PPIs and Digestive Issues: What You Need to Know
Proton pump inhibitors (PPIs) are common medicines that help reduce stomach acid (Shin JM, 2008). They often treat problems like heartburn and ulcers (Shin JM, 2008). Some worry that long-term use of these products may cause additional digestive issues, despite their short-term benefits (Yibirin M, 2021). This blog looks at what we know about the link between long-term use of PPIs and ongoing digestive issues.
Table of contents
When PPIs first emerged, they were seen as helpful and safe for short-term use. Researchers began investigating potential long-term effects as more people took them for extended periods (Yibirin M, 2021). Some studies have suggested a link between long-term use of PPIs and various problems, including chronic digestive issues. Some PPIs can be bought without a prescription (Cleveland Clinic, 2025). Because of this, people might take them for too long without consulting a doctor. This can increase the risk of experiencing long-term side effects. People need to know how to use these medications properly. Doctors should also provide clear advice on how long someone should take them.
How Do PPIs Work?
PPIs block tiny pumps in the stomach that produce acid (Osmosis, 2025). By inhibiting these pumps, they effectively reduce acid levels (Yibirin M, 2021). Upon reaching the stomach’s acidic environment, they activate and attach to pumps, inhibiting their function (Yibirin M, 2021). This long-lasting effect requires the body to make new pumps for acid production (Yibirin M, 2021). While PPIs significantly lower stomach acid, they don’t eliminate it entirely, as some acid is necessary for digestion (Wikipedia, 2025).
What are the Short and Long-Term Side Effects of PPIs?
Reducing stomach acid for a long time can help some conditions but may also cause unwanted side effects. The qualities that make PPIs effective can lead to problems if used for too long.
Short-Term Side Effects
PPIs can cause short-term side effects, which are generally not serious and infrequent (Osmosis, 2025). These may include:
- headaches
- dizziness
- fatigue
- digestive issues (nausea, pain, gas, constipation, diarrhea)
- blurry vision
- dry mouth
- increased thirst
- hiccups
- skin rashes
Often, these effects improve with continued use or can be managed with other treatments (Yibirin M, 2021).
Long-Term Side Effects
Concerns exist regarding long-term PPI use due to potential serious digestive and other issues, including:
Nutrient Deficiencies: Reduced stomach acid can hinder the absorption of essential nutrients like vitamin B12 and iron (Osmosis, 2025).
Bacterial Infections: Less acid can also mean your body is less able to fight off harmful bacteria you might swallow. This could increase your risk of getting infections in your gut and lung infections (Osmosis, 2025).
Osteoporosis: Some studies have linked long-term PPI use to a higher chance of breaking bones, especially the hips, spine, and wrists. This is possibly because of poor calcium absorption and other effects on bones (Osmosis, 2025).
Kidney disease: Some evidence suggests a possible link between long-term PPI use and kidney problems (Cleveland Clinic, 2025). Low magnesium levels have also been reported as a possible long-term side effect (bpac NZ, 2025).
Additionally, some studies have raised concerns about possible links to heart problems, memory issues, and cancer (Yibirin M, 2021). Low stomach acid can lead to increased gastrin hormone production, and researchers are investigating its long-term effects (Yibirin M, 2021).
What Does This Mean For Doctors and Patients?
Long-term PPI use can have widespread side effects beyond the stomach.
Doctors must weigh the risks and benefits before prescribing long-term PPIs.
The increased risk of infections like CDI and pneumonia highlights how vital stomach acid is for protecting our bodies.
People on long-term PPIs, especially those who are more likely to get infections, might need to be extra careful.
The potential connection to bone fractures and kidney disease is concerning, particularly for older individuals already at higher risk.
Doctors should assess individual risks and monitor those on long-term PPIs.
Several ongoing digestive issues have been possibly linked to taking PPIs for a long time.
PPIs and Digestive Issues
Small Intestinal Bacterial Overgrowth
Small Intestinal Bacterial Overgrowth (SIBO) occurs when bacteria inhabit the small intestine, causing bloating, gas, and nutrient deficiencies (HCPLive, 2025). Long-term PPI use lowers stomach acid, which could allow bacteria from the large intestine to migrate to the small intestine (Revaiah PC, 2018).
Some studies have suggested a moderate link between PPI use and a higher risk of SIBO. However, it’s essential to know that some other research hasn’t found a strong connection. So, the relationship might be more complicated and depend on other aspects of the person (HCPLive, 2025).
Also, PPIs have been shown to change the types of bacteria in the small intestine (Tian L, Huang C et al., 2023).
Problems with how food moves through the intestines, often seen in people taking PPIs for heartburn or indigestion, can lead to SIBO (Revaiah PC, 2018).
Irritable Bowel Syndrome
Irritable Bowel Syndrome (IBS) is a long-term condition with changes in bowel habits, like diarrhea, constipation, or both (Med Case Studies, 2025).
Long-term PPI use may be linked to IBS or worsening symptoms. PPIs can alter gut bacteria and lead to SIBO (Med Case Studies, 2025).
Some studies suggest that long-term PPI use may increase the risk of digestive issues and IBS (RDGM 2025). One study highlighted past PPI use as a significant risk factor for developing IBS later on (MDEdge, 2025).
People with IBS often have other conditions like heartburn and indigestion, which are treated with PPIs. This might lead to the misconception that PPIs cause IBS (Spiegel BM, 2009).
Additionally, factors such as a history of mental health issues may also influence the development of IBS. This suggests that PPI use could be one of several contributing factors (MDEdge, 2025).
Other Digestive Issues
Besides SIBO and IBS, changes in the gut bacteria caused by PPIs have also been linked to functional dyspepsia (Tian L et al., 2023). Some studies have also found a connection between PPIs and a higher risk of microscopic colitis.
How Long-Term PPI Use Affects the Digestive Tract
The link between long-term PPI use and chronic digestive issues is complex and likely involves various factors. While PPIs may alter the gut environment, overall gut health, diet, genetics, and other medications also play important roles.
Studies show varying results on the link between PPIs and SIBO, highlighting the challenges in researching gut interactions with medications. Factors like diagnostic methods, study populations, and the gut’s complexity can lead to differing findings.
PPI use is linked to bowel symptoms like diarrhea and bloating, even without SIBO. This indicates that they may impact gut function beyond altering bacteria, such as affecting intestinal movement or bile acid handling.
PPIs have a big impact on the bacteria in our gut (Maideen NMP et al, 2023).
PPIs, Gut Bacteria and the Acidity
Reducing stomach acid makes the stomach and the top part of the small intestine less acidic. This allows certain bacteria that usually can’t survive to thrive and migrate to the small intestine (Tian L, Huang C et al., 2023).
Furthermore, PPIs can directly affect bacteria that need a certain level of acidity to thrive, like Helicobacter pylori (Tian L et al., 2023). Lower stomach acid makes it easier for harmful bacteria to enter and thrive in the digestive system (Tian L et al., 2023).
PPIs, Gut Bacteria and Hormones
Besides changing the acidity, PPIs can also affect gut bacteria in other ways. They can cause changes in hormones, like making more gastrin and parathyroid hormone. This can then affect how much water is in the intestines and how the body uses minerals like calcium and phosphorus. Such changes can ultimately affect the types of bacteria that live in the gut (Tian L, Huang C, Fu W, et al., 2023).
PPIs, Gut Bacteria and Nutrient Absorption
Additionally, PPIs can change how our digestive system normally works and the contents of our digestive tract. This can affect how we absorb nutrients and what food is available for different bacteria. This leads to shifts in the types of bacteria present (Tian L, Huang C, Fu W, et al., 2023).
There’s also some evidence that PPIs might directly interact with acid pumps found in some microbes, not just the stomach. This could affect where these microbes live and how many there are (Tian L, Huanget al., 2023).
Studies have found specific changes in the types of bacteria in people who use PPIs. For example, there’s been an increase in families of bacteria called Planococcaceae, Oxalobacteraceae, Sphingomonadaceae, Staphylococcaceae, Enterococcaceae, Lactobacillaceae, Streptococcaceae, Actinomycetaceae, and Micrococcaceae.
On the other hand, there’s been a decrease in families like Bifidobacteriaceae, Ruminococcaceae, and Lachnospiraceae (Tian L, Huang C, Fu W, et al., 2023). These changes in the gut bacteria caused by PPIs are significant and have been linked to different digestive problems (Tian L, Huang C, Fu W, et al., 2023).
The fact that PPIs affect the gut bacteria in these two main ways – by changing the acidity and by having other indirect effects on our bodies – shows how complex the relationship is between these medications and our gut. More research is needed to fully understand what these interactions mean. If we can figure out which specific bacterial changes are most important in people taking PPIs, we might be able to find ways to prevent or manage the digestive issues that can sometimes occur.
Alternative Therapautic Approaches
Medications
While PPIs are a main treatment for conditions related to stomach acid, there are other medications and lifestyle changes that can help manage these digestive issues.
Histamine-2 Receptor Antagonists (H2 blockers), like famotidine, ranitidine, and cimetidine, are another type of medicine that reduces stomach acid by blocking histamine, a chemical that tells stomach cells to make acid (Wikipedia, 2025). They’re generally not as strong as PPIs but can be effective for mild to moderate symptoms (GoodRx, 2025).
Antacids, such as calcium carbonate, magnesium hydroxide, and aluminum hydroxide, work by directly neutralizing the acid that’s already in your stomach. They can give quick relief from heartburn but don’t last very long (Wikipedia, 2025).
Potassium-Competitive Acid Blockers (PCABs), like vonoprazan, are a newer type of drug that blocks acid production in a different way than PPIs and might work faster and for longer (Wikipedia, 2025).
Other medications include stomach protectors like sucralfate, which coats and protects ulcers, and misoprostol, which can help protect the stomach lining (GoodRx, 2025). Sometimes, medications called prokinetic agents, like metoclopramide, which help speed up how quickly food leaves the stomach, might be used for heartburn (GoodRx, 2025).
Dietary and Lifestyle Changes
Dietary and lifestyle changes are also very important for managing acid reflux and heartburn, and they’re often the first thing doctors recommend, especially for mild symptoms (Lehault WB et al, 2017).
Changes in diet are key, such as avoiding foods that commonly trigger problems like chocolate, coffee, peppermint, greasy and spicy foods, tomato products, alcohol, and fizzy drinks (ACG, 2025). Eating smaller meals more often can also help (ACG, 2025).
Other helpful habits include not lying down for at least 2-3 hours after eating, raising the head of your bed by 6-8 inches when you sleep, maintaining a healthy weight, quitting smoking, and avoiding tight clothes around your stomach (ACG, 2025).
Some people find relief by chewing sugar-free gum, drinking ginger tea, or using natural antacids like baking soda in small amounts (Gastrointestinal Society, 2025).
Managing stress can also be helpful (Healthline, 2025).
For stomach ulcers, it’s crucial to treat the underlying cause, such as H. pylori infection (often with antibiotics along with a PPI) or stopping the use of NSAID pain relievers (Shin JM, 2008).
In summary, the availability of different medications and the focus on lifestyle changes show that PPIs aren’t the only way to manage acid-related digestive issues.
It’s important to have a treatment plan that’s tailored to each person, considering their specific symptoms, how severe their condition is, and their individual risk factors.
Often, making changes to lifestyle can greatly improve symptoms and might reduce the need for long-term medication.
The development of newer medications like PCABs suggests that there are ongoing improvements in how we treat acid problems, potentially offering better or safer options in the future.
Current Guidelines for Using PPIs
Experts and major medical organizations have provided guidelines on when it’s appropriate to use PPIs for a long time. Groups like the American Gastroenterological Association (AGA) and the American College of Gastroenterology (ACG) suggest trying PPIs for 8 weeks for people with typical heartburn symptoms who don’t have any warning signs (UIC, 2025).
After this initial period, they recommend trying to stop or lower the dose for those whose symptoms have improved (UIC, 2025).
Long-term PPI treatment is usually recommended for people with more severe conditions, like severe damage to the esophagus, Barrett’s esophagus, or those whose symptoms come back after stopping PPIs (Kim SY et al., 2024).
The guidelines emphasize using the lowest dose of PPIs that still works for long-term management to reduce the chance of side effects (bpac NZ, 2025).
They generally don’t recommend routine testing of nutrient levels like vitamin B12 and magnesium, or bone density, for people who are on long-term PPIs but don’t have any symptoms related to these (bpac NZ, 2025).
Similarly, they don’t advise regularly using probiotics to prevent infections in this group (Freedberg DE et al., 2017) .
A key recommendation is to regularly check if someone still needs to be on long-term PPIs and to consider lowering the dose or stopping them altogether when it’s safe to do so (bpac NZ, 2025).
While they acknowledge the concerns raised by studies about potential long-term risks, experts also point out that we often don’t have clear proof that PPIs are the direct cause of these problems (Yale Medicine, 2025).
For stomach ulcers caused by H. pylori, the standard treatment is to get rid of the bacteria, which usually involves taking a PPI along with antibiotics (ACG, 2025). If someone has ulcers caused by NSAID pain relievers and can’t stop taking them, PPIs are the recommended first treatment (Kamada T et al., 2021).
These guidelines show a balanced approach, recognizing that PPIs are very helpful for certain conditions but also highlighting the need to be careful about who takes them, what dose they take, and how long they take them.
The goal is to avoid unnecessary long-term use while making sure people who really need them are treated effectively. The advice to try stopping or lowering the dose after symptoms are controlled shows that the medical community is concerned about potential long-term side effects. However, the specific recommendations for long-term use in severe esophagus problems or Barrett’s esophagus emphasize how important acid suppression is for preventing serious complications in these high-risk individuals, demonstrating a clear understanding of weighing the risks and benefits in medical practice.
Conclusion
In conclusion, while PPIs are very effective for treating acid-related conditions, using them for a long time has been linked to a possible increased risk of certain side effects, including changes in gut bacteria and the development of ongoing digestive issues like small intestinal bacterial overgrowth and irritable bowel syndrome (Yilbrin et al, 2021).
The relationship between long-term use of PPIs and these chronic digestive problems is complex and likely involves many different factors (Tian L et al, 2023).
While there’s evidence suggesting a possible connection, it’s not always clear if PPIs are the direct cause, and many studies are based on observations (Yale Medicine, 2025). Therefore, it’s important to manage each patient individually, carefully considering why they need PPIs, using the lowest dose that works, and regularly checking if they still need to be on them (bpac NZ, 2025).
Exploring other ways to manage these conditions, like lifestyle changes and other medications, is also important when appropriate (Lehault WB et al., 2024).
Ongoing research is crucial to better understand the long-term effects of PPIs on the digestive system and to find the best ways to treat acid-related disorders, ultimately leading to the best possible outcomes for patients.
References:
- Shin JM, Sachs G. Pharmacology of proton pump inhibitors. Curr Gastroenterol Rep. 2008;10(6):528-534. doi:10.1007/s11894-008-0098-4
- Shin JM, Sachs G. Pharmacology of proton pump inhibitors. Curr Gastroenterol Rep. 2008;10(6):528-534. doi:10.1007/s11894-008-0098-4
- Proton pump inhibitors (PPIs): Nursing pharmacology: Video, Causes, & Meaning | Osmosis. https://www.osmosis.org/learn/Proton_pump_inhibitors_(PPIs):_Nursing_Pharmacology
- Proton-pump inhibitor – Wikipedia. https://en.wikipedia.org/wiki/Proton-pump_inhibitor
- Proton Pump Inhibitors (PPIs): What They Are & Side Effects – Cleveland Clinic. https://my.clevelandclinic.org/health/articles/proton-pump-inhibitors
- Proton pump inhibitors: new mechanisms of action. | DrugBank Online. https://go.drugbank.com/articles/A177568
- Yibirin M, De Oliveira D, Valera R, Plitt AE, Lutgen S. Adverse Effects Associated with Proton Pump Inhibitor Use. Cureus. 2021;13(1):e12759. Published 2021 Jan 18. doi:10.7759/cureus.12759
- Are Proton Pump Inhibitors (PPIs) Safe for Long-Term Use? Yale Medicine, 2025, https://www.yalemedicine.org/news/proton-pump-inhibitors-ppi
- Stopping proton pump inhibitors in older people – bpac NZ, 2025. https://bpac.org.nz/2019/ppi.aspx
- 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;30(4):407-420. doi:10.5056/jnm24059
- Maideen NMP. Adverse Effects Associated with Long-Term Use of Proton Pump Inhibitors. Chonnam Med J. 2023;59(2):115-127. doi:10.4068/cmj.2023.59.2.115
- What is the update on long-term safety evidence with proton pump inhibitor use? UIC, 2025, https://dig.pharmacy.uic.edu/faqs/2023-2/june-2023-faqs/what-is-the-update-on-long-term-safety-evidence-with-proton-pump-inhibitor-use/
- Peptic Ulcer Disease – American College of Gastroenterology, 2025. https://gi.org/topics/peptic-ulcer-disease/
- Lehault WB, Hughes DM. Review of the Long-Term Effects of Proton Pump Inhibitors. Fed Pract. 2017;34(2):19-23.
- Tian L, Huang C, Fu W, et al. Proton pump inhibitors may enhance the risk of digestive diseases by regulating intestinal microbiota. Frontiers in Pharmacology. 2023;14. doi:https://doi.org/10.3389/fphar.2023.1217306
- PPI Use Does Not Lead to Bacterial Overgrowth – HCPLive, 2025, https://www.hcplive.com/view/ppi-use-lead-bacterial-overgrowth/1000
- Revaiah PC, Kochhar R, Rana SV, et al. Risk of small intestinal bacterial overgrowth in patients receiving proton pump inhibitors versus proton pump inhibitors plus prokinetics. JGH Open. 2018;2(2):47-53. Published 2018 Apr 2. doi:10.1002/jgh3.12045
- SIBO (Small Intestinal Bacterial Overgrowth) – Cleveland Clinic, accessed April 5, 2025, https://my.clevelandclinic.org/health/diseases/21820-small-intestinal-bacterial-overgrowth-sibo
- Case study of PPIs causing irritable bowel syndrome (IBS), Med Case Studies, 2025. https://medcasestudies.com/case-studies/ppi-omeprazole-ibs/
- Meta-analysis: proton pump inhibitors moderately increase the risk of small intestinal bacterial overgrowth – PubMed, accessed April 5, 2025, https://pubmed.ncbi.nlm.nih.gov/28770351/
- Spiegel BM, Chey WD, Chang L. Bacterial overgrowth and irritable bowel syndrome: unifying hypothesis or a spurious consequence of proton pump inhibitors?. Am J Gastroenterol. 2008;103(12):2972-2976. doi:10.1111/j.1572-0241.2008.01992.x
- Bowel symptoms in patients that receive proton pump inhibitors. Results of a multicenter survey in Mexico. RDGM 2025. http://www.revistagastroenterologiamexico.org/en-sintomas-intestinales-pacientes-que-reciben-articulo-S2255534X18300598
- Prior psychiatric disorder: An important risk factor for IBS onset – MDEdge, 2025. https://www.mdedge.com/content/prior-psychiatric-disorder-important-risk-factor-ibs-onset
- Acid Reflux/GERD | ACG – American College of Gastroenterology, 2025, https://gi.org/topics/acid-reflux/
- Exploring 9 Alternatives to Omeprazole, From H2 Blockers to Natural Products – GoodRx, 2025. https://www.goodrx.com/omeprazole/omeprazole-alternatives
- Natural and Over-the-Counter Heartburn Treatments – Gastrointestinal Society, 2025. https://badgut.org/information-centre/a-z-digestive-topics/natural-counter-heartburn-treatments/
- Alternative Remedies for Acid Reflux and GERD – Healthline, 2025. https://www.healthline.com/health/gerd/alternative-treatment
- Kamada T, Satoh K, Itoh T, et al. Evidence-based clinical practice guidelines for peptic ulcer disease 2020. J Gastroenterol. 2021;56(4):303-322. doi:10.1007/s00535-021-01769-0
- Freedberg DE, Kim LS, Yang YX. 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;152(4):706-715. doi:10.1053/j.gastro.2017.01.031
Related Links
Medical Disclaimer
The information on capitalosteopathy.ca is for general informational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay seeking it because of something you have read on this website. The services provided by Capital Osteopathy are intended to complement, not replace, the relationship between you and your current healthcare providers. Individual results may vary, and no guarantees are made regarding specific outcomes. Using this website, you acknowledge that you have read and understood this disclaimer and agree to its terms. If you disagree, please do not use this site.