#501 GERD vs NERD: Reflux Updates with Dr. James Callaway

October 13, 2025 | By Elena Gibson

Audio

Video

Transcript available via YouTube

Update your approach to the evaluation and management of GERD with Dr. James Callaway. Learn when to consider ambulatory reflux monitoring and how to determine if someone has an indication for long-term PPI therapy. 

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Show Segments

• Intro
• Case
• Definitions and symptoms
• Reflux mechanisms and triggers
• Medications for Acid suppression 
• Endoscopy and Ambulatory Reflux Monitoring 
• Stopping the PPI 
• Additional etiologies of reflux symptoms 
• Outro

Disclosures

Dr. Callaway reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures. 

GERD vs. NERD: Reflux Updates

1. GERD symptoms are typically postprandial within the first 90 minutes after a meal and reflux occurs most often in the upright position. 
2. The Five C’s are common triggers patients associate with reflux: citrus, carbonated beverages, chocolate, caffeine, cocktails
3. An eight week trial of once daily PPI is recommended for patients with no alarm symptoms and typical symptoms of GERD 
4. PPIs should be taken 30 minutes before a meal for improved efficacy 
5. Potassium competitive acid blockers (PCABs) including vonoprazan are the newest class of acid suppressive medications and have a rapid onset of action
6. If patients fail to respond to a PPI trial or if symptoms recur after the PPI is discontinued, an endoscopy should be completed OFF PPI therapy
7. If there is no endoscopic evidence of GERD (class B or higher esophagitis, long segment Barrett’s, peptic stricture) ambulatory reflux monitoring is recommended. 
8. Reflux hypersensitivity and functional heartburn should be considered in patients with ongoing symptoms despite adequate acid suppression 

GERD

Gastroesophageal reflux disease (GERD) is a common disease defined by troublesome symptoms that occur as a result of gastric acid refluxing from the stomach into the esophagus. The most common symptoms are heartburn (pyrosis) and regurgitation. Dr. Callaway recommends clearly defining what patients mean when they say “heartburn” because this can mean many different things to different people. Ask about red flags including dysphagia, anemia, bleeding, and weight loss. If pyrosis or regurgitation are new for the patient, ask about recent changes in weight or diet as potential triggers. Remember GERD symptoms are typically postprandial within the first 90 minutes after a meal and reflux occurs most often in the upright position. 

Mechanisms and Triggers

Reflux occurs when the intragastric pressures are elevated as a result of food in the stomach and there are transient lower esophageal sphincter (LES) relaxations. The LES relaxation allows gastric contents to reflux into the esophagus leading to symptoms. Additional mechanisms that contribute to GERD include anatomical changes such as a hiatal hernia, hormonal changes from pregnancy and systemic conditions such as scleroderma (Tack 2018).

Dr. Callaway describes the Five C’s as common food triggers for reflux: citrus, carbonated beverages, chocolate, caffeine, cocktails. However, there is not great evidence for specific food groups leading to objective evidence of increased acid reflux such as a higher acid exposure time. Dr. Callaway typically recommends patients decrease intake of their specific triggers. 

Initial Management 

For patients with typical reflux symptoms and no alarm symptoms an 8 week empiric trial of once daily PPI for GERD is recommended. If alarm symptoms are present, endoscopy should be the first step in management (Katz 2022). 

Proton Pump Inhibitors (PPIs) and H2 Receptor Antagonists 

Start with an 8 week trial of a once daily PPI. The initial PPI dose should be equivalent to 40mg of omeprazole, and it should be taken 30 minutes prior to the first meal of the day. H2 blockers are limited by tachyphylaxis and have decreased efficacy in healing erosive esophagitis compared to PPIs (Wang 2005), but they are an option for infrequent symptoms or step-down therapy, particularly in patients with nonerosive reflux disease (NERD)(Katz 2022).

PPI timing 

Optimal timing to take a PPI is 30 to 60 minutes before the first meal of the day to allow the meal to stimulate an acidic environment for the PPI to more effectively turn off proton pumps. If a patient is on twice daily dosing, the second dose should be taken 30 minutes prior to dinner. 

PPI side effects and adverse effects

Diarrhea, nausea and rarely vomiting are the most common gastrointestinal side effects of PPIs. Although studies have suggested an association with various adverse effects, only a slightly increased risk of enteric infections has been supported by higher quality evidence (Katz 2022). Overall, if a patient has an indication for ongoing PPI therapy the benefit of therapy is thought to outweigh potential risks in most patients. 

Potassium Competitive Acid Blockers (PCAB) 

Potassium competitive acid blockers (PCABs) such as vonoprazan are the newest class of medications used for acid reduction.PCABs work by causing reversible inhibition of the hydrogen potassium ATPase pump.PCABs have a rapid onset of action and achieve full effect with the first dose (Andersson 2005).However, they are new and costly. PCABs are primarily being utilized for severe erosive esophagitis (Laine 2023) and in the treatment of H.pylori (Chey 2024), but they were recently FDA approved for non erosive reflux disease (Laine 2024). 

Endoscopy and Ambulatory Reflux Monitoring 

One major change in the most recent ACG guidelines is the recommendation to complete an endoscopy if symptoms of GERD do not adequately respond to an 8 week PPI trial or symptoms recur after the PPI is discontinued following the 8 week trial.It is important to complete the upper endoscopy off PPI therapy, so providers should recommend patients hold their PPI medication for at least 1-2 weeks prior to the procedure. If there is endoscopic evidence of erosive reflux disease with class B or higher esophagitis, long segment Barret’s or a peptic stricture the diagnosis of GERD is confirmed. If there are no erosive changes, ambulatory reflux monitoring is recommended (Katz 2022). 

Ambulatory reflux monitoring can be completed with a wireless reflux monitor placed during endoscopy in the distal esophagus to measure the pH over a 48 to 96 hour period or with a pH impedance monitor placed with manometry. Ambulatory reflux monitoring allows for quantification of acid exposure in the esophagus and for correlation of symptoms with reflux events (Katz 2022). An acid exposure time of >6% is consistent with pathologic reflux disease (Fass 2020). 

GERD vs NERD 

GERD includes both NERD and erosive GERD subtypes. Nonerosive reflux disease (NERD) is reflux disease without evidence of erosive changes on endoscopy but abnormal acid exposure confirmed on ambulatory reflux monitoring. This distinction matters for determining when long-term PPI therapy should be considered. Indefinite PPI therapy is indicated for patients with high grades of esophagitis (class C or D), long-segment Barrett’s esophagus, and peptic stricture disease to ensure mucosal protection and prevent long term complications (Katz 2022). 

Interestingly, one study identified that individuals with NERD had a similar rate of esophageal adenocarcinoma compared to the baseline population (Holmberg 2023)

Stopping the PPI 

Patients with NERD and no other indication for long-term PPI therapy should be trialed off PPI therapy periodically. Dr. Callaway discusses the phenomenon of rebound acid production that typically occurs in the first 10 days after stopping the PPI with patients. Yadlapati et al. looked at predicting which patients could stop PPI therapy using wireless capsule monitoring over a four day period and grouped patients by zero days positive, one day positive, two days positive, three days positive, and fours days positive. The study identified that patients with one positive AET days had a 50% chance of stopping the PPI and remaining off PPI therapy three weeks after monitoring was completed. Interestingly 33% of patients with no positive AET days restarted PPI therapy, supporting the idea of variations in sensitivity to reflux (Yadlapati 2021)

On Demand PPI therapy

On demand PPI therapy is a good option for patients without an indication for long-term daily PPI therapy and a lower acid reflux burden on ambulatory monitoring. Dr. Callaway typically recommends patients take 20mg of over the counter omeprazole for a minimum of five days up to two weeks. 

Is it refractory GERD?

When a patient has ongoing symptoms of pyrosis and regurgitation despite adequate PPI therapy, it is important to consider other possibilities such as an anatomic contributor (hiatal hernia), reflux hypersensitivity or functional heartburn. Reflux hypersensitivity occurs when a patient has increased sensitivity to reflux and even weakly acidic or non acidic reflux leads to symptoms. Functional heartburn occurs when there are reflux symptoms with no evidence of pathologic reflux on endoscopy or ambulatory reflux testing and no correlation of symptoms with reflux events on ambulatory (Patel 2020)

Hiatal Hernias and Anti Reflux Surgery 

Hiatal hernias are often recognized on endoscopy, and they are frequently identified incidentally when an endoscopy is being performed for reasons other than GERD. A hiatal hernia must be greater than two centimeters in length due to normal variations in the gastroesophageal junction.Antireflux surgery should be considered as an option for long-term GERD treatment for patients with objective evidence of GERD particularly patients with LA grade C or D esophagitis, large hiatal hernias and persistent GERD symptoms (Katz 2022). 

Links

1. Hermanos Gutierrez Band

Goal

Listeners will identify and review the initial steps in the evaluation and management of gastroesophageal reflux disease (GERD).  

Learning objectives

After listening to this episode listeners will…  

1. Define common symptoms associated with GERD 
2. Identify alarm signs associated with reflux symptoms 
3. Recognize the recommended steps in the evaluation of GERD 
4. Identify which patients require further evaluation with an endoscopy and/or ambulatory reflux monitoring 
5. Define reflux hypersensitivity and functional heartburn
6. Identify when to consider surgical interventions for GERD 
7. Review the incidence of Barrett’s 

Citation

Gibson EG, Callaway J,  Williams PN, Watto MF. “501 GERD vs NERD Reflux Updates with Dr. James Callaway”. The Curbsiders Internal Medicine Podcast. thecurbsiders.com/category/curbsiders-podcast Final publishing date October 12, 2025.