Tag Archives: PPI

Worrisome Report: PPI Use and Early Onset Colorectal Cancer

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C Strong, ACG 10/28/25: Long-Term PPI Treatment Linked to Higher Risk for Early-Onset CRC Before Age 50

An excerpt:

“Long-term treatment with proton pump inhibitors (PPIs) is independently associated with an increased risk for early-onset colorectal cancer (EOCRC) among individuals aged younger than 50 years, according to study results presented at the American College of Gastroenterology (ACG) 2025 conference…”

“Researchers reviewed data from the National Inpatient Sample from 2016 to 2020. Individuals were aged 18 to 49 years and had a main diagnosis of colorectal cancer (CRC)…Investigators identified PPI exposure through diagnostic codes indicating long-term use (Z79.891) or adverse effects (T45.4X5A/D)….

“Of the 7140 hospitalizations for patients with EOCRC aged younger than 50 years, 1056 (14.8%) reported long-term PPI treatment. After multivariable adjustment, PPI users had a 41% increased risk for EOCRC vs individuals without PPI use (adjusted odds ratio [aOR], 1.41…”

My take: More studies will be needed to determine if this link between PPI use and early onset CRC is truly significant. Many prior associations between PPI and other health conditions on observational studies have not held up with well-controlled studies. There was no increased risk of cancer in a previous randomized control trial (see below).

Related blog posts:

Amicalola Falls State Park

Selective Acid Suppression for Esophageal Atresia Patients

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This year’s masterpiece!

Link from AAP HealthyChildren.org: Halloween Fun & Safety Tips for Kids of All Ages

S Zeneddin et al. J Pediatr Gastroenterol Nutr. 2025;81:960–966. Acid suppression after esophageal atresia repair: Some infants do benefit

Methods: The authors performed a retrospective study using the Pediatric Health Information System for infants undergoing EA/TEF repair between 2010 and 2022 (n=1445 infants). Acid suppression was defined as receipt of an H2 blocker or proton pump inhibitor on the day of discharge or longer than 30 inpatient days. Complex EA/TEF repair was defined as delayed repair (>7 days), G-tube placement before repair (likely a sign of a long gap or type A anomaly), prolonged hospitalization (>60 days), or multiple inpatient fluoroscopies. The authors defined stricture solely if it required intervention.

Key findings:

  • 257 (17.8%) required dilation by 1 year. Of the 688 (47.6%) infants who met criteria for complex EA/TEF, 126 (18.6%) required a dilation.
  • At 1 year, stricture rate was similar in infants with simple EA/TEF, with or without acid suppression (17.5% vs. 17.0%, p = 0.90)
  • In infants with complex EA/TEF, stricture rates were lower among those who received acid suppression compared to those who did not (15.3% vs. 26.0%, p = 0.001).

The associated editorial (D George, DK Robie. J Pediatr Gastroenterol Nutr. 2025;81:911–912) reviews some of the limitations of the study but does not provide clear recommendations on utilization of acid suppression therapy: the decision should be “should be individualized, weighing the potential benefits against the risks.”

My take: It is not surprising that more complex EA would have higher stricture rates. In my training (in the 1990s!), it was routine practice to use indefinite acid suppression. This article indicates that patients with low risk EA likely do not need acid suppression. In high risk patients, the algorithm by Yasuda et al (see post below J Am Coll Surg 2024; 238: 831-843) provides their approach to weaning acid suppression.

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Ten-Year Trends in Pediatric Pharmacology for Gastroesophageal Reflux and Pediatric Feeding Disorders

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S Hirsch et al. J Pediatr 2025;283:114628. Ten-Year Trends in Pharmacologic Management of Gastroesophageal Reflux Disease and Pediatric Feeding Disorders in Young Children

Methods: Single-center, retrospective cohort study of children less than 2 years (49,483) diagnosed with GERD or PFD (pediatric feeding disorder) between January 2014 and December 2023. Prescriptions were searched for proton pump inhibitors (PPI), H2-receptor antagonists (H2RA), cyproheptadine, erythromycin, metoclopramide, or prucalopride, and procedures were searched for intrapyloric botulinum injections.

Key findings:

  • There was an increasing number of patients seen annually (6516 in 2014 vs 9109 in 2023)
  • The percent of patients receiving any prescription for GERD or PFD declined by almost 50%, from 36.5% in 2014 to 18.7% in 2023 (P < .001)
  • There was a particular decline in PPI prescriptions, with 25.3% of patients receiving PPI in 2014 and 7.1% receiving PPI in 2023 (P < .001)
  • There was also a decline in H2RA prescriptions, with 17.0% of patients receiving H2RA in 2014 and 11.1% receiving H2RA in 2023 (P < .0001).
  • In their discussion, the authors note that: “in contrast to the current findings, prior studies typically have shown increasing PPI prescriptions, with some of these studies demonstrating declining H2RA prescriptions (9-17)…. However, it is notable that 3 more recent international studies did demonstrate declining PPI prescriptions specifically in the final years of the study (18-20).”
  • “Multiple studies have failed to demonstrate efficacy of acid suppression in infants with nonspecific gastroesophageal reflux symptoms, and there is no evidence that acid suppression affects feeding behaviors.(21-23)”
  • “In addition, there has been growing concern about PPI side effects, which include increased infections, decreased bone density, and increased allergy development
    including eosinophilic esophagitis, with numerous recent studies on these risks.(24-26)”

My take: I’ve been a big fan of the aerodigestive research from the pediatric GI group in Boston. This is another useful study showing less use of acid suppression, especially PPIs in young children and infants. This likely indicates better alignment of clinical practice with consensus recommendations that advise against acid suppression as first-line management in this population.

Related blog posts:

Early Acid Blocker Use Linked to Lung Disease in CF

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C Liu et al. J Pediatr Gastroenterol Nutr. 2024;79:1124–1133. Open Access! Impact of acid blocker therapy on growth, gut microbiome, and lung disease in young children with cystic fibrosis

Background: Historically, acid suppression has been given as adjuvant therapy to optimize PERT and thereby improve growth and nutritional needs in CF

Methods: This was a prospective cohort of 145 infants followed in 6 CF centers. This was a retrospective study examining the effects of acid blocker therapy and outcomes at 3 years of life in children with cystic fibrosis.

Key findings:

  • Acid blocker therapy (ABT) use before age 3 years was frequent, with 81 (56%) of patients on H2 receptor antagonist (H2RA) or proton pump inhibitor (PPI), and higher among pancreatic insufficient (60%) versus pancreatic sufficient (26%) children.
  • Growth improvements were not significantly greater.
  • Early-onset lung disease was more severe, in persistent ABT users compared to nonusers of ABT.
  • ABT was associated with reduced gut microbiome diversity
CFELD =CF Early-Onset Lung Disease

Discussion:

  • “Results from our FIRST cohort of infants and toddlers with CF showed that prolonged ABT was not associated with significant improvements in growth but instead significant negative alterations to the GM and progression of early-onset lung disease. Evidence from our study is in line with the growing body of literature advocating for more judicious PPI therapy as it has been associated with adverse outcomes such as pulmonary infections, fractures, and anemia.22–24“
  • One limitation, which was NOT discussed in the article, was selection bias. Since there was not randomization of PPI use, it could be that PPI prescription was more common in children with more severe disease.

My take (borrowed in part from authors): Despite the potential for selection bias, it is clear that “acid blockers are not benign.” Given the potential for worse outcomes, PPI prescription should be restricted to those with a clear indication.

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How a Study on Stress Ulcers in the PICU Can Change Clinical Practice

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D Cook et al. NEJM 2024; 391: 9-20. Stress Ulcer Prophylaxis during Invasive Mechanical Ventilation

This  international, randomized trial assigned critically ill adults (n=4821) who were undergoing invasive ventilation to receive intravenous pantoprazole (at a dose of 40 mg daily) or matching placebo. Both groups included ~22% who had had PPIs prior to hospitalization. The primary efficacy outcome was clinically important upper gastrointestinal bleeding, identified locally as overt gastrointestinal bleeding with evidence of hemodynamic compromise or leading to therapeutic interventions in the ICU (or resulted in readmission to the ICU during the index hospital stay) up to 90 days after randomization.

Key findings:

  • Clinically important upper gastrointestinal bleeding occurred in 25 of 2385 patients (1.0%) receiving pantoprazole and in 84 of 2377 patients (3.5%) receiving placebo (hazard ratio, 0.30;  P<0.001)
  • At 90 days, death was reported in 696 of 2390 patients (29.1%) in the pantoprazole group and in 734 of 2379 patients (30.9%) in the placebo group (hazard ratio, 0.94; P=0.25)
  • PPI-treated patients had similar rates of ventilator-associated pneumonia and C diff infection

In the associated editorial, (SM Brown. NEJM 2024; 391: 78-79) noted that “two previous trials, SUP-ICU1 and the cluster-randomized PEPTIC2 (which compared proton-pump inhibitors with placebo and H2-receptor blockade, respectively), suggested that the effects on mortality may differ according to patients’ disease severity — and that the drugs were potentially less safe in more severely ill patients.”

“Proton-pump inhibitors slightly but significantly decrease the risk of important gastrointestinal bleeding and have a decent chance of slightly decreasing mortality in less severely ill patients during mechanical ventilation. Moreover, we can be certain that proton-pump inhibitors do not decrease — and may slightly increase — mortality in severely ill patients…For sicker patients, I would probably reserve the use of proton-pump inhibitors for those who are being treated with antiplatelet agents, especially in the presence of therapeutic anticoagulants.” 

My take: This study and editorial helps provides insight into the narrow path of benefit that PPIs may provide for ventilated adults in the ICU. This study reinforces my view that there are few circumstances where adding empiric PPIs in children would be beneficial. Children are less likely to have significant GI bleeding than adults and have fewer comorbidities. Thus, PPIs in pediatrics need to be used mainly in the context of active GI bleeding and in children needing treatment for specific etiologies. PPIs have low value in most children as prophylaxis (e.g. children with IBD receiving steroids).

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Is PPI Use Detrimental Before or After a Diagnosis of Inflammatory Bowel Disease?

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N Singh et al. Inflamm Bowel Dis 2023; 29: 1871-1878. Proton Pump Inhibitor Use Before and After a Diagnosis of Inflammatory Bowel Disease

The authors retrospectively utilized the University of Manitoba IBD Epidemiology Database includes all Manitobans diagnosed with IBD between 1984 and 2018 (n=5920). Key findings:

  • Rates of PPI use in control subjects increased gradually from 1.5% to 6.5% over 15 years
  • Persons with IBD had a higher rate of PPI use, peaking up to 17% within 1 year of IBD diagnosis with a rate ratio (RR) of 3.1

The authors noted an abrupt increase in PPI use within 6 months of an IBD diagnosis which could indicate that IBD-related symptoms are being mistakenly treated with a PPI or that IBD may increase reflux-related symptoms. Given the higher rate of PPI use in pre-IBD diagnosis patients, compared to controls, the authors note that “it is possible that their [PPI] use enhances the likelihood of an IBD diagnosis by their role in altering the gut microbiota.” In addition, they note that “a case-control study found that PPIs were associated with an increased risk of pediatric IBD” (NR Schwartz et al. J Pediatr Pharmacol Ther 2019; 24: 489-496).

My take: PPIs are being used more frequently. Whether PPIs are detrimental before or after a diagnosis with IBD is not clear.

Chattahoochee River at Island Ford

Acid Suppression and Antibiotics in Infancy Associated with Increased Risk of Celiac Disease

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M Boechler et al. J Pediatr 2023; 254: 61-67. Acid Suppression and Antibiotics Administered during Infancy Are Associated with Celiac Disease

Methods: A retrospective cohort study was performed using the Military Healthcare System database. N=968,524 children with 1704 cases of celiac disease (CD) in this group (from 2001 to 2013) with prescription for PPIs, H2RAs or antibiotics in first 6 months of life.

Key findings:

  • PPIs (HR, 2.23; 95% CI, 1.76-2.83), H2RAs (HR, 1.94; 95% CI, 1.67-2.26), and antibiotics (HR, 1.14; 95% CI, 1.02-1.28) were all associated with an increased hazard of CD.
  • The risk is increased by use of multiple categories of these medications and/or if acid suppression medications are used for longer periods

There have been previous studies indicating an increased risk of CD in patients given acid suppression (Lebwohl et al. Dig Liver Dis 2014; 46: 36-40) and conflicting data regarding the use of antibiotics. With regard to acid suppression, recent studies have indicated that these medications in infancy may increase the risk of food allergies as well. The authors speculate in their discussion that the increased risk for CD could be related to changes in protein degradation, mucosal permeability, microbiome changes, and immune reactivity. The authors note that their dataset did NOT show an increased risk of CD associated with C-section delivery.

One of the limitations of this study is that early presentations of CD could lead to prescriptions of agents to to help reduce symptoms rather than the medications increasing the risk of developing CD. However, this is unlikely as gluten introduction is often later in infancy.

My take: Better stewardship of antibiotics and acid blockers is needed. Use of acid suppression medications is associated with an increased risk of celiac disease as well as food allergies.

Related blog posts:

Additional posts on Celiac Disease

Panoramic View of Tucson, AZ from Tumamoc Hill

Selected Slides from NASPGHAN 2022 Postgraduate Course (Part 2)

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See previous post for lecturers

Oral small molecultes in IBD. Anne Griffiths, MD
Judith Kelsen, Very early onset IBD
VEO Evaluation
VEO Treatments
Jeremy Adler and Treat to Target for IBD
Jeremy Adler and Treat to Target for IBD
Jeremy Adler and Treat to Target for IBD
Jeremy Adler and Treat to Target for IBD
Jeremy Adler and Treat to Target for IBD
Timothy Sentongo and Growth and Nutrition Issues in the NICU
Maureen Leonard and Gluten-Related Disorders Update
Maureen Leonard and Gluten-Related Disorders Update
Maureen Leonard and Gluten-Related Disorders Update
Maureen Leonard and Gluten-Related Disorders Update
Rachel Rosen and Esophageal Motor Disorders
Katja Kovacic and Functional Nausea
This study was 20 yrs ago -we can do better today

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

New Data: Acid Blockers NOT Associated with Risk of SARS-CoV-2, SARS-CoV-2 in the Pancreas, & Vaccine Passport

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X Fan et al. Gastroenterol 2021; 160: 455-458. Full text link: Effect of Acid Suppressants on the Risk of COVID-19: A Propensity Score-Matched Study Using UK Biobank

Among 9469 included participants, 1516 (16%) were regular users of acid suppressants, and 7953 (84%) were not…propensity score matching (PSM) was applied to match users of acid suppressants and nonusers. 

Key findings:

  • The odds ratio (OR) of testing positive for COVID-19 associated with PPI or H2RA therapy in the PSM cohort was 1.083 (95% confidence interval [CI], 0.892–1.315) and 0.949 (95% CI, 0.650–1.387), respectively.
  • Omeprazole use alone was significantly related to an increased risk of SARS-CoV-2 infection from the subgroup analysis in patients with upper gastrointestinal diseases (OR, 1.353; 95% CI, 1.011–1.825)

My take: This study provides reassurance that acid blockers are unlikely to contribute to the risk of SARS-CoV-2 or to related complications.

Related blog post: PPIs Associated with Increased Risk of COVID-19

Other COVID-19 Information:

Deconstructing PPI-Associated Risks with Nearly 8 Billion Data Points and More on COVID-19 GI Symptoms (Video)

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Link: 22 minute video —COVID-19 and the GI Tract -What We Know Right Now

———————

A recent study (C Ma et al. Gastroenterol 2020; 158: 780-82) used cross-sectional data from the National Ambulatory Medical Care Survey (NAMCS) (2006-2015) with a total 7,872,115,883 weighted observations.  They used this data to evaluate medication exposures and outcomes.

Key findings:

  • There was no association between PPI use and dementia, pneumonia, or intestinal infections.  There was a trend towards intestinal infections (AOR 1.48, CI 0.80-2.71) but this did not reach statistical significance. “Sensitivity analysis showed an association between PPI use and C difficile.”
  • There was an association with chronic kidney disease (CKD) (AOR 1.26); however, this was seen with a multitude of drug classes including statins, calcium channel blockers, and beta-blockers.

Discussion:

  • This study notes that a recent large randomized controlled trial found no statistically significant differences between those receiving PPIs and those receiving placebo except for intestinal infections.
  • With regard to CKD, “it is extremely unlikely that all of these medications increase the risk of CKD, and therefore, it is likely that these findings are due to residual confounding.”

My take: With the exception of C difficile/intestinal infections, this study provides further evidence of the safety of PPIs and a lack of association between these medications and purported PPI-related adverse events.  That said, it is still a good idea to limit use for appropriate indications.

Related blog posts:

Also, IOIBD recommendations for IBD patients and COVID-19 have been published.

Here is link as well:

IOIBD (International Organization for the Study of Inflammatory Bowel Disease) Recommendations (#76) for IBD Patients with Regard to COVID-19:

Full link: IOIBD Update on COVID19 for Patients with Crohn’s Disease and Ulcerative Colitis (3/26/20)