomplicated reflux who respond to a short course try to reduce or stop it 4, and that your reason for taking a PPI be reviewed regularly 20.
| Your situation | General guidance |
|---|---|
Severe erosive esophagitis, esophageal ulcer, or narrowing (stricture) |
Usually stay on a PPI long term |
Barrett’s esophagus or eosinophilic esophagitis |
Usually stay on a PPI long term |
High risk of stomach bleeding (a past bleeding ulcer, or blood thinners plus aspirin or NSAIDs) |
Usually stay on a PPI long term |
Mild reflux that’s now well controlled |
Good candidate for a lower dose or on-demand use |
Taking a PPI twice a day |
Often able to step down to once daily |
Started for a short-term reason (an ulcer, H. pylori, a hospital stay) and never stopped |
Good candidate for a trial off |
If you’re in a “stay on” group, please don’t stop on your own. If you are worried about PPI side effects, know that you can still support your gut and nutrient levels while you take it.
Rebound Acid: Why Stopping a PPI Can Feel Hard
If you’ve tried to quit a PPI and your heartburn came roaring back, you’re not imagining it. While acid is suppressed, your body builds up extra acid-making capacity. When you stop, that capacity briefly takes over. This is called rebound acid hypersecretion 6:
- About 40 to 50% of healthy volunteers with no prior heartburn developed symptoms after stopping a PPI.
- Symptoms usually start within 5 to 14 days of stopping the PPI.
- If you have taken a PPI for more than a year, rebound can last longer than 8 weeks.
Rebound heartburn is temporary, and it doesn’t automatically mean you still need your PPI. A slower taper and a plan for flare-ups make it much easier to get through.
How to Reduce Proton Pump Inhibitor Side Effects: A Stepwise Plan
In the clinic, we start with the simplest, least aggressive steps and add more only if needed. Please make any medication changes with your prescriber.
Step 1: Confirm Why You’re Taking It
Ask your prescriber why the PPI was started, whether you have a condition that requires long-term use, and whether a lower dose or on-demand use could work. If you’re in a “stay on” group, skip to Steps 3 and 4, which can ease side effects even if you continue.
Step 2: Find Your Lowest Effective Dose
- Twice daily to once daily: This is often the easiest first step 20.
- Daily to on-demand: Taking a PPI only when symptoms appear worked as well as daily use for mild reflux in a meta-analysis of 11 randomized trials, while cutting PPI use roughly in half 21.
- Give it time first: In a trial of 304 people with mild reflux, gastrin (a hormone that signals acid production) rose with daily use but not with on-demand use. However, the group still did better on daily treatment for a while before stepping down 18.
A 2024 review reached a similar conclusion: on-demand maintenance is a sensible way to limit long-term exposure in mild reflux 3.
Step 3: Build a Reflux-Friendly Foundation
The American College of Gastroenterology (AGA) recommends these habits 22:
- Finish dinner 2 to 3 hours before bed.
- Raise the head of your bed 6 to 8 inches if you have nighttime symptoms.
- Understand how excess weight increases reflux and GERD. Reaching and maintaining a healthy weight can lower acid reflux.
- If you are a smoker, talk to your medical provider about support for quitting.
- Notice personal triggers, like alcohol, fatty meals, chocolate, mint, and coffee. Foods like these are the most well-known triggers for acid reflux.
For a practical eating plan, see our diet plan for acid reflux. If a hiatal hernia plays a role, the breathing exercises in our hiatal hernia relief guide may also help.
Step 4: Support Your Gut
- Probiotics: A systematic review of 13 studies found that most studies reported better reflux symptoms with probiotics 23. The AGA doesn’t recommend them specifically to prevent infections in PPI users 4. In the clinic, we use them to ease symptoms and restore gut balance. Our Triple Therapy Probiotic combines the three most studied probiotic categories in one daily stick.
- An elemental diet reset: For stubborn bloating or SIBO-like symptoms, a short liquid elemental diet gives your gut a rest. Research for reflux is still early, but we’ve seen good results in the clinic. Many clients use Elemental Heal for a 2- to 4-day reset.
Step 5: Use Gentler Tools for Breakthrough Symptoms
A plan for flare-ups is helpful when you are tapering off PPIs. Here are a few options to discuss with your clinician:
| Tool | How it helps | Best for |
|---|---|---|
Alginates (such as Gaviscon Advance) |
Form a protective “raft” on top of stomach contents; outperform placebo and antacids for reflux 24 |
After meals and at bedtime |
H2 blockers (such as famotidine) |
Milder, shorter-acting acid reducers |
A short bridge during a taper |
Curcumin |
Matched omeprazole for indigestion in a randomized trial of 206 adults 25 |
Upper belly discomfort |
Magnesium-based antacids |
Can neutralize acid and support digestion |
People who also run low on magnesium |
If you’d like to try curcumin, CurcuSelect is the formula we use in the clinic. For more on magnesium, see our article on magnesium for acid reflux.
Step 6: Taper Slowly
The AGA considers either tapering or stopping all at once reasonable 20. In the clinic, we prefer a gradual taper because it makes rebound easier to handle:
| Phase | What to do |
|---|---|
Weeks 1 to 2 |
Drop to once daily, or to a lower daily dose |
Weeks 3 to 4 |
Take your PPI every other day |
Weeks 5 to 6 |
Take it every third day, or only as needed |
Week 7 and beyond |
Stop, and use alginates or an H2 blocker for flare-ups |
Move ahead only when you feel stable. If symptoms flare, stay at your current phase a little longer.
Clinical Observation
In the clinic, we often find that improving gut health first makes coming off a PPI much easier. Once we calm bloating and rebalance gut bacteria, many clients notice their reflux settles too, and tapering feels like a natural next step. I've seen plenty of clients who assumed they'd need acid suppression for life get down to occasional use, or none at all, within a few months.
– Dr. Michael Ruscio, DC
What to Expect When You Lower or Stop Your PPI
Knowing what’s normal helps you stay the course:
| Timeframe | What's normal | What helps |
|---|---|---|
First 1 to 2 weeks after each step down |
A mild uptick in heartburn or fullness |
Alginates after meals, an earlier dinner |
Weeks 2 to 8 |
Rebound symptoms peak, then start to fade |
Stay at your current phase until you feel steady |
Months 2 to 3 |
Most people settle into a new, calmer baseline |
Keep your diet and gut support habits going |
Ongoing |
Occasional flare-ups during stress, travel, or big meals |
Short-term on-demand use or an H2 blocker |
Many clients also notice less bloating and more regular digestion as their gut rebalances.
When to Check In With Your Clinician
Reach out promptly if you have trouble swallowing, unplanned weight loss, vomit that contains blood or looks like coffee grounds, black stools, or heartburn that doesn’t ease after several weeks. Seek emergency care for chest pain, especially with shortness of breath or pain spreading to your arm or jaw.
Proton Pump Inhibitor Side Effects FAQs
The best-supported dangers of taking proton pump inhibitors are a slightly higher risk of gut infections, a higher chance of SIBO and gut bacteria shifts, and lower magnesium, vitamin B12, and iron with long-term use. Long-term use is also linked to a modestly higher risk of gallstones.
Rarely, PPIs trigger an allergic kidney inflammation. Links to dementia, heart disease, fractures, and chronic kidney disease come mostly from observational studies, and the largest randomized trial found no increase in these over three years 8. For most people, the biggest practical risk is staying on a PPI longer than needed.
No single PPI has been proven safest, and the American College of Gastroenterology (ACG) advises against choosing one based on side effect risk alone 4. Most work about equally well. Pantoprazole has the strongest long-term safety data, from a 3-year trial of more than 17,000 people 8, and fewer drug interactions than omeprazole or esomeprazole. In practice, the safest PPI is the one you take at the lowest effective dose, for the shortest time you need it.
A few habits help your PPI work better and lower side effects. Avoid:
- Taking it with food. Take it 30 to 60 minutes before breakfast instead.
- Indefinite use without a review. Check in with your prescriber at least once a year.
- Stopping suddenly after months of use, which can trigger rebound heartburn.
- Surprise drug interactions. Tell your pharmacist about everything you take, especially clopidogrel (Plavix), antifungals, HIV medications, and methotrexate.
- Reflux triggers like late meals, large fatty meals, alcohol, and smoking.
Omeprazole is the most widely used PPI and is sold over the counter, so it appears in many of the studies behind recent headlines. Most warnings focus on long-term use without a clear reason, and they apply to all PPIs. One concern is specific: omeprazole and esomeprazole can reduce how well the blood thinner clopidogrel (Plavix) is activated, and U.S. drug labeling advises against combining them. A 2018 meta-analysis found PPIs weren’t responsible for higher heart risk in clopidogrel users 26, yet many prescribers still choose pantoprazole in this situation.
For heartburn, reflux, or ulcers, a standard course lasts 4 to 8 weeks. Conditions like severe esophagitis or Barrett’s esophagus call for long-term use, where the benefits outweigh the risks 4. There’s no fixed cutoff for everyone. Reassess with your prescriber once your symptoms are under control, and at least yearly after that. With uncomplicated reflux that responded well, guidelines recommend trying a lower dose or stopping.
The AGA considers either tapering or stopping all at once reasonable for people who no longer need a PPI 20. After months or years of use, though, stopping abruptly often triggers rebound heartburn that can last several weeks 6, which leads many people to restart. In the clinic, we usually prefer a gradual taper over 4 to 8 weeks, with alginates or an H2 blocker on hand for flare-ups. If you have severe esophagitis, Barrett’s esophagus, or a high bleeding risk, don’t stop without your prescriber’s guidance.
Yes, PPIs are linked to both. PPIs slow gut motility and reduce stomach acid, which make bacterial overgrowth more likely. A meta-analysis of 19 studies found PPI users had about 71% higher odds of SIBO 10. Common signs include bloating, gas, belching, irregular bowel movements, or feeling full quickly. If these started after you began a PPI, mention it to your clinician. Lowering your dose, a gut-friendly diet, and probiotics are good first steps.
Probiotics are a reasonable addition for many PPI users. A systematic review found that most studies reported less reflux symptoms with probiotics 23. The AGA doesn’t recommend them for the specific purpose of preventing infections in long-term PPI users 4. In the clinic, we use them to ease bloating and support healthy gut bacteria, and we judge how they’re working over 3 to 4 weeks. If you have a weakened immune system, check with your clinician first.
Several gentler options can help with mild or occasional reflux:
- Alginates (like Gaviscon Advance) form a protective raft over stomach contents 24.
- H2 blockers (like famotidine) are milder, shorter-acting acid reducers.
- Curcumin matched omeprazole for indigestion in a randomized trial 25.
- Lifestyle changes, like earlier dinners and raising the head of your bed, reduce reflux episodes 22.
- Probiotics may ease heartburn and regurgitation.
Severe or complicated reflux may still need a PPI, so work with your clinician.
Yes, long-term PPI use can gradually lower both, because stomach acid helps you absorb them. One meta-analysis found about a 43% higher risk of low magnesium in PPI users 11. Low magnesium can cause cramps, twitching, or palpitations, and low B12 can cause fatigue, brain fog, or tingling. Routine testing isn’t recommended for everyone. If you’ve used a PPI for a year or longer and have these symptoms, ask your clinician about simple blood tests.
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The Bottom Line on Proton Pump Inhibitor Side Effects
PPIs are effective, and for some people they’re the right long-term choice. Still, most proton pump inhibitor side effects come down to one thing: taking more acid suppression for longer than you need.
The most practical concerns live in your gut. Infections, SIBO, and gradual nutrient losses are real and manageable. The scarier headlines about dementia and heart disease rest on much weaker evidence.
The path forward is simple and hopeful. Start by confirming why you’re taking your PPI in the first place with your prescribing physician. From there, find your lowest effective dose, or switch to on-demand use if your reflux is mild. Build a reflux-friendly routine around your meals, sleep, and triggers, and support your gut with probiotics and, when needed, an elemental diet reset.
Talk to your medical provider about tapering off slowly, with a plan in place for any flare-ups along the way. Many people who thought they’d need a PPI forever end up using it occasionally or not at all. If you’d like personalized support, our team at the Ruscio Institute Virtual Clinic can help you build a plan that fits your history and goals, in partnership with your prescriber.
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➕ References
- Haastrup PF, Thompson W, Søndergaard J, Jarbøl DE. Side Effects of Long-Term Proton Pump Inhibitor Use: A Review. Basic Clin Pharmacol Toxicol. 2018 Aug;123(2):114–21. DOI: 10.1111/bcpt.13023. PMID: 29658189.
- Yibirin M, De Oliveira D, Valera R, Plitt AE, Lutgen S. Adverse Effects Associated with Proton Pump Inhibitor Use. Cureus. 2021 Jan 18;13(1):e12759. DOI: 10.7759/cureus.12759. PMID: 33614352. PMCID: PMC7887997.
- Kim SY, Lee KJ. Potential Risks Associated With Long-term Use of Proton Pump Inhibitors and the Maintenance Treatment Modality for Patients With Mild Gastroesophageal Reflux Disease. J Neurogastroenterol Motil. 2024 Oct 30;30(4):407–20. DOI: 10.5056/jnm24059. PMID: 39397619. PMCID: PMC11474548.
- Freedberg DE, Kim LS, Yang Y-X. The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association. Gastroenterology. 2017 Mar;152(4):706–15. DOI: 10.1053/j.gastro.2017.01.031. PMID: 28257716.
- Veettil SK, Sadoyu S, Bald EM, Chandran VP, Khuu SAT, Pitak P, et al. Association of proton-pump inhibitor use with adverse health outcomes: A systematic umbrella review of meta-analyses of cohort studies and randomised controlled trials. Br J Clin Pharmacol. 2022 Feb;88(4):1551–66. DOI: 10.1111/bcp.15103. PMID: 34622475.
- Namikawa K, Björnsson ES. Rebound Acid Hypersecretion after Withdrawal of Long-Term Proton Pump Inhibitor (PPI) Treatment-Are PPIs Addictive? Int J Mol Sci. 2024 May 17;25(10). DOI: 10.3390/ijms25105459. PMID: 38791497. PMCID: PMC11122117.
- Imhann F, Bonder MJ, Vich Vila A, Fu J, Mujagic Z, Vork L, et al. Proton pump inhibitors affect the gut microbiome. Gut. 2016 May;65(5):740–8. DOI: 10.1136/gutjnl-2015-310376. PMID: 26657899. PMCID: PMC4853569.
- Moayyedi P, Eikelboom JW, Bosch J, Connolly SJ, Dyal L, Shestakovska O, et al. Safety of Proton Pump Inhibitors Based on a Large, Multi-Year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin. Gastroenterology. 2019 Sep;157(3):682-691.e2. DOI: 10.1053/j.gastro.2019.05.056. PMID: 31152740.
- Yang M, Xia B, Lu Y, He Q, Lin Y, Yue P, et al. Association between regular use of gastric acid suppressants and subsequent risk of cholelithiasis: A prospective cohort study of 0.47 million participants. Front Pharmacol. 2021;12:813587. DOI: 10.3389/fphar.2021.813587. PMID: 35153765. PMCID: PMC8831324.
- Su T, Lai S, Lee A, He X, Chen S. Meta-analysis: proton pump inhibitors moderately increase the risk of small intestinal bacterial overgrowth. J Gastroenterol. 2018 Jan;53(1):27–36. DOI: 10.1007/s00535-017-1371-9. PMID: 28770351.
- Cheungpasitporn W, Thongprayoon C, Kittanamongkolchai W, Srivali N, Edmonds PJ, Ungprasert P, et al. Proton pump inhibitors linked to hypomagnesemia: a systematic review and meta-analysis of observational studies. Ren Fail. 2015 Aug;37(7):1237–41. DOI: 10.3109/0886022X.2015.1057800. PMID: 26108134.
- Vaezi MF, Yang Y-X, Howden CW. Complications of proton pump inhibitor therapy. Gastroenterology. 2017 Jul;153(1):35–48. DOI: 10.1053/j.gastro.2017.04.047. PMID: 28528705.
- Poly TN, Islam MM, Yang HC, Wu CC, Li YCJ. Proton pump inhibitors and risk of hip fracture: a meta-analysis of observational studies. Osteoporos Int. 2019 Jan;30(1):103–14. DOI: 10.1007/s00198-018-4788-y. PMID: 30539272.
- Nochaiwong S, Ruengorn C, Awiphan R, Koyratkoson K, Chaisai C, Noppakun K, et al. The association between proton pump inhibitor use and the risk of adverse kidney outcomes: a systematic review and meta-analysis. Nephrol Dial Transplant. 2018 Feb 1;33(2):331–42. DOI: 10.1093/ndt/gfw470. PMID: 28339835.
- Ahn N, Nolde M, Krause E, Güntner F, Günter A, Tauscher M, et al. Do proton pump inhibitors increase the risk of dementia? A systematic review, meta-analysis and bias analysis. Br J Clin Pharmacol. 2023 Feb;89(2):602–16. DOI: 10.1111/bcp.15583. PMID: 36331350.
- Sherwood MW, Melloni C, Jones WS, Washam JB, Hasselblad V, Dolor RJ. Individual proton pump inhibitors and outcomes in patients with coronary artery disease on dual antiplatelet therapy: A systematic review. J Am Heart Assoc. 2015 Oct 29;4(11). DOI: 10.1161/JAHA.115.002245. PMID: 26514161. PMCID: PMC4845227.
- Cheung KS, Chan EW, Wong AYS, Chen L, Wong ICK, Leung WK. Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori: a population-based study. Gut. 2018 Jan;67(1):28–35. DOI: 10.1136/gutjnl-2017-314605. PMID: 29089382.
- Jung DH, Youn YH, Jung H-K, Kim SY, Huh CW, Shin CM, et al. On-demand Versus Continuous Maintenance Treatment With a Proton Pump Inhibitor for Mild Gastroesophageal Reflux Disease: A Prospective Randomized Multicenter Study. J Neurogastroenterol Motil. 2023 Oct 30;29(4):460–9. DOI: 10.5056/jnm23130. PMID: 37814436. PMCID: PMC10577461.
- Chuang S-C, Lin C-C, Peng C-Y, Huang W-H, Su W-P, Lai S-W, et al. Proton pump inhibitors increase the risk of cholecystitis: a population-based case-control study. Gut. 2019 Jul;68(7):1337–9. DOI: 10.1136/gutjnl-2018-316899. PMID: 30018164.
- Targownik LE, Fisher DA, Saini SD. AGA Clinical Practice Update on De-Prescribing of Proton Pump Inhibitors: Expert Review. Gastroenterology. 2022 Apr;162(4):1334–42. DOI: 10.1053/j.gastro.2021.12.247. PMID: 35183361.
- Kang SJ, Jung H-K, Tae CH, Kim SY, Lee KJ. On-demand Versus Continuous Maintenance Treatment of Gastroesophageal Reflux Disease With Proton Pump Inhibitors: A Systematic Review and Meta-analysis. J Neurogastroenterol Motil. 2022 Jan 30;28(1):5–14. DOI: 10.5056/jnm21095. PMID: 34980685. PMCID: PMC8748841.
- Katz PO, Dunbar KB, Schnoll-Sussman FH, Greer KB, Yadlapati R, Spechler SJ. ACG clinical guideline for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2022 Jan 1;117(1):27–56. DOI: 10.14309/ajg.0000000000001538. PMID: 34807007. PMCID: PMC8754510.
- Cheng J, Ouwehand AC. Gastroesophageal reflux disease and probiotics: A systematic review. Nutrients. 2020 Jan 2;12(1). DOI: 10.3390/nu12010132. PMID: 31906573. PMCID: PMC7019778.
- Leiman DA, Riff BP, Morgan S, Metz DC, Falk GW, French B, et al. Alginate therapy is effective treatment for GERD symptoms: a systematic review and meta-analysis. Dis Esophagus. 2017 May 1;30(5):1–9. DOI: 10.1093/dote/dow020. PMID: 28375448. PMCID: PMC6036656.
- Kongkam P, Khongkha W, Lopimpisuth C, Chumsri C, Kosarussawadee P, Phutrakool P, et al. Curcumin and proton pump inhibitors for functional dyspepsia: a randomised, double blind controlled trial. BMJ Evid Based Med. 2023 Nov 22;28(6):399–406. DOI: 10.1136/bmjebm-2022-112231. PMID: 37696679.
- Demcsák A, Lantos T, Bálint ER, Hartmann P, Vincze Á, Bajor J, et al. PPIs Are Not Responsible for Elevating Cardiovascular Risk in Patients on Clopidogrel-A Systematic Review and Meta-Analysis. Front Physiol. 2018 Nov 19;9:1550. DOI: 10.3389/fphys.2018.01550. PMID: 30510515. PMCID: PMC6252380.
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